@article {pmid42565414,
year = {2026},
author = {Ramirez-Contreras, LA and Camargo-Hernández, G and Sanchez-Enriquez, S and Silva-Jara, JM and Hernández Estrada, S and Hernández Villaseñor, LA and Anaya Esparza, LM},
title = {Bioinformatic Tools to Explore the Mechanisms and the Multitarget Recognition of Huperzine A in Alzheimer's and Parkinson's Diseases.},
journal = {Current drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113894501499352260714060149},
pmid = {42565414},
issn = {1873-5592},
abstract = {INTRODUCTION: Considering the shared physiological mechanisms between Alzheimer's disease (AD) and Parkinson's disease (PD), it is plausible that certain compounds may exert therapeutic effects on both neurological disorders. This study aimed to employ in silico techniques to investigate the pharmacological mechanisms of huperzine A (HA) as an alternative treatment for PD and AD.

METHODS: Molecular targets of HA and genes associated with AD and PD were identified from public databases. Gene Ontology analysis, metabolic pathway analysis, and protein-protein interaction (PPI) network construction were performed to identify shared molecular targets. Molecular docking was performed to assess HA affinity for hub proteins and to compare it with that of drugs used to treat AD and PD.

RESULTS: The results suggested that HA interacts with 77 molecular targets common to both diseases. Enrichment analysis revealed that proteins from these targets were involved in biological functions, such as serotonin and amine binding. Hub proteins (SRC, TP53, AKT1, and CASP3) were identified from the PPI network. Furthermore, molecular docking simulations showed favorable binding of HA to the hub proteins and adequate binding to the targets of standard drugs (MAOB and ACHE). On the other hand, molecular dynamics analyses were performed to compare the binding characteristics of HA with those of the control targets.

DISCUSSION: HA may modulate SRC, CASP3, and AKT1, suggesting a pleiotropic mechanism underlying the association between AD and PD. These computational findings provide a rational basis for experimental validation by modulating signaling pathways implicated in inflammatory processes and inhibiting enzymes involved in neurotransmitter degradation.

CONCLUSION: This study contributes to the understanding of the neuroprotective activity of HA in AD and PD. However, further in vitro and in vivo investigations are required to confirm the dual therapeutic potential of HA in the treatment of AD and PD.},
}

@article {pmid42565788,
year = {2026},
author = {Keller, JL and Pennartz, KJ and Sprick, JD and Hein, EJ and Irving, BA and Vann, CG and Butlig, ER and Al-Masri, S and Nelson, AR},
title = {A peripheral perspective on brain health: vascular and skeletal muscle contributions.},
journal = {American journal of physiology. Heart and circulatory physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpheart.00462.2026},
pmid = {42565788},
issn = {1522-1539},
support = {AG079454//HHS | NIH | National Institute on Aging (NIA)/ ; NS135147//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; //Coins for Alzheimer's Research Trust (CART)/ ; AG070146//HHS | NIH | National Institute on Aging (NIA)/ ; AG054840//HHS | NIH | National Institute on Aging (NIA)/ ; AG000029//HHS | NIH | National Institute on Aging (NIA)/ ; HL153497//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; },
abstract = {Age- and disease-related declines in brain health contribute to impairments in physical function, yet effective approaches to lessen these declines remain limited. Overall health is governed by a network of interdependent organ systems, such that dysfunction in one system can propagate across others. Although the brain has been viewed as a top-down regulator of vital functions, evidence indicates that cognition is affected by signals from peripheral organs. This interorgan communication likely explains the coexistence of Alzheimer's disease and related dementias with cardiovascular and metabolic disorders characterized by overlapping pathophysiology. Skeletal muscle and the peripheral vasculature are key contributors to this and represent modifiable systems that can alter brain structure and function. Skeletal muscle regulates myokine release through motor neuron function, contractile activity, and metabolic perturbations, thereby influencing neuroplasticity, mitochondrial function, and inflammatory signaling, and may affect measures of peripheral vascular function, like reactive hyperemia. Other properties of the vasculature, including arterial stiffness, directly affect cerebral perfusion and blood-brain barrier permeability. These systems form a muscle-vascular-brain axis that contributes to brain health and impacts the risk of cognitive impairment. Therefore, our aim was to synthesize the current understanding of interactions among skeletal muscle, the peripheral vasculature, and the brain, and their collective role in maintaining cognitive health. We also highlight recent clinical trials and emerging strategies affecting interorgan crosstalk. These conclusions support a model in which lifestyle interventions targeting peripheral systems, such as resistance training, may preserve brain health across all populations, offering scalable approaches applicable across the lifespan.},
}

@article {pmid42565943,
year = {2026},
author = {Liu, Z and Nie, JF and Liu, H and Liu, Z and Pang, Y and Fu, H and Zhang, Y},
title = {Integrating Metabolomics Data, Network Pharmacology, and Molecular Docking to Investigate the Effect of Aging Times on the Functional Activity of Liupao Tea.},
journal = {Plant foods for human nutrition (Dordrecht, Netherlands)},
volume = {81},
number = {3},
pages = {},
pmid = {42565943},
issn = {1573-9104},
support = {No. GuikeLT2600640006//Guangxi Science and Technology Innovation Platform Project/ ; No. GuikeAA23023006//Guangxi Science and Technology Major Project/ ; No. Guirencaiban202401//Guangxi Bagui Youth Talent Project/ ; Nos. 22464008 and 21765007//National Natural Science Foundation of China/ ; },
mesh = {Molecular Docking Simulation ; Metabolomics ; Oxidative Stress/drug effects ; *Antioxidants/analysis/pharmacology ; Network Pharmacology ; Humans ; *Tea/chemistry ; *Camellia sinensis/chemistry ; Time Factors ; },
abstract = {Liupao tea (LPT) undergoes significant bioactive changes during aging, while the link between these chemical shifts and the regulation of oxidative stress pathologies remains unclear. Therefore, this study integrated metabolomics, network pharmacology, and molecular docking to analyze Maosheng (MS) and Tianyu (TY) LPT samples aged 0-15 and 0-10 years, respectively, and elucidated the potential mechanisms of LPT in five oxidative stress - related diseases, including depression, obesity, Alzheimer's disease, diabetes, and hypertension. Metabolomics identified 42 and 13 core antioxidant metabolites in MS and TY samples, respectively. Among them, core metabolites in MS peaked at 5 years, while TY sustained high abundance levels from 3 to 8 years. Network pharmacology revealed synergistic regulation of all five pathologies by both LPTs, and eight key components were screened from MS, and nine from TY based on degree values. Interestingly, the highest node density was shown in depression, and Sankey connectivity confirmed its strongest modulatory effect. Besides, the core depression‑related components and targets were subjected to molecular docking simulations, and binding energies ranged from - 5.37 to -8.88 kcal/mol for MS components, as well as from - 4.11 to -8.39 kcal/mol for TY components. Importantly, oleaside A and CCRIS 7793 showed the strongest affinities for GAPDH and AKT1, respectively. In general, these results laid a practical foundation for developing an LPT product aimed at relieving oxidative stress-related health issues.},
}

Molecular Docking Simulation
Metabolomics
Oxidative Stress/drug effects
*Antioxidants/analysis/pharmacology
Network Pharmacology
Humans
*Tea/chemistry
*Camellia sinensis/chemistry
Time Factors

@article {pmid42566020,
year = {2026},
author = {Lövdal, S and Meles, SK and Carli, G and Dortmond, A and Kogan, RV and Goldstein, O and Gana-Weisz, M and Orad, RI and Alcalay, RN and Bregman, N and Leenders, KL and Shiner, T},
title = {Effect of genetic factors on [[18]F]FDG PET metabolic phenotypes in dementia with Lewy bodies.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {42566020},
issn = {1619-7089},
abstract = {BACKGROUND: Neuroimaging with [[18]F]FDG PET can support the diagnosis of Dementia with Lewy Bodies (DLB), but it remains unclear how genetic factors influence metabolic phenotypes.

OBJECTIVES: To determine whether GBA1 and APOE ε4 status are associated with diverging [[18]F]FDG PET metabolic patterns in DLB.

METHODS: We analyzed [[18]F]FDG PET scans from 43 patients with DLB stratified by GBA1 and APOE ε4 status, and 35 from healthy subjects. Analyses included the cingulate island sign (CIS), regions of interest, SSM/PCA disease patterns, and a machine learning multi-class model. We evaluated the similarity of the DLB patient scans in our cohort with respect to typical DLB, Alzheimer's disease (AD) and Parkinson's disease (PD)-like patterns.

RESULTS: APOE ε4 status mainly influenced the CIS, with APOE ε4-negative patients showing greater preservation of the DLB-typical CIS pattern (p = 0.03) compared to APOE ε4 carriers. In contrast, GBA1 status influenced global metabolic phenotype. GBA1 carriers showed a more homogeneous PD/DLB-like metabolic pattern in the machine learning model (p = 0.003) compared to GBA1 non-carriers, whereas the latter group demonstrated greater heterogeneity and higher expression of the AD-related metabolic pattern (p = 0.004). These effects were observed along a metabolic spectrum rather than as distinct clusters.

CONCLUSIONS: APOE ε4 and GBA1 modulate distinct aspects of the metabolic phenotype in DLB. GBA1 non-carriers and APOE ε4 carriers showed a higher rate of atypical metabolic signatures, which may contribute to biological heterogeneity and increase the risk of diagnostic misclassification.},
}

@article {pmid42566137,
year = {2026},
author = {Barbosa, KA and Ribeiro, HM and Benevenuto, LGD and Maiorka, PC and Cominetti, MR and Amorim, RM and Cagnini, DQ},
title = {Advances in biomarker discovery for canine cognitive dysfunction: a comprehensive structured narrative review and future perspectives.},
journal = {Veterinary research communications},
volume = {50},
number = {5},
pages = {},
pmid = {42566137},
issn = {1573-7446},
mesh = {Animals ; Dogs ; *Biomarkers/cerebrospinal fluid/blood ; *Dog Diseases/diagnosis/cerebrospinal fluid/blood ; *Cognitive Dysfunction/diagnosis/cerebrospinal fluid/blood ; Amyloid beta-Peptides/cerebrospinal fluid/blood ; Glial Fibrillary Acidic Protein/cerebrospinal fluid/blood ; tau Proteins/cerebrospinal fluid/blood ; },
abstract = {Canine Cognitive Dysfunction (CCD) is a naturally occurring neurodegenerative syndrome in aging dogs that shares clinical and neuropathological parallels with Alzheimer's disease (AD). As the demand for objective diagnostic tools grows, identifying reliable biofluid biomarkers is essential for clinical staging and therapeutic monitoring. This review synthesizes evidence on cerebrospinal fluid (CSF) and blood-based biomarkers (BBM) of CCD, focusing on amyloid-β (Aβ), neurofilament light chain (NfL), tau, and glial fibrillary acidic protein (GFAP). Evidence shows that Aβ42 and Aβ42/Aβ40 ratios exhibit stage-dependent, non-linear alterations resembling early compensatory phases in human AD. In contrast, tau pathology in CCD consists mainly of pre-tangle synaptic hyperphosphorylation rather than abundant neurofibrillary tangles, limiting its current diagnostic utility. GFAP, a marker of astroglial activation, shows inconsistent associations with cognitive decline and remains exploratory. Conversely, NfL has emerged as the most robust biomarker; CSF and plasma NfL levels consistently increase with age, correlate with cognitive impairment, and reflect central axonal pathology, making it the leading candidate for staging and monitoring disease progression. Overall, the CCD biomarker landscape supports a multimodal approach integrating Aβ dysregulation, axonal injury, and glial activation. Advancing this field requires harmonized diagnostic criteria, standardized sampling, and longitudinal studies. Such efforts will strengthen the translational value of CCD as a model for human dementia, accelerating discovery and therapeutic development across species.},
}

Animals
Dogs
*Biomarkers/cerebrospinal fluid/blood
*Dog Diseases/diagnosis/cerebrospinal fluid/blood
*Cognitive Dysfunction/diagnosis/cerebrospinal fluid/blood
Amyloid beta-Peptides/cerebrospinal fluid/blood
Glial Fibrillary Acidic Protein/cerebrospinal fluid/blood
tau Proteins/cerebrospinal fluid/blood

@article {pmid42566636,
year = {2026},
author = {Chen, Y and Chen, X},
title = {Genetic evidence for a causal role of depression in late-onset Alzheimer disease: A Mendelian randomization study.},
journal = {Medicine},
volume = {105},
number = {32},
pages = {e50116},
doi = {10.1097/MD.0000000000050116},
pmid = {42566636},
issn = {1536-5964},
mesh = {*Alzheimer Disease/genetics/epidemiology ; Humans ; *Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; *Depression/genetics/complications ; Genetic Predisposition to Disease ; Age of Onset ; },
abstract = {Observational studies link psychiatric disorders to Alzheimer disease (AD), but whether these associations are causal remains unclear due to confounding and reverse causality. We aimed to dissect these relationships using genetic evidence. We performed a two-sample Mendelian randomization (MR) study to assess the causal effects of 7 psychiatric and neurodevelopmental disorders on AD and its subtypes. The primary analysis utilized the inverse-variance weighted (IVW) method, supported by comprehensive sensitivity analyses (MR Steiger test, MR-Egger, and MR-PRESSO) and a supplementary analysis excluding single nucleotide polymorphisms (SNPs) associated with potential confounders. Depression showed a significant causal association with late-onset AD (odds ratio [OR] = 1.0736, 95% confidence interval [CI]: 1.0084-1.1431, P = .0264). No significant causal associations were found for other psychiatric disorders (all P > .05). A directionality test conducted by MR Steiger confirmed our estimation of potential causal direction (P < .001). Sensitivity analyses excluding pleiotropic SNPs yielded consistent results. The causal association for depression and late-onset AD remained significant after excluding pleiotropic SNPs linked to confounders (OR = 1.0726, 95% CI: 1.0069-1.1425, P = .03). Our study provides genetic evidence supporting a causal role for depression in the etiology of late-onset AD, a link not observed for other major psychiatric disorders tested. These findings highlight the specific importance of managing depression as a potential strategy for mitigating AD risk and suggest distinct etiological pathways between different mental health conditions and neurodegeneration.},
}

*Alzheimer Disease/genetics/epidemiology
Humans
*Mendelian Randomization Analysis
Polymorphism, Single Nucleotide
*Depression/genetics/complications
Genetic Predisposition to Disease
Age of Onset

@article {pmid42566883,
year = {2026},
author = {Zhao, H and Gao, R and Zhang, B and Gao, J and Xue, B and Zhang, Y},
title = {Advances in dopamine transporter inhibitors: Design strategies, structural features, and pharmacological insights.},
journal = {European journal of medicinal chemistry},
volume = {318},
number = {},
pages = {119189},
doi = {10.1016/j.ejmech.2026.119189},
pmid = {42566883},
issn = {1768-3254},
abstract = {Dopamine transporter (DAT) plays a pivotal role in regulating synaptic dopamine homeostasis and is critically involved in various neuropsychiatric disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and substance use disorders. This review highlights cutting-edge advances in the development of DAT inhibitors, offering new insights into their structure-activity relationships, pharmacological mechanisms, and therapeutic potential. The core findings emphasize the significance of conformational selectivity in overcoming addiction-related limitations of typical inhibitors and uncover novel strategies for engineering atypical and allosteric inhibitors with improved efficacy and safety profiles. Furthermore, a comprehensive analysis of clinical trials reveals the main challenges in DAT inhibitor development, such as off-target toxicity and multitarget-related adverse effects, providing a foundation for addressing these issues. By distilling critical design strategies and lessons learned, this review provides a theoretical framework and actionable guidance for the future development of safe, selective, and effective DAT-targeting therapies.},
}

@article {pmid42566983,
year = {2026},
author = {Aaltonen, A and Palviainen, T and Heikkinen, S and Herukka, SK and Hiltunen, M and Kokkola, T and Kärkkäinen, S and Palotie, A and Runz, H and Julkunen, V and Kaprio, J and Saari, TT and Vuoksimaa, E and , },
title = {Genetic architecture of Alzheimer's disease-related plasma biomarkers.},
journal = {Neurobiology of aging},
volume = {168},
number = {},
pages = {123-131},
doi = {10.1016/j.neurobiolaging.2026.07.010},
pmid = {42566983},
issn = {1558-1497},
abstract = {Alzheimer's disease-related plasma biomarker interrelationships and factors underlying these associations remain poorly understood. To address this, we studied the heritability of plasma biomarkers and their associations with cognition. This study included 696 twins, aged 65-85, without a diagnosis of Alzheimer's disease or related dementias. Plasma amyloid beta 42 and 40, phosphorylated tau (p-tau) 181 and 217, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified with Simoa HD-X, and cognition was assessed with cCOG. Heritability of plasma biomarkers was assessed with multivariate twin models and associations with cognition with linear mixed effect models. Phenotypic associations varied from 0.22 between p-tau181 and GFAP to 0.73 between p-tau181 and p-tau217, and the heritability estimates ranged from 0.39 (p-tau181) to 0.66 (GFAP). Genetic and environmental correlations were 0.32-0.67 and 0.06-0.78, with the strongest correlations observed between p-tau181 and p-tau217. P-tau181 and p-tau217 were associated with cognition (β = -0.12; 95% CI: -0.19--0.04 and β = -0.19; 95% CI: -0.26--0.12, respectively). The observed phenotypic and genetic associations highlight shared underlying mechanisms among plasma biomarkers. Despite p-tau181 and p-tau217 having the strongest genetic and environmental correlations, neither approached unity, implying unique genetic and environmental factors. Our results offer insight into the genetic architecture of diagnostic and progression markers of Alzheimer's disease and inform their use in future gene-finding studies.},
}

@article {pmid42567320,
year = {2026},
author = {Chen, H and Wu, Z and Ge, T and Wu, M and Ye, J and Shan, S and Gao, C and Yang, Y and Yuan, C},
title = {Low-carbohydrate and low-fat diets, genetic susceptibility, and long-term risk of dementia: A prospective cohort study.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {101463},
doi = {10.1016/j.ajcnut.2026.101463},
pmid = {42567320},
issn = {1938-3207},
abstract = {BACKGROUND: Low-carbohydrate and low-fat diets (LCDs and LFDs) are promoted for cardiometabolic prevention.

OBJECTIVE: This study examined associations of LCDs and LFDs with incident dementia and evaluated modification by genetic susceptibility.

METHODS: We included 5301 dementia-free adults aged ≥55 years from the Health and Retirement Study. Overall LCD and LFD indices were constructed based on macronutrient composition rankings assessed using a food frequency questionnaire in 2013-2014. Plant-based, animal-based, healthy, and unhealthy sub-scores were derived to characterize macronutrient sources and quality. Incident dementia was defined using the Langa-Weir algorithm through 2022. Genetic susceptibility was assessed using APOE genotype and Alzheimer disease polygenic risk score (AD-PRS). Cox models estimated hazard ratios (HRs).

RESULTS: During the 9-year follow-up, 506 participants developed dementia. Greater LCD score was associated with lower dementia risk (HR per SD increment 0.90, 95% CI, 0.82, 0.99), whereas an overall LFD was not (1.05, 95% CI, 0.96, 1.15). Plant-based and healthy LCDs showed stronger inverse associations (0.85, 95% CI, 0.78, 0.94 and 0.82, 95% CI, 0.74, 0.90), while higher animal-based (1.10; 95% CI, 1.00, 1.20) and unhealthy LFDs (1.13; 95% CI, 1.04, 1.24) were linked to higher dementia risk. Associations were consistent across APOE genotype and AD-PRS strata. Higher plant-based and healthy LCDs were also associated with better global and domain-specific cognitive performance.

CONCLUSION: Adherence to LCDs, particularly plant-based and higher-quality LCDs, was associated with lower dementia risk, consistently across genetic susceptibility strata. These findings underscored the importance of macronutrient quality, in addition to quantity, in promoting cognitive health.},
}

@article {pmid42567350,
year = {2026},
author = {Yang, ZL and Zhang, C and Tang, S and Zhang, XY and Huang, LY and Tan, L and , and , },
title = {Valine modulates Alzheimer's disease risk in APOE ε4 carriers: evidence from two cohorts.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2026.08.014},
pmid = {42567350},
issn = {2090-1224},
abstract = {INTRODUCTION: The apolipoprotein E ε4 (APOE ε4) allele confers the greatest genetic risk for sporadic Alzheimer's disease (AD).

OBJECTIVES: To identify APOE ε4-associated metabolic factors related to AD risk and to provide preliminary insights into their biological and nutritional context.

METHODS: We leveraged multi-omics analyses across two independent cohorts to characterize biomarkers associated with AD. The effects of metabolite × APOE ε4 interactions were tested on incident AD and the ε4-specific metabolic signatures were pinpointed. Multimodal analyses were used to test the underlying mechanisms, including neuroimaging, cerebrospinal fluid (CSF), and PET biomarkers within the A/T/N framework, as well as plasma proteomics combined with bioinformatics enrichment analyses.

RESULTS: Across both cohorts, valine emerged as the only metabolite associated with a reduced risk of incident AD specifically among APOE ε4 carriers (P < 0.005). Significant interaction effects between valine and APOE ε4 were detected in both cohorts (P for meta-analyses < 0.005). Higher levels of valine were associated with greater total white matter and posterior cingulate cortex volumes, as well as with lower levels of CSF tau proteins. Higher valine levels also predicted a slower decline in FDG-PET metabolism. No association was found between valine and Aβ. Mediation analyses of plasma proteomic data suggested statistically significant mediation effects involving GFAP, NEFL, and APOE (P < 2 × 10[-16]).

CONCLUSION: Valine is a metabolite associated with lower AD risk in APOE ε4 carriers, with potential associations with tau pathology, neurodegeneration, and neuroinflammation-related processes. As this was an observational study, causality cannot be inferred.},
}

@article {pmid42567367,
year = {2026},
author = {Riffo-Lepe, N and Gonzalez-Sanmiguel, J and Meza, I and Saavedra-Sieyes, P and Armijo-Weingart, L and Zambrano, H and Riquelme, A and Salinas, A and Martín, LS and Aguayo, LG},
title = {Selective impairment of long-term depression in accumbal D1R+ MSNs involves calcium-permeable AMPARs in early Alzheimer's disease.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107568},
doi = {10.1016/j.nbd.2026.107568},
pmid = {42567367},
issn = {1095-953X},
abstract = {Alzheimer's disease (AD) is increasingly associated with early circuit dysfunction preceding cognitive decline, including neuronal hyperactivity and neuropsychiatric symptoms linked to mesolimbic pathways. The nucleus accumbens (NAc), a central regulator of reward and motivational processing, exhibits early alterations in excitation/inhibition balance in patients and experimental models, yet the synaptic mechanisms underlying its vulnerability remain unclear. Using a double transgenic APP/PS1 mice crossed with a Drd1a-tdTomato reporter line, we combined cell-type-specific electrophysiology, immunohistochemistry, ex vivo photometry, and behavioral assays. At a pre-plaque stage, intraneuronal Aβ accumulated in both dopamine D1 receptor-positive (D1R+) and D1R-negative medium spiny neurons (MSNs). Despite comparable Aβ levels, both high-frequency stimulation-induced long-term depression (LTD) and mGluR1/5-dependent LTD were selectively impaired in D1R+ MSNs. This vulnerability was accompanied by an increased contribution of calcium-permeable AMPA receptors (CP-AMPARs). Subsequent CP-AMPAR blockade reduced the residual evoked excitatory postsynaptic current that persisted after mGluR1/5 activation in APP/PS1 D1R+ MSNs. Because paired-pulse ratios remained unchanged, this residual response was consistent with a predominantly postsynaptic mechanism. These synaptic changes were accompanied by reduced evoked dopamine signaling, increased chocolate consumption, and altered baseline context preference, whereas standard pellet consumption, conditioned place preference, anxiety-like behavior, and social behavior were unchanged. These findings define a pre-plaque, cell-type-specific synaptic phenotype in male APP/PS1 mice in which impaired mGluR1/5-dependent plasticity and persistent CP-AMPAR signaling in D1R+ MSNs coincide with selective reward-related alterations.},
}

@article {pmid42567407,
year = {2026},
author = {Rabinovich, M and Lacham-Hartman, S and Papo, N},
title = {Modulating amyloid-β 42 aggregation and neurotoxicity by Kunitz domains and their derived peptides.},
journal = {New biotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.nbt.2026.08.001},
pmid = {42567407},
issn = {1876-4347},
abstract = {Alzheimer's disease is associated with the aggregation of amyloid-β42 (Aβ42) into species of varying sizes, with intermediate oligomers being the most neurotoxic. We recently reported that amyloid precursor protein inhibitor (APPI), a Kunitz-type protein, and a cyclic peptide derived from its β-domain reduced Aβ42-mediated neurotoxicity, the former by reducing Aβ42 aggregation and formation of toxic Aβ42 oligomers, and the latter by promoting Aβ42 aggregation to form fibrils rather than the neurotoxic Aβ42 oligomers. To address the question of whether these two inhibition mechanisms are controlled by the structure or the amino acid sequence of the protein/peptide, we exploited three Kunitz-type proteins, bikunin, bovine pancreatic trypsin inhibitor (BPTI) and tissue factor pathway inhibitor (TFPI) - chosen for their similar β-strand-rich structures but different sequences to one another and to APPI - and also short peptides that mimic their β-domains, in either cyclic or linear conformation. In-vitro studies showed that the formation of Aβ42 aggregates was reduced by the three Kunitz-type proteins and by their derived cyclic peptides, but not by the linear counterparts of the cyclic peptides. In SH-SY5Y neuroblastoma cells, the Kunitz-type proteins and the cyclic (but not the linear) peptides reduced the intracellular and extracellular accumulation of Aβ42 aggregates, respectively. Both the Kunitz-type proteins and the cyclic peptides inhibited Aβ42-induced mitochondrial membrane depolarization and reduced Aβ42-mediated apoptosis and cell death. Overall, this study thus reveals the potential of the β-hairpin structure, whether as a segment within the Kunitz-type proteins or isolated as a cyclic peptide, to interact with Aβ42, thereby reducing Aβ42 aggregation and hence its neurotoxicity.},
}

@article {pmid42567574,
year = {2026},
author = {Chen, Y and Zhang, B and Yang, S and Wang, P and Wang, X and He, H},
title = {Ultrasensitive detection of blood-based p-tau217 for Alzheimer's disease integrated antibody-oligonucleotide conjugates and RCA/Cas12a system.},
journal = {Analytica chimica acta},
volume = {1418},
number = {},
pages = {345836},
doi = {10.1016/j.aca.2026.345836},
pmid = {42567574},
issn = {1873-4324},
mesh = {*Alzheimer Disease/blood/diagnosis ; Humans ; *tau Proteins/blood/immunology ; *Oligonucleotides/chemistry ; Immunoassay/methods ; Limit of Detection ; Phosphorylation ; },
abstract = {Tau phosphorylated at threonine 217 (p-tau217) is interesting increasingly as "star biomarker" in the field of Alzheimer's disease (AD) diagnosis due to the highest accuracy in detecting AD pathology and predicting future cognitive decline. Here, we developed an ultra-trace blood-based diagnostic platform for p-tau217, termed magnetic-particle-based Immunol Rolling-circle-amplification/Cas12a Assay (MPIRCA). In this approach, the operational process included two main stages: the preparation of All@MP (encompassing immobilization, capture, and binding) and the subsequent one-pot RCA/Cas12a reaction. Through the Ab-DNA, immunoassay was successfully converted into DNA-based molecular diagnostic technology (one-pot RCA/Cas12a reaction) to achieve ultra-high sensitivity with 1 fg/mL limitation of detection. The optimized assay exhibited excellent linearity across a range from 1 fg/mL to 1 ng/mL. The study presents a high feasible diagnostic strategy that combines one-pot operation, high sensitivity and selectivity, offering considerable potential for blood-based diagnosis and management of Alzheimer's disease (AD).},
}

*Alzheimer Disease/blood/diagnosis
Humans
*tau Proteins/blood/immunology
*Oligonucleotides/chemistry
Immunoassay/methods
Limit of Detection
Phosphorylation

@article {pmid42567782,
year = {2026},
author = {Risby-Jones, G and Lee, JD and Fung, JN},
title = {Interleukin-6 trans-signalling as a selectively targetable driver of neurodegeneration.},
journal = {Trends in neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tins.2026.07.002},
pmid = {42567782},
issn = {1878-108X},
abstract = {Interleukin-6 (IL-6) exerts protective and pathogenic effects in the central nervous system through distinct receptor-signalling modes. Classical signalling via membrane-bound IL-6 receptor (IL-6R) is often associated with homeostatic and reparative functions, whereas trans-signalling, mediated by soluble IL-6R, expands IL-6 responsiveness to gp130-expressing cells and may promote chronic inflammation. Emerging evidence implicates dysregulated IL-6 trans-signalling in amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. Here, we review mechanisms linking IL-6 trans-signalling to immune, glial, neuronal, and vascular dysfunction in neurodegeneration. We highlight key knowledge gaps and discuss whether selective targeting of trans-signalling can limit inflammatory pathology while preserving beneficial classical IL-6 functions.},
}

@article {pmid42567789,
year = {2026},
author = {Hotta, M and Tabira, T and Murata, M and Yoshiura, K and Ishikawa, T and Tanaka, H and Nagata, Y and Hashimoto, M and Ikeda, M},
title = {Patterns of ADL and IADL independence across MMSE score ranges in Alzheimer's disease, dementia with Lewy bodies, and frontotemporal dementia: A cross-sectional analysis of a memory-clinic cohort.},
journal = {International psychogeriatrics},
volume = {},
number = {},
pages = {100250},
doi = {10.1016/j.inpsyc.2026.100250},
pmid = {42567789},
issn = {1741-203X},
abstract = {BACKGROUND: Domain-level ADL and IADL independence across MMSE score ranges has been less well described in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). This study described the observed proportions of basic ADL and IADL independence across MMSE score ranges in these three neurodegenerative dementias.

