@article {pmid41721140,
year = {2026},
author = {Vöglein, J and Arzberger, T and Ebner, I and Herms, J and Roeber, S and Ruf, V and Danek, A and Giese, A and Höglinger, GU and Levin, J},
title = {Accuracy of clinical diagnosis in neurodegenerative diseases - a study of 455 autopsy cases.},
journal = {Journal of neurology},
volume = {273},
number = {2},
pages = {},
pmid = {41721140},
issn = {1432-1459},
support = {EXC 2145 SyNergy - ID 390857198//Deutsche Forschungsgemeinschaft/ ; },
abstract = {BACKGROUND: Precision of clinical diagnosis in neurodegenerative diseases is critically important for clinical care and study recruitment. This study aimed to investigate the clinical accuracy using gold-standard neuropathological reference.

METHODS: Neuropathological diagnoses from the Neurobiobank München were correlated with real-world clinical diagnoses from hospitals in Germany. Accuracy metrics, including sensitivity, specificity, and area under the curve (AUC) of clinical diagnoses, were calculated.

RESULTS: Among nine neuropathologically diagnosed neurodegenerative diseases (Alzheimer's disease, argyrophilic grain disease, corticobasal degeneration, frontotemporal lobar degeneration, Huntington's disease, Lewy body disease, motor neuron disease, multiple system atrophy, and progressive supranuclear palsy) with a total of 455 cases, clinical sensitivity varied widely (0-100%) whereas specificity was consistently high (89.5-100%). Accuracy was very good (AUC > 0.9) for Huntington's disease, motor neuron disease, and multiple system atrophy; good (AUC = 0.8-0.9) for Alzheimer's disease, dementia with Lewy bodies/Parkinson's disease, and progressive supranuclear palsy; moderate (AUC = 0.7-0.8) for frontotemporal dementia, limited (AUC = 0.51-0.7) in the n = 20 cases with corticobasal degeneration, and no discriminatory capacity (AUC = 0.5) in the n = 6 cases with argyrophilic grain disease.

CONCLUSIONS: Clinical diagnostic accuracy of neurodegenerative diseases varies, with sensitivity as the main limiting factor. Improving diagnostic sensitivity will be essential for early and accurate patient identification, especially as disease-modifying therapies targeting causal proteinopathies become available. Achieving this will depend on the development and clinical implementation of reliable molecular biomarkers that indicate the causal proteinopathies of neurodegenerative diseases.},
}

@article {pmid41721036,
year = {2026},
author = {Nishinami, S and Kihara, Y and Akuta, T and Shiraki, K and Arakawa, T},
title = {Effects of Arginine on Hierarchical Protein Aggregation.},
journal = {The protein journal},
volume = {},
number = {},
pages = {},
pmid = {41721036},
issn = {1875-8355},
support = {22K19284//Japan Society for the Promotion of Science/ ; },
abstract = {Arginine is widely used in protein formulations to suppress protein aggregation and prolong the lifetime of the native, functional state which undergoes different stresses during storage, shipping and handling. However, arginine's differential effects on protein aggregation pathways remain unclear. Here, we investigated the effects of arginine on heat- and acid-induced aggregation of immunoglobulin G and heat-induced aggregation of several model proteins. Arginine suppressed the formation of insoluble aggregates but had limited impact on monomer recovery, particularly on immunoglobulin G. Instead, arginine promoted the formation of soluble aggregates, suggesting a possibility that unfolded proteins possess heterogeneous surface properties, leading to formation of soluble and insoluble aggregates that are modulated by arginine. To explain these kinetic behaviors, we propose a hierarchical aggregation model, in which arginine preferentially modulates weaker intermolecular interactions to inhibit the growth of the soluble aggregates into large insoluble aggregates. Moreover, soluble aggregates were observed in a range of proteins with varying isoelectric points and molecular weights. These results highlight a previously unrecognized aspect of soluble protein aggregation. Understanding the pathway and mechanism of soluble aggregate formation may shed light into physiologically-relevant soluble assemblies, e.g., Alzheimer's disease-associated oligomers and microtubule-derived double rings in contrast to the soluble amorphous aggregates under current study.},
}

@article {pmid41720991,
year = {2026},
author = {Dallere, S and Migheli, A and Vercelli, A},
title = {Digging Deep into Alzheimer Disease: How Electron Microscopy Helps Elucidating Its Pathogenesis.},
journal = {Cellular and molecular neurobiology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10571-026-01676-z},
pmid = {41720991},
issn = {1573-6830},
abstract = {Alzheimer disease (AD), first described by Alzheimer and Perusini in the early twentieth century, is a devastating neurodegenerative disorder without a definitive cure. Unraveling the subcellular alterations underlying AD is essential to elucidate disease mechanisms, track progression, link cellular abnormalities to functional deficits, and develop therapeutic strategies aimed at preventing, slowing or reverting the disease course. Electron microscopy (EM) has been pivotal in this field since the 1960s, when Terry and Kidd characterized the ultrastructure of amyloid-beta (Aβ) deposits and paired helical filaments (PHFs) composed of hyperphosphorylated tau. Over the decades, conventional transmission and scanning EM have been complemented by advanced approaches such as volume EM (vEM), cryo-electron microscopy (cryo-EM), and cryo-electron tomography (cryo-ET). These techniques enable three-dimensional reconstructions, minimize fixation artifacts, and provide near-native, near-atomic resolution insights into AD pathology. EM has also revealed critical contributions of other subcellular compartments to AD pathogenesis, including synapses, mitochondria, lysosomes, the blood-brain barrier, iron deposits, and inflammatory machinery. Importantly, EM studies extend beyond human tissue, encompassing animal models, cell cultures, and synthetic assemblies, thereby allowing cross-system comparisons that highlight conserved pathological features. By integrating data from diverse experimental settings, EM provides a uniquely comprehensive view of the AD subcellular landscape. This makes it an indispensable tool not only for dissecting disease mechanisms but also for guiding the rational design of therapeutic molecules with potential disease-modifying effects. This review synthesizes the state of knowledge on EM-based studies of AD, emphasizing their central role in advancing both mechanistic understanding and translational approaches.},
}

@article {pmid41720962,
year = {2026},
author = {O'Leary, K},
title = {A tumor-secreted protein alleviates Alzheimer's disease pathology.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/d41591-026-00010-w},
pmid = {41720962},
issn = {1546-170X},
}

@article {pmid41720779,
year = {2026},
author = {Contreras, AG and Walters, S and Eissman, JM and Archer, DB and Regelson, AN and Durant, A and Clifton, M and Mukherjee, S and Lee, ML and Choi, SE and Scollard, P and Trittschuh, EH and Mez, J and Bush, WS and Kunkle, BW and Cruchaga, C and Naj, AC and Gifford, KA and Bilgel, M and Kuzma, AB and , and , and , and Cuccaro, ML and Pericak-Vance, MA and Farrer, LA and Wang, LS and Schellenberg, GD and Haines, JL and Jefferson, AL and Kukull, WA and Keene, CD and Saykin, AJ and Thompson, PM and Martin, ER and Albert, MS and Johnson, SC and Engelman, CD and Ferrucci, L and Bennett, DA and Barnes, LL and Schneider, JA and Sperling, RA and Resnick, SM and Crane, PK and Dumitrescu, L and Hohman, TJ},
title = {Genetic modifiers of APOE-ε4-associated cognitive decline.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-68933-z},
pmid = {41720779},
issn = {2041-1723},
support = {AG074855//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; },
abstract = {The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease. However, APOE-ε4 is not deterministic, highlighting the need to identify additional genetic and environmental factors. APOE-ε4 has been linked to accelerated cognitive decline, so we sought to investigate genetic factors that modify APOE-ε4-associated cognitive decline. We conduct cross-ancestry APOE-ε4-stratified and interaction GWAS using harmonized cognitive data from 32,778 participants, including 29,354 non-Hispanic White and 3,424 non-Hispanic Black individuals. Our primary outcome is late-life cognition, measured using harmonized composite scores for memory, executive function, and language, modeled as continuous traits reflecting both normative cognitive aging and disease-related decline. We identify two genome-wide significant loci in APOE-ε4 carriers, reaching genome-wide significance for executive function. These loci also demonstrate nominal associations across the other domains, suggesting broad effects on cognition. In non-carriers, we identify a genome-wide significant association at ITGB8 restricted to executive function, and another locus associated with language. We further link these loci to SEMA6D, GRIN3A, and ITGB8 through expression and methylation databases. Post-GWAS analyses implicate additional genes including SLCO1A2, and DNAH11. Genetic correlation analyses reveal differences by APOE-ε4 status for immune-related traits, suggesting immune-related predispositions may exacerbate cognitive risk in APOE-ε4 carriers.},
}

@article {pmid41720774,
year = {2026},
author = {Yang, M and Wang, Q and Yan, R and Kang, D and Luo, W and Zhang, L and Liu, R and Wu, L and Gu, J and Wang, X},
title = {A neurotoxic cryptic peptide arising from TDP-43-dependent cryptic splicing of PKN1.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-68916-0},
pmid = {41720774},
issn = {2041-1723},
abstract = {Dysfunction of transactive response DNA-binding protein 43 (TDP-43) drives neurodegeneration in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), in part through inducing aberrant RNA splicing. However, whether such mis-splicing yields stable, pathogenic proteins remains unclear. Here, we identify a TDP-43-repressed cryptic exon in Protein kinase N1 (PKN1), designated PKN1-5a1, which is activated in ALS patient brains and introduces a premature termination codon. This aberrant transcript escapes nonsense-mediated decay and is translated into a truncated peptide, PKN1-N207 (PKN207), detectable in AD brains with TDP-43 pathology. In mice, PKN207 impairs cognition, memory, and synaptic plasticity. Our findings demonstrate that TDP-43 loss-induced cryptic splicing can generate stable neurotoxic polypeptides, revealing a peptide-mediated mechanism in TDP-43 proteinopathies.},
}

@article {pmid41720758,
year = {2026},
author = {Falahati, M and Orangi, K and Shaabanpoor Haghighi, A and Pouroushaninia, N and Niknam, N and Soltani, S and Radnia, P and Arab Bafrani, M and Shirdel, S and Aarabi, MH},
title = {Microstructural alterations of the amygdala in neurodegenerative and neuroinflammatory disorders: insights from diffusion tensor imaging.},
journal = {Reviews in the neurosciences},
volume = {},
number = {},
pages = {},
pmid = {41720758},
issn = {2191-0200},
abstract = {Diffusion tensor imaging (DTI) is a valuable method for evaluating microstructural changes in the amygdala associated with neurodegenerative and neuroinflammatory disorders. This systematic review examines amygdala microstructural alterations in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), and multiple sclerosis (MS) using DTI metrics. Following PRISMA 2020 guidelines, we searched PubMed, Scopus, and Web of Science databases through August 2025, identifying 4,442 records. After screening and eligibility assessment, 13 studies were included, comprising 1,412 patients and 1,146 healthy controls. Due to sample heterogeneity and lack of standardized effect size measures, meta-analysis was not performed. Across disorders, elevated mean diffusivity (MD) emerged as the most consistent finding, present in 100 % of AD patients and observed in all examined conditions. Reduced fractional anisotropy (FA) was the second most frequent alteration, with 36.6 % of AD patients showing decreased FA. In MS, increased radial diffusivity (RD) was prominent, while longitudinal DLB studies revealed progressive free water (FW) increases. These DTI-based microstructural changes often preceded volumetric atrophy and correlated with clinical severity. Our findings demonstrate that DTI metrics, particularly MD and FA, serve as sensitive markers of amygdala pathology across neurodegenerative diseases and may facilitate early diagnosis, disease monitoring, and differential diagnosis of these conditions.},
}

@article {pmid41720689,
year = {2026},
author = {Jang, S and Qin, X and Wang, MQ and Chen, J},
title = {Associations Between ACO Enrollment Status and Drug and Nondrug Costs Among Older Adults Newly Diagnosed With ADRD.},
journal = {The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jagp.2026.01.014},
pmid = {41720689},
issn = {1545-7214},
abstract = {OBJECTIVE: Despite the promising role of accountable care organizations (ACOs) in improving care coordination and lowering total costs of care, it is unclear whether ACO enrollment leads to reduced drug costs among individuals with Alzheimer's disease and related dementias (ADRD). This longitudinal cohort study examined the long-term effects of ACO enrollment on drug and nondrug Medicare payments among Medicare beneficiaries with ADRD, focusing on their comorbidity burden.

This study tracked annual Part D prescription drug and nondrug payments of 111,235 fee-for-service Medicare beneficiaries newly diagnosed with ADRD one year prior and five years after the ADRD diagnosis year (2017) by their ACO enrollment and comorbidity burden status. Comorbidity burden was assessed based on the number of comorbidities ADRD patients had, categorized into no multiple chronic conditions (No MCC; 0 or 1), low MCC (2-4), and multisystem morbidity (MM; 5≤) groups.

RESULTS: ACO enrollees spent significantly less on both drug and nondrug payments than non-ACO enrollees, with greater payment differences observed among those with higher comorbidity burden. Drug payment differences ranged from $55 to $93 among those with low MCC and $70-$119 among those with MM. Nondrug payment differences were the greatest during the diagnosis year, with $1,666 for those with MCC and $3,670 for those with MM.

CONCLUSIONS: The findings of this study underscore meaningful differences in prescription drug and nondrug payments associated with ACO enrollment among Medicare beneficiaries with ADRD, particularly among those with greater coexisting comorbidity burden.},
}

@article {pmid41720531,
year = {2026},
author = {Lazarian, A and Wartchow, KM and Bartelo, N and McIntire, LB},
title = {Detection, imaging and quantification of phosphoinositides using ion chromatography suppressed conductivity and mass spectrometry imaging.},
journal = {Methods in enzymology},
volume = {726},
number = {},
pages = {217-252},
doi = {10.1016/bs.mie.2025.11.018},
pmid = {41720531},
issn = {1557-7988},
mesh = {*Phosphatidylinositols/analysis/metabolism ; Humans ; Animals ; Chromatography, High Pressure Liquid/methods ; *Mass Spectrometry/methods ; },
abstract = {Phosphoinositide lipids have been implicated in aging, health and disease. Prior studies have identified enzymes critical for lipid metabolism, such as synthetic and degrading enzymes, which have different specificities based on the composition of the inositol ring as well as specific sub-cellular localization and multiple regulatory pathways. In addition to understanding the regulation of enzyme expression, activity and localization, it is critical to investigate levels of the specific lipids of interest. Current methods for detection and quantification of lipids include high performance liquid chromatography/ion chromatography (HPLC/HPIC) suppressed conductivity detection and mass spectrometry. Isobaric polyphosphorylated lipid species can be differentially separated using HPIC methods based on the differential chemical properties of the phosphorylation sites on the inositol ring, which are not able to be detected by mass spectrometry. However, mass spectrometry has the advantage of detecting the acyl chain composition for the individual species which has been shown to affect the signaling properties of the lipids. Emerging methods using mass spectrometry imaging offer in situ localization of the specific lipids within tissue but do not yet achieve single cell or intracellular spatial resolution. We describe methods for detection of polyphosphorylated phosphoinositides using HPIC and both untargeted and targeted imaging mass spectrometry using matrix-free desorption electrospray ionization. We also provide considerations for optimization of the methods as well as quantification of the resulting high dimensional data. Based on the central role phosphoinositides play in neuronal function and neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Down Syndrome, and Traumatic Brain Injury, sensitive and accurate detection and quantification is paramount for mechanistic studies as well as biomarker and therapeutic development.},
}

*Phosphatidylinositols/analysis/metabolism
Humans
Animals
Chromatography, High Pressure Liquid/methods
*Mass Spectrometry/methods

@article {pmid41720243,
year = {2026},
author = {Antoniolli, G and Nemr, MTM and Marques, SPD and Sebakhy, KO and Barbosa, EG and Trevisan, MTS and Coelho, F and Elshewy, A},
title = {Discovery of 6,7-Dimethoxyquinazoline-Hydrazide Hybrids as Dual Inhibitors of Acetylcholinesterase and β-Secretase.},
journal = {Biochimie},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.biochi.2026.02.015},
pmid = {41720243},
issn = {1638-6183},
abstract = {A novel series of 6,7-dimethoxyquinazoline-hydrazide hybrids 1-4 were designed, synthesized, and tested for their AChE inhibition activity using the qualitative assay, which showed that compounds 3 and 4 exhibited their activity via TLC. The compounds were characterized using HRMS, IR, [1]H NMR, and [13]C NMR spectroscopy. Further in vitro AChE and BACE-1 inhibition activities of both derivatives (3 and 4) revealed that compound 3 exhibited outstanding inhibitory activity against AChE, with IC50 of 299 nM, in comparison to the reference standard, rivastigmine (IC50 of 439 nM). Moreover, the same derivative showed inhibitory activity against BACE-1 with IC50 of 1.989 μM, superior to the standard control, quercetin (IC50 of 4.55 μM). Molecular dynamics simulations confirmed the stability of the AChE- and BACE-1-compound 3 complexes, with both systems reaching equilibrium within the first 25 ns and maintaining low RMSD values thereafter. Post-equilibration analyses revealed stable binding modes supported by key hydrogen bonds and hydrophobic interactions within the active sites. These findings highlight compound 3's strong affinity and specificity toward both targets, supporting its potential as a dual inhibitor.},
}

@article {pmid41720208,
year = {2026},
author = {Li, J and Sun, W and Guo, S and Bai, J and Yuan, T and Gao, F and Zhang, X and Ma, H and Ma, Y and An, J and Wang, R},
title = {The role of IGF1 signaling in remote ischemic conditioning-mediated amelioration of Alzheimer's disease pathology and cerebral insulin resistance.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115685},
doi = {10.1016/j.expneurol.2026.115685},
pmid = {41720208},
issn = {1090-2430},
abstract = {BACKGROUND: Alzheimer's disease (AD) and Type 2 diabetes mellitus (T2DM) share common pathological features, notably insulin resistance. Remote ischemic conditioning (RIC) is a clinically validated intervention with broad distant organ protection. Nevertheless, RIC's effects on cerebral insulin resistance (CIR) in AD animal models remain poorly understood. This study aims to investigate RIC's effects in reducing CIR and AD pathology across models.