METHODS: In a cohort of 650 patients (524 AD, 90 DLB, 36 FTD), cognitive function was assessed with the Mini-Mental State Examination (MMSE), and daily function was evaluated using the Physical Self-Maintenance Scale and the Lawton IADL scale. Patients were grouped into MMSE score ranges. For each diagnosis and MMSE score range, we calculated the observed proportion of participants rated as independent in each ADL/IADL domain and Wilson score 95% confidence intervals. Because the FTD sample was small (n = 36), with only 1-11 participants in individual five-point MMSE score ranges, and several MMSE-specific subgroup counts were sparse, the analyses were descriptive.

RESULTS: Observed independence proportions varied across ADL/IADL domains, MMSE score ranges, and diagnostic groups. In AD and DLB, shopping, food preparation, and medication management had low observed independence proportions even in higher MMSE ranges. In the MMSE 21-30 stratum, selected absolute numerical contrasts between DLB and AD ranged from 7.2 percentage points for feeding to 18.4 percentage points for bathing. Estimates for FTD, which were based on only 1-11 participants per five-point MMSE score range, and for DLB in the MMSE 0-10 stratum were based on small denominators and were therefore imprecise.

CONCLUSIONS: This study provides descriptive estimates of domain-level ADL and IADL independence across MMSE score strata in AD, DLB, and FTD. The results may contribute to domain-specific assessment and support planning for people living at home with MCI or dementia. These findings should be regarded as hypothesis-generating for future studies.},
}

@article {pmid42567790,
year = {2026},
author = {Xu, D and Zhang, H and Piao, Z and He, Y and Li, H and Zhang, N},
title = {Functional heterogeneity across structural MRI-based atrophy subtypes in Alzheimer's disease.},
journal = {International psychogeriatrics},
volume = {},
number = {},
pages = {100255},
doi = {10.1016/j.inpsyc.2026.100255},
pmid = {42567790},
issn = {1741-203X},
abstract = {OBJECTIVES: This study explored whether distinct Alzheimer's disease (AD) structural atrophy subtypes exhibit divergent functional profiles.

DESIGN: A cross-sectional multimodal neuroimaging and electrophysiological study.

SETTING: Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China.

PARTICIPANTS: A total of 116 patients with AD and 74 cognitively unimpaired controls underwent structural MRI. Patients with AD were stratified into three MRI-derived atrophy-pattern groups corresponding to hippocampal-sparing (HpSp-MRI), typical (tAD-MRI), and limbic-predominant (LP-MRI) subtypes.

MEASUREMENTS: Resting-state functional MRI was used to assess intra- and internetwork functional connectivity, and EEG was used to evaluate spectral power and microstate dynamics.

RESULTS: The HpSp-MRI subtype showed lower intranetwork connectivity than both the LP-MRI and tAD-MRI subtypes in the visual, somatomotor, and dorsal attention networks. The LP-MRI and tAD-MRI subtypes differed in ventral attention network connectivity. Moreover, the LP-MRI subtype exhibited stronger internetwork connectivity in specific network pairs compared with the other subtypes. EEG analysis suggested a possible difference in the microstate 3-to-1 transition between the LP-MRI and tAD-MRI groups.

CONCLUSIONS: MRI-derived atrophy-pattern subtypes showed different resting-state functional connectivity profiles, providing a potential basis for personalized brain network-targeted interventions in AD.},
}

@article {pmid42567919,
year = {2026},
author = {Mogavero, F and Galluzzi, G and Dolce, E and Malangone, D and Raimo, S and Di Vita, A and Galosi, E and Bruno, G and Sepe Monti, M and Talarico, G and D'Antonio, F and Palermo, L},
title = {Inside and outside the body space: a study on environmental knowledge, interoceptive and functional body representations in the prodromal stage of dementia.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {9},
pages = {},
pmid = {42567919},
issn = {1590-3478},
mesh = {Humans ; Female ; Male ; Aged ; Cross-Sectional Studies ; *Cognitive Dysfunction/physiopathology/psychology ; *Spatial Navigation/physiology ; *Prodromal Symptoms ; *Interoception/physiology ; *Body Image/psychology ; Neuropsychological Tests ; Middle Aged ; Space Perception/physiology ; *Dementia/psychology/physiopathology ; },
abstract = {BACKGROUND: There is increasing interest in identifying sensitive cognitive markers for the early detection of Alzheimer's disease (AD). Spatial navigation has emerged as a promising marker, as impairments in both egocentric and allocentric navigation have been reported in preclinical AD and mild cognitive impairment (MCI). However, findings regarding the relative involvement of these navigational representations remain inconsistent. Moreover, little is known about how MCI affects other forms of spatial representation beyond navigation.

OBJECTIVE: The present study aims to investigate navigational, inner, and outer bodily representations in individuals with MCI to provide a broader characterization of the cognitive changes associated with this condition across different bodily and navigational space representations.

METHODS: We conducted a cross-sectional comparative study involving 28 healthy controls (HC) and 25 participants diagnosed with MCI (PtwMCI). All participants completed tasks and questionnaires probing: (a) different interoceptive dimensions (interoceptive accuracy [IAcc], awareness [IAw], and sensibility [ISe]); (b) action-oriented (aBR) and nonaction-oriented (NaBR) body representations; (c) landmark, route, and survey knowledge of a virtual environment.

RESULTS: PtwMCI showed reduced IAcc and ISe and performed less accurately in landmark and route tasks compared to HC.

CONCLUSIONS: Our findings indicate early impairments in interoceptive (inner body) and navigational processing, even in the initial stages of cognitive decline. These difficulties may thus represent an early marker of neurodegeneration. The observed co-occurrence of alterations across these domains highlights the need for future studies to clarify the relationship between body-related cognitive processes and broader cognitive functions in the Alzheimer's disease continuum.},
}

Humans
Female
Male
Aged
Cross-Sectional Studies
*Cognitive Dysfunction/physiopathology/psychology
*Spatial Navigation/physiology
*Prodromal Symptoms
*Interoception/physiology
*Body Image/psychology
Neuropsychological Tests
Middle Aged
Space Perception/physiology
*Dementia/psychology/physiopathology

@article {pmid42568007,
year = {2026},
author = {Wang, Z and Chen, J},
title = {ARG128-associated recognition of nobiletin by BACE1 revealed by triplicate molecular dynamics, MM-GBSA, and residue-level decomposition.},
journal = {Molecular diversity},
volume = {},
number = {},
pages = {},
pmid = {42568007},
issn = {1573-501X},
abstract = {Alzheimer's disease (AD) remains the leading cause of dementia worldwide, and beta-secretase 1 (BACE1) remains a high-priority target for reducing amyloid-beta production. Nobiletin, a polymethoxylated flavonoid from citrus peel, has reported neuroprotective and amyloid-lowering effects in AD models, and previous enzymatic work suggested weak BACE1 inhibition; however, its replica-level binding stability and residue-level energetic determinants remain unresolved. Here, we analyzed the nobiletin-BACE1 complex using ChEMBL-based chemical-space contextualization, qualitative QSAR uncertainty assessment, molecular docking, triplicate 200-ns all-atom molecular dynamics simulations, molecular mechanics generalized Born surface area (MM-GBSA) end-point scoring, residue-level decomposition, ProLIF interaction fingerprints, electrostatic surface analysis, and a same-protocol OM99-2 structural control. The ligand remained locally accommodated within the BACE1 cleft across the sampled trajectories, with a mean internal MM-GBSA score (DeltaG_bind) of - 15.71 +/- 0.76 kcal/mol (n = 3: - 14.20, - 16.35, and - 16.57 kcal/mol). Residue-level decomposition identified ARG128 as the dominant computed hotspot (total mean = - 11.13 +/- 0.38 kcal/mol), with favorable van der Waals (VDW mean = - 6.88 +/- 0.21 kcal/mol) and Coulombic (Coulomb mean = - 4.25 +/- 0.53 kcal/mol) components. Additional hydrophobic/aromatic packing involved VAL69, TYR71, PRO70, PHE38, and PRO129, while ASP32/ASP228 were positioned outside the dominant nobiletin contact pattern. Together, these results support a putative ARG128-associated, non-dyad-dominant catalytic-cleft recognition model that should be interpreted as a hypothesis-generating computational framework for future biochemical testing and scaffold optimization.},
}

@article {pmid42568064,
year = {2026},
author = {Yang, J and Zhao, X and Liu, Y and Cai, Y and Fan, Y and , },
title = {Interactive Effects of Plasma Alzheimer Disease Biomarkers and White Matter Hyperintensities on Cognitive Decline and Clinical Progression in Nondemented Adults.},
journal = {Journal of the American Heart Association},
volume = {},
number = {},
pages = {e050676},
doi = {10.1161/JAHA.126.050676},
pmid = {42568064},
issn = {2047-9980},
abstract = {BACKGROUND: Alzheimer disease pathology and cerebral small-vessel disease frequently coexist in older adults, yet how their interaction influences early clinical progression remains poorly understood, particularly in individuals without dementia. We aimed to investigate how plasma Alzheimer disease biomarkers and white matter hyperintensities (WMHs) interact to influence cognitive trajectories and the risk of progression to cognitive impairment and dementia.

METHODS: We studied 463 nondemented participants from the ADNI (Alzheimer's Disease Neuroimaging Initiative). Linear mixed-effects models assessed interactions between plasma biomarkers and WMHs on cognitive trajectories. Cox models examined incident cognitive impairment and dementia. Moderated mediation analyses explored potential biological pathways.

RESULTS: Among 463 participants, plasma phosphorylated tau 217 to β-amyloid 42 ratio was the only biomarker that consistently interacted with WMHs across multiple stages of disease progression, including cognitive decline (Mini-Mental State Examination: β=-0.05 [95% CI, -0.06 to -0.03]; executive function: β=-0.02 [95% CI, -0.03 to -0.01]; memory: β=-0.03 [95% CI, -0.04 to -0.02]; language: β=-0.03 [95% CI, -0.04 to -0.02]; visuospatial function: β=-0.02 [95% CI, -0.04 to -0.01]) and increased clinical risk (cognitive impairment: χ[2]=15.67, P=0.047; dementia: χ[2]=15.88, P=0.044). These interactive associations were most pronounced in cognitively normal individuals and men. Moderated mediation analyses indicated that plasma glial fibrillary acidic protein partially mediated the interaction between phosphorylated tau 217 to β-amyloid 42 ratio and WMHs for executive function and language performance.

CONCLUSIONS: These findings indicate that phosphorylated tau 217 to β-amyloid 42 ratio and WMHs jointly contribute to clinical progression in nondemented individuals, with astrocytic activation potentially involved in this process.},
}

@article {pmid42568124,
year = {2026},
author = {Blujus, JK and Oh, H and , },
title = {The Impact of Denoising Approaches on the Relationship Between Alzheimer's Disease Diagnostic Status and Network Topology Measures.},
journal = {Human brain mapping},
volume = {47},
number = {11},
pages = {e70622},
doi = {10.1002/hbm.70622},
pmid = {42568124},
issn = {1097-0193},
support = {R01AG068990/NH/NIH HHS/United States ; R01AG069265/NH/NIH HHS/United States ; S10OD025181/NH/NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/physiopathology ; *Magnetic Resonance Imaging/methods/standards ; Female ; *Cognitive Dysfunction/diagnostic imaging/physiopathology ; Male ; *Brain/diagnostic imaging/physiopathology ; Aged ; *Nerve Net/diagnostic imaging/physiopathology ; *Image Processing, Computer-Assisted/methods/standards ; Aged, 80 and over ; Artifacts ; *Connectome/methods/standards ; },
abstract = {Graph theory provides a promising technique to investigate Alzheimer's disease (AD)-related alterations in brain network properties. However, there are discrepancies in the reported disruptions that occur to network topology across the AD continuum. In this study, we examined whether diagnostic group differences in graph metrics are attributed to differences in denoising approach used in fMRI processing. Resting state data from 60 cognitively normal (CN), 55 Mild Cognitive Impairment (MCI), and 38 AD participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were denoised using 11 pipelines including combinations of confound regression (head motion parameters, white matter [WM], cerebrospinal fluid [CSF], global signal), volume censoring (scrubbing, spike regression), and component-based noise removal (Independent Component Analysis-based Automatic Removal of Motion Artifacts [ICA-AROMA], anatomical and temporal component correction). Graph metrics representing network segregation (clustering coefficient, modularity, local efficiency), network integration (largest connected component, path length, global efficiency), and small-worldness were calculated. The results revealed that diagnostic group differences in modularity and local efficiency were dependent on denoising approach, especially in high-parameter regression models in combination with censoring methods (36 parameters and spike regressor or volume censoring). Independent of denoising approach, CN exhibited more segregated (clustering coefficient) but less integrated (largest component, path length, global efficiency) networks than MCI and AD. Independent of diagnosis, denoising strategy significantly affected the magnitude of all metrics, particularly models including global signal regression. Collectively, these results suggest that the directionality of the diagnostic differences in network topology, particularly in global metrics of network segregation, can vary based upon the denoising approach employed, although the effect size is small. Transparent reporting of preprocessing decisions is critical for the accurate interpretation of graph theoretical findings in the context of AD and a better understanding of the mechanisms underlying pathological aging.},
}

Humans
*Alzheimer Disease/diagnostic imaging/physiopathology
*Magnetic Resonance Imaging/methods/standards
Female
*Cognitive Dysfunction/diagnostic imaging/physiopathology
Male
*Brain/diagnostic imaging/physiopathology
Aged
*Nerve Net/diagnostic imaging/physiopathology
*Image Processing, Computer-Assisted/methods/standards
Aged, 80 and over
Artifacts
*Connectome/methods/standards

@article {pmid42568171,
year = {2026},
author = {Lv, J and Cai, X and Yang, Z and Li, B and Zhou, Y and Li, F and Fu, H},
title = {A comprehensive assessment of cholinesterase inhibitors for the treatment of Alzheimer's disease based on drug selection recommendations for Chinese Medical Institutions.},
journal = {Expert review of pharmacoeconomics & outcomes research},
volume = {},
number = {},
pages = {},
doi = {10.1080/14737167.2026.2715983},
pmid = {42568171},
issn = {1744-8379},
abstract = {BACKGROUND: Cholinesterase inhibitors (ChEIs) are widely used to treat Alzheimer's disease (AD), yet the optimal choice remains unclear.

RESEARCH DESIGN AND METHODS: This study aimed to comprehensively evaluate the overall clinical value of seven ChEI formulations (donepezil tablets, rivastigmine capsules, rivastigmine patches, galantamine tablets, galantamine orally disintegrating tablets, and two huperzine A formulations) to provide evidence-based guidance for rational AD pharmacotherapy selection. The evaluation framework used in this study was derived from the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition). This framework integrates mini-health technology assessment (mini-HTA) with the System of Objectified Judgment Analysis (SOJA). Seven formulations were assessed across five weighted dimensions: pharmacological properties (28 points), efficacy (27 points), safety (25 points), economy (10 points), and other attributes (10 points). A systematic literature search was performed using PubMed, CNKI, Wanfang, and official regulatory databases.

RESULTS: Within this assessment framework, donepezil tablets achieved the highest score (74.86), followed by rivastigmine patches (73.50) and rivastigmine capsules (72.28). These three formulations are recommended as priority options for inclusion in Chinese hospital formularies. The remaining four drugs may be prescribed according to individual patient conditions and institutional available resources.

CONCLUSIONS: This evaluation provides evidence-based guidance for clinical and institutional decision-making in AD management and delivers a generalizable assessment framework adaptable to local real-world data for healthcare institutions globally.},
}

@article {pmid42568185,
year = {2026},
author = {Larimi, MG and Thurber, KR and Tycko, R},
title = {Polymorphic structures of rapidly twisting 40-residue amyloid-β fibrils.},
journal = {Biophysical journal},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bpj.2026.08.003},
pmid = {42568185},
issn = {1542-0086},
abstract = {Fibrils formed by 40- and 42-residue amyloid-β peptides (Aβ40 and Aβ42) are polymorphic, containing molecular structures that vary with growth conditions in ways that are not fully understood. Here we use cryogenic electron microscopy to characterize the structure of rapidly twisting Aβ40 fibrils, for which the distance between apparent width minima in electron microscope images ("cross-over distances") is approximately 25 nm. From samples grown under a single set of growth conditions, we obtain high-resolution structures for three different rapidly twisting polymorphs. Although their cross-over distances are similar, the three rapidly twisting polymorphs differ in twist handedness, symmetry, molecular conformations, and intermolecular contacts. Two of the rapidly twisting polymorphs resemble Aβ40 polymorphs with longer cross-over distances that have been described previously, including polymorphs extracted from brain tissue of Alzheimer's disease patients or created by seeded growth from amyloid in brain tissue, but have shorter conformationally ordered segments and other specific conformational differences. These results contribute to our understanding of amyloid polymorphism, connections between morphology and molecular structure, and relationships between brain-derived and in vitro-grown fibrils.},
}

@article {pmid42568190,
year = {2026},
author = {Kim, B and Belza, B and Johnson, S and Waddington, E and Moczygemba, W and Fazio, S and Prophater, L},
title = {Evaluating a Coaching Intervention for Dementia Care Practice Recommendations in Care Communities: A Cluster Randomized Controlled Trial.},
journal = {The Gerontologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/geront/gnag183},
pmid = {42568190},
issn = {1758-5341},
abstract = {BACKGROUND AND OBJECTIVES: Within care communities, including nursing home and assisted living settings, person-centered dementia care, outlined by the 2018 Alzheimer's Association Dementia Care Practice Recommendations (DCPR), is foundational to quality care and improving staff outcomes. This study evaluates the effectiveness of a six-month Care Community Coaching Program in enhancing person-centered dementia care and staff outcomes in alignment with the DCPR.

RESEARCH DESIGN AND METHODS: A cluster randomized controlled trial was conducted with 77 care communities and 434 staff members-227 from 38 intervention communities and 207 from 39 control communities. Outcomes included employee satisfaction (areas: job satisfaction, team building and communication, scheduling and staffing, training, and management and leadership), person-centered care practices (areas: workplace practices, individualized care and services, caregiver-resident relationships), and dementia care confidence, measured pre- and post-intervention and at three-month follow-up. A generalized Estimating Equations (GEE) model was used to estimate intervention effects.

RESULTS: Care communities assigned to the coaching intervention showed statistically significant improvements in employee satisfaction and staff perceptions of workplace practices and individualized care. No statistically significant effects on staff perceptions of caregiver-resident relationships or on dementia care confidence were noted.

DISCUSSION AND IMPLICATIONS: Findings provide direction for future research and intervention development, including examining coaching's impact on resident quality outcomes, and incorporating skills training into future models. Collectively, findings provide evidence of the effectiveness of a Care Community Coaching Program in improving staff outcomes and person-centered practices, offering a practical path towards improving the lived experience of residents and staff in care communities.},
}

@article {pmid42568211,
year = {2026},
author = {Uruk, G and Youssef, H and Gatto, RG and Hossain, N and Whitwell, JL and Reichard, RR and Josephs, KA},
title = {Artificial intelligence-based 3D segmentation of tangle-associated TDP-43 in neurodegeneration.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70131},
doi = {10.1111/bpa.70131},
pmid = {42568211},
issn = {1750-3639},
support = {R01-AG37491/NH/NIH HHS/United States ; },
abstract = {TAR DNA-binding protein 43 (TDP-43) inclusions are often associated with hyperphosphorylated tau, thus neurofibrillary tangles as the hallmark of Alzheimer's disease (AD) and primary age-related tauopathy (PART). TDP-43 in AD is associated with cognitive impairment, and while staging is known, the localization, cellular and inclusion characteristics of TDP-43 are yet to be elucidated. We investigate relationships between TDP-43 inclusions and the tangle maturation continuum in AD, PART, and co-pathologies by multiplex immunostaining combined with artificial intelligence (AI)-based segmentation via object recognition, reconstruction, and quantification. We performed anti-phosphorylated TDP-43 immunofluorescence with phosphorylated tau labeling different stages and modifications of tangles (AT8, pS396, TauC3, MN423, GT38) in three controls, three cases with PART and TDP-43 (PART-TDP), five cases with high likelihood AD and TDP-43 (AD-TDP), and four cases of high likelihood AD with TDP-43 and Lewy Body disease (AD-TDP-LBD). Confocal imaging was taken from eight regions: amygdala (amygdala-BL and amygdala-CM) and hippocampus (Cornu Ammonis (CA)-1, CA2/3, CA4, dentate gyrus (DG), subiculum (SUB)), and entorhinal cortex (ERC) and quantified with AI segmentation to identify 3D spatial relations, thus the maturity of neurofibrillary tangle associated TDP-43 (TAT) inclusions. TATs, which were either identified by pTDP-43 and AT8 or pTDP-43 and pS396 double positivity, were also investigated by Thioflavin S (ThioS) histochemistry. We found pS396 labeled mature TATs predominated in PART and AD in every region. Basolateral and centromedial amygdala displayed overall greatest number of pre-TATs and mature TATs. Mature TATs were homogenously distributed among hippocampal subfields whereas CA4 and DG had the greatest mature TAT composition. ERC revealed closer numbers of pre-TATs and mature TATs yet mature TATs predominated all groups. Unbiased AI-based object identification, reconstruction, and TAT maturation analysis pipeline in conjunction with TDP-43, tau, and ThioS multiplex immunostaining demonstrated unique aggregation and maturation patterns, highlighting region-specific dynamics in the neurodegenerative processes of PART and AD.},
}

@article {pmid42568438,
year = {2026},
author = {Sun, C and Zhang, T and Fan, B and Zhang, X and Zhao, N},
title = {Aerobic exercise combined with FK866 ameliorates Alzheimer's disease-like pathology in APP/PS1 mice with NAMPT abnormality.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1876444},
pmid = {42568438},
issn = {1664-3224},
mesh = {Animals ; *Nicotinamide Phosphoribosyltransferase/metabolism ; *Alzheimer Disease/therapy/pathology/metabolism ; *Piperidines/pharmacology ; Mice ; Amyloid beta-Protein Precursor/genetics ; *Acrylamides/pharmacology ; Mice, Transgenic ; *Physical Conditioning, Animal ; Disease Models, Animal ; *Cytokines/metabolism ; Presenilin-1/genetics ; NAD/metabolism ; Mitochondria/metabolism ; Amyloid beta-Peptides/metabolism ; Male ; Brain/metabolism/pathology ; Humans ; },
abstract = {Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD[+] salvage pathway, has emerged as an important regulatory node linking metabolic homeostasis to neuroinflammatory responses. However, although pharmacological inhibition of NAMPT may attenuate inflammatory activation, it may also reduce intracellular NAD[+] availability, thereby exacerbating mitochondrial dysfunction and disturbances in energy metabolism. Here, we found that 6-month-old APP/PS1 mice exhibited an abnormal, cell type-specific distribution of NAMPT in the brain, characterized by reduced neuronal NAMPT and increased microglial NAMPT. This abnormality was accompanied by disrupted NAD[+] homeostasis, marked neuroinflammatory activation, mitochondrial structural and functional impairment, increased β-amyloid (Aβ) burden, and impaired learning and memory ability. FK866 (1 mg/kg per injection, once every other day for 12 weeks) alone exerted limited effects and was insufficient to ameliorate the overall pathological phenotype. By comparison, a 12-week aerobic treadmill exercise program markedly ameliorated cognitive impairment, attenuated Aβ pathology, suppressed neuroinflammation, and improved mitochondrial integrity and bioenergetic function in APP/PS1 mice. More importantly, under NAMPT-inhibited conditions, exercise still preserved hippocampal NAD[+] homeostasis and maintained significant neuroprotective effects. Compared with exercise alone, the combined intervention with exercise and FK866 further improved selected indices related to Aβ pathology, neuroinflammation, oxidative stress, and mitochondrial damage. These additional effects may be associated with increased NAD[+] biosynthesis through the NMNAT3 pathway, as well as reduced NAD[+] consumption and neuroinflammatory activation through the suppression of CD38 and PARP1 expression.},
}

Animals
*Nicotinamide Phosphoribosyltransferase/metabolism
*Alzheimer Disease/therapy/pathology/metabolism
*Piperidines/pharmacology
Mice
Amyloid beta-Protein Precursor/genetics
*Acrylamides/pharmacology
Mice, Transgenic
*Physical Conditioning, Animal
Disease Models, Animal
*Cytokines/metabolism
Presenilin-1/genetics
NAD/metabolism
Mitochondria/metabolism
Amyloid beta-Peptides/metabolism
Male
Brain/metabolism/pathology
Humans

@article {pmid42568451,
year = {2026},
author = {Guo, J and Li, J and Gao, B and Liu, K and Sun, X and Ye, D and Mao, Y},
title = {Independent and combined associations of diabetes and thyroid disorders with risks of incident dementia.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1874555},
pmid = {42568451},
issn = {1664-2392},
mesh = {Humans ; *Thyroid Diseases/complications/epidemiology ; Female ; *Dementia/epidemiology/etiology ; Male ; Risk Factors ; *Diabetes Mellitus/epidemiology ; Incidence ; Aged ; United Kingdom/epidemiology ; Middle Aged ; },
abstract = {BACKGROUND: Diabetes and thyroid disorders are modifiable risk factors for cognitive impairment. However, no studies have been conducted to comprehensively examine associations of different types of the two diseases, as well as their combinations, with dementia risks.

METHODS: Based on the data from UK Biobank study, patients with different types of diabetes and thyroid disorders were identified with the hospital inpatient record. Status of dementia was assessed with multi-source information. Independent and combined associations of diabetes and thyroid disorders with dementia were estimated with Cox regression models.

RESULTS: Among 284,081 participants, 8,236 incident cases of all-cause dementia (ACD) [3,755 Alzheimer's disease (AD) cases, 1,893 vascular dementia (VD) cases] were identified over a mean [standard deviation (SD)] follow-up of 13.03 (2.29) years. Four types of diabetes and two types of thyroid disorders were significantly associated with increased risks of dementia. Compared with participants without diabetes and thyroid disorders, those with only thyroid disorders [hazard ratio (HR) = 1.33, 95% confidence interval (CI) = 1.21 to 1.47, P < 0.001], only diabetes (HR = 1.76, 95% CI = 1.64 to 1.89, P < 0.001), and both (HR = 2.16, 95% CI = 1.84 to 2.53, P < 0.001) had elevated risks of ACD (P trend < 0.001), as well as higher risks of AD and VD. Combined associations of hypothyroid and diabetes and of hyperthyroid and diabetes were also significantly positive (all P values < 0.05). Moreover, cumulative years of diabetes and thyroid were related to higher risks of dementia.

CONCLUSIONS: Diabetes, thyroid disorders, and their combinations were associated with increased risks of dementia in adults aged 55 years and older.},
}

Humans
*Thyroid Diseases/complications/epidemiology
Female
*Dementia/epidemiology/etiology
Male
Risk Factors
*Diabetes Mellitus/epidemiology
Incidence
Aged
United Kingdom/epidemiology
Middle Aged

@article {pmid42568502,
year = {2026},
author = {Han, D and Yang, C},
title = {Infection-driven gut dysbiosis and epigenetic programming of microglia: toward a systems level framework linking microbial metabolites, neuroinflammation, synaptic dysfunction, and probiotic modulation.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1815265},
pmid = {42568502},
issn = {2235-2988},
mesh = {*Microglia/metabolism/immunology ; Humans ; *Epigenesis, Genetic ; *Dysbiosis/microbiology ; *Probiotics ; Animals ; *Neuroinflammatory Diseases ; *Gastrointestinal Microbiome ; Inflammation ; Neurodegenerative Diseases ; Synapses ; },
abstract = {Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases are increasingly viewed as conditions influenced by systemic immune and metabolic disturbances beyond the central nervous system (CNS). Emerging evidence suggests that infection-driven intestinal dysbiosis may function as an upstream contributor to systemic inflammation through disruption of gut barrier integrity. Increased permeability can facilitate the translocation of microbial components and metabolites into circulation, potentially influencing host immune programming via epigenetic mechanisms. Among CNS immune cells, microglia appear particularly susceptible to such peripheral cues due to their longevity and capacity for stimulus-dependent transcriptional adaptation. Experimental studies indicate that transient systemic immune challenges may induce persistent chromatin-level alterations within microglial regulatory regions, thereby reshaping their responsiveness to subsequent inflammatory stimuli or age-related stressors, including oxidative stress, chronic low-grade inflammation (inflammaging), and age-associated decline in cellular homeostatic and repair mechanisms. This phenomenon, often described as innate immune memory, may contribute to sustained neuroinflammatory activity and impaired synaptic function across the lifespan. Microbiota-derived metabolites, including short-chain fatty acids and tryptophan catabolites, have been implicated in modulating host transcriptional pathways through histone deacetylase inhibition and receptor-mediated signaling.},
}

*Microglia/metabolism/immunology
Humans
*Epigenesis, Genetic
*Dysbiosis/microbiology
*Probiotics
Animals
*Neuroinflammatory Diseases
*Gastrointestinal Microbiome
Inflammation
Neurodegenerative Diseases
Synapses

@article {pmid42568632,
year = {2026},
author = {Liu, J and Chen, W},
title = {Identification and validation of mitophagy and astrocyte-related molecular signature in the pathogenesis of Alzheimer's disease: evidence from ensemble learning-driven multi-omics and clinical validation.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1910621},
pmid = {42568632},
issn = {1662-4548},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited diagnostic tools and therapeutic options. Dysregulated mitophagy in astrocytes plays a pivotal role in AD pathogenesis. This study aims to identify a mitophagy and astrocyte (MA)-associated molecular signature for AD diagnosis and therapeutic targeting.

METHODS: Limma, WGCNA, xCell, PPI network and integrated machine learning pipeline coupled with SHAP were deployed on AD patient hippocampal bulk profiles (GSE28146, GSE36980, GSE29378, GSE48350) for identification of MA-associated predictive model and hub gene. Next, astrocyte patten and MA-associated hub gene molecular performance were estimated in hippocampal single-cell profile of AD patients (GSE163577) via advanced analytical frameworks. In addition, active learning framework and molecular docking was deployed in GSE29378 for identification of therapeutic candidate for AD patients by targeting MA-associated hub gene. Furthermore, AD hippocampal tissues were collected, and then MA-associated hub gene expression was estimated.

RESULTS: A core 8-gene MA signature (ITSN1, VLDLR, CYP7A1, SREBF2, RASL12, TPMT, CYP4X1, ARHGEF) was identified, which can guide the molecular subgroup identification and predictive model construction for AD patients. ITSN1 can be considered as the MA-associated hub gene in AD pathogenesis, which was up-regulated and predominantly expressed in astrocytes. Drug repositioning identified BRD-K10008415 as the potential compound predicted to reverse the AD signature by targeting ITSN1.

CONCLUSIONS: This study identified ITSN1 as a MA-associated critical hub potential connecting mitophagy dysregulation and astrocyte dysfunction in AD. We also identified MA-associated molecular signatures that can potentially elaborate predictive effects on AD pathogenesis. BRD-K10008415 can be considered as potential candidate for AD treatment by targeting ITSN1.},
}

@article {pmid42569056,
year = {2026},
author = {Dowjat, WK and Hwang, YW},
title = {Overexpression of DYRK1A in down syndrome: Analysis of kinase activity.},
journal = {Biochemistry and biophysics reports},
volume = {47},
number = {},
pages = {102722},
pmid = {42569056},
issn = {2405-5808},
abstract = {DYRK1A (dual-specificity tyrosine phosphorylation regulated kinase 1A) is known to play critical roles in regulating numerous cellular functions like cell cycle, neuronal development, and immune homeostasis. Altered expression DYRK1A is implicated in Alzheimer's Disease and various features of Down Syndrome (DS). The DYRK1A gene is located on chromosome 21 and due to trisomy of this chromosome in DS, the level of DYRK1A is elevated in the gene-dosage dependent manner. Nevertheless, how an increase in DYRK1A protein level would affect its activity in DS remains to be determined. The question was examined by performing side by side comparison of protein levels and the activity of DYRK1A extracted from control and DS samples. We show that DYRK1A activity elevation in DS is in parallel to that of DYRK1A protein level regardless of the status of kinase phosphorylation. This suggests that DYRK1A catalytic activity in DS is mainly regulated by protein level.},
}

@article {pmid42569203,
year = {2026},
author = {Wu, HY and Hou, JH and Huang, LY and Tan, L and Xu, W},
title = {APOE Genotypes Modulate the Relationship of Hypertension With Alzheimer's Disease: Associations and Clues of Peripheral Mechanisms.},
journal = {Biological psychiatry global open science},
volume = {6},
number = {5},
pages = {100773},
doi = {10.1016/j.bpsgos.2026.100773},
pmid = {42569203},
issn = {2667-1743},
abstract = {BACKGROUND: Gene-environment interplay contributes to the heterogeneous etiology of Alzheimer's disease (AD). Hypertension (HTN) is a major modifiable vascular risk factor, but whether its association with AD differs across APOE genotypes remains unclear. We examined the interaction between HTN and APOE genotypes in relation to incident AD and explored plasma proteomic correlates as potential biological clues.

METHODS: Longitudinal data from 318,923 UK Biobank participants without dementia were analyzed; participants had a mean age of 56.24 years, an APOE ε4 frequency of 28.29%, and a median follow-up period of 13 years. Cox proportional hazards models with competing-risk adjustment for death were used to assess additive and multiplicative interactions between HTN and APOE genotypes. Plasma proteomic data from 34,141 participants, covering 2790 proteins, were further analyzed using mediation and bioinformatics approaches.

RESULTS: HTN showed a significant multiplicative interaction with APOE ε4 status for incident AD (p < .001). The association between HTN and AD risk was strongest among APOE ε2 carriers, followed by ε33 carriers and ε4 carriers, with hazard ratios of 1.570, 1.213, and 1.129, respectively. Among APOE ε2 carriers, prosaposin and ganglioside GM2 activator significantly mediated the HTN-AD association, with mediation proportions of 10.46% and 3.37%, respectively. These proteins were enriched in sphingolipid metabolism and lysosomal function.

CONCLUSIONS: The association between HTN and incident AD varies across APOE genotype strata, with the strongest relative association observed among APOE ε2 carriers. These findings suggest genotype-dependent heterogeneity in vascular contributions to AD risk. Proteomic results should be interpreted as exploratory biological clues and require further validation.},
}

@article {pmid42569234,
year = {2026},
author = {Rizvi, B and Adams, JN and Bamford, A and Kim, S and Sathishkumar, M and Tustison, NJ and Taylor, L and Tuteja, N and McMillan, L and Nan, B and Cai, H and Escalante, YY and Meza, NJ and Harris, AL and Malhas, R and Brickman, AM and Mapstone, M and Thomas, EA and Yassa, MA},
title = {Parallel neuroinflammatory pathways to cerebrovascular burden and amyloid beta in Alzheimer's disease.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {3},
pages = {e70415},
doi = {10.1002/dad2.70415},
pmid = {42569234},
issn = {2352-8729},
abstract = {INTRODUCTION: Upstream neuroinflammation plays an important role in Alzheimer's disease (AD) but remains poorly understood. We tested whether two distinct neuroinflammatory markers are associated with cerebrovascular burden and amyloid beta (Aβ), and downstream, with plasma phosphorylated tau (p-tau217), medial temporal lobe (MTL) cortical and hippocampal atrophy, and memory deficits.

METHODS: Cognitively unimpaired older adults without dementia or mild cognitive impairment were recruited from a community sample (Biomarker Exploration in Aging, Cognition, and Neurodegeneration; [BEACoN]; N = 126). We used structural equation modeling to test whether plasma chitinase-3-like protein 1 (YKL-40) and glial fibrillary acidic protein (GFAP) contribute to distinct pathways.

RESULTS: Higher plasma YKL-40 was associated with greater white matter hyperintensity (WMH), whereas higher plasma GFAP was related to increased 18F-florbetapir (FBP) standardized uptake value ratio (SUVR). Higher plasma GFAP, WMH, and FBP SUVR were independently associated with increased p-tau217. Plasma p-tau217 was associated with reduced MTL cortical thickness and hippocampal volume. Reduced hippocampal volume was related to worse memory.

DISCUSSION: Future work can further investigate these neuroinflammatory pathways as potential therapeutic targets for AD.},
}

@article {pmid42569297,
year = {2026},
author = {Ortuño-Sahagún, D and Carrera-Quintanar, L},
title = {Editorial: Nutrients and bioactive compounds: preventing and treating neurodegenerative diseases and disorders.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1908638},
doi = {10.3389/fnut.2026.1908638},
pmid = {42569297},
issn = {2296-861X},
}

@article {pmid42569462,
year = {2026},
author = {Alruwais, N and Althobaiti, GA and Alaql, YB and Almutairi, SAH and Alshareef, WM and Mahrous, FA and Aloqaybi, SAS and Lasloom, RAA and Aljasser, AA},
title = {Retinal Microvascular Biomarkers Measured by Optical Coherence Tomography Angiography in Neurodegenerative and Neurovascular Disorders: A Systematic Review and Meta-Analysis.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {609387},
doi = {10.2147/OPTH.S609387},
pmid = {42569462},
issn = {1177-5467},
abstract = {PURPOSE: Neurodegenerative and neurovascular disorders are increasingly recognized as major causes of disability worldwide and require accessible biomarkers for early detection and monitoring. Given the close anatomical and microvascular relationship between the retina and the central nervous system, optical coherence tomography angiography (OCTA) has emerged as a promising non-invasive technique for assessing retinal microvascular alterations associated with neurological disease. This systematic review and meta-analysis evaluated OCTA-derived retinal microvascular parameters as potential biomarkers of neurovascular dysfunction.

METHODS: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420261305354). PubMed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from January 2015 to December 2025. Studies comparing OCTA-derived retinal vascular parameters between patients with neurodegenerative or neurovascular disorders and healthy controls were included. Primary outcomes were superficial capillary plexus vessel density (SCP-VD), deep capillary plexus vessel density (DCP-VD), and foveal avascular zone (FAZ) area. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random-effects models.

RESULTS: Thirteen studies were included in the quantitative synthesis. Compared with healthy controls, patients with neurodegenerative or neurovascular disorders demonstrated significantly reduced SCP vessel density (SMD -0.60, 95% CI -0.78 to -0.43; I[2] = 43%) and DCP vessel density (SMD -0.84, 95% CI -1.15 to -0.53; I[2] = 78%). FAZ area was significantly enlarged in disease groups (SMD 0.62, 95% CI 0.29 to 0.94; I[2] = 83%). Disease-specific subgroup analyses demonstrated generally consistent trends across the included disorders.

CONCLUSION: OCTA-derived retinal microvascular alterations were consistently associated with neurodegenerative and neurovascular disorders. Reduced retinal vessel density, particularly within the deep capillary plexus, and enlargement of the FAZ may reflect underlying neurovascular dysfunction. While these findings support the potential role of OCTA as a non-invasive biomarker of neurological disease, the available evidence remains limited by methodological heterogeneity and predominantly observational study designs. Further longitudinal studies using standardized OCTA protocols are needed to establish the diagnostic and prognostic utility of these biomarkers.},
}

@article {pmid42569517,
year = {2026},
author = {Chen, M and Cao, C and Chen, T and Alhamad, D and Liu, T and Su, L and Zhu, D},
title = {Fine-scale individualized gyral folding-based cortical similarity networks reveal distinct organizational patterns in Alzheimer's disease and Lewy body dementia.},
journal = {Imaging neuroscience (Cambridge, Mass.)},
volume = {4},
number = {},
pages = {},
doi = {10.1162/IMAG.a.1322},
pmid = {42569517},
issn = {2837-6056},
abstract = {Alzheimer's disease (AD) and Lewy body dementia (LBD) are common neurodegenerative dementias with overlapping clinical presentations, making differential diagnosis challenging. While structural magnetic resonance imaging (MRI) has revealed characteristic regional atrophy patterns, regional morphometric measures alone may not fully capture distributed cortical alterations. Morphometric similarity networks (MSNs) offer a systems-level framework to characterize coordinated structural organization, but existing approaches typically rely on atlas-based parcellations that may obscure individual-specific cortical folding geometry. Here, we propose a fine-scale, folding-informed cortical similarity network framework based on automatically detected three-hinge gyral (3HG) landmarks. Using a thickness-constrained arealization strategy in native surface space, we define individualized cortical regions and construct subject-specific MSNs without cross-subject registration. We then investigate how network topology relates to landmark-defined node count and how these properties differ between AD and LBD. We find that several graph theoretical metrics, particularly global efficiency and characteristic path length, exhibit clear associations with the number of detected landmarks, indicating that topology in individualized networks is partly shaped by node availability. When accounting for landmark count, several apparent group differences in global topology are attenuated, whereas multiple heterogeneity-related metrics remain significant, indicating that node-count scaling substantially influences the interpretation of individualized network topology. Nevertheless, multivariate topological patterns remain informative for AD/LBD classification after residualizing for node count, and landmark count itself provides modest diagnostic information. These findings highlight node-count scaling as a key methodological consideration in individualized structural networks and suggest that folding-based MSNs capture disease-related variation in cortical network organization between AD and LBD.},
}

@article {pmid42569620,
year = {2026},
author = {Ip, J and Heindel, WC and Ott, BR and Festa, EK},
title = {Distinct theta and alpha electrophysiological dynamics during audiovisual semantic processing in healthy aging and mild cognitive impairment.},
journal = {Aging brain},
volume = {10},
number = {},
pages = {100163},
doi = {10.1016/j.nbas.2026.100163},
pmid = {42569620},
issn = {2589-9589},
abstract = {Semantic memory decline is increasingly recognized as an early feature of Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), yet the neural dynamics supporting automatic and controlled semantic retrieval in healthy aging remain poorly defined. This study examined task-evoked oscillatory activity during audiovisual object recognition in young adults (YA; N = 27), healthy older adults (OA; N = 33), and individuals with amnestic MCI (N = 21). Participants judged object orientation while viewing living and nonliving images paired with congruent or incongruent characteristic sounds, allowing semantic relationships to be manipulated under implicit retrieval demands. Accuracy was high across groups, although participants with MCI showed reduced performance under the more perceptually challenging inverted conditions. Reaction times were slower in OA than YA and further slowed in MCI, with group differences varying by object animacy and semantic congruency. Event-related spectral perturbation analyses revealed distinct group-related patterns. Healthy older adults showed reduced early and increased late theta activity in frontocentral and parieto-occipital regions, consistent with delayed recruitment of control-related and perceptual-attentional processes. In contrast, MCI participants showed elevated and less condition-sensitive posterior alpha power, together with task- and condition-specific differences in frontocentral theta. The principal pattern of delayed theta recruitment in healthy aging and elevated posterior alpha in MCI was also observed in a supplementary task requiring explicit audiovisual semantic judgments. These findings provide preliminary evidence that healthy aging and amnestic MCI are associated with partly distinct patterns of task-evoked oscillatory activity during audiovisual semantic processing.},
}

@article {pmid42569823,
year = {2026},
author = {Oblak, AL and Sasner, M and Carter, GW and Howell, GR and Sukoff Rizzo, SJ and Leal, K and Territo, PR and Lamb, BT},
title = {The past, the present, and the future of preclinical mouse models for Alzheimer's disease and related dementias.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71741},
doi = {10.1002/alz.71741},
pmid = {42569823},
issn = {1552-5279},
support = {U54AG054345/NH/NIH HHS/United States ; },
mesh = {Animals ; *Disease Models, Animal ; *Alzheimer Disease/genetics/pathology ; Humans ; Mice ; },
abstract = {Over the past decade, the Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease (MODEL-AD) consortium has transformed preclinical Alzheimer's disease (AD) research by addressing critical limitations in traditional mouse models that failed to translate to human disease. By leveraging human genetic discoveries, MODEL-AD has developed > 70 genetically informed mouse models, standardized phenotyping pipelines, and an open-access data infrastructure aligned with late-onset AD biology. These models incorporate human risk variants, environmental factors, and aging to better capture disease complexity, including emerging recognition of mixed pathologies such as vascular contributions, Lewy body disease, and TDP-43 proteinopathy. Despite substantial progress, key challenges remain, including modeling multimorbidity, integrating aging, and improving translational predictability. Here, we outline a strategic roadmap spanning short-, intermediate-, and long-term approaches to refine disease modeling, enhance preclinical testing rigor, and support precision medicine. Continued investment in MODEL-AD will be essential to accelerate therapeutic discovery and establish a scalable framework for studying complex neurodegenerative diseases.},
}

Animals
*Disease Models, Animal
*Alzheimer Disease/genetics/pathology
Humans
Mice

@article {pmid42569825,
year = {2026},
author = {Zhu, X and Haure-Mirande, JV and Bicak, M and Dong, P and Kruglikov, I and Li, A and Al-Subaie, A and Fossati, V and Noggle, S and Gandy, S and Ehrlich, ME},
title = {miR155, triplicated in Down syndrome, regulates the development of neural stem cells and GABAergic interneurons in Alzheimer's disease mouse and human iPSC models.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71684},
doi = {10.1002/alz.71684},
pmid = {42569825},
issn = {1552-5279},
support = {RF1AG058469/NH/NIH HHS/United States ; },
mesh = {Animals ; *MicroRNAs/genetics/metabolism ; Humans ; *Down Syndrome/genetics/metabolism ; *Alzheimer Disease/genetics/metabolism/pathology ; *Induced Pluripotent Stem Cells/metabolism ; *Interneurons/metabolism ; *Neural Stem Cells/metabolism ; Disease Models, Animal ; Mice ; *GABAergic Neurons/metabolism ; Amyloid beta-Protein Precursor/genetics/metabolism ; Mice, Transgenic ; Mice, Knockout ; },
abstract = {INTRODUCTION: Dysfunctional microRNAs and GABAergic interneurons are features of Alzheimer's disease (AD). The role of neuronal microRNA155 (miR155), elevated in both AD and Down syndrome (DS), remains unknown.

METHODS: We utilized in silico analyses of published databases, MIR155-deleted and -overexpressing human induced pluripotent stem cell (hiPSC)-derived cells, cortical organoids, and amyloid beta precursor protein (APP)/PS1-miR155 knockout mouse.

RESULTS: MIR155HG (miR155 host gene) colocalizes with APP in a neuron-specific, topologically associated domain (TAD) in chromosome 21. In human neural stem cells (NSCs), neurons, and cortical organoids, MIR155 deletion enhanced NSC proliferation and GABAergic interneuron generation. MIR155 overexpression inhibited NSC marker expression and GABAergic interneuron generation. In APP/PS1 mice, miR155 deletion induced the expansion of hippocampal NSCs and increased hippocampal GABAergic interneurons.

DISCUSSION: Our findings, alongside the extensive studies of the role of microglial miR155 in neuroinflammation, reveal previously unrecognized miR155 roles in hippocampal NSC dynamics and GABAergic interneuron development, highlighting miR155 as a therapeutic target.},
}

Animals
*MicroRNAs/genetics/metabolism
Humans
*Down Syndrome/genetics/metabolism
*Alzheimer Disease/genetics/metabolism/pathology
*Induced Pluripotent Stem Cells/metabolism
*Interneurons/metabolism
*Neural Stem Cells/metabolism
Disease Models, Animal
Mice
*GABAergic Neurons/metabolism
Amyloid beta-Protein Precursor/genetics/metabolism
Mice, Transgenic
Mice, Knockout

@article {pmid42569826,
year = {2026},
author = {Groeneveld, J and Perlaza, D and Olivé, C and Grangeon, L and Tesi, N and Nicolas, A and Jiang, C and de Rojas, I and Wallon, D and Rousseau, S and Rovira, M and de Asúa, DR and Moldenhauer, F and Mu, R and Cassinari, K and Zarea, A and Escabias, JA and Lambert, JC and Pijnenburg, YAL and Hulsman, M and Vijverberg, EGB and Levin, J and Jucker, M and McDade, E and Fortea, J and Holstege, H and Duits, FH and Vermunt, L and Patel, M and Johnson, M and Renton, AE and Goate, AM and Cruchaga, C and Pottier, C and Fernandez, MV and Belbin, O and Nicolas, G and Dols-Icardo, O and van der Lee, SJ and , },
title = {APOE and genetic risk variants influence Alzheimer's disease onset in carriers of an extra copy of APP, with and without Down syndrome.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71738},
doi = {10.1002/alz.71738},
pmid = {42569826},
issn = {1552-5279},
support = {1051003212000/ZONMW_/ZonMw/Netherlands ; #73305095007/ZONMW_/ZonMw/Netherlands ; //Stichting Alzheimer Nederland and Stichting Steun Alzheimercentrum Amsterdam/ ; //Stichting Dioraphte/ ; #LSHM20106//Health∼Holland, Topsector Life Sciences & Health/ ; //SURF Cooperative/ ; 15318/NWO_/Dutch Research Council/Netherlands ; 17232/NWO_/Dutch Research Council/Netherlands ; PI21/01395//Institute of Health Carlos III/ ; PI24/01087//Institute of Health Carlos III/ ; FI20/00215//Institute of Health Carlos III/ ; PI19/01301//Institute of Health Carlos III/ ; PI19/01240//Institute of Health Carlos III/ ; P22/I01403//Institute of Health Carlos III/ ; FI24/00029//Institute of Health Carlos III/ ; INT21/00073//Institute of Health Carlos III/ ; PI20/01473//Institute of Health Carlos III/ ; PI23/01786//Institute of Health Carlos III/ ; //Fondo Europeo de Desarrollo Regional, Unión Europea, "Una manera de hacer Europa./ ; PDC-2023-51//Jerome Lejeune Foundation/ ; AARF-22-924456/ALZ/Alzheimer's Association/United States ; SG-20-690363-DIAN/ALZ/Alzheimer's Association/United States ; //Fundación bancaria "La Caixa," Fundación ADEY, Fundación Echevarne and Grífols SA (GR@ACE project)/ ; //Ace Alzheimer Center Barcelona is one of the participating centers of the Dementia Genetics Spanish Consortium (DEGESCO)/ ; AC19/00097//PREADAPT Joint Program for Neurodegenerative Diseases (JPND)/ ; //German Research Foundation/ ; //Fondo de Investigaciones Sanitario/ ; CB06/05/2004//Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII)/ ; CB18/05/00010//Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII)/ ; //Fondo Europeo de Desarrollo Regional, Unión Europea, Una manera de hacer Europa/ ; 1R01AG056850-01A1//National Institutes of Health grants/ ; R21AG056974//National Institutes of Health grants/ ; R01AG061566//National Institutes of Health grants/ ; 1R01AG081394-01//National Institutes of Health grants/ ; 1R61AG066543-01//National Institutes of Health grants/ ; SLT006/17/00119//Department de Salut de la Generalitat de Catalunya/ ; IIBSP-DOW-2020151//Fundación Tatiana Pérez de Guzmán el Bueno/ ; H2020-SC1-BHC-2018-2020//Horizon2020-Research and Innovation Framework Programme from the European Union/ ; U19AG032438//Institute on Aging/ ; //German Center for Neurodegenerative Diseases/ ; //Raul Carrea Institute for Neurological Research (FLENI)/ ; //Research and Development/ ; //Research and Development Grants for Dementia from Japan Agency for Medical Research and Development (AMED)/ ; //Korea Health Industry Development Institute (KHIDI), Korea Dementia Research Center (KDRC)/ ; RS-2024-00344521//Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea/ ; #733050512//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; 2023-1334//Pascual Maragall Researchers Program/ ; },
mesh = {Humans ; *Down Syndrome/genetics/complications ; *Alzheimer Disease/genetics/epidemiology/complications ; *Amyloid beta-Protein Precursor/genetics ; Female ; Age of Onset ; Male ; Middle Aged ; *Genetic Predisposition to Disease ; *Apolipoproteins E/genetics ; Heterozygote ; Genetic Risk Score ; Risk Factors ; Apolipoprotein E4/genetics ; },
abstract = {INTRODUCTION: An extra copy of the amyloid precursor protein (APP) gene causes autosomal dominant Alzheimer's disease (AD) and AD in Down syndrome (DS), but the factors underlying variability in age at onset (AAO) remain unclear. We investigated whether sporadic AD risk variants modify AAO.