METHODS: The study used ICV streptozotocin (STZ) to induce sporadic AD (sAD) and APP/PS1 transgenic rats as familial AD (fAD) models. RIC was established by three cycles of five minutes of ischemia followd by five minutes of reperfusion in rats' hindlimbs, conducted five times a week over four weeks. Additional experiments generated AD cell models with OAβ1-42, STZ, or mature TauP301L in primary hippocampal neurons and SH-SY5Y cells. CIR and AD pathology-related behavioral and biomarker assessments were performed.

RESULTS: RIC intervention reduces CIR, β-amyloid (Aβ) and Tau pathology. Additionally, RIC improves anxiety-like, depression-like behaviors and cognitive impairments in sAD rats. Mechanistically, it increases peripheral/central IGF1 levels, activates the IGF1R/IRS1-AKT-GSK3β pathway in sAD/fAD models, and enhances GLUT1-AMPK pathway for glucose metabolism. Additionally, RIC boosts antioxidative and anti-apoptotic responses by modulating FOXO3a phosphorylation and nuclear translocation. In vitro, IGF1 administration mirrored RIC's protective effects against OAβ1-42, TauP301L, or STZ administration.

CONCLUSIONS: Findings show that RIC effectively inhibits CIR by enhancing the IGF1R/IRS1-AKT-GSK3β pathway and glucose-mitochondrial energy metabolism. This study identifies a novel RIC neuroprotective mechanism, offering a multi-target AD prevention/treatment strategy.},
}

@article {pmid41720188,
year = {2026},
author = {Silva-Araújo, ER and Toscano, AE and Cavalcanti Bezerra Gouveia, HJ and Pontes, PB and Pereira Dos Santos Júnior, J and Henrique Dos Santos-Júnior, O and Teixeira Beltrão de Lemos, MD and Caroline de Oliveira Melo, N and Viana de Melo, J and Padrón-Hernández, E and Manhães-de-Castro, R},
title = {Unraveling riboflavin-mediated mitochondrial modulation as a therapeutic pathway in neurological disorders: an integrative systematic review.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {101427},
doi = {10.1016/j.tjnut.2026.101427},
pmid = {41720188},
issn = {1541-6100},
abstract = {BACKGROUND: Mitochondrial dysfunction is recognized as a key pathophysiological mechanism in neurodegenerative diseases. Alterations in mitochondrial dynamics-including imbalances in fission and fusion, impaired biogenesis, and disrupted mitophagy-contribute to the onset and progression of neurological disorders. In this context, mitochondrial modulation has emerged as a promising therapeutic strategy.

OBJECTIVE: This systematic review examined the role of riboflavin, a water-soluble vitamin and essential mitochondrial cofactor, in neurological interventions through mitochondrial modulation, with emphasis on elucidating the underlying molecular mechanisms.

METHODS: A search of the PubMed, Embase, Scopus, and Web of Science databases identified 23 eligible studies, comprising 6 in vitro experiments, 10 rodent models, and 7 clinical trials.

RESULTS: These studies evaluated the effects of riboflavin in monogenic, neurodegenerative, and demyelinating mitochondrial diseases, cerebrovascular/hypoxic injury, and pain/migraine. Clinical evidence indicated that riboflavin may regulate oxidative stress in stroke and perinatal asphyxia, with associated functional improvements. Preclinical findings revealed mechanisms of action involving energy homeostasis, cell cycle regulation, and mitochondrial dynamics across monogenic mitochondrial disorders, neurodegenerative diseases, hypoxic injury, and models of pain and migraine. Possibly through mitochondrial modulation, riboflavin appeared to reduce α-synuclein aggregation in Parkinson's disease, increase the number of tyrosine-hydroxylase-positive neurons in Alzheimer's disease models, enhance neuronal survival in Brown-Vialetto-Van Laere and Huntington's disease models, and normalize neuronal excitability in ataxia and migraine. In contrast, no therapeutic effects were observed in demyelinating diseases.

CONCLUSIONS: Overall, the findings suggest that riboflavin may promote neuroprotection through redox modulation and gene regulation, stabilization of membrane potential, and enhanced mitochondrial complex activity via flavin cofactors, ultimately supporting neuronal metabolism and functional outcomes. Despite advances in mechanistic understanding, clinical applications in humans remain insufficiently defined for most conditions, with clearer dosage regimens currently established only for stroke and migraine.},
}

@article {pmid41720152,
year = {2026},
author = {Murali, KP and Hua, M and Stone, PW and Dick, A and Gracner, T},
title = {State POLST Program Maturity Status and Dying in the Nursing Home or Hospice in the United States: An Event Time Study.},
journal = {Journal of the American Medical Directors Association},
volume = {},
number = {},
pages = {106134},
doi = {10.1016/j.jamda.2026.106134},
pmid = {41720152},
issn = {1538-9375},
abstract = {OBJECTIVES: State Physician Orders for Life-Sustaining Treatment (POLST) programs ensure documentation of orders for treatment are documented for the provision of goal-concordant care at the end of life. The national POLST organization tracks the maturity stages of state programs and categorizes them as developed (beginning of use) and endorsed (benchmarks and standardized use). Examining the association between POLST program maturation and the likelihood of dying in place can help clarify how implementation stage may affect end-of-life care and place of death. This study examined the association between the state POLST program maturity stage with place of death of nursing home (NH) residents (eg, nursing home or hospice).

DESIGN: An event time study.

SETTING AND PARTICIPANTS: This study included a 10% random sample of NH residents aged 65 and older who died between 2012 and 2018 in the United States.

METHODS: Data for NH residents were merged with data on each state's POLST development and endorsement year. Place and date of death were identified using the Minimum Data Set 3.0 and National Vital Statistics. A linear probability model assessed the likelihood of dying in a NH or hospice vs elsewhere before and after POLST implementation.

RESULTS: Among 225,149 NH residents, 74.3% had Alzheimer's disease or dementia, 67% were women, and 82.2% were White. Following POLST program development, the probability of dying in a NH or hospice increased by 1.6 percentage points (pp) in the first year (95% CI, 0.006-0.027; P = .003) and by 5.6 pp after 5 years (95% CI, 0.041-0.070). A sustained increase in likelihood of dying in place was also observed after POLST endorsement.

CONCLUSIONS AND IMPLICATIONS: POLST program maturity is associated with a higher likelihood of NH residents dying in place or in hospice, potentially supporting goal-concordant care and reducing burdensome hospital transfers near the end of life.},
}

@article {pmid41720088,
year = {2026},
author = {Luo, S and Liu, H and Xiao, T and Li, Y and Liu, X and Xiao, X and Liao, X and Liu, Y and Zhou, Y and Wang, JL and Guo, J and Tu, T and Yan, X and Tang, B and Zhang, Z and Jiao, B and Shen, L},
title = {Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzheimer's disease.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {102631},
doi = {10.1016/j.xcrm.2026.102631},
pmid = {41720088},
issn = {2666-3791},
abstract = {Early intervention is the most effective strategy to impede the progression of Alzheimer's disease (AD), depending on the identification of early diagnostic biomarkers. Here, we isolate neuron-derived exosomes (NDEs) from plasma of familial AD (FAD), presymptomatic FAD (pre-FAD), and healthy controls (cognitively normal [CN]), followed by label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. A specific peptide from protein phosphatase 2 regulatory subunit B'β (PPP2R5C) shows a progressive decrease from CN to pre-FAD and FAD patients. This decline is further validated in plasma NDEs and brain tissue from amnestic mild cognitive impairment (aMCI) and sporadic AD (SAD) patients. Two independent cohorts confirm the early and differential diagnostic value of plasma PPP2R5C. Immunohistochemistry of Tau Braak-staged brains reveals PPP2R5C reduction preceding Tau hyperphosphorylation. Mechanistically, PPP2R5C interacts with Tau, reducing Tau levels and phosphorylation via unc-51-like kinase 1 (ULK1)-dependent autophagolysosomal activation and PP2A regulation. Our findings suggest that plasma PPP2R5C has the potential to serve as an ideal biomarker for the early diagnosis of AD.},
}

@article {pmid41719498,
year = {2026},
author = {Villain, N},
title = {Reader Response: Alzheimer Disease Is a Specific Disorder Defined by Neuropathology Detectable During Life.},
journal = {Neurology},
volume = {106},
number = {6},
pages = {e210188},
doi = {10.1212/WNL.0000000000210188},
pmid = {41719498},
issn = {1526-632X},
}

@article {pmid41719497,
year = {2026},
author = {Villain, N and Hanseeuw, BJ and Planche, V and Paretsky, MS},
title = {Author Response: The Great Debate in Diagnosing Alzheimer Disease: More Than Just a β Test.},
journal = {Neurology},
volume = {106},
number = {6},
pages = {e210240},
doi = {10.1212/WNL.0000000000210240},
pmid = {41719497},
issn = {1526-632X},
}

@article {pmid41719496,
year = {2026},
author = {Ganesh, A and Galetta, SL},
title = {Editors' Note: Diagnostic and Prognostic Implications of Biomarker-Based Criteria for Alzheimer Disease.},
journal = {Neurology},
volume = {106},
number = {6},
pages = {e214259},
doi = {10.1212/WNL.0000000000214259},
pmid = {41719496},
issn = {1526-632X},
}

@article {pmid41719495,
year = {2026},
author = {Bieger, A and Brum, WS and Borelli, WV and Ferrari-Souza, JP and DaCosta, JC and Castilhos, RM and Schumacher Schuh, AF and Pascoal, T and Rosa-Neto, P and Schilling, LP and Zimmer, ER},
title = {Reader Response: The Great Debate in Diagnosing Alzheimer Disease: More Than Just a β Test.},
journal = {Neurology},
volume = {106},
number = {6},
pages = {e210159},
doi = {10.1212/WNL.0000000000210159},
pmid = {41719495},
issn = {1526-632X},
}

@article {pmid41719130,
year = {2026},
author = {Böken, D and Huang, M and Wu, Y and Fertan, E and Cotton, MW and Meisl, G and Lam, JYL and Baig, S and Rowe, JB and Smith, C and Quaegebeur, A and Cox, D and McEwan, WA and Klenerman, D},
title = {Nanoscopic tau aggregates are not shared intermediates but disease-specific entities across tauopathies.},
journal = {Cell reports},
volume = {45},
number = {2},
pages = {116934},
doi = {10.1016/j.celrep.2026.116934},
pmid = {41719130},
issn = {2211-1247},
abstract = {Tauopathies are neurodegenerative diseases marked by pathological tau aggregation. While disease-specific folds of insoluble tau filaments have been established, it remains unclear whether the smaller, earlier species also differ across tauopathies. Here, we characterize these small tau aggregates from postmortem brain of individuals with Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration, Pick's disease, and healthy controls. Using two complementary single-molecule assays, we confirm that small tau aggregates vary in abundance, morphology, and post-translational modifications. AD features specific long, fibrillar-shaped aggregates enriched in phospho-epitopes, while PSP aggregates are shorter, round, and selectively phosphorylated at serine 356, a site we identify as correlating with markers of inflammation and apoptosis. Aggregate properties co-vary with cellular stress signatures and align with disease-specific seeding profiles, suggesting distinct pathological mechanisms. These findings suggest that small tau aggregates are not a shared intermediate but instead encode disease-specific mechanisms, with potential as both biomarkers and therapeutic targets.},
}

@article {pmid41719080,
year = {2026},
author = {Kato, K and Nakashima, A and Shinagawa, S and Kobayashi, A and Ohkido, I and Urashima, M and Yokoo, T},
title = {Neurofilament Light Chain and Cognitive Dysfunction in Patients Undergoing Hemodialysis: A Cross-Sectional Exploratory Study.},
journal = {Kidney360},
volume = {},
number = {},
pages = {},
doi = {10.34067/KID.0000001162},
pmid = {41719080},
issn = {2641-7650},
abstract = {BACKGROUND: Cognitive dysfunction is frequently observed in patients undergoing hemodialysis in clinical settings; however, its pathophysiology remains uncertain. In recent years, noninvasive blood biomarkers have garnered increasing attention in predicting Alzheimer's disease development. Within the general population, neurofilament light chain levels have been used to prognosticate changes in cognitive function alongside the amyloid beta 1-42/1-40 (Aβ1-42/1-40) ratio. Nevertheless, this has not been studied in patients with chronic kidney disease, particularly those undergoing hemodialysis.

METHODS: This exploratory cross-sectional study investigated the association of the serum Aβ1-42/1-40 ratio and neurofilament light chain levels with cognitive function, assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), in patients undergoing hemodialysis.

RESULTS: We included 384 patients with a median age of 74 (interquartile range [IQR]: 70-80) years. The median (IQR) MoCA and MMSE scores were 25 (22-26) and 28 (26-29), respectively. The median (IQR) Aβ1-42/1-40 ratio and neurofilament light chain level were 0.04 (0.03-0.06) and 196.2 pg/mL (146.5-262.2), respectively. The multivariate linear regression analysis indicated a weak negative association between the log-transformed neurofilament light chain levels and cognitive function, after adjusting for confounding factors including age (β coefficient [95 % confidence interval], -0.98 [-1.81, -0.15]; P = 0.021 for MoCA and -0.66 [-1.32, -0.01]; P = 0.046 for MMSE). However, the Aβ1-42/1-40 ratio was not associated with cognitive function.