METHODS: We analyzed clinical and genetic data from 100 APP duplication (APPdup) carriers and 957 individuals with DS. Cox models assessed associations of apolipoprotein E (APOE) ε2 and ε4 and the AD genetic risk score (AD-GRS; excluding APOE and chromosome 21 variants) with AAO.

RESULTS: Mean AAO was earlier in APPdup than DS (51 ± 7 vs. 53 ± 6 years; P = 0.0005). APOE ε2 delayed onset (hazard ratio [HR] = 0.47, P < 0.0001), whereas APOE ε4 (HR = 1.5, P = 0.0003) and higher AD-GRS (HR = 1.3 per standard deviation, P < 0.0001) accelerated onset. Predicted median AAO differed by 10 years between lowest and highest genetic risk.

DISCUSSION: Sporadic AD genetic risk factors are important modifiers of AAO in APPdup and DS, explaining part of the marked variability in onset.},
}

Humans
*Down Syndrome/genetics/complications
*Alzheimer Disease/genetics/epidemiology/complications
*Amyloid beta-Protein Precursor/genetics
Female
Age of Onset
Male
Middle Aged
*Genetic Predisposition to Disease
*Apolipoproteins E/genetics
Heterozygote
Genetic Risk Score
Risk Factors
Apolipoprotein E4/genetics

@article {pmid42569829,
year = {2026},
author = {Ehrenberg, AJ and Falgàs, N and Jacobs, HIL and Grinberg, LT and , },
title = {Neuromodulatory subcortical systems in Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71747},
doi = {10.1002/alz.71747},
pmid = {42569829},
issn = {1552-5279},
}

@article {pmid42569895,
year = {2026},
author = {Qi, X and Belloy, ME and Gu, J and Liu, X and Tang, H and He, Z},
title = {Robust Inference With Ghostknockoffs in Genome-Wide Association Studies With Sample Relatedness.},
journal = {Genetic epidemiology},
volume = {50},
number = {6},
pages = {e70051},
doi = {10.1002/gepi.70051},
pmid = {42569895},
issn = {1098-2272},
support = {AG066206/NH/NIH HHS/United States ; GM127063/NH/NIH HHS/United States ; AG066515/NH/NIH HHS/United States ; },
mesh = {*Genome-Wide Association Study/methods ; Humans ; *Models, Genetic ; Alzheimer Disease/genetics ; Polymorphism, Single Nucleotide ; Computer Simulation ; Phenotype ; UK Biobank ; },
abstract = {Genome-wide association studies (GWASs) have been extensively adopted to depict the underlying genetic architecture of complex traits. Recent studies show that knockoff-based methods can identify variants with unique, potentially causal effects on phenotypes. However, their statistical validity and effectiveness in studies with related individuals, such as the UK Biobank, remain unexplored. In this paper, we extensively evaluate a simple and effective analytical strategy that integrates GhostKnockoffs and state-of-the-art marginal association tests. We show that this approach is robust to arbitrary relatedness structure as long as the input Z-scores are derived from valid generalized linear mixed models. This robustness also extends GhostKnockoffs to other GWASs settings, including meta-analysis of studies with sample overlap when the input score test Z-scores are properly calibrated, and association test statistics beyond score tests in independent sample settings. We demonstrate the method's validity and practical utility using simulation studies and a meta-analysis of nine European ancestral genome-wide association studies and whole exome/genome sequencing studies for the Alzheimer's disease.},
}

*Genome-Wide Association Study/methods
Humans
*Models, Genetic
Alzheimer Disease/genetics
Polymorphism, Single Nucleotide
Computer Simulation
Phenotype
UK Biobank

@article {pmid42570063,
year = {2026},
author = {Paelaong, N and Sripha, K and Boondam, Y},
title = {Discovery of Anti-Neuroinflammatory Compounds in Alzheimer's Disease: Current Trends and Future Perspectives.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42570063},
issn = {1559-1182},
mesh = {*Alzheimer Disease/drug therapy ; Humans ; Animals ; *Drug Discovery/trends/methods ; *Anti-Inflammatory Agents/therapeutic use/chemistry/pharmacology ; *Neuroinflammatory Diseases/drug therapy ; Inflammation/drug therapy ; },
abstract = {Chronic neuroinflammation in response to abnormal protein aggregates has been implicated as a critical mechanism in several neurodegenerative diseases, and the modulation of signaling pathways associated with inflammation is being explored as a potential strategy for new therapeutics. In Alzheimer's disease (AD), the neuroinflammation hypothesis also starts to influence the landscape of drug discovery in place of the previously regarded amyloid hypothesis. As such, the objective of this review is to compile recent advanced in the discovery of anti-neuroinflammatory compounds developed through chemical synthesis and structural modification, providing an overview of current trends in drug discovery strategies and scaffold redesign for the development of the next-generation of anti-neuroinflammatory therapeutics. It was found that the compounds described in the publications could be categorized into four groups: modification of natural compounds, rational drug design, drug screening approaches, and drug repurposing. While the categorization seems to be similar to drug discoveries in other fields, with the modification of natural compounds accounting for most publications, specific observations could still be made. Namely, the growing interest in the multitarget-directed ligand approach reflects the increasing recognition of AD as a multifactorial disease. Despite this, further research is required to identify additional effective activities or the appropriate combinations besides anti-neuroinflammatory activity. Lastly, this review also gives brief overview regarding physicochemical properties of central nervous system-active agents, of which anti-neuroinflammatory compounds are parts of, and suggests the adoption of in silico prediction models as screening tools before the use of in vitro or in vivo models.},
}

*Alzheimer Disease/drug therapy
Humans
Animals
*Drug Discovery/trends/methods
*Anti-Inflammatory Agents/therapeutic use/chemistry/pharmacology
*Neuroinflammatory Diseases/drug therapy
Inflammation/drug therapy

@article {pmid42471758,
year = {2026},
author = {Zhang, T and Dai, L and Ma, Y and Xu, S and Liu, X and Zhao, M and Li, W and Wang, J and Liu, Y},
title = {Conformational bifurcation of tau R3-R4 oligomers underlies fibril polymorphism.},
journal = {Biophysical journal},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bpj.2026.07.020},
pmid = {42471758},
issn = {1542-0086},
abstract = {Tau aggregation into amyloid fibrils is a central pathological feature of multiple neurodegenerative diseases, yet identical tau sequences can adopt structurally distinct fibril conformations associated with different disorders. How such disease-specific folds emerge from the same sequence remains poorly understood. Here, we use metadynamics and all-atom molecular dynamics simulations to elucidate the folding mechanisms of tau trimers comprising the R3-R4 region, the minimal aggregation nucleus of tau fibrils. By constructing the folding free-energy landscape within a pre-organized fibril-like scaffold, we identify a shared, partially folded intermediate from which two energetically comparable minimum free-energy pathways diverge, leading to either a compact Alzheimer's disease-like or a more open chronic traumatic encephalopathy-like C-shaped conformation. Structural analysis reveals that the β4-β6 triangular region acts as the central determinant of this bifurcation. Hydrophobic-core rearrangements within this region provide the primary energetic driving force for compaction, whereas the conformational flexibility of the 332PGGG335 hinge modulates whether this tendency can be structurally realized. Additional simulations show that stable formation of the triangular region requires cooperative multichain interactions; reducing oligomer size destabilizes this scaffold and abolishes ordered folding. Together, our results establish a mechanistic framework in which identical tau sequences access alternative folding routes through a common intermediate, explaining the emergence of disease-specific fibril polymorphism at the oligomeric level and highlighting early folding intermediates as potential targets for therapeutic intervention.},
}

@article {pmid42560407,
year = {2026},
author = {Feng, X and Yu, W and Guo, S and Ji, Y and Li, J and Wang, L and Zhong, G and Li, S and Niu, L and Zhu, D and Zhou, K and Du, Y},
title = {Aurantio-Obtusin Attenuates Aβ-Induced Cognitive Impairment and Synaptic Dysfunction by Suppressing Neuroinflammation in Mice.},
journal = {Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology},
volume = {21},
number = {1},
pages = {},
pmid = {42560407},
issn = {1557-1904},
support = {82371194//the National Natural Science Foundation of China/ ; CSTB2024NSCQ-QCXMX0004//the Natural Science Foundation of Chongqing Municipality/ ; },
mesh = {Animals ; Male ; Mice ; *Amyloid beta-Peptides/toxicity ; Mice, Inbred C57BL ; *Neuroinflammatory Diseases/drug therapy/chemically induced/metabolism ; *Synapses/drug effects/metabolism ; *Anthraquinones/pharmacology/therapeutic use ; *Peptide Fragments/toxicity ; *Cognitive Dysfunction/chemically induced/drug therapy/metabolism ; Maze Learning/drug effects ; },
abstract = {Alzheimer's disease (AD) features Aβ-driven neuroinflammation and synaptic dysfunction that converge on cognitive decline, underscoring the potential value of multi-target interventions. Aurantio-obtusin (AO), a bioactive anthraquinone from Cassia obtusifolia L., exhibits reported anti-inflammatory and antioxidant activities; however, whether AO counteracts Aβ-associated behavioral impairment through coordinated modulation of inflammatory and synaptic alterations remains unclear. Here, we investigated whether AO alleviates Aβ1-42-induced cognitive deficits and examined synapse- and inflammation-related molecular correlates. Male C57BL/6 mice received intracerebroventricular Aβ1-42 to establish an acute AD-like model and were treated with AO (10 mg/kg/day, oral gavage) for consecutive weeks. The results showed that AO improved spatial learning and memory in the Morris water maze, recognition memory in the novel object recognition test, and working memory in the Y-maze, without affecting spontaneous locomotor activity. Furthermore, AO alleviated synaptic dysfunction by restoring synaptophysin expression and upregulating GAD65, and mitigated neuroinflammation by elevating anti-inflammatory factors (IL-4, IL-10, ARG1) and reducing TNF-α. In vitro experiments confirmed that AO was non-cytotoxic to N2A[APP] cells across 0-80 μM, mildly downregulated BACE1 expression, and suppressed the Aβ-induced upregulation of pro-inflammatory mediators (IL-6, iNOS) in BV2 microglial cells. Overall, AO attenuated Aβ1-42-driven behavioral impairment in parallel with improvements in synapse-associated markers and inflammatory readouts. These findings support further evaluation of AO as a natural compound associated with modulation of Aβ-related neuroinflammatory and synapse-associated alterations.},
}

Animals
Male
Mice
*Amyloid beta-Peptides/toxicity
Mice, Inbred C57BL
*Neuroinflammatory Diseases/drug therapy/chemically induced/metabolism
*Synapses/drug effects/metabolism
*Anthraquinones/pharmacology/therapeutic use
*Peptide Fragments/toxicity
*Cognitive Dysfunction/chemically induced/drug therapy/metabolism
Maze Learning/drug effects

@article {pmid42560467,
year = {2026},
author = {Brimson, S and Thitilertdecha, P and Kumaree, KK and Brimson, JM},
title = {Sigma-1 Receptor Ligand Blarcamesine (ANAVEX 2-73) for Alzheimer's Disease: A Systematic Review.},
journal = {CNS drugs},
volume = {},
number = {},
pages = {},
pmid = {42560467},
issn = {1179-1934},
abstract = {BACKGROUND AND OBJECTIVES: Alzheimer's disease (AD) remains a major cause of dementia, and currently available therapies provide only modest clinical benefit or are limited by intravenous administration and treatment-related adverse effects. Blarcamesine (ANAVEX 2-73) is an orally administered sigma-1 receptor (S1R) agonist that has demonstrated neuroprotective effects in preclinical studies and has progressed through Phase I, Phase II and Phase IIb/III clinical trials. This systematic review evaluated the current clinical evidence for the efficacy and safety of blarcamesine in early-stage and mild-to-moderate AD.

METHODS: A systematic literature search was conducted in PubMed (including MEDLINE), Scopus, and Google Scholar, together with clinical trial registries, with the final search performed in September 2025. Reference sections of manuscripts were searched, and authors were contacted for additional data. Studies investigating only blarcamesine in participants with mild-to-moderate AD were included. Blarcamesine for other diseases or severe AD were excluded. Data were summarised descriptively in accordance with PRISMA guidelines. The risk of bias was assessed using version 2 of the Cochrane Risk of Bias tool (RoB2) for randomised, placebo-controlled trials, and an adapted version of RoB2 for cross-over trials.

RESULTS: One Phase I first-in-human study in healthy volunteers and ten reports describing two randomised clinical trials (NCT02244541, a randomised open-label study, and NCT03790709, a randomized placebo-controlled study) and their associated open-label extension studies (NCT02756858 and NCT04314934) were identified, including two peer-reviewed manuscripts, two preprints, and six conference abstracts. Thirty-two participants were enrolled in the Phase IIa open-label dose-finding study, where outcome measures were compared to baseline (NCT02244541). In the extended open-label study exploring the cognitive effect for another 52 weeks, 21 of 32 remained in the study (NCT02756858). The randomised placebo-controlled trial (NCT03790709) enrolled 509 participants and randomised them into three groups: 167 treated with 30 mg blarcamesine, 168 treated with 50 mg blarcamesine and 168 treated with placebo (for 30 mg blarcamesine, 112 completed the study; for 50 mg blarcamesine, 90 completed the study; and for placebo, 136 completed the study). Subsequently, 300 of 509 participants remained in the open-label extension (NCT04314934). Across these two studies, blarcamesine was generally well tolerated, with adverse events that were predominantly mild, transient, and dose-related. Treatment was associated with slower cognitive and functional decline, improvements in multiple clinical outcome measures, and reduced brain atrophy in genetically defined subgroups. Participants carrying the SIGMAR1 and COL24A1 wild-type genotypes were associated with greater therapeutic benefit, supporting the potential value of pharmacogenomic patient stratification.

CONCLUSIONS: Current clinical evidence suggests that blarcamesine is a promising orally administered therapeutic candidate for early-stage AD with an acceptable safety profile and encouraging efficacy, particularly in genetically defined populations. However, the available evidence is derived from a limited number of clinical studies, including secondary analyses and conference reports. Additional independent randomised clinical trials are required to confirm these findings and further define the role of blarcamesine in the treatment of AD.

PROSPERO REGISTRATION: CRD420251142826.},
}

@article {pmid42560687,
year = {2026},
author = {Joyce, NR and Balog, S and Gaither, R and Pfeiffer, MR and Bhondoekhan, F and Ott, BR and Margolis, SA and Curry, AE and Zullo, AR},
title = {A Motor Vehicle Crash as an Early Signal of Alzheimer's Disease and Related Dementias.},
journal = {Journal of the American Geriatrics Society},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgs.70630},
pmid = {42560687},
issn = {1532-5415},
support = {R01HD096221//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01AG065722/AG/NIA NIH HHS/United States ; R01AG065722-S1/AG/NIA NIH HHS/United States ; R01AG079295/AG/NIA NIH HHS/United States ; },
abstract = {BACKGROUND: People with Alzheimer's disease and related dementias (ADRD) are at increased risk of motor vehicle crash (MVC) due to cognitive decline, which often begins years before diagnosis. MVC could serve as an indicator of ADRD-related cognitive impairment and facilitate earlier diagnosis.

METHODS: We conducted a matched cohort study of Medicare beneficiaries in New Jersey aged ≥ 69 years with incident ADRD diagnoses from 2010 to 2017 compared to individuals without ADRD and with four other medical conditions: acute myocardial infarction (AMI), asthma, chronic obstructive pulmonary disease (COPD), and diabetes. Comparison groups were sampled with replacement and matched on sex, age, and calendar quarter of diagnosis or claim (for the non-ADRD group). Crash prevalence at 6 months and 1, 2, and 3 years before diagnosis was compared using chi-square tests, and the monthly prevalence was plotted to examine longitudinal trends in crashes.

RESULTS: We identified 43,115 eligible individuals with incident ADRD diagnosis from 2010 to 2017. MVC crash prevalence was higher in the ADRD group than in non-ADRD and negative control groups at all measured pre-diagnosis time points: 6 months (2.99% vs. 2.31%-2.53%), 1 year (5.26% vs. 4.18%-4.65%), 2 years (9.52% vs. 7.88%-8.67%), and 3 years (13.64% vs. 11.29%-12.37%). The ADRD group was more likely to have multiple crashes in the pre-diagnosis period, but multiple events were rare overall (< 3%). Differences were statistically significant but represented small changes in prevalence. Crash prevalence did not reveal a clear signal of cognitive decline in the years leading up to the index diagnosis.

CONCLUSIONS: Older adults with ADRD had slightly higher prevalence of MVC in the 3 years before diagnosis than matched comparison groups, but absolute differences were small and recurrent crashes were rare. MVC alone is too rare to serve as a signal of incipient ADRD, highlighting the need for more sensitive measures.},
}

@article {pmid42560912,
year = {2026},
author = {Zhao, BW and Zhao, HF and Huang, YA and Hu, PW and You, ZH and Hu, L},
title = {A Novel Graph Transformer Framework for Predicting Drug-Disease Associations with Structural Awareness.},
journal = {IEEE transactions on computational biology and bioinformatics},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TCBBIO.2026.3721658},
pmid = {42560912},
issn = {2998-4165},
abstract = {Accurately predicting drug-disease associations (DDAs) is essential for accelerating the discovery of novel therapeutics. Graph representation learning-based computational models have become increasingly popular for this task due to their efficiency and cost-effectiveness. However, existing approaches often suffer from structural inductive biases and a limited ability to capture the rich heterogeneous context of biomedical molecules, which constrains their capacity to learn expressive drug and disease representations. To address this issue, we propose SGTL-DDA, a novel graph transformer framework designed to incorporate structural information and domain-specific knowledge from heterogeneous biological information networks (HBINs). SGTL-DDA integrates a meta-path-guided sampling strategy with a multi-level attention mechanism, enabling the model to jointly learn from both structural dependencies and attribute semantics in an end-to-end manner. Extensive experiments on two benchmark datasets demonstrate that SGTL-DDA consistently outperforms state-of-the-art methods in terms of Accuracy, F1-score, and AUC under a ten-fold cross-validation scheme. Furthermore, case studies on Alzheimer's disease and breast cancer confirm the predictive capability of SGTL-DDA, as it successfully identifies both known therapeutics and novel repositioning candidates, supported by molecular docking results and literature evidence.},
}

@article {pmid42560982,
year = {2026},
author = {Takeoka, C and Yada, T and Yamazaki, T and Kuroiwa, Y and Hirai, T and Fujino, K and Mizusawa, H and Takao, M and Terao, Y and Yamada, M},
title = {Classification of sporadic Creutzfeldt-Jakob disease based on resting state scalp-recorded electroencephalogram-derived indices.},
journal = {PloS one},
volume = {21},
number = {8},
pages = {e0355367},
pmid = {42560982},
issn = {1932-6203},
mesh = {Humans ; *Creutzfeldt-Jakob Syndrome/classification/diagnosis/physiopathology ; *Electroencephalography/methods ; Aged ; Female ; Male ; *Scalp/physiopathology ; Alzheimer Disease/physiopathology/diagnosis ; Middle Aged ; Rest ; },
abstract = {Prion disease is a general term for a disease that causes cognitive disorders due to the accumulation of abnormal prion protein in the brain. Creutzfeldt-Jakob disease (CJD) is the most common case of prion disease, and sporadic Creutzfeldt-Jakob disease (sCJD) accounts for more than 70% of CJD cases. Early and accurate diagnosis of sCJD remains challenging. The aim of this study is to classify 6 sCJD patients from 10 healthy older adults and 23 Alzheimer's disease (AD) patients using resting-state scalp-recorded electroencephalogram (EEG)-derived indices. Power spectrum, SL values by Synchronization Likelihood (SL), and graph metrics by SL values were calculated for 5 frequency bands as EEG-derived indices. In addition, power spectrum and SL values were standardized and exponentially transformed for each subject and each frequency band. Graph metrics were calculated by these SL values. These indices were used as features for classification. Classifiers were constructed by features selected by Recursive Feature Elimination (RFE). The highest classification accuracy was 97.44% using a 12-dimensional feature. This accuracy was confirmed by indices after standardization and exponential transformation. Additional validation analyses were performed to assess the reliability of the selected classifier. Accuracy of nested LOOCV was 84.62%, supporting meaningful classification ability under a leakage-controlled validation framework. An analysis of robustness removing a group of subjects with high similarity with many others showed that the selected classifier maintained a micro-F1 score of 90.32%. Permutation test indicated that the observed performance was significantly higher than chance level, and repeated stratified 10-fold cross-validation showed relatively stable performance across different data partitions. These findings suggest that resting-state EEG-derived indices may provide useful candidate features for classification of sCJD, AD, and healthy older adults. However, further validation using larger independent cohorts is required to establish the generalizability and clinical reliability of the proposed classifier.},
}

Humans
*Creutzfeldt-Jakob Syndrome/classification/diagnosis/physiopathology
*Electroencephalography/methods
Aged
Female
Male
*Scalp/physiopathology
Alzheimer Disease/physiopathology/diagnosis
Middle Aged
Rest

@article {pmid42561097,
year = {2026},
author = {Paladugu, L and Gharaibeh, A and Kolli, N and Learman, C and Hall, TC and Li, L and Rossignol, J and Maiti, P and Dunbar, GL},
title = {RETRACTED: Paladugu et al. Liraglutide Has Anti-Inflammatory and Anti-Amyloid Properties in Streptozotocin-Induced and 5xFAD Mouse Models of Alzheimer's Disease. Int. J. Mol. Sci. 2021, 22, 860.},
journal = {International journal of molecular sciences},
volume = {27},
number = {15},
pages = {},
pmid = {42561097},
issn = {1422-0067},
abstract = {The journal retracts the article entitled "Liraglutide Has Anti-Inflammatory and Anti-Amyloid Properties in Streptozotocin-Induced and 5xFAD Mouse Models of Alzheimer's Disease" [...].},
}

@article {pmid42561134,
year = {2026},
author = {Ehn, E and Thonberg, H and Nennesmo, I and Lindstrand, A and Kvarnung, M and Graff, C},
title = {Clinical genome sequencing in neurodegenerative diseases-outcome in the first 500 patients.},
journal = {Human molecular genetics},
volume = {35},
number = {16},
pages = {},
doi = {10.1093/hmg/ddag072},
pmid = {42561134},
issn = {1460-2083},
mesh = {Humans ; *Whole Genome Sequencing/methods ; *Neurodegenerative Diseases/genetics/diagnosis ; Amyotrophic Lateral Sclerosis/genetics/diagnosis ; Female ; C9orf72 Protein/genetics ; DNA Copy Number Variations/genetics ; Male ; Middle Aged ; Alzheimer Disease/genetics/diagnosis ; Genetic Predisposition to Disease ; Frontotemporal Dementia/genetics/diagnosis ; Aged ; DNA Repeat Expansion/genetics ; Adult ; Polymorphism, Single Nucleotide ; Phenotype ; },
abstract = {Neurodegenerative diseases (NDDs) are clinically and genetically heterogeneous, requiring neuropathology or molecular testing for a definitive diagnosis. Clinical whole genome sequencing (WGS) enables comprehensive variant calling across flexible gene lists that can be tailored to the clinical presentation. By allowing simultaneous detection of single-nucleotide variants, copy-number variants, structural variants, and repeat expansions, WGS has the potential to improve diagnostic yield, facilitate genetic counseling and support clinical trial inclusion. This study assesses the diagnostic performance of WGS in individuals with NDD. WGS in 500 individuals representing a wide spectrum of NDDs identified a disease-causing variant in 61 cases, resulting in a diagnostic yield of 12%. These variants were found in 16 different genes, with C9orf72 being the most prevalent. Repeat expansions represented the largest variant class, accounting for 35 of 61 LP/P cases (57%); most of which were C9orf72 expansions (31/35). In the largest phenotype groups, frontotemporal dementia (FTD) had the highest diagnostic yield (19%) followed by amyotrophic lateral sclerosis (ALS, 13%), whereas an underlying monogenic cause was expectedly low in Alzheimer disease (AD, 4%). A positive family history was present in the majority (74%) of FTD, ALS, combined ALS-FTD and AD cases with an LP/P finding. Clinical WGS provides a clear diagnostic advantage in NDDs marked by substantial clinical and genetic overlap. WGS enables comprehensive variant detection and mapping of genotype-phenotype relationships across the disease continuum. In FTD and ALS, these results support universal access to genetic testing independent of age at onset or family history.},
}

Humans
*Whole Genome Sequencing/methods
*Neurodegenerative Diseases/genetics/diagnosis
Amyotrophic Lateral Sclerosis/genetics/diagnosis
Female
C9orf72 Protein/genetics
DNA Copy Number Variations/genetics
Male
Middle Aged
Alzheimer Disease/genetics/diagnosis
Genetic Predisposition to Disease
Frontotemporal Dementia/genetics/diagnosis
Aged
DNA Repeat Expansion/genetics
Adult
Polymorphism, Single Nucleotide
Phenotype

@article {pmid42561290,
year = {2026},
author = {Frota, LS and Barbosa, SICG and Prado, JCS and Ishiki, HM and Fontenelle, ROS and Morais, SM},
title = {Evaluation of bioactive compounds from Libidibia ferrea (Mart. Ex Tul) LP Queiroz: Antioxidant and antifungal activities, acetylcholinesterase inhibition, and implications in Alzheimer's disease.},
journal = {Anais da Academia Brasileira de Ciencias},
volume = {98},
number = {2},
pages = {e20250618},
doi = {10.1590/0001-3765202620250618},
pmid = {42561290},
issn = {1678-2690},
mesh = {*Cholinesterase Inhibitors/pharmacology/isolation & purification ; *Antifungal Agents/pharmacology/isolation & purification ; *Antioxidants/pharmacology/isolation & purification ; *Plant Extracts/pharmacology/chemistry ; Microbial Sensitivity Tests ; Alzheimer Disease/drug therapy ; *Candida albicans/drug effects ; Molecular Docking Simulation ; *Burseraceae/chemistry ; Plant Leaves/chemistry ; },
abstract = {Fungal infections caused by Candida albicans represent a global health concern, with increasing antifungal resistance and potential links to neurodegenerative diseases such as Alzheimer's. In this context, this study evaluated the antifungal, antioxidant and acetylcholinesterase inhibitory activities of the hydroethanolic leaf extract of Libidibia ferrea, a species used in traditional medicine. The antioxidant potential was determined using DPPH and ABTS assays, while acetylcholinesterase inhibition was assessed by an in vitro enzymatic assay. Antifungal activity was assessed against Candida albicans strains by broth microdilution and molecular docking was employed to predict the interactions of the main phenolic compounds with acetylcholinesterase and sterol 14-α-demethylase. The extract showed potent antioxidant activity (CI50 = 9.68 ± 0.51 μg/mL for DPPH) and high inhibition of acetylcholinesterase (CI50 = 15.02 ± 0.16 μg/mL). It also showed fungistatic and fungicidal effects, with MIC values ranging from 0.118 to 0.469 mg/mL. In silico analyses highlighted rutin, catechin and ellagic acid as compounds with strong binding affinities to both enzymes, suggesting dual antifungal and neuroprotective effects. These results corroborate Libidibia ferrea as a promising source of bioactive compounds with potential therapeutic applications for fungal infections and neurodegenerative diseases, such as Alzheimer's.},
}

*Cholinesterase Inhibitors/pharmacology/isolation & purification
*Antifungal Agents/pharmacology/isolation & purification
*Antioxidants/pharmacology/isolation & purification
*Plant Extracts/pharmacology/chemistry
Microbial Sensitivity Tests
Alzheimer Disease/drug therapy
*Candida albicans/drug effects
Molecular Docking Simulation
*Burseraceae/chemistry
Plant Leaves/chemistry

@article {pmid42561582,
year = {2026},
author = {Kumari, P and Lipton, RB and Aschenbrenner, AJ and Sperling, R and Donohue, MC and Grober, E},
title = {Stages of objective memory impairment (SOMI) as a predictor of clinical progression in the A4 study.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {8},
pages = {100641},
doi = {10.1016/j.tjpad.2026.100641},
pmid = {42561582},
issn = {2426-0266},
abstract = {BACKGROUND: About one third of amyloid positive, cognitively normal individuals develop mild cognitive impairment or clinical Alzheimer dementia (AD) over 5 years of follow-up. Sensitive cognitive measures, in addition to biomarkers of amyloid pathology, add to the efficiency of secondary prevention trials by identifying cognitively normal individuals at greatest risk of clinical progression. The Stages of Objective Memory Impairment (SOMI) system, based on the picture version of the Free and Cued Selective Reminding Test with immediate recall (pFCSRT+IR), predicted clinical progression in two observational studies.