CONCLUSIONS: Our exploratory analysis identified a weak negative association between serum neurofilament light chain levels and cognitive function in patients undergoing hemodialysis.},
}

@article {pmid41718392,
year = {2026},
author = {Gasca-Martínez, Y and Ontiveros-Torres, MA and López-Gallegos, I and Jarero-Basulto, JJ},
title = {Amyloid Beta Oligomers as Early Triggers of Neuronal Cytoskeleton Dysfunction in Alzheimer's Disease.},
journal = {Pathophysiology : the official journal of the International Society for Pathophysiology},
volume = {33},
number = {1},
pages = {},
doi = {10.3390/pathophysiology33010014},
pmid = {41718392},
issn = {1873-149X},
abstract = {Alzheimer's disease (AD) is characterized by progressive cognitive decline, with amyloid beta oligomers (AβOs) emerging as the most neurotoxic species and acting as early triggers of cellular alterations. Before the appearance of other protein aggregates, AβOs disrupt the dynamics and stability of the neuronal cytoskeleton, a structure essential for maintaining neuronal morphology, axonal transport, and synaptic plasticity. Experimental evidence demonstrates that AβOs promote microtubule disassembly, Tau hyperphosphorylation, reduced kinesin levels, impaired axonal transport, and alterations in actin dynamics through the LIMK-cofilin signaling pathway. In addition, increased levels of neurofilament light chain have been identified as an early biomarker of axonal damage. Notably, these cytoskeletal disturbances arise in the absence of extensive neuronal death, underscoring the cytoskeleton as a critical early target in AD pathogenesis. In this review, we analyze cytoskeletal alterations induced by AβOs in neurons and discuss how these changes may contribute to disrupted neuronal communication, a defining early hallmark of AD pathology.},
}

@article {pmid41718152,
year = {2026},
author = {Jorda, A and Alvarez-Gamez, K and Campo-Palacio, I and Campos-Campos, J and Colmena, C and Singh, SK and Miralles, MJC and Aldasoro, C and Aldasoro, M and Valles, SL},
title = {Inflammatory Mediators of Alzheimer's Disease Characterized in a Mouse Model (APP/PS1).},
journal = {NeuroSci},
volume = {7},
number = {1},
pages = {},
doi = {10.3390/neurosci7010023},
pmid = {41718152},
issn = {2673-4087},
abstract = {Alzheimer's disease (AD) is marked by amyloid plaques, hyperphosphorylated TAU proteins, and neuroinflammation. The APP/PS1 mouse model is widely used to study AD pathogenesis. In this study, we investigated the expression of chemokines and their receptors, which may play a role in AD's pathological mechanisms, using brain cortex tissue from female APP/PS1 mice aged 20-21 months. We analyzed several chemokine receptors (CCR1, CCR2, CCR3, CCR4, CCR6, CCR7, CCR9, and CCR10) by Western blot and focused on CCR6, CCR7, and CCR10 using RT-PCR. Additionally, we quantified the levels of chemokines (CCL6, CCL8, CCL19, CCL20, CCL24, and CCL27) by RT-PCR. Our results showed a significant decrease in CCL8 and CCL19, along with their respective receptors, in the APP/PS1 mice compared to controls. On the other hand, we observed a notable increase in CCL6, CCL24, CCL20, CCL27, and their receptors. Chemokines like CCL8 and CCL20, involved in inflammatory responses, may reveal how neuroinflammation contributes to AD. CCL19 and CCL27 are linked to immune cell trafficking, which may help explain immune cell interactions with amyloid plaques and TAU tangles in the CNS. Overall, the altered expression of chemokines such as CCL24 could serve as biomarkers for early AD detection and monitoring disease progression. These findings suggest potential therapeutic targets to modulate immune responses and reduce neuroinflammation in AD.},
}

@article {pmid41717979,
year = {2026},
author = {Petrovsky, DV and Sefcik, JS and McPhillips, MV and Bradt, J and Pan, W and Wu, B and Hodgson, NA},
title = {A Research Protocol to Develop a Prototype of a Music-Based Mobile Application to Improve Sleep in Persons Living With Dementia and Their Caregivers.},
journal = {Research in nursing & health},
volume = {},
number = {},
pages = {},
doi = {10.1002/nur.70060},
pmid = {41717979},
issn = {1098-240X},
support = {K23AG073618/NH/NIH HHS/United States ; 23AARG-1019200/ALZ/Alzheimer's Association/United States ; },
abstract = {Sleep disturbances, particularly insomnia, significantly impact individuals living with Alzheimer's disease and related dementias (ADRD), leading to accelerated cognitive decline, increased institutionalization rates, and faster disease progression. While pharmacological interventions exist, their potential side effects necessitate the exploration of safer, non-pharmacological alternatives. Music interventions have shown promise in addressing sleep disturbances among older adults, yet existing solutions are neither tailored to nor extensively tested in persons living with dementia (PLWD). This study presents the research protocol for CoMPoSER (Calming Music Personalized for Sleep Enhancement in PeRsons living with Dementia), a mobile application designed specifically for PLWD and their caregivers. In the first two phases, the study will involve the development of the application and in the third phase we will employ a pilot randomized controlled trial to assess preliminary effects of the intervention and explore its mechanism of action. The research objectives include developing and refining the CoMPoSER mobile application prototype, investigating its underlying mechanisms, and evaluating its impact on both PLWD and caregiver outcomes. By developing and systematically testing approaches that address sleep disturbances in PLWD, this study aims to expand the repertoire of evidence-based interventions available to PLWD and their families, ultimately contributing to improved quality of life and disease management.},
}

@article {pmid41717904,
year = {2026},
author = {Lisgaras, CP and Scharfman, HE},
title = {The cholinergic system exerts opposing effects on memory at different stages of disease progression in Alzheimer's and Down syndrome model systems.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71154},
doi = {10.1002/alz.71154},
pmid = {41717904},
issn = {1552-5279},
support = {R01 AG-055328/AG/NIA NIH HHS/United States ; R21 AG-086880/AG/NIA NIH HHS/United States ; 1466036//CURE Epilepsy Award/ ; //New York State Office of Mental Health/ ; },
mesh = {Animals ; *Down Syndrome/metabolism ; *Alzheimer Disease/drug therapy/metabolism ; Disease Models, Animal ; Donepezil ; Disease Progression ; Mice ; Mice, Transgenic ; Cholinesterase Inhibitors/pharmacology ; Scopolamine/pharmacology ; *Memory/drug effects/physiology ; Male ; Piperidines/pharmacology ; Indans/pharmacology ; Muscarinic Antagonists/pharmacology ; },
abstract = {INTRODUCTION: The long-standing cholinergic hypothesis posits that cholinergic signaling is uniformly deficient in Alzheimer's disease (AD) and Down syndrome (DS). We tested the hypothesis that this deficiency occurs primarily late in disease, while early stages involve excessive cholinergic signaling, with distinct implications for memory.

METHODS: Tg2576 (AD model; n = 38), Ts65Dn (DS model; n = 14), and wild-type (WT; n = 17) mice at young (3 to 4 months) and old (>14 months) ages received treatments to reduce cholinergic signaling (medial septum chemogenetic inhibition, muscarinic antagonist scopolamine) or enhance it (acetylcholinesterase inhibitor donepezil). Memory assessments used novel object recognition.

RESULTS: Anticholinergic manipulations restored memory in young Tg2576 and Ts65Dn mice but impaired age-matched WT mice. Conversely, donepezil improved the memory of old Tg2576, Ts65Dn, and WT but not young Tg2576 and Ts65Dn animals.

DISCUSSION: These findings refine and challenge the cholinergic hypothesis, revealing for the first time a functional shift from cholinergic hyperactivity driving early cognitive impairment to late-stage degeneration requiring enhancement.},
}

Animals
*Down Syndrome/metabolism
*Alzheimer Disease/drug therapy/metabolism
Disease Models, Animal
Donepezil
Disease Progression
Mice
Mice, Transgenic
Cholinesterase Inhibitors/pharmacology
Scopolamine/pharmacology
*Memory/drug effects/physiology
Male
Piperidines/pharmacology
Indans/pharmacology
Muscarinic Antagonists/pharmacology

@article {pmid41717900,
year = {2026},
author = {Wang, J and Chen, T and Lin, Y and Shen, X and Zhou, M},
title = {Gastrodin and Gastrodigenin as Potential Neuroprotectors for the Treatment of Neurodegenerative Diseases.},
journal = {The American journal of Chinese medicine},
volume = {},
number = {},
pages = {},
doi = {10.1142/S0192415X26500199},
pmid = {41717900},
issn = {1793-6853},
abstract = {Neurodegenerative diseases (NDDs), characterized by a progressive neuronal loss that leads to cognitive and motor deficits, both pose a significant global health challenge and have limited treatment options. This review explores the therapeutic potential of gastrodin (GAS) and gastrodigenin (HBA), which are the key bioactive constituents of Gastrodia elata Blume (GEB). These compounds demonstrate significant neuroprotective effects across various NDD models which include Alzheimer's disease (AD) and Parkinson's disease (PD). Their mechanisms involve multi-target actions such as inhibiting pathological protein aggregation (Aβ, tau, α-synuclein), attenuating neuroinflammation via the TLR4/NF-κB and NLRP3 pathways, reducing oxidative stress through Nrf2 activation, mitigating mitochondrial dysfunction, inhibiting ferroptosis, and counteracting glutamate excitotoxicity. While pharmacokinetic studies reveal favorable brain distribution for HBA, its clinical translation faces challenges including blood-brain barrier penetration and the need for human trials. Advances in delivery systems, like focused ultrasound, show promise. This review both synthesizes the current evidence on GAS and HBA to highlight their multifaceted mechanisms and potential as multi-target agents for NDD intervention, and outlines future research directions for their clinical development.},
}

@article {pmid41717780,
year = {2026},
author = {Duncan, MJ and Hawkins, MR and Bytyqi, L and Whitlock, HR and Shepard, SM and Cox, MF and Drinkard, EG and Macheda, T and Roberts, KN and Kohler, K and Schmidt, MC and Johnson, CE and Sunderam, S and O'Hara, BF and Murphy, MP and Bachstetter, AD},
title = {Dim light at night impacts circadian rhythms and Alzheimer's disease-like neuroinflammation and neuropathology in humanized APP SAA knock-in mice.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsag041},
pmid = {41717780},
issn = {1550-9109},
abstract = {Artificial light at night (light pollution) is widespread but understudied in the context of Alzheimer's disease (AD). Sleep and circadian disruption have been linked to amyloid-β (Aβ) accumulation and neuroinflammation, but whether dim light at night (dLAN) modifies these processes remains unclear. We tested whether chronic dLAN exposure (8 lux during the dark phase, 8 weeks) alters circadian rhythms, amyloid pathology, and neuroinflammation in 12-13 month-old humanized APP knock-in (KI) mice. hAPPSAA KI mice, which develop plaques, were compared with hAPPWT KI controls carrying only a humanized APP sequence. dLAN reduced circadian rhythm amplitude and stability while increasing fragmentation in both genotypes within two weeks. In hAPPSAA KI mice, dLAN modestly increased hippocampal plaque burden and soluble neocortical Aβ. Astrocyte reactivity was elevated by genotype but not altered by nighttime light exposure. In contrast, microglial markers (CD45, MHCII) were increased with dLAN with CD45+ area elevated in hippocampus, and MHCII+ cell counts greater in the cortex and hippocampus of hAPPSAA KI mice. There were also distinct spatial responses between the microglia markers suggesting that dLAN primes microglia toward an antigen-presenting phenotype (MHCII) in the presence of Aβ. Yet, the microglia/macrophage priming was not associated with amplified cytokine or chemokine levels at the 8-week dLAN exposure timepoint in the brain. These findings add to growing evidence that nighttime light exposure can disrupt circadian and immune regulation, and suggest that environmental light pollution should be further explored as a modifiable factor contributing to Alzheimer's disease progression.},
}

@article {pmid41717646,
year = {2026},
author = {Behrens, LL and Van Haitsma, KS and Ryan, SL and Crimi, KH and Boltz, ML and Kraschnewski, JL},
title = {Community-engaged intervention mapping for developing the DIGNITY program: Supporting decision-making in aging and dementia for autonomy in rural nursing homes.},
journal = {Journal of clinical and translational science},
volume = {10},
number = {1},
pages = {e26},
pmid = {41717646},
issn = {2059-8661},
abstract = {BACKGROUND: Person-centered care that honors individual preferences can improve the well-being of nursing home (NH) residents with Alzheimer's disease and related dementias (ADRD). However, preferences such as going outside independently are often restricted due to perceived safety risks. There is a critical need for strategies that help NH staff balance safety concerns with residents' autonomy.

MATERIALS AND METHODS: We developed the Decision-making In aGing and demeNtIa for autonomy (DIGNITY) intervention using the Community-Engaged Intervention Mapping (CEIM) Model. This multilevel, theory informed program was codesigned with NH stakeholders to support shared decision-making and promote preference-congruent dementia care.

RESULTS: A total of 53 stakeholders participated in focus groups and engagement sessions. Feedback informed six key refinements to the DIGNITY program: manual formatting, communication strategies, staff role delineation, addressing resident decision-making capacity, and identifying implementation barriers and facilitators. The final intervention includes a structured manual, decision-making tools, and a training and coaching program to support NH staff in honoring resident preferences while managing perceived risks.

CONCLUSION: DIGNITY is a novel, stakeholder-informed intervention designed to support preference-based dementia care in rural NHs. Future research should assess its feasibility, acceptability, and impact on staff attitudes and resident outcomes.},
}

@article {pmid41717632,
year = {2026},
author = {Perezcano, C and Pérez-Coria, M},
title = {An integrative neurogenomics workflow for precision medicine in neurodegenerative disorders.},
journal = {Frontiers in dementia},
volume = {5},
number = {},
pages = {1745504},
pmid = {41717632},
issn = {2813-3919},
abstract = {Neurodegenerative diseases represent an expanding global health challenge, with rapidly increasing prevalence and substantial economic impact. The therapeutic clinical approach continues to seek solutions through pharmacological means-such as inhibitors and antibodies-which, while sometimes controlling symptoms, have not addressed the underlying pathophysiology. By integrating advanced genomics with selected biochemical markers, under the continuous oversight of a multidisciplinary team working in consensus, it is possible to achieve a more comprehensive understanding of individual phenotypes, enabling the design of truly personalized neurogenomics-based functional plans. This article outlines the steps of the proposed integrative neurogenomics workflow, discussing its advantages and limitations, and presents highlights from an illustrative case intended as a potential reference model to establish the foundation for a new standard of personalized genomic medicine in neurodegeneration. The workflow underscores the importance of considering the additive burden of genetic variants typically classified as benign-beyond the ACMG pathogenicity framework-for accurate phenotypic assessment. It further demonstrates the feasibility of developing actionable and highly precise functional interventions by integrating genomic and biochemical data. Findings from the case example reveal correlations between genetic variants and biochemical markers, providing the basis for personalized recommendations in nutrition, lifestyle, and supplementation. This framework aims to establish the foundations of personalized genomic medicine in neurodegenerative diseases, underscoring the urgent need to move beyond one-size-fits-all approaches.},
}

@article {pmid41717610,
year = {2026},
author = {Zhao, N and Chen, Z and Sun, H},
title = {Long-term exposure to ambient particulate matter and its association with Alzheimer's disease: influencing factors and a systematic review with meta-analysis.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1757872},
pmid = {41717610},
issn = {2296-2565},
mesh = {Humans ; *Particulate Matter/adverse effects/analysis ; *Alzheimer Disease/epidemiology ; *Environmental Exposure/adverse effects/statistics & numerical data ; *Air Pollution/adverse effects ; *Air Pollutants/adverse effects/analysis ; Risk Factors ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) poses a pressing public health burden globally. Evidence linking long-term ambient particulate matter exposure to AD risk remains inconsistent, necessitating systematic quantification to inform prevention policies.

METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library up to September 2025 for cohort studies with ≥1 year of particulate exposure (PM2.5, PM10, NO2, NOx, O3) and incident/diagnosed AD. Quality was assessed via the Newcastle-Ottawa Scale (NOS), with random-effects models pooling hazard ratios (HRs) and 95% CIs; subgroup analyses explored heterogeneity by study design, region, and follow-up duration.

RESULTS: Twenty-five high-quality (NOS ≥ 7/9) cohort studies involving over 170 million participants were included. Meta-analyses showed higher AD risk with each 5 μg/m[3] increase in PM2.5 (HR = 1.24, 95%CI: 1.10-1.39), 10 μg/m[3] in PM10 (HR = 1.16, 95%CI: 1.01-1.33), 10 μg/m[3] in NO2 (HR = 1.06, 95%CI: 1.00-1.12), and 10 μg/m[3] in NOx (HR = 1.05, 95%CI: 1.03-1.07). For O3, four included studies showed no significant association (HR = 1.23, 95%CI: 0.65-2.31) with extremely high heterogeneity (I [2] = 99.8%), indicating inadequate and unstable evidence. Subgroup analyses confirmed effect modification by study design, region, and follow-up duration; publication bias was low for most pollutants.

CONCLUSION: We recommend high-risk population screening, stricter emission standards, and prioritizing emission reduction in AD primary prevention-aligning with global efforts to address environmental determinants of neurological health.

PROSPERO with the registration number CRD420251174986, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251174986.},
}

Humans
*Particulate Matter/adverse effects/analysis
*Alzheimer Disease/epidemiology
*Environmental Exposure/adverse effects/statistics & numerical data
*Air Pollution/adverse effects
*Air Pollutants/adverse effects/analysis
Risk Factors

@article {pmid41717608,
year = {2026},
author = {Dworak, EM and Pila, S and Novack, MA and Hosseinian, Z and Ho, EH and Ece, B and Karpouzian-Rogers, T and Mather, MA and Han, YC and Bucko, P and Cella, D and Gershon, RC and Weintraub, S},
title = {A scoping review of emotion and non-cognitive measures of decision-making ability in older adults by the ARMCADA study.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1718861},
pmid = {41717608},
issn = {2296-2565},
mesh = {Humans ; *Decision Making ; *Emotions ; Aged ; Male ; Cognition ; Female ; *Aging/psychology ; },
abstract = {INTRODUCTION: Decision-making is a complex form of cognitive function that declines with age and is highly susceptible to impairment from dementia due to Alzheimer's and related neurogenerative diseases. Emotions and other non-cognitive assets are also believed to influence decision-making ability. The Advancing Reliable Measurement in Cognitive Aging and Decision-making Ability (ARMCADA) research initiative seeks to understand how measures of emotion and non-cognitive influences of decision-making (ENC DM) have been used in research and clinical settings. The scoping review examined the recent literature on decision-making measures involving emotion and non-cognitive domains in aging samples.

METHODS: Using a well-established scoping review methodology framework we conducted a systematic search across six databases-Embase (Elsevier), MEDLINE (Ovid), PsycINFO (EbscoHost), Cochrane Library, Web of Science (Clarivate), and Scopus (Elsevier)-to identify studies published between January 2018 and November 2023 that met our predefined eligibility criteria. In line with recommended best practices, sample selection was carried out in two-stages: First, two reviewers independently screened titles and abstracts for relevance; second, full-text articles were reviewed, and data were extracted from those that met the inclusion criteria.

RESULTS: The final dataset included 232 articles and, among them, 143 unique emotion and non-cognitive decision-making measures. Twenty-eight percent of manuscripts used measures with a clinical sample, 26% used measures with a normative adult sample, and 47% used measures with both clinical and non-clinical samples. The five most frequent measures used were: Iowa Gambling Task, Balloon Analogue Risk Task, Delay Discounting Task, Decisional Conflict Scale, and Cambridge Gambling Task.

DISCUSSION: Results of the most common decision-making measures reflect a preference for assessing risk-taking and impulsivity in the sphere of non-cognitive and emotion function. Such trends were also found in clinical samples of older adults with neurodegenerative diseases. These findings inform the larger ARMCADA project in the development of reliable and validated measurement of decision-making among older adults. It will also support researchers studying older adults' decision-making skills and their vulnerability to diseases that cause cognitive impairment and dementia, with an understanding of the current assessments used to track ENC DM.

https://bmjopen.bmj.com/content/14/12/e084178.},
}

Humans
*Decision Making
*Emotions
Aged
Male
Cognition
Female
*Aging/psychology

@article {pmid41717317,
year = {2026},
author = {Tian, S and Zong, W and Zeng, Z and Wang, J and Niu, Q and Zhang, S and Zhang, H and Li, B},
title = {Analysis of the Genetic Comorbid Mechanisms of Type 2 Diabetes, Alzheimer's Disease, and Hypertension Using Network Modularization.},
journal = {BioMed research international},
volume = {2026},
number = {},
pages = {8877510},
pmid = {41717317},
issn = {2314-6141},
mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics/epidemiology ; *Alzheimer Disease/genetics/epidemiology ; *Hypertension/genetics/epidemiology ; *Gene Regulatory Networks/genetics ; Comorbidity ; Transcriptome/genetics ; Databases, Genetic ; Gene Expression Profiling ; Genetic Predisposition to Disease ; Signal Transduction/genetics ; },
abstract = {BACKGROUND: Type 2 diabetes mellitus (T2DM), Alzheimer's disease (AD), and hypertension (HTN) tend to be comorbidities and mutually influence each other; however, the mechanisms underlying their association remain unclear. This study was aimed at identifying genes associated with susceptibility to these three diseases and their mechanisms of action using integrated network modularization analysis.

METHODS: The transcriptome data of T2DM, AD, and HTN were downloaded from the GEO database to identify the differentially expressed genes (DEGs), and the coexpression modules of each disease were detected by WGCNA. Z summary algorithm was used to identify the common modules of three diseases, and the driver genes of their comorbidity were identified by flow centrality (FC) and shortest distance indexes. Gene set enrichment analysis (GSEA) was performed to define the biological functions and pathways for each module and driver genes. The HPA database and CIBERSORT method were used to analyze the mechanisms of the shared key genes from the types of single cells and immune infiltration analysis.

RESULTS: Based on the 343 overlapping DEGs that were identified, four common modules between AD, T2DM, and HTN were identified using Z summary. GSEA revealed that the DEGs were mainly involved in the MAPK and mTOR signaling pathways. Eight key genes (ACTN4, BGN, PRELP, TSFM, UBC, ELAVL1, NRF1, and SUMO2) related to the comorbidities AD, T2DM, and HTN were identified by integrating the shared genes at the levels of DEGs, common modules, and FC-based driver genes. As potential biomarkers, the expression of these key genes was significantly different between the three disease groups, and they were mainly expressed in endothelial cells, Langerhans cells, smooth muscle cells, and T cells. Immune infiltration analysis revealed that five different types of immune cells were related to these three diseases, including T-regs and nonclassical monocytes.

CONCLUSIONS: Common modules between T2DM, AD, and HTN and eight key susceptibility genes were identified, which may reflect the underlying mechanism of the comorbidity of T2DM, AD, and HTN. These results provide insights for the development of clinical therapies for these diseases.},
}

Humans
*Diabetes Mellitus, Type 2/genetics/epidemiology
*Alzheimer Disease/genetics/epidemiology
*Hypertension/genetics/epidemiology
*Gene Regulatory Networks/genetics
Comorbidity
Transcriptome/genetics
Databases, Genetic
Gene Expression Profiling
Genetic Predisposition to Disease
Signal Transduction/genetics

@article {pmid41717287,
year = {2026},
author = {Facal, CL and Páez-Paz, I and Pereyra, AE and Gaguine, C and Clerici-Delville, R and Foltran, R and Soiza-Reilly, M and Avale, ME},
title = {Artificial microRNAs targeting tau enable post-symptomatic functional recovery in aged tauopathy mice.},
journal = {Molecular therapy. Nucleic acids},
volume = {37},
number = {1},
pages = {102843},
pmid = {41717287},
issn = {2162-2531},
abstract = {Tauopathies are a group of neurodegenerative disorders, including Alzheimer's disease, frontotemporal dementia, and progressive supranuclear palsy, characterized by the pathological accumulation of tau protein. While tau reduction has emerged as a promising disease-modifying strategy, most preclinical studies have focused on preventive approaches, and the therapeutic potential after clinical onset remains largely unexplored. This limitation is critical, as patients are typically diagnosed after symptoms emerge. Furthermore, global tau suppression may disrupt physiological tau functions and lead to adverse effects, underscoring the need for targeted interventions. In this sense, RNA interference (RNAi)-mediated therapies using viral vectors offer high specificity, regional and cell-specific expression, and sustained target knockdown. We have engineered artificial microRNAs (Tau-miRNAs) to selectively reduce tau in vulnerable brain regions, minimizing off-target effects. Here, we tested the efficacy of these Tau-miRNAs in a tauopathy mouse model at advanced disease stages, delivering them into the prefrontal cortex after cognitive and electrophysiological deficit onset. This post-symptomatic intervention led to long-term improvements in memory, restoration of neuronal firing properties, and reduced pathological tau at synapses. Our findings highlight the potential of spatially targeted RNA-based tau-lowering strategies for late-stage intervention in tauopathies, addressing a critical unmet need in the treatment of these devastating disorders.},
}

@article {pmid41717278,
year = {2026},
author = {Chattopadhyay, T and Senthilkumar, P and Ankarath, RH and Patterson, C and Gleave, EJ and Thomopoulos, SI and Huang, H and Shen, L and You, L and Zhi, D and Thompson, PM},
title = {Deep learning to predict future cognitive decline: a multimodal approach using brain MRI and clinical data.},
journal = {Frontiers in neuroimaging},
volume = {5},
number = {},
pages = {1726037},
pmid = {41717278},
issn = {2813-1193},
abstract = {Predicting the trajectory of clinical decline in aging individuals is a pressing challenge, especially for people with mild cognitive impairment, Alzheimer's disease, Parkinson's disease, or vascular dementia. Accurate predictions can guide treatment decisions, identify risk factors, and optimize clinical trials. In this study, we compared two deep learning approaches for forecasting changes, over a 2-year interval, in the Clinical Dementia Rating scale 'sum of boxes' score (sobCDR), as a continuous outcome (regression). This is a key metric in dementia research and clinical trials, and scores range from 0 (no impairment) to 18 (severe impairment). To predict decline, we trained a hybrid convolutional neural network (CNN) that integrates 3D T1-weighted brain MRI scans with tabular clinical and demographic features (including age, sex, body mass index (BMI), and baseline sobCDR). We benchmarked its performance against AutoGluon, an automated multimodal machine learning framework that selects an appropriate neural network architecture (an 'autoML' approach). We evaluated the models using data from 2,319 unique participants drawn from three independent cohorts-ADNI, OASIS-3, and NACC. For each participant, we used one T1-weighted brain MRI scan along with corresponding clinical and demographic information. Our results demonstrate the importance of combining image and tabular data in predictive modeling for this clinical application. Deep learning algorithms can fuse information from image-based brain signatures and tabular clinical data, with potential for personalized prognostics in aging and dementia. Rather than concluding that multimodal fusion uniformly improves performance, our results show that deep learning applied to volumetric MRI data may struggle to add predictive value, particularly when clinical covariates explain substantial variance and provide a strong baseline. In other conditions and tasks, it may help to have a hybrid system that can learn from both data types, and their relative value may be different. Conversely, AutoML-based multimodal fusion provides a robust baseline when tabular data already provide strong predictive value for the task. These insights clarify how different multimodal strategies could be selected in clinical prognostic applications.},
}

@article {pmid41717267,
year = {2025},
author = {Zhou, Y and Zhou, F and Li, H},
title = {Daphnetin Ameliorates the Amyloid β-Induced Alzheimer Disease via Restoring Potassium-Chloride Co-Transporter 2 (KCC2) Ion Channel Functions in Mice.},
journal = {Iranian journal of pharmaceutical research : IJPR},
volume = {24},
number = {1},
pages = {e164601},
pmid = {41717267},
issn = {1726-6890},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by downregulation of potassium voltage-gated channel subfamily a member 2 (KCNA2) proteins. Potassium voltage-gated channel subfamily a member 2 is involved in the regulation of neuronal excitability by restoring neuronal potassium-chloride co-transporter 2 (KCC2) functions. Coumarin derivatives exert neuroprotective effects via upregulation of KCC2 proteins. Daphnetin (DPN; 7,8-dihydroxy coumarin) is a polyphenolic compound known to attenuate cognitive dysfunction. However, the role of DPN in the attenuation of AD-associated cognitive dysfunctions through regulation of KCC2 functions has not yet been investigated.

OBJECTIVES: The present study was designed to investigate the role of DPN against amyloid-β oligomer-induced AD in mice.

METHODS: In this study, a total of six groups with eight male Swiss albino mice per group were used. The simple randomization method was adopted for unbiased assignment of animals based on age, sex, and weight variations. Alzheimer's disease in mice was induced by intracerebroventricular (i.c.v.) injection of amyloid-β oligomer (Aβ; 4 μg/4 μL). The test compounds, i.e., DPN (40, 80, and 120 mg/kg of body weight), and donepezil (DP, 2 mg/kg), were administered orally (p.o.) for 21 consecutive days. Behavioral changes, including the Morris water maze (MWM) test, water Y-maze alternation test (WYMA), and novel object recognition test (NORT), were assessed according to the experimental protocol. Furthermore, hippocampal brain tissue biomarkers, namely acetylcholinesterase (AChE) activity, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and KCC2 levels, were also estimated. In addition, Aβ-associated brain histopathological changes were evaluated using the eosin and hematoxylin staining method. Six mouse hippocampus tissue samples were used for the assessment of tissue biomarkers, and the remaining two brain tissues were used for histological observations. Behavioral data were statistically analyzed by two-way analysis of variance (ANOVA), and biomarkers were analyzed by one-way ANOVA. The 95% confidence level (P < 0.05) was set for confirmation of statistical significance.

RESULTS: The results revealed that administration of Aβ enhanced escape latency time (ELT) and reduced time spent in the target quadrant (TSTQ) values in the MWM test; increased transfer latency (TL) values in the WYMA test; and reduced percentage location preference (%LP) while increasing percentage Recognition Index (%RI) in the NORT test. Furthermore, Aβ induced increases in AChE activity and TBARS levels, along with reductions in GSH and KCC2 levels. It also caused neurodegeneration in the CA3 hippocampus region. However, DPN ameliorated the above Aβ-induced changes in cognitive behaviors, biomarkers, and histopathological levels.

CONCLUSIONS: Daphnetin attenuates Aβ-associated AD progression via inhibition of AChE activity, scavenging of free radicals, reduction of inflammation, and restoration of neuronal KCC2 channels. Hence, it may be a potential therapeutic agent for the treatment of AD. However, more extensive studies are required to confirm this therapeutic potency in different AD conditions and various animal species.},
}

@article {pmid41717239,
year = {2026},
author = {Ran, AR and Hu, X and Hui, HYH and Dai, J and Chan, VTT and Ho, K and Au, LWC and Ng, CF and Sham, K and Zheng, C and Liu, X and He, Q and Tham, CC and Kwok, TCK and Hilal, S and Cheng, CY and Chua, J and Schmetterer, L and Liu, TYA and Tham, YC and Li-Hsian Chen, C and Wong, TY and Mok, VCT and Cheung, CY},
title = {An Ensemble Learning Artificial Intelligence Model for Alzheimer's Disease Detection Using OCT.},
journal = {Ophthalmology science},
volume = {6},
number = {3},
pages = {101066},
pmid = {41717239},
issn = {2666-9145},
abstract = {PURPOSE: There has been significant progress in detecting Alzheimer's disease (AD) using retinal imaging. We developed an ensemble learning-based deep learning (DL) model, integrating different inputs from OCT for the detection of AD-dementia and early AD.

DESIGN: A retrospective multicenter case-control study.

PARTICIPANTS: A total of 190 participants with AD-dementia and 623 cognitively normal controls were recruited from 2 cohorts in Hong Kong and Singapore as the training and internal validation sets. A total of 46 participants with AD-dementia, 79 participants with mild cognitive impairment (MCI), and 52 cognitively normal controls from 2 cohorts with amyloid-β status identified from positron emission tomography (PET) available in Hong Kong and Singapore as External-1 and External-2, respectively.

METHODS: We developed DL models for identifying AD-dementia versus cognitively normal and also tested the proposed ensemble model for classifying MCI (symptom-based) and AD-MCI (PET-based). Inputs were generated from a commercially available OCT device (Cirrus HD-OCT, Carl Zeiss Meditec, Inc), including optic nerve head (ONH)-centered and macula-centered en face images along with retinal nerve fiber layer thickness and deviation maps, ganglion cell-inner plexiform layer thickness and deviation maps, and macular thickness map. Then, to integrate multiple algorithms and inputs simultaneously, we developed an ensemble model that integrated 2 base DL models-ONH model and the macula model, developed by OCT inputs from the ONH and macula regions, respectively-to provide a unified classification via majority voting.

MAIN OUTCOME MEASURES: Discriminative performance of the ensemble model for detecting AD-dementia, MCI, and AD-MCI.

RESULTS: For detecting AD-dementia, the ensemble model achieved the area under the receiver operating characteristic curve (AUROC) of 0.943 (95% confidence interval, 0.906-0.980), 0.786 (95% confidence interval, 0.673-0.899), and 0.795 (95% confidence interval, 0.716-0.874) in the internal validation, External-1, and External-2, respectively. For detecting AD-MCI defined by PET biomarkers, the ensemble model achieved AUROCs of 0.787 (95% confidence interval, 0.643-0.931) and 0.791 (95% confidence interval, 0.694-0.888) in the External-1 and External-2, respectively.

CONCLUSIONS: Our proposed ensemble model, integrating multiple base models and inputs from OCT analysis, demonstrates strong potential for leveraging OCT imaging in detecting both AD-dementia and early-stage AD, enabling opportunistic screening for AD during ophthalmic visits.

FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}

@article {pmid41717228,
year = {2026},
author = {Ramos, C and Madrigal, C and García, J and Giraldo, M and Aguillón, D and Markova, I and Yepes, C},
title = {Understanding illness awareness in Alzheimer's disease: a qualitative study with patient-caregiver dyads in Colombia.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1742428},
pmid = {41717228},
issn = {1663-4365},
abstract = {BACKGROUND: Diminished awareness of illness is a frequent neuropsychiatric symptom in people with Alzheimer's disease. It has been linked to emotional and behavioral challenges such as depression, apathy, irritability, and poor adaptation to loss of function. Despite its clinical importance, little is known about how individuals and their caregivers understand and experience illness awareness, particularly in low- and middle-income countries.

OBJECTIVE: To explore the meaning of illness awareness and the factors associated with its impairment, as experienced and described by people living with Alzheimer's disease and their caregivers in Medellín, Colombia.

METHODS: Semi-structured interviews were conducted with 20 individuals diagnosed with major neurocognitive disorder due to Alzheimer's disease and 24 caregivers. A grounded theory approach guided data collection and analysis, allowing for an inductive exploration of shared meanings and contextual influences.

RESULTS: For these patient-caregiver dyads, being aware of illness meant recognizing cognitive, emotional, and behavioral changes linked to the neurodegenerative process. Awareness and its disruption were shaped by personal characteristics (such as personality and emotional resilience), prior life experiences, socioeconomic conditions, and the quality of social support. Caregivers who felt emotionally supported and well-informed about the disease were better equipped to support changes in awareness in the person with dementia without increasing distress.

CONCLUSION: Understanding the cultural and interpersonal dimensions of illness awareness offers critical insights for the design of interventions that address absence of awareness with sensitivity and compassion. Recognizing how awareness is formed, preserved, or lost can inform more person-centered approaches to care.},
}

@article {pmid41717227,
year = {2026},
author = {Park, S and Byeon, Y and Lim, JI and Kim, H and Lee, JY},
title = {Medial prefrontal activation as a neural predictor of cognitive training gains in older adults with amnestic mild cognitive impairment: exploratory evidence.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1733025},
pmid = {41717227},
issn = {1663-4365},
abstract = {BACKGROUND: Not all individuals benefit equally from cognitive training, making it essential to identify neural markers that can predict individual responsiveness, particularly among those at the early stages of cognitive impairment.