OBJECTIVE: Our objective was to extend SOMI's findings to clinical trials using participants from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's(A4) study.

METHODS: Eligible participants were cognitively normal, had a Clinical Dementia Rating (CDR) =0, an elevated amyloid level, the pFCSRT+IR, pTau217, and longitudinal data on the CDR. Cox proportional hazards model was used to assess the association of baseline SOMI stage for clinical progression defined by time to the first of 2 consecutive CDRs > 0 or CDR>0 at last assessment. The sample was censored at 4.5 years of follow-up.

RESULTS: Of the 911 eligible participants, mean age was 72 years, 59% were female, 62% were APOE ε4 carriers, and 37% progressed over 4.5 years. Hazard ratios (HR) for progression were estimated with follow-up time as the timescale and the SOMI 0 group as the reference. The HRs for progression across SOMI stage increased from 1.48(1.15-1.92 p=.003) for SOMI-1, to 1.83 (1.32-2.54, p ≤ 0.001) for SOMI-2, and to 3.04 (1.97-4.68, p ≤ 0.001) for SOMI 3/4. SOMI remained an independent and significant predictor when pTau217 was added to the model.

CONCLUSION: SOMI's risk profile in A4 was similar to prior findings in observational cohorts. SOMI provides a low-cost, non-invasive enrichment tool for identifying individuals at risk for early cognitive decline in secondary prevention trials.},
}

@article {pmid42561602,
year = {2026},
author = {Hajeforoosh, P and Moghaddam, AH and Jelodar, SK},
title = {Insulin resistance as a driver of neuroinflammation and oxidative stress in Alzheimer's disease: Mechanistic links and therapeutic approaches.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {202},
number = {},
pages = {119760},
doi = {10.1016/j.biopha.2026.119760},
pmid = {42561602},
issn = {1950-6007},
abstract = {Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disorder characterized by the accumulation of amyloid-β plaques and hyperphosphorylated tau protein aggregates, leading to progressive cognitive decline. Growing evidence suggests that AD may also be considered a metabolic disorder closely associated with insulin resistance (IR). Impaired insulin signaling disrupts the PI3K/Akt and GSK3-β pathways, resulting in synaptic dysfunction, neuronal loss, and aberrant protein phosphorylation. Moreover, IR contributes to mitochondrial dysfunction, oxidative stress, and chronic neuroinflammation within the central nervous system (CNS). These metabolic alterations, together with impaired energy homeostasis, dysregulate intracellular signaling cascades and exacerbate amyloid and tau pathology. This narrative review examines the mechanistic interplay among insulin resistance, oxidative stress, and neuroinflammation in AD, with particular emphasis on the shared cellular pathways that underlie disease progression. In addition, it summarizes emerging therapeutic strategies targeting insulin signaling, including pharmacological insulin-sensitizing agents, incretin-based therapies, lifestyle interventions, and bioactive natural compounds. The review also highlights advances in intranasal delivery strategies, which have emerged as a promising approach for enhancing brain targeting and improving therapeutic efficacy. Despite substantial progress, the precise mechanisms linking insulin resistance to neurodegeneration remain incompletely understood. Further mechanistic and translational studies are urgently required to elucidate these interactions and advance the development of effective therapeutic interventions.},
}

@article {pmid42561665,
year = {2026},
author = {Tyagi, P and Kumari, S and Sharma, P and Dhapola, R and Paidlewar, M and Medhi, B and HariKrishnaReddy, D},
title = {HMGB1 signalling in Alzheimer's disease: pathogenic roles and therapeutic prospects.},
journal = {International immunopharmacology},
volume = {187},
number = {},
pages = {117204},
doi = {10.1016/j.intimp.2026.117204},
pmid = {42561665},
issn = {1878-1705},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by the gradual loss of neurons, especially in the hippocampus and cerebral cortex. This neuronal loss results in cognitive decline, memory problems, and changes in behaviour. It accounts for roughly 90% of all cases, making it the most common reason for dementia worldwide, with a marked rise in its occurrence as one ages. AD is pathologically marked by the presence of intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein and the formation of extracellular amyloid-β plaques. Along with these defining characteristics, oxidative stress and chronic neuroinflammation, which are triggered by prolonged astrocyte and microglia activation and excessive reactive oxygen species production, play crucial roles in the development of the illness. The majority of cases of AD are sporadic late-onset illness, but the less common familial variant is linked to mutations in the APP, PSEN1, and PSEN2 genes that cause aberrant amyloid-β formation. High mobility group box 1 (HMGB1) is a crucial modulator of neuroinflammation in AD, according to new research. By activating the receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4), HMGB1, especially in its pro-inflammatory disulfide state, hinders memory and learning. RAGE/CaMKKβ-AMPK, ERK1/2, GSK-3β, NF-κB, MAPKs, and NLRP3 inflammasome cascades are among the overlapping downstream signalling pathways that these receptors initiate. Together, these pathways induce tau hyperphosphorylation, amyloid-β buildup, and persistent inflammatory responses. Therefore, a viable treatment approach for reducing neuroinflammation and associated pathologies with AD. is to target HMGB1-mediated signalling networks.},
}

@article {pmid42561776,
year = {2026},
author = {Chen, W and Zhan, K and Xu, C and Sun, S and Yang, X and Lei, H},
title = {Structure-based identification of novel indole-fused polycyclic derivatives as potent acetylcholinesterase inhibitors.},
journal = {Bioorganic & medicinal chemistry},
volume = {142},
number = {},
pages = {118765},
doi = {10.1016/j.bmc.2026.118765},
pmid = {42561776},
issn = {1464-3391},
abstract = {The pathogenesis of Alzheimer's disease (AD) is closely associated with cholinergic neuronal impairment, which is induced by excessive degradation of acetylcholine (ACh) mediated by acetylcholinesterase (AChE). In this study, a series of novel indole-fused polycyclic derivatives (1-28) were designed, synthesized, and assessed for their AChE inhibitory activities. The biological evaluation results demonstrated that most of the compounds exhibited moderate to excellent AChE inhibitory activities. Among them, compounds 8, 9, 21, and 26 showed leading AChE inhibitory activity with IC50 values of 0.29 μM, 1.5 μM, 1.2 μM, and 1 μM, respectively, which were superior to the positive control galantamine (IC50 = 2.2 μM). Furthermore, favorable drug-likeness profiles and optimal pharmacokinetic properties were confirmed for compound 8 through ADME analysis. Stable binding interactions between compound 8 and AChE were validated by the results of 100 ns molecular dynamics simulations. Overall, compound 8 was characterized as a potent and well-qualified AChE inhibitor, and further systematic investigations are warranted for its application in the treatment of AD-related diseases.},
}

@article {pmid42561934,
year = {2026},
author = {Li, W and Rimal, S and Bhurtel, S and Yeung, L and Lu, BG and Grinberg, LT and Spina, S and Sillero, MIC and Seeley, WW and Guo, S and Lu, B},
title = {Tau-induced mitochondrial reverse electron transport drives neurodegeneration.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2026.07.012},
pmid = {42561934},
issn = {1097-4199},
abstract = {Hyperphosphorylation and aggregation of tau are pathological hallmarks of tauopathies. Mitochondrial dysfunction is also a common feature of tauopathies. The mechanistic link between tau abnormalities and mitochondrial dysfunction and its relationship to the physiological function of tau, however, is unclear. Here, we demonstrate that tau regulates mitochondrial reverse electron transport (RET), which produces excess reactive oxygen species (ROS), reduces the NAD[+]/NADH ratio, and is activated by aging or stress. In flies, mice, and human induced pluripotent stem cell (hiPSC)-derived neurons, tau depletion eliminates stress-induced RET and confers resilience. Mechanistically, tau enters mitochondria and directly interacts with the complex I subunit NDUFS3 to promote RET in a phosphorylation-dependent manner. Elevated RET further drives tau hyperphosphorylation, establishing a self-perpetuating pathological loop. Inhibition of RET ameliorates tau toxicity across species. RET regulation thus represents a previously unrecognized normal function of tau that becomes pathological in disease, providing a therapeutic target for various conditions characterized by tau abnormalities and mitochondrial dysfunction.},
}

@article {pmid42562307,
year = {2026},
author = {Yadav, A and Verma, H and Kumari, S and Gangwar, P and Rao, R and Yadav, B and Kaur, S and Dhiman, M and Mantha, AK},
title = {The emerging role of NADPH oxidases (NOX) in Alzheimer's disease pathogenesis.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.08.004},
pmid = {42562307},
issn = {1873-7544},
abstract = {Alzheimer's disease (AD) is a slow-progressing neurodegenerative disease, mainly characterized by the accumulation of amyloid beta (Aβ) plaques and intracellular hyperphosphorylated Tau protein, along with the generation of free radicals. In normal physiology free radicals play a promising role. However, the imbalance in the formation and clearance of the free radicals or reactive oxygen species/reactive nitrogen species (ROS/RNS) disrupts redox homeostasis, resulting in oxidative stress. Cellular disruption through the oxidation of lipids, proteins, and nucleic acids along with the disruption of the blood-brain barrier (BBB) integrity, and neuroinflammation are linked with AD pathogenesis. Albeit there are various ROS-generating sources, notably mitochondria, endoplasmic reticulum (ER), peroxisomes, NADPH oxidase (NOX), and several other oxidases, but out of all, the second most well-studied ROS-generating component after mitochondria is thought to be NOX. It is a multi-subunit enzyme family, activated by the phosphorylation of its cytosolic subunit, culminating in the production of superoxide (O2[•-]) anions. It comprises seven different isoforms, where NOX2 is the most studied isoform found to be the major source of ROS production in the brain. Therefore, inhibiting NOX-induced oxidative stress in the brain might be a promising therapeutic approach for AD. Thus, the current review enlightens the role of NOX in neurodegenerative AD progression, Aβ pathology and focusing on the therapeutic interventions by employing different phytochemicals as natural inhibitors and the synthetic inhibitors to combat the pathogenicity associated with NOX in the case of AD.},
}

@article {pmid42562385,
year = {2026},
author = {Gauch, M and Ablinger, I and Corsten, S and Dörr, F and Flöel, A and Grewe, T and Foede, J and Heinrich, I and Knels, C and Köb, AL and Meinzer, M and Rosenkranz, A and Schmischke, A and Unger, N and Volkmer, A and Wuttke, T and Rysop, AU},
title = {Mapping PPA Care: Results of a Survey Study on Speech and Language Therapy for People With Primary Progressive Aphasia Across Germany.},
journal = {Dementia (London, England)},
volume = {},
number = {},
pages = {14713012261473983},
doi = {10.1177/14713012261473983},
pmid = {42562385},
issn = {1741-2684},
abstract = {Background: Primary Progressive Aphasia (PPA) is a rare condition characterised by a gradual loss of language due to neurodegenerative processes including frontotemporal lobar degeneration and Alzheimer's disease. Speech and language therapy is one of the main treatment options for people with PPA (PwPPA). International survey studies among speech and language therapists (SLTs) have revealed considerable shortcomings in treatment options for this patient group. To date, there has been no survey on speech and language therapy for PwPPA in Germany. Methods: We translated a survey that was originally developed to describe speech and language therapy for PPA in the UK into German and adapted it to the German healthcare system. The final 32-item survey covering demographics of SLTs and PwPPA, referral patterns, as well as diagnostic and therapeutic procedures, was distributed online. Results: Data from 46 SLTs, from 10 of Germany's 16 federal states with experience in treating PwPPA were included. These 46 SLTs had treated 158 PwPPA in the last 24 months and reported working with PwPPA for >20 sessions on average. PwPPA were most frequently referred to speech and language therapy 2-3 years after symptom onset with word finding difficulties. Qualitative content analysis revealed barriers on multiple levels to access speech and language therapy. Informal assessments, including analysis of spontaneous speech, interviews with PwPPA and/or carers and screening of language and communication skills were reported as most frequently used. SLTs rated life story work, activity and participation-focused therapy and symptom-focused therapy. for language disorders as the most commonly used for PwPPA. Discussion: This study provides an overview of the current state of speech and language therapy for PwPPA in Germany. It shows that there is currently no clear pathway for PPA care that covers all levels of the International Classification of Functioning Disability and Health and encompasses both assessment and treatment approaches. A comparison of the results obtained from this survey study with those from other similar studies in the UK, Turkey and Italy revealed both similarities and differences. Our findings underscore the need for further research, the development of standardized, evidence-based assessment and intervention tools, and targeted professional training.},
}

@article {pmid42562450,
year = {2026},
author = {Mendes Ferreira, V and Viana-Baptista, M},
title = {Family history of cognitive impairment as a diagnostic clue in Fragile X-associated tremor/ataxia syndrome.},
journal = {BMJ case reports},
volume = {19},
number = {8},
pages = {},
doi = {10.1136/bcr-2026-273818},
pmid = {42562450},
issn = {1757-790X},
mesh = {Humans ; Male ; *Fragile X Syndrome/diagnosis/genetics/complications ; *Tremor/genetics/diagnosis ; *Ataxia/genetics/diagnosis/complications ; Fragile X Messenger Ribonucleoprotein 1/genetics ; *Cognitive Dysfunction/genetics/diagnosis/etiology ; Magnetic Resonance Imaging ; Diagnosis, Differential ; Middle Aged ; },
abstract = {Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by premutation alleles (55-200 CGG repeats) in the FMR1 gene, typically presenting in later adulthood with intention tremor, cerebellar ataxia and cognitive impairment. We report a male patient in his 5th decade presenting with progressive bilateral action tremor initially suggestive of essential tremor. Neurological examination revealed postural and intention tremor with mild dysdiadochokinesia. A family history of early-onset cognitive decline in a first-degree relative prompted brain MRI, which demonstrated bilateral T2 hyperintensities of the middle cerebellar peduncles, suggestive of FXTAS. Subsequent genetic testing confirmed an FMR1 premutation with 115 CGG repeats, establishing the diagnosis of FXTAS. Review of the brother's records revealed progressive cognitive impairment previously attributed to Alzheimer's disease, raising the possibility of unrecognised FXTAS. This case highlights the importance of family history and neuroimaging in distinguishing FXTAS from more common tremor disorders and dementia syndromes.},
}

Humans
Male
*Fragile X Syndrome/diagnosis/genetics/complications
*Tremor/genetics/diagnosis
*Ataxia/genetics/diagnosis/complications
Fragile X Messenger Ribonucleoprotein 1/genetics
*Cognitive Dysfunction/genetics/diagnosis/etiology
Magnetic Resonance Imaging
Diagnosis, Differential
Middle Aged

@article {pmid42562606,
year = {2026},
author = {Karagianni, S and Moscoso, A and Raghavan, S and van Essen, M and Mainta, I and Camacho, V and Rodríguez-Fonseca, O and Silva-Rodríguez, J and Perissinotti, A and Gu, Y and Yun, J and Franzmeier, N and Grothe, MJ and Seo, SW and Frisoni, GB and Garibotto, V and Schwarz, CG and Petersen, RC and Jack, CR and Vemuri, P and Schöll, M},
title = {Concordance Between [[18]F]Flortaucipir PET Visual Reads and CenTauR-Based Quantification.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.126.272722},
pmid = {42562606},
issn = {1535-5667},
abstract = {Tau PET imaging with [[18]F]flortaucipir allows for the visualization and mapping of aggregated tau deposits, a key neuropathologic feature of Alzheimer disease (AD). A visual interpretation method for [[18]F]flortaucipir was approved by the Food and Drug Administration and European Medicines Agency and has been implemented for a standardized, clinically usable definition of tau PET positivity. The CenTauRz method, on the other hand, offers the possibility to harmonize the definition of tau PET positivity across different radiotracers using quantitative metrics, but its concordance with clinically relevant [[18]F]flortaucipir visual reads remains unclear. Methods: A convenience sample of 3991 participants, including cognitively unimpaired (CU) and cognitively impaired (CI) individuals (i.e., those with mild cognitive impairment or AD dementia), underwent [[18]F]flortaucipir PET imaging. Each [[18]F]flortaucipir scan was assessed by 3 trained readers using the approved visual interpretation method and quantified using the CenTauRz quantification pipeline in different regions of interest (ROIs). Concordance between positive visual reads and CenTauRz-defined positivity (i.e., >2 on the CenTauRz scale) was assessed using Cohen κ. Receiver-operating-characteristic (ROC) analysis evaluated the discriminative power of continuous CenTauRz values in distinguishing between negative and positive visual reads. Generalized additive models examined clinical progression on the basis of visual and CenTauRz-based assessments of tau PET positivity. Results: Concordance between visual reads and CenTauRz-based assessments of tau PET positivity was moderate, particularly in CU individuals (κ = 0.23-0.55 for CU participants, κ = 0.57-0.82 for CI participants, depending on the ROI). ROC analysis revealed that the agreement remained moderate, independent of the CenTauRz cut point used (area under the ROC curve, 0.72-0.87 vs. 0.87-0.97 for CU and CI individuals, respectively). Among discordant cases, participants with visually positive/CenTauRz-negative tau PET scans were more frequently amyloid-positive and exhibited faster clinical progression compared with visually negative/CenTauRz-positive individuals. Conclusion: Our findings highlight the relatively limited agreement between the visual assessment of [[18]F]flortaucipir PET images and CenTauRz-based quantification, particularly in CU individuals. Participants with visually positive/CenTauRz-negative tau PET scans showed a high frequency of amyloid positivity and faster clinical progression, suggesting that visual reads are more sensitive to heterogeneous, clinically relevant tau accumulation patterns not captured by ROI-based methods. These findings underscore the need for new quantification approaches to better capture the complex patterns of tau deposition, important for early AD detection and monitoring.},
}

@article {pmid42562773,
year = {2026},
author = {Zheng, X and Zhang, N and Wang, L and Zhao, H and Liu, C and Wang, J and Zhao, W and Zhao, J and Yang, P and Robinson, L and Hunt, L and Lokken, A and Lin, L and Nelson, PT and Kofler, J and Xie, H and Xia, H and Mao, Q},
title = {A phosphorylation‑independent monoclonal antibody improves detection of TDP‑43 pathology across frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and limbic predominant age related TDP‑43 encephalopathy neuropathological change.},
journal = {Journal of neuropathology and experimental neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnen/nlag085},
pmid = {42562773},
issn = {1554-6578},
support = {GC-202008-2020689//Alzheimer's Drug Discovery Foundation/ ; R21AG080502/AG/NIA NIH HHS/United States ; R21AG088509/AG/NIA NIH HHS/United States ; R01AG097508/AG/NIA NIH HHS/United States ; },
abstract = {TDP-43 proteinopathies encompass frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), amyotrophic lateral sclerosis (ALS-TDP), and limbic predominant age related TDP-43 encephalopathy neuropathological change (LATE-NC). These proteinopathies exhibit subtype-specific aggregate architectures that may constrain epitope accessibility in situ. We compared a phosphorylation-independent monoclonal antibody targeting a C-terminal epitope (MAb No. 9) with the phospho-specific pSer409/410 antibody to determine whether its signal relates to regional neurodegeneration in a multicenter autopsy cohort spanning FTLD-TDP types A-C, ALS-TDP, and Alzheimer disease neuropathologic change (ADNC) with or without LATE-NC. Immunolabeling with MAb No. 9 detected pathological TDP-43 across all diagnostic groups with enhanced labeling of dystrophic neurites and thread/dot-like pathology in FTLD-TDP types A/B and in ALS-TDP. MAb No. 9 performance was equivalent to p409/410 in FTLD-TDP type C. In ADNC with stage 3 LATE-NC, MAb No. 9 revealed a greater limbic burden and labeled both α type and β type inclusions. Dual label immunofluorescence demonstrated strong spatial overlap with p409/410 but additionally highlighted fine punctate pathology. MAb No. 9 burden in FTLD-TDP type A correlated strongly with cortical neurodegeneration but showed weaker and variable associations, particularly in severely atrophic cortex. These findings indicate that filament architecture governs C-terminal epitope accessibility and that MAb No. 9 may be a complementary tool for subtype refinement, clinicopathologic correlation and translational biomarker development in TDP-43 proteinopathies.},
}

@article {pmid42562777,
year = {2026},
author = {Shao, R and Li, W and Su, H and Zhou, S and Lan, M and Li, D},
title = {Impact of Narrative Nursing and Cognitive Behavioral Rehabilitation on Cognitive Function and Anxiety in Patients With Alzheimer's Disease.},
journal = {Geriatrics & gerontology international},
volume = {26},
number = {8},
pages = {e70719},
doi = {10.1111/ggi.70719},
pmid = {42562777},
issn = {1447-0594},
mesh = {Humans ; Male ; Female ; *Alzheimer Disease/psychology/rehabilitation ; *Cognitive Behavioral Therapy/methods ; Aged ; *Quality of Life ; *Cognition/physiology ; *Anxiety/etiology ; Activities of Daily Living ; Treatment Outcome ; *Narrative Therapy/methods ; Middle Aged ; },
abstract = {OBJECTIVE: Alzheimer's disease (AD) progressively impairs cognitive function and quality of life (QoL). Patients frequently experience anxiety, which may accelerate cognitive decline. This study aimed to investigate the effects of narrative nursing combined with cognitive behavioral rehabilitation on cognitive function and anxiety in AD patients.

METHODS: In this randomized controlled trial, 172 AD patients were assigned to a control group (conventional care, n = 86) or an observation group (additional 6-month narrative nursing and cognitive behavioral rehabilitation, n = 86). Outcomes were assessed at baseline and after the 6-month intervention using validated Chinese versions of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Generalised Anxiety Disorder-7 (GAD-7), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Quality of Life in Alzheimer's Disease (QoL-AD) scales.

RESULTS: Baseline characteristics, including age (mean: 68.5 ± 10.2 years), sex distribution (57.6% men), body mass index (22.95 ± 3.44 kg/m[2]), disease duration (5.32 ± 0.79 years), and baseline cognitive scores (MMSE: 19.25 ± 2.88; MoCA: 17.00 ± 2.55), did not differ significantly between groups. After 6 months of intervention, the observation group demonstrated greater improvement in cognitive function (MMSE: F = 4.461, p = 0.039; MoCA: F = 5.441, p = 0.040), anxiety (GAD-7: F = 14.937, p < 0.001), ADL (ADCS-ADL: F = 11.967, p < 0.001), and QoL (QoL-AD: F = 7.307, p < 0.001) than the control group. Adherence was high (92%), with no significant group differences. Missed sessions were primarily attributable to acute illness, transportation difficulties, or family commitments. Medication regimens (cholinesterase inhibitors, memantine, and antidepressants) remained stable between groups, with no significant interaction with the intervention.

CONCLUSION: Narrative nursing combined with cognitive behavioral rehabilitation can effectively increase cognitive function, reduce anxiety, and improve the ADL and QoL of patients with AD.

TRIAL REGISTRATION: ISRCTN10742199.},
}

Humans
Male
Female
*Alzheimer Disease/psychology/rehabilitation
*Cognitive Behavioral Therapy/methods
Aged
*Quality of Life
*Cognition/physiology
*Anxiety/etiology
Activities of Daily Living
Treatment Outcome
*Narrative Therapy/methods
Middle Aged

@article {pmid42562893,
year = {2026},
author = {Khaki, PSS and Guillen-Poza, PA and Wong, C and Kan, C and Sharma, R and Sugimura, R and Robinson, AC and Valbuena, A and Ng, RC and Yang, Y and Hervas, R},
title = {Distinct amyloid-β filament fold in individuals with APP Flemish mutation.},
journal = {Nature structural & molecular biology},
volume = {},
number = {},
pages = {},
pmid = {42562893},
issn = {1545-9985},
abstract = {The dominantly inherited Flemish mutation-an A692G substitution in the amyloid precursor protein, corresponding to an A21G change in amyloid-β (Aβ)-causes a rare, early-onset form of Alzheimer disease characterized by pronounced cerebral amyloid angiopathy and unusually large senile plaque cores. Here, we report cryo-electron microscopy structures of amyloid filaments extracted from the postmortem parietal lobes of two individuals representing the only two known Flemish pedigrees worldwide. Although tau paired helical filaments were present, the predominant filaments comprise Aβ40-A21G, assembled as two identical protofilaments (D1-V40) packed with two-start helical symmetry. Aβ40-A21G and wild-type Aβ42 filaments share a substructure preceding the substitution site (Y10-F19); however, loss of the methyl group at residue 21 gives rise to a distinct arrangement, termed the 'Flemish fold', which differs from all previously characterized Aβ folds and is defined by a unique hydrophobic interface. Using a cell-based assay, we find that this distinctive fold is associated with the vascular tropism characteristic of the Flemish variant. Together, our structural and cellular data define a familial Alzheimer-disease-associated amyloid fold and provide insight into the molecular basis of Flemish-type dementia and cerebral hemorrhage.},
}

@article {pmid42562894,
year = {2026},
author = {},
title = {Alzheimer's disease-linked Flemish APP mutation defines a distinct amyloid-β fold.},
journal = {Nature structural & molecular biology},
volume = {},
number = {},
pages = {},
pmid = {42562894},
issn = {1545-9985},
}

@article {pmid42563066,
year = {2026},
author = {Almirón, RS and Tettamanti, C and Martinez, S and Antonino, M and Marmo, P and Debiagge, Á and Toselli, D and Moro, L and Allemandi, D and Lorenzo, A and Quinteros, DA and Bignante, EA},
title = {Gallein-Loaded Albumin Nanoparticles Prevent Amyloid-β-Induced Amyloidogenic APP Processing, Synaptic Loss, and Dendritic Pathology.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42563066},
issn = {1559-1182},
support = {ANPCyT PICT 2021-GRF-TI-00561//Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación/ ; ANPCyT PICT 2019-282//Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación/ ; PIDTA-SECYT 2023-2027//Secretaria de Ciencia y Tecnología - Universidad Nacional de Córdoba/ ; PIP 2022-2024//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PIP 2020-2022//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; AARGD-22-926476/ALZ/Alzheimer's Association/United States ; },
mesh = {Animals ; *Nanoparticles/chemistry ; *Amyloid beta-Peptides/toxicity/metabolism ; Humans ; *Synapses/pathology/drug effects/metabolism ; *Dendrites/pathology/drug effects/metabolism ; *Amyloid beta-Protein Precursor/metabolism ; Mice ; Rats ; *Albumins ; Neurons/metabolism/drug effects/pathology ; Cell Line, Tumor ; },
abstract = {Alzheimer's disease (AD) is a multifactorial and highly debilitating disorder with a long clinical course. The development of new therapeutic strategies capable of mitigating or delaying disease progression remains a major challenge. We previously identified the amyloid precursor protein (APP) as a receptor for aggregated amyloid-β (Aβ) species that signals through a Go/Gβγ-dependent pathway, thereby promoting amyloidogenesis and neurotoxicity. In this context, gallein (GAL), a selective inhibitor of Gβγ signaling, has demonstrated robust neuroprotective effects in preclinical AD models. However, GAL exhibits poor stability and limited aqueous solubility, which may restrict brain bioavailability. To overcome these limitations, a nanotechnology-based formulation strategy was implemented. Here, we report the design and generation of human serum albumin-based nanoparticles (HSA NPs) loaded with GAL (NP-GAL) using a green desolvation method followed by thermal stabilization. Using murine neuroblastoma cells, primary rat cortical neurons, and human iPSC-derived neurons, we demonstrate that NP-GAL effectively prevents Aβ-induced amyloidogenic APP processing, dendritic dystrophy, and presynaptic loss. In addition, both empty NPs and NP-GAL exhibit association with Aβ aggregates, suggesting an additional benefit, as these nanoparticles mitigate amyloid-associated toxicity. Notably, the nanoparticles themselves exert beneficial effects on dendritic morphology and provide protection against neurotoxic insults beyond amyloid pathology, including those induced by rotenone, a widely used experimental model of Parkinson's disease. Together, these in vitro findings suggest that HSA-based nanoparticles hold potential as a platform to stabilize GAL and exert intrinsic neuroprotective effects. These results provide a proof-of-concept for exploring nanoparticle-mediated Gβγ inhibition to counteract Aβ-induced neuronal dysfunction and synaptic pathology.},
}

Animals
*Nanoparticles/chemistry
*Amyloid beta-Peptides/toxicity/metabolism
Humans
*Synapses/pathology/drug effects/metabolism
*Dendrites/pathology/drug effects/metabolism
*Amyloid beta-Protein Precursor/metabolism
Mice
Rats
*Albumins
Neurons/metabolism/drug effects/pathology
Cell Line, Tumor

@article {pmid42563554,
year = {2026},
author = {Asghariahmadabad, M and Metanat, P and Thomas, M and Bonham, LW and Lam, T and Kurt, M and Nguyen, H and Ellingson, T and Zucchelli, M and Casagranda, S and Lu, Q and Rauschecker, AM and Sugrue, L and Savastano, LE and Hess, CP and Ranasinghe, K and Josephson, SA and Miller, BL and Yokoyama, JS and Rabinovici, GD and Ljubenkov, PA and VandeVrede, L and Nael, K},
title = {Arterial Spin-Labeling MRI at the Cortical-CSF Interface: A Novel Biomarker in Alzheimer Disease.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70498},
pmid = {42563554},
issn = {2328-9503},
abstract = {BACKGROUND/OBJECTIVE: Arterial spin-labeling (ASL) MRI can measure perfusion signal adjacent to CSF spaces and may provide information regarding CSF-adjacent water transport physiology. We developed an automated pipeline to extract cortical-CSF interface (IF) perfusion for comparison between Alzheimer disease (AD) and cognitively normal controls.

METHODS: In this retrospective study, participants with AD and cognitively normal controls with ASL and 3D T1-weighted MRI were included. Parenchymal cerebral blood flow (CBF) was evaluated globally (whole brain, gray matter, white matter) and across 12 brain regions. IF-perfusion values were quantified using an automated pipeline with tissue segmentation, registration, partial-volume-aware masking, and arterial-signal exclusion. Multivariable sensitivity analysis was performed, adjusting for age, sex, scanner vendor, and acquisition site. Predictive modeling was performed using LASSO-regularized logistic regression with nested repeated stratified cross-validation, and feature contributions were summarized using SHAP.

RESULTS: A total of 51 patients with AD, age (median: 73 years) and 53 cognitively normal subjects (median age: 69) were included. Global CBF did not differ between groups. However, IF-perfusion values were significantly lower in AD (median 4.4, IQR 3.2-4.8) than in controls (median 5.2, IQR 4.5-6.3; p < 0.001). In multivariable analysis, AD remained independently associated with lower IF-perfusion after adjustment for age, sex, scanner vendor, and acquisition site (β = -1.88, 95% CI: -3.52 to -0.25; p = 0.025). In LASSO-regularized logistic regression model, only IF-perfusion and cuneus-CBF remained as significant contributing features for the prediction of AD probability with the highest contribution from IF. The final model showed mean ROC-AUC 0.81 in the training and AUC of 0.78 in the testing dataset.

CONCLUSION: ASL-derived IF-perfusion is reduced in AD and may represent a promising imaging marker of altered CSF-adjacent water transport physiology. Further validation against established biomarkers of CSF dynamics and clearance pathways is warranted.},
}

@article {pmid42563724,
year = {2025},
author = {Yun, JE and Choi, S},
title = {Expanding the health belief model on dementia knowledge, fear, and preventive behaviors among older adults in Korea: a cross-sectional descriptive study.},
journal = {Journal of Korean biological nursing science},
volume = {27},
number = {1},
pages = {60-71},
pmid = {42563724},
issn = {2383-6423},
abstract = {PURPOSE: This study aimed to expand the health belief model by incorporating dementia knowledge and fear and to assess the effects of these variables on dementia prevention behaviors among older adults.

METHODS: In total, 199 elderly individuals from 10 senior centers in Korea completed a structured questionnaire assessing characteristics, dementia knowledge, fear, health beliefs, and prevention behaviors. Measures included the Alzheimer's Disease Knowledge Scale, the Korean version of the Fear of Alzheimer's Disease Scale, and the Korean version of the Motivation to Change Lifestyle and Health Behavior for Dementia. Hierarchical polynomial regression was conducted to examine the impact of integrating dementia knowledge and fear into the health belief model.

RESULTS: Hierarchical polynomial regression across four models revealed significant effects of various factors on dementia prevention behaviors, explaining 12%-36% of the variance. Perceived barriers significantly decreased dementia prevention behaviors, while higher levels of self-efficacy and cues to action had a positive influence. Additionally, a nonlinear relationship was identified between dementia knowledge and prevention behaviors, with the positive impacts of increased knowledge potentially diminishing beyond a certain point.

CONCLUSION: Our findings underscore the necessity of modifying the health belief model to integrate dementia knowledge and fear, which play critical roles in shaping preventive behaviors among older adults. Future investigations should examine the optimal level of dementia knowledge to promote these behaviors and elucidate the intricate relationship between knowledge and actions.},
}

@article {pmid42563959,
year = {2026},
author = {Liu, Y and Yi, M and Tang, C and Wang, T and Li, X},
title = {MEOX2: a homeobox transcription factor with multifaceted biological functions and broad disease associations.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1895187},
pmid = {42563959},
issn = {2296-634X},
abstract = {The mesenchymal homeobox transcription factor MEOX2 is recognized for its roles in development and homeostasis, but the full landscape of its complex and often contradictory functions in human diseases, along with its potential unifying regulatory logic, remains to be systematically elucidated. This Review synthesizes current evidence to provide a comprehensive overview of MEOX2's widespread roles in both neoplastic and non-neoplastic diseases. MEOX2 is remarkably context-dependent: it acts as an oncogene in glioblastoma and lung cancer, but as a tumour suppressor in breast cancer, hepatocellular carcinoma and other tumour types. Its dysregulation is also linked to neurovascular deficits in Alzheimer disease (AD), cardiovascular disorders, metabolic fibrosis and developmental malformations. This functional versatility stems from MEOX2's role as a key signalling integrator, subject to fine-tuned regulation by epigenetic mechanisms, non-coding RNA networks and core pathways including PI3K/AKT, ERK and Hedgehog (Hh). Given the strong association between MEOX2 expression and clinical outcomes, it has emerged as a potential diagnostic and prognostic biomarker for several diseases. Intervention strategies targeting MEOX2 and its regulatory networks show translational promise. This Review proposes a conceptual framework placing MEOX2 as a 'cross-disease core regulatory node', systematically delineates its complex disease associations and molecular mechanisms, and charts a course for the future development of precision medicine strategies targeting MEOX2.},
}

@article {pmid42564156,
year = {2026},
author = {Ali, N and Chakbazof, N and Ghasem Pour, S and Contreras, L and Estrada, J and Alexander, GE and Raichlen, DA and Yassine, HN},
title = {APOE ε4, physical activity, and the brain: a review of systematic reviews.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1798639},
pmid = {42564156},
issn = {1663-4365},
abstract = {BACKGROUND: Physical activity (PA) is often proposed as a modifiable strategy to reduce cognitive decline and dementia risk, particularly among individuals at elevated genetic risk for Alzheimer's disease (AD). However, it remains unclear whether the existing literature tests PA at the disease stage and in the populations most likely to show benefit.

OBJECTIVE: This umbrella review evaluated whether associations between PA and cognitive, fluid biomarker, neuroimaging, and vascular/metabolic outcomes differ by apolipoprotein E ε4 (APOE ε4) genotype across stages of cognitive aging, with particular attention to how study design and baseline cognitive status shape interpretation of the evidence.

METHODS: Systematic reviews and meta-analyses were screened for primary studies examining PA in adults classified by baseline cognitive status as cognitively unimpaired, mild cognitive impairment (MCI), or dementia. Primary studies reporting APOE ε4-stratified outcomes were extracted and qualitatively synthesized by outcome domain, cognitive stage, and study design.

RESULTS: Of 2,100 records identified, seven systematic reviews met inclusion criteria, yielding 68 unique primary studies. Favorable associations between PA and cognitive, biomarker, neuroimaging, and vascular/metabolic outcomes were most often reported in observational studies of younger or cognitively unimpaired adults. Several studies suggested stronger associations among APOE ε4 carriers, including midlife cognitive associations, neuroimaging markers, and vascular/metabolic outcomes such as lipid profiles. In contrast, randomized controlled trials were few, generally enrolled older adults with MCI or dementia, included small APOE ε4 subgroups, and reported largely null or mixed genotype-specific effects.

CONCLUSION: The current evidence does not establish a definitive APOE ε4-specific preventive effect of PA. Future studies may be most informative if they target earlier-stage, low-active, or metabolically at-risk APOE ε4 carriers using objective PA measures and proximal vascular, metabolic, imaging, or blood-based biomarker outcomes.},
}

@article {pmid42564234,
year = {2026},
author = {Macías, M and Escriche, E and Molina, M and Esnaola, I and Jiménez, A and Razquin-Sola, S and Roldan, M and Urdánoz-Casado, A and Sobrino, N and Fernández, C and Rubio, I and Aspra, D and Jáuregui, C and Muñoz, R and Herrera, M and Mendioroz, M},
title = {Association of acute-phase plasma pTau217 levels with long-term post-stroke cognitive impairment.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1839662},
pmid = {42564234},
issn = {1663-4365},
abstract = {BACKGROUND: Post-stroke cognitive impairment (PSCI) is a common complication affecting stroke survivors, yet early biomarkers for risk stratification remain scarce. Plasma pTau217 has emerged as a specific biomarker for Alzheimer's disease pathology. This study explores whether acute-phase pTau217 levels are associated with PSCI.

METHODS: We conducted a nested case-control study including 48 patients who developed PSCI within 5 years and 48 age and sex-matched patients as controls without cognitive decline. Plasma pTau217 was measured within 24 h after stroke onset using SIMOA. Statistical analysis included multivariable logistic regression, dose-response assessment via quartile stratification, and ROC curves.

RESULTS: Plasma pTau217 levels were significantly higher in PSCI cases than controls [0.313 (0.196-0.562) vs. 0.203 (0.126-0.343) pg/mL; p-value < 0.01]. Notably, pTau217 levels were not correlated with stroke severity (NIHSS at baseline) or atrial fibrillation, suggesting that pTau217 may reflect baseline neurobiological vulnerability. In multivariable models, ln-pTau217 levels were independently associated with PSCI risk (OR = 2.28; 95%CI = 1.19-4.37; p-value < 0.05). A significant linear dose-response relationship was observed, with PSCI risk increasing from 29.2% in the lowest quartile to 64.0% in the highest (p-value for trend < 0.05). The biomarker alone showed a significant discriminative capacity for clinically documented PSCI (AUC = 0.660; 95%CI = 0.552-0.768; p-value < 0.01). Furthermore, sex-stratified analysis revealed that the association was primarily driven by females.

CONCLUSION: Higher acute-phase pTau217 levels were associated with an increased likelihood of clinically documented cognitive impairment during follow-up. These exploratory findings suggest that acute-phase pTau217 may be associated with long-term cognitive outcomes after stroke, although larger prospective studies, integrating additional biomarkers with standardized neuropsychological assessment are needed.},
}

@article {pmid42564239,
year = {2026},
author = {Cretin, B and Philippi, N and Bousiges, O and Dibitonto, L and Blanc, F},
title = {The impact of long-term antiseizure treatment on cognitive decline in late-onset epileptic prodromal Alzheimer's disease: an exploratory study.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1786247},
pmid = {42564239},
issn = {1663-4365},
abstract = {BACKGROUND: The well-documented bidirectional relationship between Alzheimer's disease (AD) and epilepsy suggests that seizures are not merely a complication of AD but may also contribute to disease progression. Emerging evidence indicates that antiseizure medications (ASMs) could potentially slow the disease course and act as disease-modifying agents if initiated early.

OBJECTIVES: We investigated the long-term cognitive and functional effects of ASMs when introduced at the prodromal stage of AD.

METHODS: Twenty-two sporadic epileptic prodromal AD patients (epADs) and 21 matched subjects without epilepsy (nepADs) were followed for a median of 7 years. Baseline cognition, daily functioning, clinical/paraclinical features, and pharmacological profiles were compared. Annual assessments included cognition, pharmacological burden, and functional impairment.

RESULTS: At the final follow-up, epADs evidenced more preserved cognition than nepADs, reflecting a significantly slower annual rate of cognitive decline (-1.2 ± 0.9 vs. -2.7 ± 2.4 points/year on the MMSE score, respectively; p = 0.01). They were also less likely to require neuroleptics (9.1% vs. 47.6%, p < 0.01) or memantine (0% vs. 28.6%, p < 0.01). However, epADs and nepADs had the same proportion of Alzheimer's dementia at the final follow-up visit (90.9% vs. 90.5%, p = 0.96). Despite being significant, these results had low statistical power due to our small sample size and should be considered exploratory.

CONCLUSION: Our findings support the idea that early ASM treatment may attenuate cognitive decline in sporadic prodromal AD patients with comorbid epilepsy. However, these benefits were not accompanied by a lower dementia rate at the final follow-up visit, suggesting that ASMs alone are insufficient for sustained disease modification. Combinatorial therapeutic strategies may be needed to achieve long-term neuroprotection in AD.},
}

@article {pmid42564294,
year = {2026},
author = {Zhao, M and Sui, X and Li, J and Wang, Q and Sun, Y and Zheng, H and Li, B},
title = {Ferroptosis-related biomarkers for diagnosis and mechanistic insights into Alzheimer's disease.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1857642},
pmid = {42564294},
issn = {1663-4365},
abstract = {BACKGROUND: Alzheimer's disease (AD) lacks reliable early diagnostic biomarkers and effective disease-modifying therapies. Ferroptosis has been increasingly implicated in AD pathogenesis; however, ferroptosis-related genes with diagnostic and mechanistic relevance remain insufficiently characterized.

METHODS: Transcriptomic datasets were obtained from the GEO database and analyzed using differential expression analysis and WGCNA, followed by integration with ferroptosis-related gene sets. Key targets were identified through PPI networks and machine learning approaches, including LASSO regression and random forest. A diagnostic model was constructed and its discriminative performance was assessed across independent datasets by cohort-specific refitting. Functional roles were explored using GSEA, and experimental validation was conducted by qPCR in Aβ-treated PC12 cells. Potential therapeutic compounds were predicted using the CMAP database.

RESULTS: A total of 52 ferroptosis-related candidate genes were identified. Among these, three genes, NFKBIA, ATP6V1E1, and SUB1, were consistently selected as core features by machine learning algorithms. A diagnostic model based on these genes demonstrated strong performance in the training cohort (AUC > 0.8) and reproducible discriminative ability across external datasets, albeit with cohort-dependent variability. Functional analysis suggested that these genes are involved in pathways related to neuroinflammation, lysosomal activity, and oxidative stress, indicating a potential link between ferroptosis and key pathological processes in AD. qPCR validation confirmed the differential expression trends of these genes. In addition, several candidate compounds, including etomoxir and tubastatin A, were predicted to potentially modulate these pathways.

CONCLUSION: Three ferroptosis-related genes, NFKBIA, ATP6V1E1, and SUB1, were identified in Alzheimer's disease and showed consistent discriminative ability across multiple cohorts, with links to neuroinflammation, lysosomal function, and oxidative stress. These findings highlight their potential as candidate biomarkers warranting further investigation, although prospective validation in independent cohorts is required to confirm their diagnostic utility.},
}

@article {pmid42564336,
year = {2026},
author = {Chi, M and Zhao, A and Zhang, Y and Fan, L and Wang, Q and Tang, B and Tao, M},
title = {Electroencephalography for early Alzheimer's disease diagnosis: from advanced feature engineering to interpretable ai and clinical translation.},
journal = {Frontiers in psychiatry},
volume = {17},
number = {},
pages = {1819726},
pmid = {42564336},
issn = {1664-0640},
abstract = {OBJECTIVE: This review aims to comprehensively review the methodologies and advancements in using electroencephalography (EEG) for the early diagnosis of Alzheimer's disease (AD), addressing the limitations of traditional diagnostic tools.

METHODS: We conducted a comprehensive analysis of current research, encompassing the complete EEG analysis pipeline from signal acquisition and preprocessing to feature extraction-including time-frequency and brain network metrics-and the application of machine learning and deep learning algorithms.

RESULTS: Characteristic EEG alterations, such as spectral slowing and reduced signal complexity, are associated with early AD. Advanced feature extraction combined with intelligent algorithms significantly enhances diagnostic performance, with some studies reporting classification accuracies exceeding 95%. Integration of EEG with multimodal data (e.g., MRI, genetic markers) further improves diagnostic robustness.

CONCLUSIONS: EEG is a promising, non-invasive, and cost-effective tool for early AD detection in appropriate clinical and research settings. The integration of advanced signal processing with intelligent algorithms can significantly improves diagnostic precision, though clinical translation requires standardized protocols and validation on larger, diverse cohorts.

SIGNIFICANCE: This work highlights the potential of EEG to facilitate accessible, early-stage AD screening, which is crucial for timely intervention and may contribute to reducing the disease's future socioeconomic burden.},
}

@article {pmid42564343,
year = {2026},
author = {Liu, H and Liu, X and Chen, Y and Pan, M and Fu, Y and Ma, C and Ge, W},
title = {Serum elemental profile-based machine learning models for Alzheimer's disease identification and cognitive score prediction.},
journal = {Neuroprotection (Chichester, England)},
volume = {},
number = {},
pages = {},
pmid = {42564343},
issn = {2770-730X},
abstract = {BACKGROUND: Current diagnostic approaches for Alzheimer's disease (AD) largely rely on cerebrospinal fluid biomarkers and neuroimaging, which may be invasive, costly, and not readily accessible in routine clinical settings. We investigated whether serum elemental profiling combined with machine learning could provide complementary information for AD identification and exploratory cognitive score prediction.

METHODS: This retrospective cross-sectional study included 874 participants enrolled between 2017 and 2023 from the Brain Aging National Cohort-Peking Union Medical College cohort, comprising 427 cognitively normal controls (NCs) and 447 patients with clinically defined AD. Serum concentrations of 20 elements were quantified by inductively coupled plasma mass spectrometry. Associations between serum element concentrations and AD status were evaluated using age- and sex-adjusted logistic regression models with false discovery rate (FDR) correction. Associations with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores were assessed using linear regression models with FDR correction. Machine learning classification models were developed for AD identification, whereas regression models were developed for exploratory MMSE and MoCA score prediction. Model performance was evaluated in an internal hold-out test set.

RESULTS: Age did not differ significantly between NC and AD participants (66.4 ± 9.9 vs. 67.1 ± 9.0 years; t(872) = -1.13, p = 0.260), whereas the proportion of women was higher in the AD group than in the NC group (255/447 [57.0%] vs. 211/427 [49.4%]; χ [2](1) = 5.11, p = 0.024). MMSE scores were significantly lower in patients with AD than in NC participants (AD: n = 277, median [interquartile range (IQR)] = 24 [19-27]; NC: n = 427, median [IQR] = 30 [30-30]; Mann-Whitney U = 3043.5, p < 0.001), as were MoCA scores (AD: n = 240, median [IQR] = 18.00 [14.00-20.25]; NC: n = 427, median [IQR] = 30 [30.00-30.00]; Mann-Whitney U = 13.5, p < 0.001). After adjustment for age and sex, higher serum lead (Pb) and tin (Sn) levels were associated with increased odds of AD (Pb: odds ratio [OR] = 4.95, 95% confidence interval [CI]: 3.42-7.37; Sn: OR = 1.45, 95% CI: 1.20-1.78), whereas higher serum antimony, nickel, manganese, cobalt, selenium, and calcium levels were associated with lower odds of AD (OR range: 0.50-0.81; all FDR-adjusted p-values < 0.05). Among the eight classification models evaluated in the internal hold-out test set, the random forest model showed the highest apparent performance for distinguishing AD from NC, achieving an accuracy of 88% and an area under the receiver operating (AUC) (acharacteristic curv of 0.94. Among the three regression models evaluated, the random forest regression showed the highest apparent performance for cognitive score prediction, yielding the strongest correlations between predicted and observed scores for both MMSE (r = 0.48, p < 0.001) and MoCA (r = 0.62, p < 0.001).

CONCLUSION: Serum elemental profiles combined with machine learning may provide a minimally invasive and accessible complementary approach for AD identification and cognitive assessment.},
}

@article {pmid42564398,
year = {2026},
author = {Shi, P and Wang, S and Zang, Z and Wang, D and Yang, C and Tao, J and Liu, J and Sun, J and Shen, W and Wang, R and Sun, M},
title = {Barrier-to-Autointegration Factor 1: a key regulator of nuclear envelope integrity, genome stability, and disease progression.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1870828},
pmid = {42564398},
issn = {1664-3224},
mesh = {Humans ; *Genomic Instability ; *DNA-Binding Proteins/genetics/metabolism ; Animals ; *Nuclear Envelope/metabolism/genetics ; *Nuclear Proteins/genetics/metabolism ; Disease Progression ; Neoplasms/genetics/pathology/metabolism ; DNA Repair ; Neurodegenerative Diseases/genetics/metabolism ; cGAS-STING Signaling Pathway ; },
abstract = {Barrier-to-Autointegration Factor 1 (BANF1) is a self-associating protein encoded within the q13.1 locus of chromosome 11. It is integral to multiple cellular processes, including cell cycle regulation, chromatin organization, gene expression modulation, nuclear envelope (NE) repair, DNA damage repair (DDR), innate immune function, and viral infection control. While prior investigations have provided preliminary phenotypic and bioinformatic characterizations of BANF1 across various disease states, comprehensive analyses detailing its functional roles and mechanistic underpinnings in diverse pathological contexts remain scarce. In cancer, BANF1 is frequently upregulated, with cancer cells leveraging its functions to preserve NE integrity, inhibit activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) immune pathway, and facilitate epithelial-mesenchymal transition (EMT). These activities contribute to enhanced genomic stability and promote tumor cell proliferation and migration, thereby conferring oncogenic properties. In neurodegenerative diseases, BANF1 is implicated in disease pathogenesis, exemplified by its mediation of glutamate-induced oxidative stress and apoptosis in neuronal cells, as observed in Alzheimer's disease (AD). Additionally, rare mutations in BANF1 are associated with hereditary conditions: the recessive Ala12Thr (A12T) variant causes Néstor-Guillermo progeria syndrome (NGPS), whereas the dominant Gly16Arg (G16R) mutation results in dominant motor neuronopathy. This review further synthesizes recent progress in exploring BANF1 as a therapeutic target, encompassing the development of small-molecule inhibitors, immunomodulatory approaches, and its potential applications in cancer treatment. Overall, this article provides a comprehensive overview of BANF1's structural features, cellular functions, and involvement in disease initiation and progression, with particular emphasis on its expression profiles in malignancies and the therapeutic promise of BANF1-directed interventions.},
}

Humans
*Genomic Instability
*DNA-Binding Proteins/genetics/metabolism
Animals
*Nuclear Envelope/metabolism/genetics
*Nuclear Proteins/genetics/metabolism
Disease Progression
Neoplasms/genetics/pathology/metabolism
DNA Repair
Neurodegenerative Diseases/genetics/metabolism
cGAS-STING Signaling Pathway

@article {pmid42564476,
year = {2026},
author = {Allaham, SMI},
title = {Diagnostic Accuracy of MRI-Based Artificial Intelligence Models for Distinguishing Alzheimer's Disease and Mild Cognitive Impairment From Cognitively Normal Controls: A Systematic Review and Meta-Analysis.},
journal = {Dementia and neurocognitive disorders},
volume = {25},
number = {3},
pages = {141-151},
pmid = {42564476},
issn = {2384-0757},
abstract = {Magnetic resonance imaging (MRI)-based artificial intelligence (AI) models are increasingly applied to brain MRI for diagnosing Alzheimer's disease (AD) and mild cognitive impairment (MCI), but their overall diagnostic performance remains unclear. We systematically searched PubMed/MEDLINE, Embase, Web of Science, Scopus, and IEEE Xplore until February 15, 2026, for diagnostic accuracy studies of machine-learning or deep-learning models using structural brain MRI to distinguish AD vs. cognitively normal (CN) controls and MCI or late mild cognitive impairment (LMCI) vs. CN controls. Seven studies met inclusion criteria, contributing five AD vs. CN and two MCI/LMCI vs. CN tasks, predominantly using deep-learning architectures applied to Alzheimer's Disease Neuroimaging Initiative cohorts. For AD vs. CN (five studies), pooled sensitivity was 0.96 (95% confidence interval [CI], 0.93-0.97) and pooled specificity was 0.95 (95% CI, 0.92-0.97), indicating excellent discrimination. For MCI/LMCI vs. CN (two studies), sensitivity was consistently high (0.91-0.93), whereas specificity varied widely (0.54-0.98), limiting the interpretability of pooled estimates. MRI-based AI models therefore show strong performance for established AD but heterogeneous specificity for MCI, underscoring the need for larger, externally validated studies in diverse populations.},
}

@article {pmid42564518,
year = {2026},
author = {Park, J},
title = {Druggable Pathophysiologic Targets in Alzheimer Disease: From Amyloid and Tau to Biomarker-Guided Multimodal Therapy.},
journal = {Dementia and neurocognitive disorders},
volume = {25},
number = {3},
pages = {152-163},
pmid = {42564518},
issn = {2384-0757},
abstract = {Alzheimer disease (AD) is no longer viewed only as a clinical syndrome of memory impairment but as a biological disease continuum driven by interacting amyloid-β, tau, glial, vascular, metabolic, and synaptic mechanisms. This shift has practical therapeutic consequences. Symptomatic agents such as cholinesterase inhibitors and memantine remain useful for selected patients, but they do not directly modify the core neurodegenerative process. In contrast, amyloid-β monoclonal antibodies have provided proof that biomarker-confirmed early AD can be slowed, although the magnitude of clinical benefit is modest, treatment is restricted to carefully selected patients, and amyloid-related imaging abnormalities require structured monitoring. Tau pathology, neuroinflammation, blood-brain barrier dysfunction, mitochondrial and oxidative stress, and impaired proteostasis are therefore increasingly important druggable axes rather than secondary background phenomena. A staged, biomarker-guided druggability framework can evaluate each target by biological proximity to clinical decline, biomarker measurability, therapeutic modifiability, implementation feasibility, and suitability for sequencing or combination therapy. Validated and emerging targets are summarized with emphasis on how biomarkers reshape patient selection and outcome assessment and how anti-amyloid therapy can be integrated with stage-specific interventions targeting tau propagation, glial activation, vascular injury, clearance failure, and metabolic vulnerability. The central conclusion is that AD drug development should move from a single-target rescue model toward biomarker-guided, mechanism-matched, and combination-ready strategies that can be tested earlier in the disease course while maintaining realistic safety and implementation standards.},
}

@article {pmid42564648,
year = {2026},
author = {Lee, S and Woo, SH and Nam, KC and Moon, C and Lee, K and Kim, KK and Kim, HR and Suh, J},
title = {Gait Analysis Using Wearable Sensors in Patients With Alzheimer's Dementia: A Preliminary Report.},
journal = {Dementia and neurocognitive disorders},
volume = {25},
number = {3},
pages = {178-190},
pmid = {42564648},
issn = {2384-0757},
abstract = {BACKGROUND AND PURPOSE: Gait dysfunctions have been frequently observed in patients with Alzheimer's disease (AD). Previous studies have used various methods to assess the gait impairment in AD. Here, we developed a wearable gait sensor, a Smart-insole, which is embedded in shoe insoles. We evaluated whether gait parameters measured using the Smart-insole were associated with cognitive performance in patients with AD.