METHODS: This study investigated whether prefrontal activation measured by functional near-infrared spectroscopy (fNIRS) during three categories of training tasks (attentional, imagery, and associative) predicts cognitive gains in older adults. Twenty-two older adults with amnestic mild cognitive impairment (aMCI) completed a 12-week digital-device-based cognitive training program comprising 12 tasks (6 attentional, 3 imagery, 3 associative). Prefrontal activation was recorded via fNIRS during each task. Cognitive improvement was assessed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale at baseline and 3 months (n = 22).

RESULTS: Among the three task categories, only attentional training was associated with prefrontal activation patterns that significantly predicted cognitive improvement at 3 months. Specifically, greater activation in the left mPFC during attentional training was negatively associated with ADAS-Cog scores (β = -.443, p = 0.039), indicating that individuals with higher activation exhibited greater cognitive improvement.

CONCLUSION: The findings suggest that increased medial prefrontal activation during attentional training reflects compensatory engagement and task-related control processes, which in turn predict larger cognitive gains in individuals with aMCI. These results indicate that neural activation measured during training can serve as a reliable predictor of subsequent cognitive gains, offering a potential foundation for designing personalized and adaptive educational programs.},
}

@article {pmid41717226,
year = {2026},
author = {Zucca, FA and Cassidy, CM and Sturini, M and Tuominen, L and Adorni, F and Cheung, V and Casella, L and Sulzer, D and Pezzoli, G and Isaias, IU and Horga, G and Zecca, L},
title = {Neuromelanin, iron and MRI measurements in midbrain tissues of Parkinson's and Alzheimer's subjects.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1672578},
pmid = {41717226},
issn = {1663-4365},
abstract = {BACKGROUND: In Parkinson's disease, decreased neuromelanin and increased Fe concentrations derive from the loss of neuromelanin-containing neurons in the substantia nigra, which is spared in Alzheimer's disease. We aimed to measure neuromelanin and Fe concentrations in post mortem midbrain subregions of patients with Parkinson's and Alzheimer's disease, and to investigate their effect on MRI signals.

METHODS: We imaged neuromelanin in brain slices of Parkinson's (N = 4) and Alzheimer's disease (N = 7) subjects using neuromelanin-sensitive MRI sequences, compared the results with neuromelanin and Fe concentrations in the same sections, and calculated imaging maps for each subject.

RESULTS: Both neuromelanin and Fe concentrations provided unique contributions to neuromelanin-MRI. Compared to Alzheimer's disease, subjects with Parkinson's disease exhibited increased neuromelanin-MRI values in the superior colliculus and periaqueductal gray matter, and higher Fe concentration in the substantia nigra.

CONCLUSION: Results support the use of neuromelanin-MRI to study neuromelanin and Fe in substantia nigra and neighboring regions for investigating patients with Parkinson's disease and other movement disorders.},
}

@article {pmid41717225,
year = {2026},
author = {Zhao, Y and Che, T and Wang, X and Li, S},
title = {Forecasting individualized progression of Alzheimer's disease using structural MRI and population spatiotemporal priors.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1691084},
pmid = {41717225},
issn = {1663-4365},
abstract = {OBJECTIVE: Alzheimer's disease (AD), the most common neurodegenerative disorder, involves the progressive loss of vulnerable neurons. Tracking its progression via structural magnetic resonance imaging (sMRI), which captures subtle brain anatomical changes, is vital for advancing diagnosis and treatment. Although generative models show promise in simulating disease progression by forecasting future magnetic resonance imaging (MRI) sequences, generating high-quality MRI with faithful anatomical structures remains challenging.

METHODS: To narrow this gap, we proposed a progress map-guided generative adversarial network (pg-GAN) that leverages population-level longitudinal data to enhance individual-level prediction. First, progress maps were constructed by averaging intensity residuals between MRI scans acquired at different time points across a population, thereby preserving the comprehensive volumetric evolution of the brain over time. Then, the progress maps served as spatiotemporal priors and were embedded into a backbone generative adversarial network (GAN) via a proposed feature-wise fusion module (FFM) to predict future MRI for individuals.

RESULTS: We performed extensive experiments on 210 individuals with longitudinal MRIs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. The results demonstrated that our pg-GAN outperformed other conditioning models. The quantitative results showed that the normalized root mean squared error (NRMSE) decreased from 0.1623 to 0.1549, while the peak signal-to-noise ratio (PSNR) increased from 25.9353 dB to 26.3157 dB.

CONCLUSION: Incorporating group-level progression priors into the generative model can significantly improve the accuracy and anatomical fidelity of predicted MRIs, enhance the visualization of disease progression at the voxel level, and advance the development of precision treatment for AD.},
}

@article {pmid41717085,
year = {2026},
author = {Clifford, DB and Benzinger, TLS and Han, JY and Powles, S and Paczynski, M and Ances, BM and Campbell, JW},
title = {Treating Alzheimer's disease in a person living with HIV.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70259},
pmid = {41717085},
issn = {2352-8729},
abstract = {INTRODUCTION: Human immunodeficiency virus (HIV) therapies now support survival into advanced ages by suppressing HIV replication and preserving immune function. Alzheimer's disease (AD), the most common neurologic degenerative condition, may now be treated with anti-amyloid therapies (AAT). HIV was an exclusionary criterion in clinical trials for AAT, leaving the safety and efficacy of these medications unknown in this setting.

METHODS: We report the development of AD supported by careful evaluations and biomarkers over a 10-year period in a person living with well-controlled HIV infection.

RESULTS: AD was diagnosed with consistent clinical and biomarker evidence. AAT was successfully administered without complications. HIV therapy remained effective.

DISCUSSION: This report provides early evidence that AAT can be safely administered without detrimental effects on HIV therapy. The rapidly enlarging elderly HIV population will include an increasing number of individuals with AD who may benefit from this knowledge.},
}

@article {pmid41717083,
year = {2026},
author = {Mohammadnia, H and Bohlooli, M and Ghaffari-Moghaddam, M and Khajeh, M and Taghavi, F},
title = {β-Hydroxybutyrate attenuates glycation-induced structural destabilization and amyloidogenic aggregation in human serum albumin.},
journal = {Biochemistry and biophysics reports},
volume = {45},
number = {},
pages = {102487},
pmid = {41717083},
issn = {2405-5808},
abstract = {Protein aggregation and amyloid fibril formation are key events in neurodegenerative disorders such as Alzheimer's disease, and are worsened by non-enzymatic glycation, which destabilizes protein structure. Glycation by reducing sugars like glucose produces advanced glycation end products (AGEs), promoting misfolding and aggregation. β-Hydroxybutyrate (BHB), a ketone body with anti-glycation and neuroprotective properties, may counteract these effects. This study examined structural, aggregation, and fibrillar changes of human serum albumin (HSA) after prolonged glucose-induced glycation, and evaluated the modulatory role of BHB via a multi-technique approach. HSA was incubated for 120 days under four conditions: control, BHB alone, glucose alone, and glucose + BHB. Analyses included atomic force microscopy (AFM), circular dichroism (CD) spectroscopy, ANS fluorescence, Thioflavin T (ThT) fluorescence, and Congo Red assays. AGE formation was quantified to link biochemical modifications with aggregation patterns. Glucose treatment markedly increased AGE levels. AFM revealed extensive aggregation and high surface coverage in the glucose group, partially reduced by BHB. CD spectroscopy showed α-helix loss and β-sheet enrichment with glycation, while BHB preserved structure. ANS fluorescence indicated glucose-enhanced hydrophobic exposure, reduced by BHB. ThT and Congo Red assays confirmed less amyloid fibril formation in glucose + BHB samples versus glucose alone. These results suggest that glucose induces marked glycation, structural disruption, and amyloidogenic aggregation in HSA, whereas BHB provides partial protection, likely through structural stabilization and aggregation pathway modulation. BHB may offer therapeutic promise for limiting amyloid-related neurodegenerative diseases.},
}

@article {pmid41716662,
year = {2026},
author = {Ohara, H and Yamanaka, M and Okada, F and Okazaki, A and Dizon, MD and Elangovan, A and Babu, HWS and Iyer, M and Vellingiri, B and Kinoshita, M},
title = {Case Report: Distinctive features of cognitive dysfunction and amelioration by antiseizure medication in neuronal intranuclear inclusion disease.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1734078},
pmid = {41716662},
issn = {1662-4548},
abstract = {AIM: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. We investigated a role of nonconvulsive status epilepticus (NCSE) in cognitive dysfunction in pathologically confirmed NIID. We also analyzed distinctive factors to differentiate NIID from Alzheimer's disease (AD).

METHODS: A 63-year-old man presented with transient consciousness disturbance (Day 1). For previous 6 years he had been suffering from similar episodes and gradually progressive cognitive decline. Clinical characteristics and response to antiseizure medications (ASM) were analyzed with a narrative literature review.

RESULTS: Neurological examination showed disorientation, memory disturbance, aphasia, agraphia, and impaired visuospatial ability. On Day 27, his MMSE scored 10. Diffusion-weighted MRI showed high intensity signal in the corticomedullary junction of the frontal lobe, which could not explain his neurological manifestations. EEG showed seizure patterns arising from the bilateral occipital areas. ASM improved MMSE score to 23. Skin biopsy confirmed his diagnosis as dementia-dominant sporadic NIID. He died on Day 77. Cognitive dysfunction in visuospatial execution, manifested by impaired pentagon drawing and agraphia of both kanji (Japanese morphograms) and kana (Japanese syllabograms), its fluctuating course, and reactivity to ASM were clear distinction from AD.

CONCLUSION: NCSE can accelerate cognitive decline and ASM can improve cognitive function in NIID. Cognitive evaluation using pentagon drawing and handwriting of both morphograms and syllabograms can be useful to differentiate NIID from AD.},
}

@article {pmid41716658,
year = {2026},
author = {Grazia, A and Levin, F and Jessen, F and Wagner, M and Peters, O and Priller, J and Schneider, A and Wiltfang, J and Düzel, E and Buerger, K and Perneczky, R and Laske, C and Spottke, A and Ramirez, A and Teipel, SJ},
title = {Predicting longitudinal basal forebrain volume in the Alzheimer's disease spectrum: the role of sex and ApoE epsilon 4 genotype.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1730947},
pmid = {41716658},
issn = {1662-4548},
abstract = {INTRODUCTION: Imaging studies showed early atrophy of the cholinergic basal forebrain (BF) already at prodromal stages of sporadic Alzheimer's disease (AD). Women and carriers of the ApoE epsilon 4 (ApoE ε4) allele are more likely to develop the disease; however, the underlying mechanisms are still unclear. Here we aimed at exploring the impact of sex and ApoE ε4 genotype in the AD spectrum on longitudinal measures of the basal forebrain and hippocampus, as a comparison region.

METHODS: We leveraged the German multi-centered study DELCODE and analyzed 712 individuals (median age: 71.25 years, interquartile range [IQR] = 9.22) with follow-up MRI scans (median time: 2.8 years, [IQR] = 1.75). Diagnostic groups comprised cognitively normal (N = 184), subjective cognitive decline (N = 331), mild cognitive impairment (N = 128) and AD (N = 69). Regarding ApoE genotype, 5% of participants were ε4 homozygotes, while 27% were heterozygotes. Volume segmentation and linear mixed-effect models were used to calculate the effects of ApoE ε4 genotype, sex, diagnosis, age, time and their interactions in TIV-adjusted basal forebrain and hippocampal volumes.

RESULTS: The hippocampus, but not the basal forebrain, showed significant atrophy over time (Hipp: β = -0.014, p < 0.001; BF: β = 0.040, p = 0.044). Post-TIV correction, female participants had significantly larger baseline basal forebrain (β = 0.300, p < 0.001) and hippocampal volumes (β = 0.273, p < 0.001). ApoE ε4 predicted smaller baseline volumes in both regions. After adjusting for multiple comparisons, faster longitudinal atrophy was observed only for ApoE ε4 homozygotes in the hippocampus (β = -0.037, p < 0.001), with no corresponding effect in the basal forebrain (β = 0.000, p = 0.841).

DISCUSSION: Our findings did not show the anticipated longitudinal effects of sex and ApoE ε4 on longitudinal basal forebrain volume. Only hippocampal atrophy progressed significantly faster in ApoE ε4 homozygote carriers. This dissociation may reflect stage-dependent neurodegenerative processes, with early basal forebrain vulnerability followed by more rapid hippocampal decline, as well as methodological and sample-related constraints. If replicated, these findings suggest that hippocampal measures may be more sensitive longitudinal biomarkers in ApoE ε4 homozygotes, while sex- and ApoE ε4-related effects on the cholinergic system may be more prominent at earlier disease stages.},
}

@article {pmid41716572,
year = {2026},
author = {Chen, B and Liang, S and Su, T and Zheng, Y and He, W and Zhou, H and Wang, Q and Yang, M and Lin, G and Xu, D and Chen, Y and Li, J and Liu, Q and Yao, K and Wu, Z and Zhang, M and Hou, L and Zhang, Y and Zhong, X and Ning, Y},
title = {Altered dynamic functional connectivity of orbitofrontal cortex underlies olfactory and cognitive impairment in late-life depression.},
journal = {Psychoradiology},
volume = {6},
number = {},
pages = {kkag002},
pmid = {41716572},
issn = {2634-4416},
abstract = {BACKGROUND: Late-life depression (LLD) and odor identification (OI) dysfunction are risk factors for dementia, but the underlying neural mechanisms remain unclear. This study investigated dynamic functional connectivity (dFC) in olfactory brain regions of LLD patients with and without OI dysfunction and examined how dFC moderates the OI-cognition link.

METHODS: Resting-state functional magnetic resonance imaging data were acquired from 51 LLD patients with OI deficits (LLD-OID), 59 LLD patients without deficits (LLD-noOID), and 51 healthy controls (HC). A sliding-window approach (50 TR width, 1 TR step) was used to estimate dFC variability between the orbitofrontal cortex (OFC) and the whole brain. Bayesian regression and moderation analyses assessed associations among OFC dFC, OI scores, and cognitive measures. Results were robust across window sizes.

RESULTS: Compared to LLD-noOID and HC, LLD-OID showed decreased OFC-left inferior frontal gyrus dFC variability (P < 0.01) and increased OFC-right middle frontal gyrus (MFG) variability (P < 0.001). Higher OFC-MFG variability was associated with worse OI and cognitive performance and significantly moderated the OI-global cognition relationship (β = 1.06, P = 0.027, 95% CI [0.12, 2.0]). No group differences were found in primary olfactory regions.