METHODS: Participants aged 45-90 years, who were either cognitively unimpaired (CU) or had Alzheimer's disease dementia (ADD) were recruited from a hospital-based outpatient clinic, between January and December 2023. Participants performed three gait tasks (walk straight and turn test, timed up and go test, and ramp and stair test) while wearing the Smart-insole. The association of gait parameters with individual's cognitive status (CU vs. ADD) and cognitive test scores (Mini-Mental State Examination [MMSE] and various domain-specific cognitive tests from the Seoul Neuropsychological Screening Battery, 2[nd] Edition) was assessed.

RESULTS: Patients with ADD demonstrated decreased gait pace, rhythm, and stability as evidenced by longer task, cycle, and stance times, a higher number of steps, greater variability in swing time, and lower cadence during the gait task. Furthermore, gait parameters showed nominal associations with individual's MMSE score and each cognitive domain score (fronto-executive, memory, and language function).

CONCLUSIONS: Smart-insole wearable sensors showed exploratory gait-related alterations in patients with ADD. These hypothesis-generating findings suggest that wearable insole-based gait assessment may provide complementary information for characterizing gait and cognitive dysfunction in ADD.},
}

@article {pmid42564689,
year = {2026},
author = {Chen, L and Zhou, X and Zhang, B and Hou, Y and Sun, Y and Peng, D and , },
title = {Thalamic volume alterations mediate glymphatic function and cognitive dysfunction in Alzheimer's disease.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {3},
pages = {e70304},
pmid = {42564689},
issn = {2352-8737},
abstract = {INTRODUCTION: Glymphatic dysfunction is implicated in Alzheimer's disease (AD), but its mechanism remains unclear. This study investigated the associations of the analysis along the perivascular space (ALPS) index, brain reserve, and cognitive outcomes across the AD continuum.

METHODS: This study enrolled two cohorts from the local hospital (n = 95) and the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 178). We calculated the diffusion tensor image ALPS to assess the whole-brain glymphatic function and evaluated its associations with cognition and brain structure.

RESULTS: A higher ALPS index was positively associated with better executive, memory, and language abilities (p < 0.05). A lower ALPS index correlated with thalamic atrophy, involving the anterior, lateral, ventral, and midline thalamic nuclei. Thalamic atrophy mediated the link between glymphatic dysfunction and worse cognition via structural association of full or part mediation.

CONCLUSIONS: Glymphatic system deterioration correlates with cognitive decline, potentially mediated by thalamic atrophy. The thalamic nuclei may be critical in this pathway.},
}

@article {pmid42564853,
year = {2026},
author = {Zelek, MC and Walker, JQ and Sabbagh, MN},
title = {Management of multimorbidity in the midst of cognitive decline through clinical decision-support software.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {3},
pages = {e70395},
pmid = {42564853},
issn = {2352-8729},
abstract = {INTRODUCTION: Multimorbidity - the coexistence of multiple chronic conditions - is common among older adults with cognitive impairment but is rarely addressed in an integrated manner.

METHODS: We analyzed 17,915 adults aged 55 to 84 years (8997 receiving uMETHOD clinical decision-support care plans and 8918 from the National Health and Nutrition Examination Survey). The mean age was 69.0 years (SD 7.65; 95% CI: 68.86 to 69.1). Multimorbidity was quantified from diagnoses, labs, medications, vitals, and platform-inferred conditions. Associations with cognitive impairment were modeled using age- and sex-adjusted logistic regression.

RESULTS: Cognitive impairment was reported in 25.91% of participants (97.5% with ≥2 conditions); each additional condition was associated with higher odds (odds ratio: 1.069; 95% CI: 1.061 to 1.077; p < 0.0001). Prominent clusters included vascular-metabolic disorders and micronutrient deficiencies.

DISCUSSION: Cognitive vulnerability rises stepwise with disease burden. Precision, multimorbidity-aware decision support that integrates multidomain data can align cognitive and systemic care in real-world practice.},
}

@article {pmid42564867,
year = {2026},
author = {Mancy, AS},
title = {SIRT6 signaling as an underexplored mechanistic node in nanoformulation-based neuroinflammation therapy for Alzheimer's disease.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {3},
pages = {e70305},
pmid = {42564867},
issn = {2352-8737},
abstract = {Chronic microglial neuroinflammation is a core driver of Alzheimer's disease (AD). Wei et al. recently reported a blood-brain barrier (BBB)-penetrating, microglia-targeting nanomodulator (Res@TcMNP/ASO) that simultaneously suppressed NF-κB signaling and enhanced NRF2-dependent antioxidant defense in chronically activated microglia, yet the molecular node coupling these two opposing circuits was not identified. In this perspective, drawing on primary literature spanning microglial inflammation, neuronal genome maintenance, tau regulation, and oncology, I propose that sirtuin 6 (SIRT6) is a plausible upstream candidate for this coordinated effect. SIRT6, a NAD[+]-dependent chromatin deacetylase, restrains NF-κB through H3K9 deacetylation at RELA target promoters and, in parallel, deacetylates and stabilizes NRF2 to amplify antioxidant transcription; its decline in the aging and AD brain promotes DNA damage and GSK3-driven tau hyperphosphorylation. Because a microglia-restricted carrier confines pathway modulation to the relevant cell population, this delivery strategy is well matched to a SIRT6-centered mechanism, while the context-dependent, potentially oncogenic nature of systemic SIRT6 activation reinforces the rationale for such restricted delivery. I outline specific loss- and gain-of-function experiments to test whether microglial SIRT6 mediates the dual-pathway effects of Res@TcMNP/ASO, offering a falsifiable hypothesis to guide future mechanistic and therapeutic work.},
}

@article {pmid42564896,
year = {2026},
author = {Kadaba Sridhar, S and Eastman, A and Wilson, P and Mishra, S and Broadbent, C and Truwit, C and Kuang, R and Samadani, U},
title = {Automatic coarse-to-fine AC-PC localization on CT using registration-guided 3D-UNets.},
journal = {Frontiers in neuroinformatics},
volume = {20},
number = {},
pages = {1853412},
pmid = {42564896},
issn = {1662-5196},
abstract = {INTRODUCTION: Automatically localizing the Anterior Commissure (AC) and Posterior Commissure (PC) is foundational for CT-based algorithmic disease screening, yet robust computational methods for this on CT remain lacking. We developed a registration-guided 3D-UNet framework for CT-based AC-PC localization, demonstrating its utility in computing ventriculomegaly features for Normal Pressure Hydrocephalus (NPH) detection.

METHODS: Framework development and evaluation were on an internal cohort of scans from patients with NPH, Alzheimer's disease, post-traumatic volume loss, and headache (Veterans Affairs [VA]-Cohort, n = 427). External validation was on separate datasets (VA-ExtCohort, University of California, Santa Barbara [UCSB]-ExtCohort). AC-PC reference standard definition, model development, and evaluation were on 1 mm[3]-resampled scans.

RESULTS: On 1-mm[3] resampled scans, test-set AC-PC mean radial errors (MREs) were 1.64/1.49 mm on the VA-Cohort, 2.42/1.79 mm on the VA-ExtCohort (n = 40), and 2.31/1.93 mm on the UCSB-ExtCohort (n = 43). Notably, the upper limits of the 95% confidence intervals (CIs) for localization errors across all cohorts were well below 3.2 mm; we empirically determined this to be a clinically relevant threshold beyond which the discriminative power of AC-PC-referenced ventriculomegaly features degrades. Ventriculomegaly features assessed using our framework's predictions successfully distinguished NPH from Alzheimer's disease, post-traumatic volume loss, and headache on a chart-verified VA-Cohort subset (n = 238) with a test-set Area Under the Receiver Operating Characteristic Curve (AUC) of 0.95, closely matching the performance of features assessed using manual AC-PC localization.

CONCLUSION: The proposed registration-guided 3D-UNet framework accurately and automatically localizes the AC-PC on CT despite varied structural degeneration, enabling standardized radiological feature computation. This approach can augment neurodegenerative disease screening on CT, the primary modality for elderly patients evaluated for falls and altered mentation.},
}

@article {pmid42564946,
year = {2026},
author = {Gardener, SL and Al Shamsi, HSS and Rainey-Smith, SR and Sohrabi, HR and Taddei, K and Masters, CL and Martins, RN and Binosha Fernando, WMAD and , },
title = {The moderating effect of dietary fiber and protein on the relationship between symptoms of depression and anxiety and cognitive decline.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {3},
pages = {e70292},
pmid = {42564946},
issn = {2352-8737},
abstract = {INTRODUCTION: Depression and anxiety often co-occur with Alzheimer's disease, exacerbating the associated cognitive impairment. This study examined moderating effects of dietary protein and fiber intake on relationships between depressive and anxiety symptoms, and cognitive decline.

METHODS: Cognitively unimpaired (n = 553; 39.4% male, 70.6 ± 9.6 years) provided baseline fiber and protein intake, and had repeated cognitive testing and symptoms of depression/anxiety measured (baseline and up to eight follow-ups over 144 months). Moderation and simple slope analyses were employed in the cohort as a whole and following stratification by sex.

RESULTS: Fiber intake moderated the relationship between change in depressive symptoms and decline in language (β = -0.005, p < 0.001) and Preclinical Alzheimer Cognitive Composite (PACC); scores (β = -0.003, p = 0.010). In males, fiber intake moderated the relationship between change in anxiety symptoms and executive function decline (β = -0.003, p = 0.018), with protein intake moderating change in depressive symptoms and decline in attention (β = 0.006, p = 0.011).

DISCUSSION: Adequate dietary fiber and protein intake moderated association between depressive and anxiety symptoms and cognitive decline, supporting their potential role within multidomain strategies aimed at maintaining cognitive health in older adults.},
}

@article {pmid42565151,
year = {2026},
author = {Ramireddy, VVS and Shaikh, RG and Pednekar, AR and Tripathi, D and Munde, CT and Wagh, K},
title = {A Systematic Literature Review of Emerging Advances in Neurological Disorders: Diagnostic Innovations, Therapeutic Strategies, and Future Directions.},
journal = {Cureus},
volume = {18},
number = {7},
pages = {e112202},
pmid = {42565151},
issn = {2168-8184},
abstract = {Neurological disorders remain a major clinical burden because they affect cognition, movement, vascular function, behavior, psychological health, and long-term independence. Recent advances in imaging, biomarkers, artificial intelligence, regenerative therapy, immunotherapy, and targeted pharmacology have expanded diagnostic and therapeutic possibilities, yet the evidence remains dispersed across different neurological conditions and study designs. This review aimed to synthesize emerging advances in neurological disorders, focusing on diagnostic innovations, therapeutic strategies, and future clinical directions. A systematic literature review approach was applied using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-based screening principles. Eleven studies were included, covering ischemic stroke, glioblastoma, Alzheimer's disease, multiple sclerosis, Parkinson's disease, motor neuron disease, episodic migraine, transient ischemic attack, and postoperative delirium. Data were extracted on study design, condition, intervention or diagnostic method, comparator, outcomes, and key findings. Risk of bias was assessed using the Risk of Bias 2 (RoB 2) tool for randomized trials, the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) for nonrandomized, uncontrolled, post hoc, feasibility, and biomarker-monitoring studies, and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) for diagnostic and radiomics studies. Findings showed increasing use of radiomics, circulating tumor DNA, rhythm monitoring, vascular imaging, inflammatory markers, biologics, cell therapy, psychological intervention, and lipid-lowering therapy. Several studies reported promising clinical or biomarker signals, while others clarified treatment limitations in specific disease subtypes. Overall, the findings suggest an emerging shift toward precision-oriented neurology, but larger controlled trials, prospective biomarker validation, standardized outcomes, and longer follow-up are required before routine implementation.},
}

@article {pmid42565245,
year = {2026},
author = {Lynch, SY and Wang, Y and Wang, D and Bachhav, SS and Xiong, H and Boiser, J and Stage, E and Bannon, AW and Graff, O and Florian, H},
title = {A randomized phase 1b/2 trial of ABBV-916 in adults with early Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71715},
doi = {10.1002/alz.71715},
pmid = {42565245},
issn = {1552-5279},
support = {//AbbVie Inc./ ; },
mesh = {Humans ; *Alzheimer Disease/drug therapy/diagnostic imaging ; Female ; Male ; Double-Blind Method ; Aged ; Amyloid beta-Peptides ; Positron-Emission Tomography ; Dose-Response Relationship, Drug ; Middle Aged ; Aged, 80 and over ; *Antibodies, Monoclonal, Humanized/therapeutic use/pharmacokinetics ; Treatment Outcome ; Biomarkers/blood ; },
abstract = {INTRODUCTION: ABBV-916, an anti-amyloid immunotherapy, was evaluated in patients with early Alzheimer's disease (AD).

METHODS: This phase 1b/2, double-blind, placebo-controlled study consisted of two stages: multiple ascending dose (Stage A) and dose expansion (Stage B). In Stage A, patients were randomized to one of six planned cohorts to receive intravenous ABBV-916 (10 mg to 3000 mg) or placebo monthly through week 24. Assessments included amyloid PET, blood-based biomarkers, pharmacokinetics (PK), and safety. Dose selection for Stage B was to be based on results from Stage A.

RESULTS: One hundred six patients were randomized to ABBV-916 or placebo. The 3000 mg dose was reduced to 2000 mg and subsequently to 900 mg after safety review. Dose-proportional PK were observed, and amyloid reduction was observed over 24 weeks at doses ≥300 mg. Most adverse events were non-serious amyloid-related imaging abnormalities. The program ended before dose expansion due to business considerations.

DISCUSSION: Amyloid clearance rate and safety of ABBV-916 were generally comparable to approved anti-amyloid AD therapies.

NCT05291234.},
}

Humans
*Alzheimer Disease/drug therapy/diagnostic imaging
Female
Male
Double-Blind Method
Aged
Amyloid beta-Peptides
Positron-Emission Tomography
Dose-Response Relationship, Drug
Middle Aged
Aged, 80 and over
*Antibodies, Monoclonal, Humanized/therapeutic use/pharmacokinetics
Treatment Outcome
Biomarkers/blood

@article {pmid42565246,
year = {2026},
author = {Kolling, LJ and Wang, R and Gaudencio, GS and Fishbeyn, JS and James, TD and Mason, SM and McCoy, RO and Song, Z and McConnell, IP and Ziemke, K and Janik, KM and Xu, Y and Bierlein-De La Rosa, G and Ismail, S and Marcinkiewcz, CA},
title = {Dorsal raphe tau pathology disrupts sleep-wake orchestration and sleep architecture in a sex-specific manner.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71687},
doi = {10.1002/alz.71687},
pmid = {42565246},
issn = {1552-5279},
support = {//Alzheimer's Association and the Michael J. Fox Foundation for Parkinson's Research: 26BFDN-1576146A/ ; //Iowa Neuroscience Institute Research Program of Excellence (RPOE)/ ; R01 AG070841/AG/NIA NIH HHS/United States ; F32AG084196-01/AG/NIA NIH HHS/United States ; //Pappajohn Biomedical Institute/ ; //University of Iowa/ ; },
mesh = {Animals ; Male ; Female ; *Dorsal Raphe Nucleus/pathology/metabolism ; *tau Proteins/metabolism ; Mice ; Electroencephalography ; *Sleep/physiology ; *Sleep Wake Disorders/pathology/physiopathology/etiology ; *Sex Characteristics ; Serotonin/metabolism ; Alzheimer Disease ; *Tauopathies/pathology ; Wakefulness/physiology ; },
abstract = {INTRODUCTION: Sleep disturbances are frequent symptoms of Alzheimer's disease (AD), mirrored by early pathology in the dorsal raphe nucleus (DRN). Whether early DRN pathology can drive sleep disturbances, and the relative contributions of serotonin (5-HT) and sex, has not been directly tested.

METHODS: We isolate tau pathology to whole DRN (DRN[Tau]), serotonin neurons of the DRN (5-HT[Tau]), or non-serotonergic neurons of the DRN (non5HT[Tau]). We use longitudinal EEG recordings, in male and female mice, to determine the contributions of DRN neuronal subtypes to sleep disruption within the context of prodromal AD.

RESULTS: DRN[Tau], 5-HT[Tau], and non5HT[Tau] disrupt sleep architecture. 5-HT[Tau] and non5HT[Tau] further disrupt sleep-wake orchestration and exhibit sex-dependent alterations that coincide with changes in delta wave power.

DISCUSSION: Tau-mediated sleep dysfunction may be driven by various cellular subtypes of the DRN, are primarily sexually divergent, and may resultant in changes in 5-HT activity and relative spectral brain wave contributions.},
}

Animals
Male
Female
*Dorsal Raphe Nucleus/pathology/metabolism
*tau Proteins/metabolism
Mice
Electroencephalography
*Sleep/physiology
*Sleep Wake Disorders/pathology/physiopathology/etiology
*Sex Characteristics
Serotonin/metabolism
Alzheimer Disease
*Tauopathies/pathology
Wakefulness/physiology

@article {pmid42565249,
year = {2026},
author = {Kim, YM and Colcord, K and Sajjadi, SA and Andrews, EJ and Schneider, JA and Kawas, CH and Corrada, MM},
title = {Hormone replacement therapy and its association with LATE-NC in older adults.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71730},
doi = {10.1002/alz.71730},
pmid = {42565249},
issn = {1552-5279},
support = {P30AG072975/NH/NIH HHS/United States ; R01AG17917/NH/NIH HHS/United States ; R01AG067482/NH/NIH HHS/United States ; R01AG042210/NH/NIH HHS/United States ; UCI MIND/WAM 01-2024//Women's Alzheimer's Movement (WAM)/ ; },
mesh = {Humans ; Female ; *Hormone Replacement Therapy ; Male ; Aged, 80 and over ; Aged ; Aging ; Dementia ; TDP-43 Proteinopathies ; },
abstract = {INTRODUCTION: Limbic-predominant age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy neuropathological change (LATE-NC) is a cause of dementia resembling Alzheimer's disease (AD). The 90+ Study found women using hormone replacement therapy (HRT) two to three decades before death had lower odds of LATE-NC. We attempted to replicate this finding in a different cohort.

METHODS: Participants (n = 2056) included males (n = 640) and females (n = 1416) aged ≥65 from the Religious Orders Study and Memory and Aging Project with HRT and neuropathology data. We examined the association between HRT and LATE-NC in males and females and between HRT-related and reproductive variables in relation to LATE-NC in females using logistic regression.

RESULTS: HRT use within 5 years before or after menopause (odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.50 to 0.98, p = 0.03) or for 8 to 16 years (OR = 0.44, 95% CI = 0.24 to 0.79, p = 0.006) was associated with lower odds of LATE-NC.

DISCUSSION: This finding identifies a potential factor related to LATE risk and highlights the importance of HRT timing and duration for its potential neuroprotective effects.},
}

Humans
Female
*Hormone Replacement Therapy
Male
Aged, 80 and over
Aged
Aging
Dementia
TDP-43 Proteinopathies

@article {pmid42565262,
year = {2026},
author = {Collins, EC and Lu, M and Beck, R and Hendrix, J and Hodsdon, ME and Hansson, O},
title = {Plasma P-tau217 for detecting amyloid clearance after donanemab in Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71740},
doi = {10.1002/alz.71740},
pmid = {42565262},
issn = {1552-5279},
support = {//Eli Lilly and Company/ ; },
mesh = {Humans ; *Alzheimer Disease/drug therapy/blood/diagnostic imaging ; *tau Proteins/blood ; Positron-Emission Tomography ; Biomarkers/blood ; Phosphorylation ; Female ; Male ; Aged ; *Amyloid beta-Peptides/metabolism ; *Amyloid/metabolism ; ROC Curve ; Antibodies, Monoclonal, Humanized ; },
abstract = {INTRODUCTION: This analysis of the phase 3 TRAILBLAZER-ALZ 2 trial examined whether plasma tau protein phosphorylated at threonine 217 (p-tau217) level can reliably monitor treatment-related amyloid clearance (TRAC) after donanemab treatment in early symptomatic Alzheimer's disease (AD).

METHODS: Amyloid positron emission tomography (PET) and plasma p-tau217 levels were assessed at baseline and longitudinally during study treatment. The diagnostic performance of p-tau217 in detecting post-treatment TRAC (< 24.1 Centiloids [CL]) was evaluated by receiver operating characteristic (ROC) analysis.

RESULTS: Plasma p-tau217 showed suboptimal performance in detecting TRAC by PET in donanemab-treated participants (N = 830), with an area under the ROC curve of 0.61 at 52 weeks.

DISCUSSION: Despite reductions in plasma p-tau217 with donanemab treatment, this biomarker cannot currently be used to accurately detect TRAC by PET (< 24.1 CL) in individuals with early symptomatic AD.},
}

Humans
*Alzheimer Disease/drug therapy/blood/diagnostic imaging
*tau Proteins/blood
Positron-Emission Tomography
Biomarkers/blood
Phosphorylation
Female
Male
Aged
*Amyloid beta-Peptides/metabolism
*Amyloid/metabolism
ROC Curve
Antibodies, Monoclonal, Humanized

@article {pmid42565396,
year = {2026},
author = {Alpidovskaya, OV and Tikhonov, BV},
title = {[Clusterin as a biomarker for Alzheimer's disease].},
journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova},
volume = {126},
number = {7},
pages = {22-28},
doi = {10.17116/jnevro202612607122},
pmid = {42565396},
issn = {1997-7298},
mesh = {Humans ; *Clusterin/blood/metabolism ; *Alzheimer Disease/diagnosis/blood/metabolism ; Biomarkers/blood ; Oxidative Stress ; },
abstract = {OBJECTIVE: To examine and systematically review the existing literature regarding clusterin (CLU) as a potential biomarker for Alzheimer's disease.

MATERIAL AND METHODS: A comprehensive analysis of data, including generalization, comparison, and systematization, was conducted to review findings from both Russian and international publications. The study included a thorough search of the PubMed (MEDLINE) database and other scientific information sources over the last decade. The collected data underwent analytical scrutiny to elucidate the potential significance of CLU in AD pathogenesis.

RESULTS: This article presents evidence indicating that clusterin (CLU) may play a significant role in AD pathogenesis through various mechanisms, including regulation of inflammation, modulation of cellular apoptosis, facilitation of clearance of pathological proteins, and affecting oxidative stress and the aggregation and folding of extracellular proteins. CLU plays a vital role in promoting cell survival under stressful conditions. It offers protection against oxidative stress, ensuring both immediate resistance to damage and prolonged cellular viability. A loss of soluble clusterin (sCLU) protective function in response to ROS-induced damage may render neurons more susceptible to additional insults, such as Aβ, which generates H2O2 and other reactive oxygen species. Furthermore, CLU can activate the PI3K/Akt signaling pathway, which functions as an effector of mTOR and NF-κB. Inhibition of mTOR has been associated with a slowing of AD progression. Notably, elevated plasma levels of CLU in healthy older adults may precede significant Aβ deposition in the brain by as much as ten years, suggesting an early elevation of CLU within the pathogenesis of AD and its potential pathological implications.

CONCLUSIONS: Clusterin should be considered a significant biomarker for Alzheimer's disease, supporting the use of enzyme-linked immunosorbent assays to measure plasma CLU concentrations. This approach may serve as an additional tool for early screening and therapeutic interventions in Alzheimer's disease.},
}

Humans
*Clusterin/blood/metabolism
*Alzheimer Disease/diagnosis/blood/metabolism
Biomarkers/blood
Oxidative Stress

@article {pmid37496245,
year = {2024},
author = {Singh, M and Panda, SP},
title = {The Role of Monosodium Glutamate (MSG) in Epilepsy and other Neurodegenerative Diseases: Phytochemical-based Therapeutic Approa-ches and Mechanisms.},
journal = {Current pharmaceutical biotechnology},
volume = {25},
number = {2},
pages = {213-229},
doi = {10.2174/1389201024666230726161314},
pmid = {37496245},
issn = {1873-4316},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/chemically induced/metabolism ; *Sodium Glutamate/adverse effects ; Animals ; *Epilepsy/drug therapy/chemically induced/metabolism ; *Phytochemicals/therapeutic use/pharmacology ; Glutamic Acid/metabolism ; },
abstract = {Epilepsy is a common neurological disease affecting 50 million individuals worldwide, and some forms of epilepsy do not respond to available treatments. Overactivation of the glutamate pathway and excessive entrance of calcium ions into neurons are proposed as the biochemical mechanisms behind epileptic seizures. However, the overactivation of neurons has also been associated with other neurodegenerative diseases (NDDs), such as Alzheimer's, Parkinson's, Huntington's, and multiple sclerosis. The most widely used food ingredient, monosodium glutamate (MSG), increases the level of free glutamate in the brain, putting humans at risk for NDDs and epilepsy. Glutamate is a key neurotransmitter that activates nerve cells. MSG acts on glutamate receptors, specifically NMDA and AMPA receptors, leading to an imbalance between excitatory glutamate and inhibitory GABA neurotransmission. This imbalance can cause hyperexcitability of neurons and lead to epileptic seizures. Overuse of MSG causes neuronal cells to become overexcited, which in turn leads to an increase in the flow of Ca[2+] and Na[+] ions, mutations, and upregulation in the enzymes superoxide dismutase 1 (SOD-1) and TDP43, all of which contribute to the development of NDDs. While TDP43 and SOD-1 protect cells from damage, a mutation in their genes makes the proteins unprotective and cause neurodegeneration. Yet to what extent mutant SOD1 and TDP43 aggregates contribute to neurotoxicity is generally unknown. This study is focused on neuroprotective herbal medications that can pass the blood-brain barrier and cure MSGinduced NDDs and the factors that influence MSG-induced glutaminergic, astrocyte, and GABAergic neuron abnormalities causing neurodegeneration.},
}

Humans
*Neurodegenerative Diseases/drug therapy/chemically induced/metabolism
*Sodium Glutamate/adverse effects
Animals
*Epilepsy/drug therapy/chemically induced/metabolism
*Phytochemicals/therapeutic use/pharmacology
Glutamic Acid/metabolism

@article {pmid37537932,
year = {2024},
author = {Semwal, BC and Singh, B and Murti, Y and Singh, S},
title = {Therapeutic Potential of Ascorbic Acid in the Management of Alzheimer's Disease: An Update.},
journal = {Current pharmaceutical biotechnology},
volume = {25},
number = {2},
pages = {196-212},
doi = {10.2174/1389201024666230804102617},
pmid = {37537932},
issn = {1873-4316},
mesh = {*Alzheimer Disease/drug therapy/metabolism ; *Ascorbic Acid/therapeutic use/pharmacology ; Humans ; Animals ; *Antioxidants/therapeutic use/pharmacology ; Oxidative Stress/drug effects ; },
abstract = {BACKGROUND: Ascorbic acid is a potent natural antioxidant that protects against oxidative stress and performs various bodily functions. It is commonly found in fruits and vegetables.

OBJECTIVE: The manuscript has been written to provide valuable insights into ascorbic acid in managing Alzheimer's disease.

METHODS: The data has been gathered from web sources, including PubMed, Science Direct, Publons, Web of Science, and Scopus from 2000-2022 using AA, ascorbic acid, Alzheimer's diseases, memory, dementia, and antioxidant keywords.

RESULTS: In the present manuscript, we have summarized the impact of ascorbic acid and its possible mechanism in Alzheimer's disease by, outlining the information currently available on the behavioral and biochemical effects of ascorbic acid in animal models of Alzheimer's disease as well as its usage as a therapeutic agent to slow down the progression of Alzheimer disease in human beings. Oxidative stress plays a significant role in the advancement of AD. AA is a wellknown antioxidant that primarily reduces oxidative stress and produces protein aggregates, which may help decrease cognitive deficits in Alzheimer's disease. The current paper analyses of ascorbic acid revealed that deficiency of ascorbic acid adversely affects the central nervous system and leads to cognitive defects. However, the results of clinical studies are conflicting, but some of the studies suggested that supplementation of ascorbic acid improved cognitive deficits and decreased disease progression.

CONCLUSION: Based on clinical and preclinical studies, it is observed that ascorbic acid supplementation improves cognitive deficits and protects the neurons from oxidative stress injury.},
}

*Alzheimer Disease/drug therapy/metabolism
*Ascorbic Acid/therapeutic use/pharmacology
Humans
Animals
*Antioxidants/therapeutic use/pharmacology
Oxidative Stress/drug effects

@article {pmid42554889,
year = {2026},
author = {Shi, C and Liu, Y and Zhu, Y},
title = {DNA Sensing Pathways in Innate Immunity: Implications for Alzheimer's Disease Progression and Therapy.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42554889},
issn = {1559-1182},
mesh = {Humans ; *Alzheimer Disease/immunology/therapy/pathology ; *Immunity, Innate/immunology ; Animals ; *Disease Progression ; *Signal Transduction ; Innate Immunity Recognition ; *DNA/metabolism/immunology ; cGAS-STING Signaling Pathway ; Toll-Like Receptor 9/metabolism ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; },
abstract = {DNA sensors are emerging regulators of innate immune activation in Alzheimer's disease (AD). In addition to detecting microbial DNA, these pattern-recognition receptors can respond to cytosolic or endosomal self-DNA generated by DNA damage, mitochondrial dysfunction, impaired DNA repair, cellular stress, or neuronal injury. Aberrant activation of DNA-sensing pathways may amplify neuroinflammation through type I interferon (IFN-I) signaling, inflammasome activation, pyroptosis, and microglial dysfunction, thereby contributing to amyloid pathology, tau-related inflammation, synaptic loss, and cognitive decline. In this review, we summarize current evidence linking major DNA sensors, including cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING), absent in melanoma 2 (AIM2), toll-like receptor 9 (TLR9) to AD pathogenesis. We emphasize the strongest available evidence for cGAS-STING and AIM2, discuss the context-dependent roles of TLR9, and highlight less-established sensors requiring further validation. Finally, we evaluate therapeutic strategies targeting DNA-sensing pathways, including pathway inhibition and controlled immune activation, and discuss translational challenges such as blood-brain barrier penetration, off-target effects, dose dependency, and disease-stage-specific modulation.},
}

Humans
*Alzheimer Disease/immunology/therapy/pathology
*Immunity, Innate/immunology
Animals
*Disease Progression
*Signal Transduction
Innate Immunity Recognition
*DNA/metabolism/immunology
cGAS-STING Signaling Pathway
Toll-Like Receptor 9/metabolism
Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase

@article {pmid42554922,
year = {2026},
author = {Fang, Y and Zhou, R},
title = {Two-stage deep learning framework for the restoration of incomplete-ring PET images.},
journal = {Medical & biological engineering & computing},
volume = {},
number = {},
pages = {},
pmid = {42554922},
issn = {1741-0444},
support = {12175212//Innovative Research Group Project of the National Natural Science Foundation of China/ ; },
abstract = {Positron Emission Tomography (PET) is an important molecular imaging tool widely used in medicine. Traditional PET systems rely on complete detector rings for full angular coverage and reliable data collection. However, incomplete-ring PET scanners have emerged due to hardware failures, cost constraints, or specific clinical needs. Standard reconstruction algorithms often suffer from performance degradation with these systems because of reduced data completeness and geometric inconsistencies. We present a two-stage deep-learning framework that, without incorporating any time-of-flight (TOF) information, restores high-quality images from data with about 50% missing coincidences-double the loss levels previously addressed by CNN-based methods. The pipeline operates in two stages: a projection-domain Attention U-Net first predicts the missing sections of the sinogram by leveraging spatial context from neighbouring slices, after which the completed data are reconstructed with OSEM algorithm and passed to a cascaded U-Net & warm-start diffusion model for image refinement. This module starts the reverse diffusion process from the U-Net coarse prediction rather than pure Gaussian noise. Using 613 simulated brain volumes from real scans (196 healthy brain samples, 217 Alzheimer's disease samples, and 200 Mild Cognitive Impairment samples), the results show that our model successfully preserves most anatomical structures and tracer distribution features with PSNR of 38.18 to 38.59 dB and SSIM of 0.9904 to 0.9925. Our two-stage deep-learning framework effectively restores high-quality PET images from over 50 % incomplete-ring data, achieving near-complete anatomical fidelity and robust performance without requiring TOF information.},
}

@article {pmid42554925,
year = {2026},
author = {Lin, K and Sachdev, PS and Jiang, J and , },
title = {The Associations of cerebral blood flow and white matter hyperintensities with tau and amyloid-beta across the Alzheimer's disease spectrum.},
journal = {Brain imaging and behavior},
volume = {20},
number = {4},
pages = {},
pmid = {42554925},
issn = {1931-7565},
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/physiopathology/metabolism/pathology ; *tau Proteins/metabolism ; *Amyloid beta-Peptides/metabolism/blood ; *White Matter/diagnostic imaging/pathology/metabolism ; Female ; *Cerebrovascular Circulation/physiology ; Male ; Cross-Sectional Studies ; Positron-Emission Tomography ; Aged ; Magnetic Resonance Imaging ; Brain/diagnostic imaging/pathology/metabolism ; Longitudinal Studies ; Aged, 80 and over ; Perfusion Magnetic Resonance Imaging ; Biomarkers/blood ; },
abstract = {Although the associations between cerebrovascular dysfunctions and Alzheimer's disease are increasingly appreciated, the relationship of cerebral blood flow and white matter hyperintensities with tau and amyloid-β pathology remains unclear, particularly in the longitudinal context. This study investigated cross-sectional and longitudinal associations of cerebral blood flow and white matter hyperintensities with tau and amyloid-β pathology using multimodal imaging and blood biomarkers in 179 participants from the ADNI3 cohort. Participants underwent structural (T1-weighted, T2-weighted FLAIR) and arterial spin labelling perfusion MRI, tau and amyloid-β PET, and plasma assay tests for amyloid-β 42, amyloid-β 40, and phosphorylated tau-217. Tau from PET was negatively associated with cerebral blood flow both cross-sectionally and longitudinally in the posterior brain, independent of amyloid-β quantified from PET. Higher white matter hyperintensities volumes were associated with higher levels of tau and amyloid-β at baseline, but the associations were significantly attenuated after further adjusting for amyloid-β and tau, respectively. Plasma amyloid-β 42/40 ratio was negatively associated with white matter hyperintensity volumes both cross-sectionally and longitudinally. In conclusion, tau pathology showed spatially specific associations with cerebral hypoperfusion, independent of amyloid-β, particularly in posterior regions. The attenuation of associations of white matter hyperintensities with amyloid-β and tau after adjustment may reflect shared disease-related variance rather than distinct independent effects.},
}

Humans
*Alzheimer Disease/diagnostic imaging/physiopathology/metabolism/pathology
*tau Proteins/metabolism
*Amyloid beta-Peptides/metabolism/blood
*White Matter/diagnostic imaging/pathology/metabolism
Female
*Cerebrovascular Circulation/physiology
Male
Cross-Sectional Studies
Positron-Emission Tomography
Aged
Magnetic Resonance Imaging
Brain/diagnostic imaging/pathology/metabolism
Longitudinal Studies
Aged, 80 and over
Perfusion Magnetic Resonance Imaging
Biomarkers/blood

@article {pmid42554945,
year = {2026},
author = {Yang, S and Li, Y and Guo, Y and Li, Y and Li, M and Li, H and Zhang, Y},
title = {GPR146 Deficiency Enhances Microglial Phagocytosis and Blood-Brain Barrier-Associated Markers in an Acute Amyloid-β Model.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42554945},
issn = {1559-1182},
mesh = {Animals ; *Blood-Brain Barrier/metabolism/pathology ; *Amyloid beta-Peptides/metabolism/toxicity ; *Receptors, G-Protein-Coupled/deficiency/metabolism ; *Microglia/metabolism/pathology ; *Phagocytosis/drug effects ; *Biomarkers/metabolism ; Disease Models, Animal ; Mice, Knockout ; Mice, Inbred C57BL ; Male ; Signal Transduction ; },
abstract = {Dysregulation of brain cholesterol homeostasis is increasingly recognized as a critical driver of Alzheimer's disease (AD) pathogenesis. G protein-coupled receptor 146 (GPR146) has emerged as a pivotal regulator of systemic cholesterol metabolism; however, its role in the central nervous system and AD remains elusive. Here, we report that GPR146 deficiency in mice modulates ERK/PKA signaling without affecting baseline physiology or general behavior. Following intracerebroventricular (i.c.v.) injection of amyloid-β (Aβ)42 oligomers, GPR146 was associated with altered Aβ42-evoked ERK/PKA/Akt signaling both in vivo and in vitro. Mechanistically, Gpr146 ablation potentiated microglial Aβ phagocytosis, which correlated with the transcriptional upregulation of phagocytic receptors, including TREM2, GPR34, P2Y6, and CR3, alongside increased expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Moreover, GPR146 deficiency was linked to elevated levels of blood-brain barrier (BBB)-associated markers Cldn-5 and Glut-1 protein levels, while attenuating Aβ‑induced inflammatory responses in brain endothelial cells. At the metabolic level, GPR146 knockout modulated the expression of key enzymes governing glucose (GLUT1, GLUT3, G6PD, PFK, HK) and lipid (HMGCS1, ACACA, FASN, SCD1) metabolism and markedly reduced Aβ‑elicited lipid droplet accumulation in the cortex and hippocampus. Collectively, our findings establish GPR146 as a novel neurometabolic regulator whose deficiency correlates with enhanced Aβ phagocytosis, maintenance of BBB-associated proteins, and altered cerebral metabolism, thereby presenting a potential therapeutic axis for early AD intervention.},
}

Animals
*Blood-Brain Barrier/metabolism/pathology
*Amyloid beta-Peptides/metabolism/toxicity
*Receptors, G-Protein-Coupled/deficiency/metabolism
*Microglia/metabolism/pathology
*Phagocytosis/drug effects
*Biomarkers/metabolism
Disease Models, Animal
Mice, Knockout
Mice, Inbred C57BL
Male
Signal Transduction

@article {pmid42554959,
year = {2026},
author = {Welsh, TJ and Chen, Y and Kennelly, SP and Quinn, TJ and Religa, D and Shenkin, SD and Soysal, P and Roitto, HM},
title = {From memory clinics to Brain Health Services: implications for older adults and the future of cognitive care in Europe.},
journal = {European geriatric medicine},
volume = {},
number = {},
pages = {},
pmid = {42554959},
issn = {1878-7649},
abstract = {AIM: To explore the implications of transitioning from traditional memory clinics to Brain Health Services (BHS) for older adults, and to advocate for a geriatric-informed, equitable, and function-oriented approach to brain health care.

METHODS: This perspective article draws on discussions within the EuGMS Brain Health and Dementia Specialist Interest Group and relevant literature to examine the implications of emerging Brain Health Services for older adults.

RESULTS: The emergence of Brain Health Services represents a significant shift in cognitive healthcare, moving beyond traditional memory clinic models focussed primarily on dementia diagnosis and management towards prevention, risk reduction, and maintenance of cognitive function. Potential benefits include earlier engagement with cognitive care, multidomain lifestyle interventions, reduction of stigma surrounding dementia, and facilitation of access to emerging disease-modifying therapies. However, substantial challenges remain. Biomarker-driven approaches may overemphasise Alzheimer's disease-centric frameworks despite the high prevalence of mixed pathologies and complex comorbidity in older adults. Ethical concerns surrounding risk disclosure, inequitable access, and resource allocation are also considerable, particularly if services disproportionately benefit younger, healthier, or socioeconomically advantaged populations.

CONCLUSIONS: Brain Health Services should be reframed through a gerontologically informed lens that prioritises function, independence, quality of life, and equitable access alongside prevention. Integration with comprehensive geriatric assessment and existing older persons' care pathways is essential. Future research should focus on pragmatic real-world evaluation, inclusive outcome measures, and personalised approaches that account for heterogeneity in ageing. Ultimately, the success of BHS will depend on their ability to support healthy ageing while remaining responsive to the lived realities and priorities of older adults.},
}

@article {pmid42554972,
year = {2026},
author = {Wang, X and Tao, Y and Li, Q and Yang, J and Liu, Q and Xu, A},
title = {The Therapeutic Efficacy of Gold Needle "Regulating Spirit" Acupuncture for Amnestic Mild Cognitive Impairment: Protocol for a Randomized Controlled Trial.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e96326},
pmid = {42554972},
issn = {1929-0748},
mesh = {Humans ; *Cognitive Dysfunction/therapy ; *Acupuncture Therapy/methods/instrumentation ; *Needles ; *Gold/therapeutic use ; Aged ; Female ; Male ; Middle Aged ; Treatment Outcome ; Biomarkers/blood ; },
abstract = {BACKGROUND: Amnestic mild cognitive impairment (aMCI), the predominant subtype of mild cognitive impairment, carries the highest risk of progression to Alzheimer disease among all mild cognitive impairment subtypes. Currently, clinical practice lacks an established, authoritative treatment method for this condition. Prior clinical evidence indicates acupuncture may enhance cognitive function in individuals with mild cognitive impairment. Further clinical evidence suggests Gold Needle therapy demonstrates significant therapeutic effects for challenging and refractory conditions; however, a critical gap exists: no clinical trials currently ascertain whether Gold Needle therapy surpasses conventional acupuncture in treating aMCI. This trial aims to rigorously evaluate the therapeutic efficacy and safety of the Gold Needle "Regulating Spirit" method for clinical symptoms in patients with aMCI, alongside investigating its underlying imaging and biochemical mechanisms.

OBJECTIVE: This proposed study aims to identify imaging and laboratory biomarkers for the early diagnosis of aMCI, thereby providing a theoretical foundation for clinical practice.

METHODS: This randomized controlled trial will recruit 90 patients diagnosed with aMCI from the Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, alongside 20 healthy volunteers. The 90 patients with aMCI will be randomly allocated to 1 of 3 groups: the Gold Needle "Regulating Spirit" group uses gold-based needles, the general acupuncture "Regulating Spirit" group, or a sham acupuncture control group. The Gold Needle "Regulate Spirit" group uses gold-based needles, the general acupuncture "Regulate Spirit" group uses standard needles, and the sham acupuncture group administers Park needles. Participants will undergo 3 sessions per week of their assigned acupuncture or placebo treatment over a continuous 12-week period.

RESULTS: This study was initiated on September 1, 2023. As of October 30, 2025, 110 eligible participants had been enrolled, and data collection had been completed in full. Data analysis is currently underway, and the preliminary results are expected to be available by June 2025. We hypothesize that, compared with the filiform needle-based mind-regulating acupuncture group, the golden needle-based mind-regulating acupuncture group will demonstrate superior efficacy in improving cognitive impairment. This superiority will be reflected in multiple key outcome measures, including Montreal Cognitive Assessment and Mini-Mental State Examination scores, plasma biomarkers, and functional magnetic resonance imaging findings.

CONCLUSIONS: We anticipate that by the end of the trial, we will be able to definitively ascertain whether the gold acupuncture needle technique for "regulating spirit" offers a significant advantage in treating aMCI, and further investigate the nature of this therapeutic benefit, to offer a more efficacious intervention for the clinical management of aMCI and the prevention of Alzheimer disease.},
}

Humans
*Cognitive Dysfunction/therapy
*Acupuncture Therapy/methods/instrumentation
*Needles
*Gold/therapeutic use
Aged
Female
Male
Middle Aged
Treatment Outcome
Biomarkers/blood

@article {pmid42554979,
year = {2026},
author = {Fang, JR and Vogel, AP and Velakoulis, D and Yuan, Y and Nayler, D and Loi, SM and Joubert, L},
title = {Interventions for caregivers of persons with young-onset dementia in hospital environments: A systematic scoping review.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261469822},
doi = {10.1177/13872877261469822},
pmid = {42554979},
issn = {1875-8908},
abstract = {BackgroundCaregivers of patients with young-onset dementia (YOD), most commonly Alzheimer's disease and frontotemporal dementia, face unique challenges balancing employment, childcare, finances, and complex care responsibilities. Tailored interventions delivered in hospital environments may provide timely support and optimize caregiver preparedness, but evidence regarding these interventions remains limited.ObjectiveTo map and synthesize evidence on interventions supporting caregivers of individuals with YOD within hospital environments offering diagnostic services, multidisciplinary care, and opportunities for caregiver engagement. Intervention types, delivery modes, outcomes, and evidence gaps will be highlighted.MethodsA systematic scoping review adhering to PRISMA-ScR guidelines was conducted. Medline, Embase, PsycINFO, EBM Reviews, SocINDEX, CINAHL, and Scopus were searched for studies published up to 2025. Peer-reviewed studies in English describing or evaluating interventions for YOD caregivers were included. Data on study characteristics, intervention type, delivery, outcomes, and key findings were extracted and synthesized narratively.ResultsEight studies met the inclusion criteria. Interventions were largely focused on psychoeducation and support groups. Most studies targeted spouses with few including other caregiver types. Interventions addressed caregiver functions such as task management, safety, information, and caregiver needs related to emotional support and burden reduction, but rarely were both comprehensively addressed. Quantitative outcomes were mixed while qualitative findings consistently reported improved preparedness, support, and coping.ConclusionsEvidence on caregiver interventions in hospital environments is limited and largely exploratory. Future work should embed supports within diagnostic pathways, incorporate structured assessment, tailor interventions by subtype and caregiver role, and use outcome measures sensitive to early, meaningful changes.},
}

@article {pmid42554980,
year = {2026},
author = {Goldstein, FC and Hales, CM and Parker, MW and Trammell, AR and Manzanares, CM and Heldenberg, SC and Hanfelt, JJ and Levey, AI and Lah, JJ},
title = {Performance of the participant self-rating version of the Quick Dementia Rating System in a racially diverse cohort of non-demented older adults.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261471427},
doi = {10.1177/13872877261471427},
pmid = {42554980},
issn = {1875-8908},
abstract = {BackgroundEarly detection of clinical Alzheimer's disease and related dementias is a public health priority. The Clinical Dementia Rating is used for staging but is time intensive. The Quick Dementia Rating System (QDRS) is a brief, self-administered alternative, although studies have focused on informant rather than patient ratings.ObjectiveThis study evaluated the clinical utility of the QDRS Participant Self-Rating version for classifying cognitive status of White and Black/African Americans.MethodsParticipants (79 White, 95 Black/African American) enrolled in the Goizueta Alzheimer's Disease Research Center with Clinical Dementia Rating (CDR) Global scores of 0.0 or 0.5 completed the QDRS. Concordance rates and associations with the Montreal Cognitive Assessment (MoCA) were examined.ResultsAgreement between QDRS and CDR Global scores was 69% (κ = 0.36), and comparable between racial groups. QDRS Sum of Boxes demonstrated moderate correlations with CDR Sum of Boxes for the full sample and each group. Participants classified as impaired on the QDRS had lower MoCA Total and Memory Index scores, with similar effect sizes between racial groups. ROC analyses demonstrated good discrimination of CDR 0.0 versus 0.5 for the overall sample (AUC = 0.789, SE = 0.040, 95% CI = 0.711-0.866) and for White (AUC = 0.792, SE = 0.055, 95% CI = 0.683-0.900) and Black/African American participants (AUC = 0.777, SE = 0.058, 95% CI = 0.663-0.891). Positive predictive value of the QDRS Global score was 50%, and negative predictive value was 85%.ConclusionsThe QDRS Participant Self-Rating version is a clinically useful prescreening tool to rule out cognitive impairment in both White and Black/African American persons with early cognitive impairment.},
}

@article {pmid42554985,
year = {2026},
author = {Sánchez-Juan, P and García-Arcelay, E and Almagro, M and Balasa, M and Piñol-Ripoll, G and Boada, M and Landete, L and Abellan, I and Berbel, A and Espejo, B and Baquero, M and Marin, J and Franco-Macias, E and Villarejo-Galende, A and Viñuela Fernández, F and Feria Vilar, I and Perez-Vieitez, C and Rodríguez-Espinosa, N and Puig-Pijoan, A and Bargay Pizarro, E and Rodríguez-Rodríguez, E and Rodrigo, J and Maurino, J and Manzano, S},
title = {Burden, perception of stigma, and gender differences among informal care partners of individuals with mild cognitive impairment.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261474135},
doi = {10.1177/13872877261474135},
pmid = {42554985},
issn = {1875-8908},
abstract = {BackgroundCaring for individuals with mild cognitive impairment (MCI) is increasingly recognized as a significant clinical challenge. However, the latent burden, driven by perceived stigma and gender-specific vulnerabilities, remains poorly characterized during these early stages of cognitive decline.ObjectiveThis study aimed to evaluate the prevalence of care partner strain and affiliate stigma, and to identify independent correlates of psychological distress and protective factors among informal care partners of individuals with MCI.MethodsWe conducted a multicenter, observational, cross-sectional study across 19 memory clinics in Spain. Care partners (n = 196) were evaluated using the Zarit Burden Interview, Affiliate Stigma Scale, and validated instruments assessing resilience, relationship quality, coping strategies, and psychological distress. Multivariate logistic regression models identified independent predictors of burden and stigma.ResultsSignificant care partner strain affected 59.7% of the cohort, while 39.3% perceived themselves as stigmatized. Multivariate analysis revealed that high burden was independently associated with anxiety symptoms (OR = 1.13, p = 0.017) and perceived stigma (OR = 1.07, p = 0.007). High resilience served as the primary determinant protecting the 60.7% of partners who did not report significant stigma (OR = 1.05, p < 0.001). Compared to their male counterparts, female care partners were significantly younger and reported higher levels of burden, anxiety, and stigma.ConclusionsCare partner strain and affiliate stigma are correlated phenomena that emerge long before formal patient dependency. These findings underscore the need for gender-sensitive clinical frameworks and specific interventions that actively strengthen resilience immediately upon MCI diagnosis to mitigate early psychological deterioration.},
}

@article {pmid42554989,
year = {2026},
author = {Qiu, J and Zhang, Y and Shang, Y and Shang, Q and Li, L and Chen, Y and Dai, S and Ai, M and Xi, X and Huang, W and Zhang, J and Liu, X},
title = {Impact of SARS-CoV-2 infection on the progression of Alzheimer's disease: A prospective cohort study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261469118},
doi = {10.1177/13872877261469118},
pmid = {42554989},
issn = {1875-8908},
abstract = {BackgroundSARS-CoV-2 infection is associated with neurological sequelae and may accelerate Alzheimer's disease (AD) progression through neuroinflammation and protein aggregation. However, longitudinal evidence regarding the cognitive impact of COVID-19 in patients with AD remains scarce, and this interaction requires further clarification.ObjectiveTo explore whether COVID-19 accelerates cognitive decline in patients with AD.MethodsA total of 120 participants were enrolled, including 63 in the COVID-19 group and 57 in the non-COVID-19 group. The primary outcomes were disease decline and disease deterioration over three months, assessed using CDR-SB. Disease deterioration indicated clinically meaningful worsening, whereas disease decline captured subtler progression. Multivariable logistic regression adjusted for demographic, clinical, lifestyle, genetic, and disease severity factors. Overlap-Weighted Propensity Score Matching was additionally performed to reduce confounding during the 3-month follow-up.ResultsCOVID-19 significantly increased the risk of disease decline (OR = 10.39, 95% CI:3.87 to 27.87, p < 0.001) and disease deterioration (OR = 10.37, 95% CI: 2.71 to 39.65, p = 0.001). APOE ε4 carrier status was associated with a higher risk of deterioration (OR = 1.72), while those with unknown APOE status exhibited an even greater risk (OR = 5.20, 95% CI:1.32 to 20.53, p = 0.019). Secondary analyses confirmed that COVID-19 patients experienced significantly greater increases in CDR-SB scores compared to non-COVID-19 patients.ConclusionsSARS-CoV-2 infection was associated with greater short-term cognitive worsening over a three-month period in patients with AD, underscoring its potential public health relevance and the need for early surveillance to guide timely clinical management.},
}