CONCLUSION: LLD patients with OI dysfunction exhibited more disrupted dFC in secondary olfactory regions compared with those without OI dysfunction. Dynamic OFC-MFG disconnectivity may index vulnerability to cognitive decline and dementia risk in LLD patients.},
}

@article {pmid41716393,
year = {2026},
author = {Mukherjee, K and Bhattacharyya, SN},
title = {The role of miRNAs in the development of Super-Tregs as a potential therapy for neurodegenerative diseases.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1708031},
pmid = {41716393},
issn = {1664-3224},
mesh = {Humans ; *MicroRNAs/genetics/immunology ; Animals ; *Neurodegenerative Diseases/therapy/immunology/genetics ; *T-Lymphocytes, Regulatory/immunology/metabolism/transplantation ; Extracellular Vesicles ; },
abstract = {Regulatory T cells, or Tregs, are designed to limit unnecessary inflammation and serve as a safeguard mechanism to prevent tissue damage caused by heightened inflammatory responses from activated macrophages or effector T cells. Impaired Treg function has implications in autoimmunity and neuroinflammation. Neuroinflammation triggered by amyloid proteins and protein aggregates accelerates neurodegeneration due to increased cytokines and chemokines in the brains of individuals with Alzheimer's Disease and Parkinson's Disease. A simple approach involves preventing inflammation by suppressing T-effector cell activity in affected brains through boosting Tregs' function. Super-Tregs, with enhanced anti-inflammatory properties, can be engineered in vitro to combat inflammation in various tissues and, after homotropic transfer to the target tissue, prevent damage caused by inflammation. The development of Super-Tregs can be achieved through specific genetic and epigenetic modifications. Efforts to generate Super-Tregs utilizing miRNAs and miRNA-containing extracellular vesicles hold promise in treating neuroinflammation with miRNA-engineered Super-Tregs. In this review, we discuss the potential, progress, challenges, and limitations of Super-Treg development and their application in the treatment of neurodegeneration.},
}

Humans
*MicroRNAs/genetics/immunology
Animals
*Neurodegenerative Diseases/therapy/immunology/genetics
*T-Lymphocytes, Regulatory/immunology/metabolism/transplantation
Extracellular Vesicles

@article {pmid41716297,
year = {2026},
author = {Osse, AML and Zhou, Y and Kinney, JW and Hooyman, A and Sengupta, A and Fonseca, J and Burstein, AH and Owen, M and Nisenbaum, L and Fillit, HM and Cheng, F and Cummings, JL},
title = {Biomarkers in Alzheimer's disease clinical trials: 2025.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {1},
pages = {e70217},
pmid = {41716297},
issn = {2352-8737},
abstract = {Biomarkers play an important role in Alzheimer's disease (AD) clinical trials in several contexts of use, including defining trial eligibility and serving as outcome measures. Utilizing clinicaltrials.gov, a registry of clinical trials, we assessed biomarker usage across all active AD disease-targeted therapeutic (DTT) trials. Biomarkers are widely used in AD DTT trials, with 84% including a fluid, imaging, and/or digital biomarker, either as an inclusion criterion or as an outcome measure. In DTT trials, biomarkers were included in 83% of Phase 3 trials, 91% of Phase 2 trials, and 72% of Phase 1 trials. Biomarkers were used for trial inclusion in 58% of DTT trials and as a primary outcome measure in 36%. Characterization of biomarker usage in AD clinical trials offer valuable insights across the drug development spectrum, with the goal of increasing trial efficiency and interpretation, while reducing time for new therapies to become available.},
}

@article {pmid41716273,
year = {2026},
author = {Wang, J and Zhang, Y and Wu, Q and Zhong, Y and Xu, Z and Yang, J},
title = {Interactions of bile acids and gut microbiota modulate neurological health: a comprehensive review on mechanisms and therapeutic potential of dietary phytochemicals.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1757551},
pmid = {41716273},
issn = {1664-302X},
abstract = {Bile acids (BAs), classically regarded as detergents for dietary lipid absorption, have emerged as pivotal signaling molecules with systemic endocrine functions. The discovery of the Farnesoid X Receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) as BAs-activated receptors unveiled their profound influences on glucose, lipid, and energy metabolism. BAs are first synthesized in hepatocytes and further metabolized by gut microbes, can either circulate in enterohepatic system or be found in circulations to exert various effects. More recently, the gut-brain axis has been identified as a critical pathway through which BAs exert significant effects on central nervous system (CNS) function and health. Based on research progresses mentioned above, this review systematically delineates the synthesis, metabolism, and classification of BAs, with a focus on the intricate crosstalk between the hepatic-gut BA axis and the brain. In addition, we explore the compelling evidences linking BAs dysregulation to a spectrum of neurological disorders, including neurodegenerative diseases (Alzheimer's and Parkinson's disease), depression, and hepatic encephalopathy. Besides, the potential mechanisms, such as alleviating neuroinflammation, maintaining the integrity of blood-brain barrier, increasing the neuronal survival, and modulating neurotransmitter systems are further elucidated. Finally, strategies of dietary intervention through phytochemicals to modulate the BAs pool for improved neurological outcomes are summarized and discussed. By integrating pre-clinical and clinical findings, this review aims to establish a foundation for understanding BAs as novel therapeutic targets in neurology and nutritional neuroscience.},
}

@article {pmid41716231,
year = {2026},
author = {Akushevich, I and Yashkin, A and Kovtun, M and Arbeev, K and Kravchenko, J and Yashin, A},
title = {Development of an Exact Theory of Decomposing Population Attributable Fractions and Application to Decomposition of Alzheimer's Disease Risk.},
journal = {Mathematical population studies},
volume = {},
number = {},
pages = {},
pmid = {41716231},
issn = {0889-8480},
abstract = {A new mathematically exact method of population attributable fraction (PAF) decomposition free of limitations inherent in existing approaches was developed and compared to existing methods based on the Miettinen, Norton, and Niedhammer-Chastang formulae. The developed approach is applicable for two broadly used study designs involving either a single or multiple data sources to measure the predictors and outcomes of interest. The approach was applied to Medicare data to estimate six disease-specific contributions to the overall PAF of Alzheimer's disease risk: stroke (7.2%), hypertension (6.5%), diabetes (4.4%), renal disease (0.9%), traumatic brain injury (0.9%), and depression (9.6%). We found that the approximation based on the Norton formula was the best approach among the methods utilized prior to the development of our approach. However, the quality of such approximations and the respective biases should be re-estimated on a case-by-case basis. An extension of the approach to health disparities was proposed and discussed.},
}

@article {pmid41716137,
year = {2026},
author = {Li, X and Yang, H and Liang, Z and Zeng, A and Zou, Y and Dai, J and Zhu, B and Yang, J and Zhang, L and Wang, J},
title = {A Smart Dicyano-Based Fluorescent Probe for In Vivo Amyloid-β Visualization to Illuminate Alzheimer's Disease.},
journal = {Molecular pharmaceutics},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.molpharmaceut.5c01177},
pmid = {41716137},
issn = {1543-8392},
abstract = {Amyloid-β (Aβ) is a key biomarker for Alzheimer's disease (AD), with its abnormal aggregation closely linked to AD pathology. Fluorescence imaging shows promise for Aβ detection but faces challenges such as optical instability, a short blood half-life, and poor blood-brain barrier (BBB) permeability. Additionally, only a few probes could target Aβ oligomers with a higher neurotoxicity. In this study, we designed and synthesized 14 fluorescent probes using the dicyano group as an electron acceptor. Among them, Dicyano-18 emerged as the most promising probe, with a binding affinity for Aβ aggregates (Kd = 21 nM) and strong binding to Aβ oligomers. It operates at a free-state emission wavelength of above 700 nm, offering low cytotoxicity, good serum stability, and efficient BBB permeability. In brain slice staining, Dicyano-18 robustly bound to Aβ plaques in both AD mice and human brain slices. Meanwhile, Dicyano-18 also exhibited the capability of staining Aβ oligomers in the 4 month AD brain slice. Most important, Dicyano-18 demonstrated robust imaging capabilities in AD mice of different ages and diverse AD mouse models in an in vivo study. These findings suggest that Dicyano-18 could be a valuable tool for understanding AD pathology and aiding diagnosis.},
}

@article {pmid41716078,
year = {2026},
author = {Biltekin Kaleli, SN and Önay Uçar, E and Şahin, Z and Berk, B and Demirayak, Ş},
title = {Targeting Inflammatory and Oncogenic Pathways: Cyclooxygenase-2, Epidermal Growth Factor Receptor, and p38 Mitogen-Activated Protein Kinase Inhibition by Pyrazolone Derivatives.},
journal = {ChemMedChem},
volume = {21},
number = {4},
pages = {e202500778},
doi = {10.1002/cmdc.202500778},
pmid = {41716078},
issn = {1860-7187},
support = {Grant 24496//Istanbul University Research Foundation, Türkiye/ ; },
mesh = {*Pyrazolones/pharmacology/chemistry/chemical synthesis ; Humans ; *Cyclooxygenase 2/metabolism ; *p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism ; *ErbB Receptors/antagonists & inhibitors/metabolism ; Structure-Activity Relationship ; Molecular Structure ; *Protein Kinase Inhibitors/pharmacology/chemistry/chemical synthesis ; *Anti-Inflammatory Agents, Non-Steroidal/pharmacology/chemistry/chemical synthesis ; *Cyclooxygenase 2 Inhibitors/pharmacology/chemistry/chemical synthesis ; Dose-Response Relationship, Drug ; Inflammation/drug therapy/metabolism ; Antineoplastic Agents/pharmacology/chemistry/chemical synthesis ; },
abstract = {Acute and chronic inflammation are known to contribute to the pathogenesis of various diseases, including cardiovascular disorders, Parkinson's, Alzheimer's, diabetes, and cancer. Classical nonsteroidal anti-inflammatory drugs reduce inflammation primarily by suppressing the cyclooxygenase (COX) pathway. COX enzymes facilitate the conversion of membrane phospholipids into prostaglandins and play functional roles in several metabolic processes, including analgesia, anti-inflammation, apoptosis, angiogenesis, and drug resistance. Moreover, they are also implicated in cancer development, invasion, metastasis, and the differentiation. In this study, eight pyrazolone derivative compounds with potential anti-inflammatory properties were synthesized. Their structures were successfully characterized using [1]H nuclear magnetic resonance (NMR), [13]C NMR, infrared spectroscopy (IR), and high-resolution mass spectrometry (HRMS) spectroscopy. Their inhibitory activities againt COX-1, COX-2, and 5-lipoxygenase were evaluated to determine their anti-inflammatory potential. Epidermal growth factor receptor inhibition assays were performed for the active compounds 7 and 8, while compound 7, the most potent molecule, was further assessed for p38 mitogen-activated protein kinase inhibition. Several compounds exhibited selective cytotoxicity toward cancer cell lines. Notably, compounds 7 and 8 showed no inhibitory activity against COX-1 yet demonstrated considerable selectivity toward COX-2. Interestingly, some derivatives displaying selective cytotoxic effects were not among the most potent COX-2 inhibitors. Overall, the findings indicate that the synthesized pyrazolone derivatives represent promising lead candidates for the development of anti-inflammatory and anticancer agents.},
}

*Pyrazolones/pharmacology/chemistry/chemical synthesis
Humans
*Cyclooxygenase 2/metabolism
*p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
*ErbB Receptors/antagonists & inhibitors/metabolism
Structure-Activity Relationship
Molecular Structure
*Protein Kinase Inhibitors/pharmacology/chemistry/chemical synthesis
*Anti-Inflammatory Agents, Non-Steroidal/pharmacology/chemistry/chemical synthesis
*Cyclooxygenase 2 Inhibitors/pharmacology/chemistry/chemical synthesis
Dose-Response Relationship, Drug
Inflammation/drug therapy/metabolism
Antineoplastic Agents/pharmacology/chemistry/chemical synthesis

@article {pmid41716040,
year = {2026},
author = {Irandoust, M and Ghasemi, A and Abdul-Azeez Al-Safar, AA and Kelkawi, AHA and Mohammad-Zaheri, M and Saboury, AA and Seyedarabi, A},
title = {The Aromatherapeutic Effects of Herbal Compounds in Inhibiting Metal-Induced Structural Changes in Tau Protein Fibrillar Aggregates.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00501},
pmid = {41716040},
issn = {1948-7193},
abstract = {The aggregation of tau protein into fibrillary structures within nerve cells is a hallmark of Alzheimer's disease (AD). There is growing evidence that metal ion accumulation in the brain may be associated with the onset and progression of this disease. Since tau protein undergoes structural changes upon binding metal ions including Zn[2+], Cu[2+], and Fe[3+], this study aimed to explore compounds that can inhibit these metal-induced alterations. The following four herbal volatile compounds including α-Asarone (ASA), β-Caryophyllene (BCP), Cinnamaldehyde (Cin), and Phenylethyl alcohol (PEA), with known neuroprotective effects, were assessed for their ability to prevent tau fibrillation or aggregation in the presence of metal ions. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and atomic force microscopy (AFM) analyses confirmed that metal ions promote tau fibrillation. The efficacy of the herbal volatile compounds varied in the presence of metal ions: ASA and BCP showed strong inhibitory effects, while Cin and PEA were less effective when metal ions were present. Tau samples treated with ASA and BCP in the presence of metal ions exhibited lower fluorescence intensity, reduced β-sheet content, increased 5,5'-dithio bis(2-nitrobenzoic) (DTNB) release, and the formation of less toxic species. In contrast, Cin, in the presence of any of the metal ions, led to the formation of neurotoxic species, while this was visible for PEA only in the presence of Fe[3+] ions.},
}

@article {pmid41715836,
year = {2026},
author = {Amoroso, N and Pantaleo, E and La Rocca, M and Bellantuono, L and Pascazio, S and Tangaro, S and Monaco, A and Bellotti, R},
title = {Exponential random graph-based eXplainable Artificial Intelligence for Alzheimer disease.},
journal = {Physical review. E},
volume = {113},
number = {1-1},
pages = {014401},
doi = {10.1103/dkn2-9b2t},
pmid = {41715836},
issn = {2470-0053},
mesh = {*Alzheimer Disease/diagnostic imaging/pathology/physiopathology ; Humans ; Brain/pathology/diagnostic imaging/physiopathology ; Magnetic Resonance Imaging ; *Artificial Intelligence ; Models, Neurological ; },
abstract = {The use of statistical physics models to investigate real-world networks and reveal their underlying dynamics has shown promising results and acquired increasing attention. Here, we show how exponential random-graph (ERG) models can be suitably adopted to characterize how Alzheimer's disease (AD) affects brain connectivity. Magnetic-resonance imaging (MRI) of the brain was used to define a brain connectivity network whose nodes are the different brain regions, and the links indicate the pairwise structural relationships. Based on T1-weighted MRI brain scans of 126 normal controls (NC) and 92 AD patients, ERGs were able to outline both "global" and "local" disease patterns. Our findings demonstrate that ERGs accurately highlight how AD affects brain connectivity reaching an overall classification accuracy of 0.82±0.08. Besides, ERGs outline which regions of the brain are the most affected by the disease, thus proving to be a formidable instrument also to investigate the disease pathological mechanisms; more importantly, as these effects are evaluated at patient level, they can be exploited to design innovative diagnosis support systems or to provide a novel explainable framework for decision support systems. Finally, thanks to its generality, the approach proposed in this study paves the way for further applications and investigations inquiring into the use of ERGs for other diseases and different data sources or the use of alternative models.},
}

*Alzheimer Disease/diagnostic imaging/pathology/physiopathology
Humans
Brain/pathology/diagnostic imaging/physiopathology
Magnetic Resonance Imaging
*Artificial Intelligence
Models, Neurological

@article {pmid41715294,
year = {2026},
author = {Mele, A and Serrano, A and Zabala-Rodriguez, MC and Evangelista, BA and Lehew, H and Kovacevic, J and Taylor, M and Tatulian, SA and Teter, K},
title = {Protein disulfide isomerase dissolves and detoxifies oligomeric assemblies of amyloid beta peptide.},
journal = {FEBS letters},
volume = {},
number = {},
pages = {},
doi = {10.1002/1873-3468.70311},
pmid = {41715294},
issn = {1873-3468},
support = {21A06//The Florida Department of Health, Ed and Ethel Moore Alzheimer's Disease Research Program/ ; 8ZA12//The Florida Department of Health, Ed and Ethel Moore Alzheimer's Disease Research Program/ ; },
abstract = {Aggregated amyloid beta peptide (Aβ) contributes to Alzheimer's disease through neurotoxic effects and a prion-like mode of transmission. We report that protein disulfide isomerase (PDI) exhibits disaggregase activity against oligomeric but not fibrillar forms of Aβ. PDI did not bind monomeric Aβ, indicating its highly effective inhibition of fibril formation occurs through reversal of early-stage oligomers rather than prevention of the initial aggregate. Cells exposed to both PDI and oligomeric Aβ were protected from Aβ-induced toxicity. An S-nitrosylated form of PDI that is associated with neurodegeneration could not bind to oligomeric Aβ, thereby eliminating its neuroprotective disaggregase activity. Our observations suggest PDI could be used both physiologically and therapeutically to dissolve the oligomeric forms of Aβ.},
}

@article {pmid41715292,
year = {2026},
author = {Mathoux, G and Harput, E and Peretti, DE and Boccalini, C and Garibotto, V},
title = {Clinical amyloid and tau positron emission tomography imaging in Alzheimer's disease: image interpretation in the era of anti-amyloid therapies.},
journal = {Current opinion in neurology},
volume = {},
number = {},
pages = {},
doi = {10.1097/WCO.0000000000001471},
pmid = {41715292},
issn = {1473-6551},
abstract = {PURPOSE OF REVIEW: The introduction of disease-modifying anti-amyloid therapies has shifted the role of positron emission tomography (PET) imaging in Alzheimer's disease from confirming diagnosis to actively guiding clinical decision-making within the AT(N) framework.

RECENT FINDINGS: Amyloid PET has become central for confirming treatment eligibility, quantifying biological response, and supporting PET-guided strategies for treatment duration, particularly through standardized visual interpretation and Centiloid-based quantification. Tau PET provides complementary information by reflecting disease stage and the burden of pathology most closely associated with cognitive impairment, thereby helping to contextualize expected clinical benefit. Recent clinical trials have integrated PET imaging to monitor therapeutic effects and to support translation into routine clinical practice.

SUMMARY: This review focuses on practical aspects of visual interpretation and semi-quantitative analysis of amyloid and tau PET, discusses tracer-specific considerations and ongoing harmonization efforts, and summarizes the expanding clinical role of PET imaging. Together, amyloid and tau PET support a more biologically grounded and individualized approach to Alzheimer's disease care in the era of disease-modifying therapies.},
}

@article {pmid41715230,
year = {2026},
author = {Spicer, RM and Olofsson, PS and Harrison, FE},
title = {Exploring vagus nerve stimulation in postoperative delirium and dementia.},
journal = {Bioelectronic medicine},
volume = {12},
number = {1},
pages = {5},
pmid = {41715230},
issn = {2332-8886},
support = {AG075341/AG/NIA NIH HHS/United States ; },
}

@article {pmid41715219,
year = {2026},
author = {Dong, YC and Habte, RF and Dessa, KM and Fletcher, ME and Ianni, AM and Lopresti, BJ and Aizenstein, HJ and Cohen, AD and Karikari, TK and Weinstein, AM and Gebara, MA and Wallace, ML and Buysse, DJ and Wilckens, KA},
title = {The Alzheimer's Pathways Sleep Study (ALPS): an experimental randomized controlled trial to improve cognition and Alzheimer's pathophysiology through slow-wave sleep.},
journal = {Trials},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13063-026-09505-w},
pmid = {41715219},
issn = {1745-6215},
support = {R01 AG068001/AG/NIA NIH HHS/United States ; K01 AG049879/AG/NIA NIH HHS/United States ; P01 AG025204/AG/NIA NIH HHS/United States ; },
abstract = {BACKGROUND: Slow-wave activity (0.5-4 Hz electroencephalographic activity) during non-rapid eye movement sleep is consistently associated with better cognitive performance in older adults. Slow-wave activity is known to regulate synaptic plasticity and may thereby mitigate excitotoxicity and accumulation of Alzheimer's pathology. Paradoxically, longer total sleep times in older adults are often associated with poorer cognition and general health. Conventional behavioral sleep treatments robustly increase sleep efficiency and sleep time, but do not consistently enhance slow-wave activity and have shown only subtle effects on cognition. Thus, enhancement of slow-wave activity may be a critical target for sleep-based cognitive enhancement. The Alzheimer's Pathways Sleep Study (ALPS) uses a novel time-in-bed (TiB) restriction intervention designed to increase slow-wave activity through homeostatic sleep drive and assesses improvements in measures of excitotoxic hippocampal hyperactivation, plasma levels of amyloid beta (Aβ), and overnight memory retention.

METHODS: ALPS is a randomized controlled trial designed to increase slow-wave activity behaviorally in older adults with poor sleep. Target enrollment is 116 participants aged 65-85. Participants are randomized to a TiB restriction intervention or an attention-matched control intervention. Participants randomized to TiB restriction follow a sleep schedule restricting their TiB to 85% of their habitual TiB for 4 weeks. The control group follows their habitual TiB for 4 weeks. Both groups are monitored with diary, actigraphy, check-in calls, and sleepiness ratings over the 4 weeks. The primary outcomes for four specific aims are (1) absolute power in the slow oscillation (0.5-1 Hz) range during non-rapid eye movement sleep, (2) hippocampal activation during memory encoding, (3) plasma Aβ1-42, and (4) overnight word pair memory retention. Here we describe how the ALPS intervention is administered, the protocols and scripts implemented to maximize adherence and safety, and outcomes measured to test the proposed conceptual model linking slow-wave activity with excitotoxic hyperactivation, Alzheimer's pathophysiology, and memory performance.

DISCUSSION: Behavioral enhancement of homeostatic sleep drive through TiB restriction is a promising approach to improve memory performance and Alzheimer's pathophysiology. Safety measures, as described here, should be implemented to minimize risks associated with TiB restriction.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05138848. Registered on December 1, 2021.},
}

@article {pmid41715194,
year = {2026},
author = {Wang, B and Pan, M and Yang, L and Xu, J and Ye, C and Li, Y and Gong, Q and Liu, C and Li, L and Qin, J and Ren, D and Zhao, C and Liang, C},
title = {Akkermansia muciniphila reduces neuroinflammation and Aβ deposition via tryptophan metabolism in the APP/PS1 mouse model of Alzheimer's disease.},
journal = {Alzheimer's research & therapy},
volume = {18},
number = {1},
pages = {41},
pmid = {41715194},
issn = {1758-9193},
support = {20224Y0251//Shanghai Clinical Research Foundation of China/ ; 2024YQ01//Training Plan for Outstanding Young Talents in Medical and Health Care of Jing'an District of Shanghai/ ; U24A2072//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Alzheimer Disease/metabolism ; *Tryptophan/metabolism ; Mice ; Mice, Transgenic ; Gastrointestinal Microbiome/physiology ; Disease Models, Animal ; *Akkermansia ; *Amyloid beta-Peptides/metabolism ; *Neuroinflammatory Diseases/metabolism ; Amyloid beta-Protein Precursor/genetics ; Presenilin-1/genetics ; Brain/metabolism ; Male ; Mice, Inbred C57BL ; },
abstract = {Akkermansia muciniphila (A. muciniphila), a beneficial gut bacterium, has increasingly attracted interests in Alzheimer's disease (AD) research, its specific role in the microbiota-gut-brain axis still remains unclear. In this study, we demonstrated that A. muciniphila administration improve cognitive deficits and reduce amyloid-beta (Aβ) deposition in APP/PS1 mice, a transgenic model of AD. Subsequently, it is revealed that A. muciniphila administration significantly alters gut microbiota diversity and composition. Mechanically, our metabolomics analysis of cecal contents indicates A. muciniphila administration increases short-chain fatty acids (SCFAs) derived from the intestinal microbiota, including butyric acid and acetic acid. Significantly, in APP/PS1 mice with the A. muciniphila administration, targeted metabolomics identify that the production of 62 metabolites are increased such as indole-3-acetic acid (IAA), tryptophan, acetic acid and cinnamic acid, as well as aconitic acid and threonine, et al.; the production of 28 metabolites are decreased such as isoleucine and N-acetylneuraminic acid (NANA) as well as ornithine and docosapentaenoic acid (DPA), et al. It is also identified by cytokine analysis of plasma that A. muciniphila administration reduces peripheral pro-inflammatory cytokines interleukin-6 (IL-6), IL-1β, IL-17 and tumor necrosis factor-alpha (TNF-α), et al., whereas it increases anti-inflammatory cytokines, such as IL-4, IL-10 and IL-22, et al. There is no any change of other cytokines, such as interferon-gamma (IFN-g), IL-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF), et al. Interestingly, a significant positive correlation is observed between the increased IAA, tryptophan as well as acetic acid and cognitive function indicators. At the same time, A. muciniphila administration improves cognitive deficits, alleviates neuroinflammation and Aβ deposition via AhR/NF-κB/NLRP3 signaling pathway in APP/PS1 mice. In summary, our findings suggest A. muciniphila is a promising approach for preventing AD progression by microbiota-gut-brain axis.},
}

Animals
*Alzheimer Disease/metabolism
*Tryptophan/metabolism
Mice
Mice, Transgenic
Gastrointestinal Microbiome/physiology
Disease Models, Animal
*Akkermansia
*Amyloid beta-Peptides/metabolism
*Neuroinflammatory Diseases/metabolism
Amyloid beta-Protein Precursor/genetics
Presenilin-1/genetics
Brain/metabolism
Male
Mice, Inbred C57BL

@article {pmid41715163,
year = {2026},
author = {Lv, L and Jia, Y and Zhang, C and Gao, Q and Han, H and Li, J and Cai, Z and Liu, M and Zhang, Y and Liu, J and Zhu, H},
title = {Upregulation of SLC38A2 by melatonin attenuates hippocampal ferroptosis in Alzheimer's disease.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-01990-0},
pmid = {41715163},
issn = {1758-9193},
support = {82370279//National Natural Science Foundation of China/ ; 2023-KYYWF-0251//Scientific Research Project of Basic Scientific Research Business of Heilongjiang Provincial Colleges and Universities/ ; CZKYF2023-1-A011//Scientific Research Project of the Provincial Scientific Research Institute of Heilongjiang Province/ ; },
}

@article {pmid41715082,
year = {2026},
author = {Gosch Berton, G and Lima Fonseca Rodrigues, AC and Mombelli Mattei, N and Dreon Calza, F and Hanel Dias, R and Menegat, ÉL and de Abreu Brkanitch, I and Lago, JA and Hadley, G},
title = {The impact of chronic and acute sleep deprivation on key Alzheimer's disease biomarkers: a systematic review and meta-analysis.},
journal = {Fluids and barriers of the CNS},
volume = {23},
number = {1},
pages = {31},
pmid = {41715082},
issn = {2045-8118},
}

@article {pmid41715029,
year = {2026},
author = {Mohammadi, H and Maghsoudpour, A and Noroozian, M and Mohammadian, F},
title = {Turning versus straight walking under dual-task conditions: a preliminary study for identifying mild cognitive impairment and Alzheimer's disease.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-04723-w},
pmid = {41715029},
issn = {1471-2377},
}

@article {pmid41715018,
year = {2026},
author = {Rasi, R and Guvenis, A and , },
title = {Subregional limbic radiomics on FDG-PET provides accurate early detection of Alzheimer's disease.},
journal = {BMC medical imaging},
volume = {26},
number = {1},
pages = {98},
pmid = {41715018},
issn = {1471-2342},
}

@article {pmid41714795,
year = {2026},
author = {Ledford, H},
title = {Blood test holds promise for predicting when Alzheimer's symptoms will start.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {41714795},
issn = {1476-4687},
}

@article {pmid41714746,
year = {2026},
author = {Petersen, KK and Milà-Alomà, M and Li, Y and Du, L and Xiong, C and Tosun, D and Saef, B and Saad, ZS and Du-Cuny, L and Coomaraswamy, J and Mordashova, Y and Rubel, CE and Meyers, EA and Shaw, LM and Dage, JL and Ashton, NJ and Zetterberg, H and Ferber, K and Triana-Baltzer, G and Baratta, M and Rosenbaugh, EG and Cruchaga, C and McDade, E and Holtzman, DM and Morris, JC and Sabandal, JM and Bateman, RJ and Bannon, AW and Potter, WZ and Schindler, SE and , and , },
title = {Predicting onset of symptomatic Alzheimer's disease with plasma p-tau217 clocks.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {41714746},
issn = {1546-170X},
support = {R01AG070941//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG070941//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG070941//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG067505//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; RF1R01AG053550//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG070941//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; P30AG066444//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; P01AG003991//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; P01AG026276//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; },
abstract = {Predicting not just if, but also when, cognitively unimpaired individuals are likely to develop onset of Alzheimer's disease (AD) symptoms would be useful to clinical trials and, eventually, clinical practice. Although clock models based on amyloid and tau positron emission tomography have shown promise in predicting the onset of AD symptoms, a model based on plasma biomarkers would be more accessible. Using longitudinal plasma %p-tau217 (the ratio of phosphorylated to non-phosphorylated tau at position 217) from two independent cohorts (n = 258 and n = 345), clock models were used to estimate the age at plasma %p-tau217 positivity. The estimated age at plasma %p-tau217 positivity was associated with the age at onset of AD symptoms (adjusted R[2] of 0.337-0.612) with a median absolute error of 3.0-3.7 years. Notably, the time from %p-tau217 positivity to onset of AD symptoms was markedly shorter in older individuals. Similar models were constructed with data from one p-tau217/Aβ42 immunoassay and four plasma p-tau217 immunoassays. These findings suggest that the time until onset of AD symptoms can be estimated using a single blood test within a margin of error that is acceptable for use in clinical trials.},
}

@article {pmid41716754,
year = {2024},
author = {Ereira, S and Waters, S and Razi, A and Marshall, CR},
title = {Early detection of dementia with default-mode network effective connectivity.},
journal = {Nature. Mental health},
volume = {2},
number = {7},
pages = {787-800},
pmid = {41716754},
issn = {2731-6076},
abstract = {Altered functional connectivity precedes structural brain changes and symptoms in dementia. Alzheimer's disease is the largest contributor to dementia at the population level, and disrupts functional connectivity in the brain's default-mode network (DMN). We investigated whether a neurobiological model of DMN effective connectivity could predict a future dementia diagnosis at the single-participant level. We applied spectral dynamic causal modeling to resting-state functional magnetic resonance imaging data in a nested case-control group from the UK Biobank, including 81 undiagnosed individuals who developed dementia up to nine years after imaging, and 1,030 matched controls. Dysconnectivity predicted both future dementia incidence (AUC = 0.82) and time to diagnosis (R = 0.53), outperforming models based on brain structure and functional connectivity. We also evaluated associations between DMN dysconnectivity and major risk factors for dementia, revealing strong relationships with polygenic risk for Alzheimer's disease and social isolation. Neurobiological models of effective connectivity may facilitate early detection of dementia at population level, supporting rational deployment of targeted dementia-prevention strategies.},
}

@article {pmid41714635,
year = {2026},
author = {Sun, J and Han, JJ and Chen, W},
title = {Deep learning models identify brain changes during the progression of Alzheimer's disease.},
journal = {NPJ systems biology and applications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41540-026-00666-7},
pmid = {41714635},
issn = {2056-7189},
support = {92049302, 32088101, 32330017//National Natural Science Foundation of China/ ; 12026210//National Natural Science Foundation of China/ ; },
abstract = {Alzheimer's disease (AD) is an irreversible neurodegenerative disorder whose progression is closely associated with time. However, most diagnostic models are based on single time-point data, overlooking longitudinal disease characteristics. Structural magnetic resonance imaging (sMRI) has been widely utilized in the study of AD. To address the need for multi-time series analysis in longitudinal AD research and the integration of features from different brain tissues, we propose a Multi-Branch Fusion Channel Attention Network (MBFCA-Net) for disease diagnosis. This network leverages the temporal correlations across longitudinal scans for effective AD detection. We further conduct retrospective interpretability analysis to quantify the contributions of brain regions across disease stages. This enables a detailed investigation of dynamic changes in brain regions associated with AD and normal aging. The results indicate that the importance of regions such as the amygdala, parahippocampal gyrus, and temporal lobe undergoes dynamic changes throughout the progression of AD. Furthermore, AD-related voxel clusters exhibit a developmental trend, shifting from the hippocampus to the temporal lobe and transitioning from a dispersed to a more aggregated distribution. Our study provides novel insights into the longitudinal patterns of AD-related changes, offering valuable contributions to early diagnosis and pathological understanding of the disease.},
}

@article {pmid41714576,
year = {2026},
author = {Lu, X and Xu, K and Zhou, Z and Ding, G and Zhang, Y and Liang, Y and Zhou, J and Jia, M and Zhang, Y and Shen, L and Li, H},
title = {Chaetoglobosin F Attenuates Amyloid-β-Induced Neurotoxicity in Caenorhabditis elegans by Regulating Autophagy and Oxidative Stress Via the Insulin/IGF-1 and p38 MAPK Pathways.},
journal = {Neurochemical research},
volume = {51},
number = {2},
pages = {80},
pmid = {41714576},
issn = {1573-6903},
mesh = {Animals ; Caenorhabditis elegans/drug effects ; *Amyloid beta-Peptides/toxicity ; *Oxidative Stress/drug effects/physiology ; *Autophagy/drug effects/physiology ; p38 Mitogen-Activated Protein Kinases/metabolism ; Insulin-Like Growth Factor I/metabolism ; Insulin/metabolism ; Animals, Genetically Modified ; *Indole Alkaloids/pharmacology ; *MAP Kinase Signaling System/drug effects/physiology ; Caenorhabditis elegans Proteins/metabolism ; Neuroprotective Agents/pharmacology ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disease for which no effective clinical therapies currently exist. The neuroprotective potential of Chaetoglobosin F (CF), a fungal secondary metabolite, was investigated in this study using a Caenorhabditis elegans (C. elegans) model of AD that are transgenic nematodes expressing amyloid-beta (Aβ). Key parameters evaluated included paralysis rate, lifespan, motor and cognitive functions, Aβ plaque aggregation, intracellular reactive oxygen species (ROS), and autophagosome formation. The transcriptional levels of genes were examined by real time PCR. Results showed that treatment with CF significantly delayed paralysis, extended lifespan, and ameliorated Aβ-induced deficits in locomotion and chemotaxis. CF markedly reduced Aβ plaque accumulation, suppressed intracellular ROS levels, and promoted autophagosome formation. Furthermore, CF had potent inhibitory effects on acetylcholinesterase (AChE) activity. These beneficial effects were correlated with the upregulation of crucial genes, including daf-16, skn-1, pmk-1, mtl-1, unc-51, bec-1, lgg-1, sod-1 and sod-3, which confirmed the improving antioxidant defenses and autophagy. Our findings demonstrate that CF confers strong neuroprotection against Aβ-induced toxicity in C. elegans by co-regulating oxidative stress and autophagy through the Insulin/IGF-1 (IIS) and p38 MAPK signaling pathways. These results suggest that CF is a promising natural compound for further investigation as a potential therapeutic agent for AD.},
}

Animals
Caenorhabditis elegans/drug effects
*Amyloid beta-Peptides/toxicity
*Oxidative Stress/drug effects/physiology
*Autophagy/drug effects/physiology
p38 Mitogen-Activated Protein Kinases/metabolism
Insulin-Like Growth Factor I/metabolism
Insulin/metabolism
Animals, Genetically Modified
*Indole Alkaloids/pharmacology
*MAP Kinase Signaling System/drug effects/physiology
Caenorhabditis elegans Proteins/metabolism
Neuroprotective Agents/pharmacology

@article {pmid41714374,
year = {2026},
author = {Chauhan, N and Jain, S and Gupta, P and Dwivedi, J and Paliwal, S and Sharma, S and Mishra, A and Singh, S and Beth, MRM and Arunraj, M},
title = {Identification of a novel GSK-3β inhibitor for Alzheimer's disease using In-Silico prediction and experiment cycling, validated in a streptozotocin-induced Alzheimer's disease mouse model.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {41714374},
issn = {1432-1912},
abstract = {GSK-3β has been a key target in Alzheimer's disease (AD) research for over two decades. To identify novel GSK-3β inhibitors, 333 compounds from the National Cancer Institute (NCI) database were screened using a validated ligand-based pharmacophore model with four essential features (two hydrogen bond acceptors, one hydrophobic, and one aromatic ring). After tapering screening with refined boundaries, two top compounds (NSC 275 and NSC 3198) were identified. Molecular docking and simulation studies confirmed their strong binding affinity to GSK-3β. ELISA analysis revealed that their half maximal inhibitory concentration (IC50) values were comparable to the standard GSK-3β inhibitor, CHIR99021. Subsequent in-vivo studies assessed the efficacy of these chemical entities in tested mouse model. Acute toxicity studies demonstrated no observed adverse effect level (NOAEL). Whereas behavioral tests, using the Morris water maze, the tested compounds (5 mg/kg and 10 mg/kg) exhibited cognitive improvements comparable to those of the donepezil group (1 mg/kg), an approved AD treatment. Further analysis of oxidative stress, histopathology, and immune responses in the hippocampus (CA1) indicated that the NSC 275 and NSC 3198 reversed cognitive deficits similarly to the donepezil treated group. The results suggested that combination of in-silico, in-vitro, and in-vivo approaches demonstrates the potential of NSC 275 and NSC 3198 as promising GSK-3β inhibitors for AD treatment.},
}

@article {pmid41714121,
year = {2026},
author = {Koo, H and Mattay, V and Hofling, AA and Wang, SJ and Krainak, D and Kim, Y and Krudys, K and Buracchio, T and Marzella, L},
title = {Advancing Theranostics in Alzheimer Disease: FDA Approval of Amyloid-β PET Drugs for Selection of Patients for Amyloid-β-Directed Therapies and Other Labeling Updates.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.271312},
pmid = {41714121},
issn = {1535-5667},
}

@article {pmid41713702,
year = {2026},
author = {Keil, SA and Li, Y and Krieger, AC and Wang, XH and Nguyen, TD and Ivanidze, J and Chiang, GC and Butler, TA and Zhou, L},
title = {Increased MRI-derived parenchymal cerebral spinal fluid mapping in untreated obstructive sleep apnea patients.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107325},
doi = {10.1016/j.nbd.2026.107325},
pmid = {41713702},
issn = {1095-953X},
abstract = {BACKGROUND: Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with increased risk of Alzheimer's disease (AD) and cognitive decline. The mechanisms underlying the relationship between OSA and disease progression remain undefined, but may involve impairment in the glymphatic system, a perivascular network responsible for cerebrospinal fluid and interstitial fluid exchange and waste clearance. This study evaluated MRI-visible perivascular spaces (PVS) and parenchymal CSF mapping (pCSF) as non-invasive proxies of glymphatic function in untreated and CPAP-treated OSA relative to healthy controls.

METHODS: Forty-two adults (n = 16 healthy controls, n = 14 untreated OSA, n = 12 CPAP-treated OSA) were retrospectively evaluated. Participants underwent MRI and cognitive testing, and a sub-cohort (n = 25) received [11]C-PIB amyloid PET. Enhanced PVS contrast (EPC) mapping segmentation quantified MRI-visible PVS, while multi-echo FAST-T2 MR derived pCSF mapping provided voxelwise quantification of glymphatic fluid distribution. Between-group differences were assessed using nonparametric statistics and multivariable regression analyses controlled for age and sex.

RESULTS: Segmented MR-visible PVS did not differ between groups. Comparatively, untreated OSA subjects had higher ADmask pCSF versus than controls (p = 0.0155), with exploratory analyses displaying a similar relationship across regions including cerebral grey and white matter. Intriguingly, CPAP-treated individuals exhibited pCSF levels statistically comparable to controls. In the sub-cohort, higher ADmask pCSF independently predicted greater amyloid burden on PET (β = 0.616, p = 0.007).

CONCLUSIONS: Untreated OSA is associated with higher parenchymal glymphatic fluid burden consistent with impaired perivascular fluid dynamics. CPAP-treated participants exhibited pCSF levels comparable to controls. pCSF mapping represents a sensitive biomarker for evaluating perivascular fluid distribution, a positive association with amyloid deposition, and monitoring potential treatment-related differences in OSA.},
}

@article {pmid41713500,
year = {2026},
author = {Liu, S and Cheng, Y and Zhang, X and Shen, Y and Wu, S and Chen, Y and Shi, D and Zhuang, C and Chen, B and Zhong, Y and Wang, X and Wen, Y and Zheng, X and Jia, Y and Guan, J and Yan, G and Wu, R},
title = {Assessing Effects of Microwave Electromagnetic Field in APP/PS1 Mice by In Vivo GABA-weighted Imaging via Variable delay Multipulse-Chemical Exchange Saturation Transfer MRI.},
journal = {Neurochemistry international},
volume = {},
number = {},
pages = {106131},
doi = {10.1016/j.neuint.2026.106131},
pmid = {41713500},
issn = {1872-9754},
abstract = {Electromagnetic fields (EMFs) have been shown to be beneficial in treating Alzheimer's disease (AD), but the underlying neurophysiological mechanisms remain unclear. It has been proposed that EMF promotes GABAergic neurogenesis and that abnormal GABA levels are an important influence on the progression of AD. To achieve in vivo GABA-weighted imaging in the brain in APP/PS1 mice, we utilized variable delay multi-pulse (VDMP)-chemical exchange saturation transfer (CEST)- magnetic resonance imaging (MRI) and pathological validation to measure GABA levels in APP/PS1 mice under microwave EMF and explore the therapeutic mechanism. The APP/PS1 mice received a 4-week microwave EMF treatment. The findings show that microwave EMF stimulation significantly increased GABA-weighted signals on MRI of APP/PS1 mouse hippocampus. VDMP-CEST was sensitive in detecting GABA-weighted signals. ELISA showed that microwave EMF stimulation elevated GABA levels in the hippocampus. Compared to in vitro levels, VDMP-CEST accurately detected GABA-weighted signal changes. With the pathological validations, we found that microwave EMF exposure can elevate hippocampal GABA levels by promoting AQP4 polarizion, reducing Aβ accumulation and neuronal degeneration, improving cognitive impairment, and may have slowed AD progression. Collectively, microwave EMF treatment could increase GABA-related changes, which corresponded to the accumulation of Aβ and improvement in the water maze. VDMP-CEST detected levels are highly consistent with pathological evidence, implying that VDMP-CEST is an effective modality for in vivo GABA-weighted imaging during microwave EMF treatment, providing more objective imaging-based diagnostic evidence for monitoring GABA-related pathological changes in AD.},
}

@article {pmid41713452,
year = {2026},
author = {Bray, NW and Adriano, DAC and Grant, S and Kendall, KD and Hill, MD and Stewart Longman, R and Matar, AA and Alghasab, N and Mahdi, N and Afshar, EE and Bruce Pike, G and Poulin, MJ and Eskes, GA},
title = {Sex-Specific Contributions to Single- and Dual-Task Walking in Adults at Risk of Alzheimer Disease and Related Dementias.},
journal = {Journal of aging and physical activity},
volume = {},
number = {},
pages = {1-12},
doi = {10.1123/japa.2025-0148},
pmid = {41713452},
issn = {1543-267X},
abstract = {BACKGROUND/OBJECTIVE: Walking reflects a complex interaction between physiological systems that deteriorate with age and do so more rapidly in those living with diseases. We conducted a sex-specific cross-sectional analysis to determine the contribution of modifiable (risk) factors to single- and dual-task gait performance in older adults at risk of Alzheimer disease and related dementias.

METHODS: We included participants (n = 103; 60.4% female; mean age 63.7 ± 6.2) who had completed a preintervention assessment for a randomized controlled trial. We used the following factors in hierarchical regressions while controlling for age, muscle strength, cardiorespiratory fitness, and global cognition. Participants walked at their usual pace on an electronic walkway and completed the two-back version of the n-back test either separately or together.

RESULTS: Males and females demonstrated reduced gait speed when comparing single to dual tasking (p < .001), but only females demonstrated increasing (i.e., worse) gait variability (p = .007). In females, the dual-task velocity model was significant, F(3, 56) = 5.173, with muscle strength (p = .006) and cardiorespiratory fitness (p = .049) contributing significantly. For males, the models were significant across all conditions, but muscle strength was the only significant (modifiable) factor (single task, p = .023; dual task, p = .046).

CONCLUSION: Dual-task gait velocity is associated with a combination of modifiable factors. However, the importance of each factor differs between males and females. Significance/Implications: Such findings have implications for understanding gait decline and potential sex-specific intervention strategies in those at risk of Alzheimer disease and related dementias.},
}

@article {pmid41713228,
year = {2026},
author = {Pulok, MMH and Akter, F and Islam, MT and Kumar, P and Enan, ME and Khaled Bhuiyan, AFM and Azmi, AM and Ahammed, T and Billah, MM and Das, SK and Islam, MS and Abdullah, M and Khanom, T and Hossain, MS and Faruk, MAZ},
title = {Integrative structure-based approach for phytocompound-based dual therapeutics targeting Alzheimer's and Parkinson's disease.},
journal = {Journal of molecular graphics & modelling},
volume = {144},
number = {},
pages = {109319},
doi = {10.1016/j.jmgm.2026.109319},
pmid = {41713228},
issn = {1873-4243},
abstract = {Neurodegenerative diseases like Alzheimer's and Parkinson's are growing global health concerns with limited treatment options. In this study, we explored four natural compounds-Baicalein, Vincarubine, Rutin, and Luteolin-for their potential as multi-target drugs using computational methods. These compounds were tested against key proteins involved in disease progression, including LRRK2, APP, and Tau kinase. Molecular docking showed that Vincarubine had the strongest binding with LRRK2 and APP, while Rutin interacted best with Tau kinase. Molecular dynamics simulations further supported Rutin's strong and stable binding, with low fluctuation and deviation values. Although Vincarubine showed high binding affinity, it also displayed greater structural flexibility, suggesting it may need some modifications for better stability. Pharmacokinetic analysis revealed that most of the compounds followed drug-likeness rules, but Rutin and Vincarubine had some limitations in size and brain permeability, meaning advanced delivery systems like nanoparticles may be needed. Toxicity tests showed that Baicalein and Rutin were generally safe, while Vincarubine had potential risks for the kidneys and lungs. When compared to commonly used drugs like Donepezil, Memantine, and Levodopa, these natural compounds showed even better binding strength and stability in simulations. Overall, the results suggest these phytocompounds could be promising candidates for treating neurodegenerative diseases. However, further lab-based studies, both in cells and animals, are essential to confirm their real-world potential. Future research should be focused on improving their structures, delivery methods, and possible combinations to boost their effectiveness.},
}

@article {pmid41714582,
year = {2026},
author = {Li, N and Look, KA and Chou, LN},
title = {Dementia Family Caregivers' Involvement and Perceived Challenges in Health Care Interactions: Informing the GUIDE Model.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {41714582},
issn = {1525-1497},
abstract = {BACKGROUND: Health care interaction tasks, such as making appointments and coordinating care, are vital but often overlooked caregiver tasks. The Guiding an Improved Dementia Experience (GUIDE) Model began in 2024 and aims to support dementia family caregivers through care coordination.

OBJECTIVE: This observational study described the characteristics of dementia family caregivers and their perceived challenges in performing health care interaction tasks before the start of the GUIDE Model.

DESIGN: Cross-sectional nationally representative survey.

PARTICIPANTS: Primary family caregivers for those with probable dementia from the National Study of Caregiving (NSOC) Round 13 and the National Health and Aging Trends Study (NHATS). We also conducted subgroup analyses examining caregivers' difficulty performing health care interaction tasks.

MAIN MEASURES: Dementia family caregivers were asked whether they had helped with any of the nine health care interaction tasks. Only caregivers who answered yes to the task questions were asked about their difficulty performing the respective health care interaction tasks. We compared the characteristics of caregivers who performed versus did not perform these tasks, as well as those who reported any difficulty versus no difficulty.

KEY RESULTS: Our study included 467 caregivers. Most (92.5%) caregivers performed at least one health care interaction task. The most frequently performed health care interaction tasks were speaking to providers (82.2%), making appointments (79.0%), and sitting in on doctor appointments (68.4%). The tasks caregivers rated as being most difficult were transitioning care after a hospital stay (58.9%), coordinating care (43.0%), and handling insurance matters (39.8%). Over half of caregivers assisting after an overnight hospital stay received post-hospital training (58.2%).

CONCLUSIONS: Family caregivers commonly perform health care interaction tasks, and their difficulties, particularly transitioning care after a hospital stay, should be recognized and assessed across care settings and providers in the GUIDE Model.},
}

@article {pmid41714332,
year = {2026},
author = {Li, C and Chia, XW and Xu, G and Ang, LF and Makino, H},
title = {Vulnerability of short-term memory in a mouse model of Alzheimer's disease.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-69619-2},
pmid = {41714332},
issn = {2041-1723},
support = {MOE2017-T3-1-002//Ministry of Education - Singapore (MOE)/ ; JP25H01750//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JP25H02511//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; },
abstract = {Interference from distracting stimuli renders short-term memory vulnerable. While behavioral evidence suggests short-term memory deficits in Alzheimer's disease (AD), the underlying neural mechanisms remain poorly understood. Using a mouse model of AD (APP-KI), we identified increased susceptibility of short-term memory to sensory perturbations. Simultaneous two-photon calcium imaging across eight cortical regions during a delayed-response task showed that distractors disrupted neural selectivity at both single-neuron and population levels in APP-KI mice. Recurrent neural network models replicating the neural activity of APP-KI mice exhibited decreased stability, consistent with reduced functional connectivity across the dorsal cortex. Furthermore, analyses of multi-regional corticocortical communication revealed reduced spatiotemporal degeneracy in activity transmission within the dorsal cortex of APP-KI mice, which could account for their attenuated robustness during sensorimotor transformations. Collectively, these findings identify reduced functional connectivity and impaired spatiotemporal degeneracy as central mechanisms of short-term memory deficits in the APP-KI mouse model of AD.},
}

@article {pmid41714304,
year = {2026},
author = {Ruankham, W and Prachayasittikul, V and Pingaew, R and Jeungprasopsuk, W and Tantimongcolwat, T and Prachayasittikul, V and Prachayasittikul, S and Phopin, K},
title = {Unraveling Network Pharmacology-Based Therapeutics of Anthranilate Sulfonamides via Sirtuins/FOXO3a Cascade in Alzheimer's Disease.},
journal = {Journal of neurochemistry},
volume = {170},
number = {2},
pages = {e70377},
doi = {10.1111/jnc.70377},
pmid = {41714304},
issn = {1471-4159},
support = {//National Science Research and Innovation Fund (NSRF)), Thailand/ ; },
mesh = {Humans ; *Sirtuins/metabolism ; *Alzheimer Disease/drug therapy/metabolism ; *Forkhead Box Protein O3/metabolism ; *Sulfonamides/pharmacology/chemistry/therapeutic use ; *Network Pharmacology/methods ; Molecular Docking Simulation ; *Neuroprotective Agents/pharmacology ; *ortho-Aminobenzoates/pharmacology/therapeutic use ; Signal Transduction/drug effects ; Cell Line, Tumor ; Animals ; },
abstract = {Sulfonamide-based compounds have been a clinically attractive scaffold for drug development and proven as antioxidant and antimicrobial agents, but their pharmacological derivatives containing anthranilates (SA1-4) and therapeutic targets are not clearly clarified. To unravel the neuroprotective roles and underlying mechanisms of SA1-4 against oxidative injury and healthy longevity crosstalk, a combination of in vitro experiments, in silico modeling, and network pharmacology was employed. Pretreatment with SA1-4 in human neuronal SH-SY5Y cells significantly regulated sirtuins (SIRTs)/forkhead box class O 3a (FOXO3a)-mediated longevity signaling pathway via targeting endogenous antioxidant enzymes (i.e., superoxide dismutase 2 [SOD2] and catalase [CAT]), apoptotic cascades (i.e., Bcl-2-associated X-protein [BAX] and B-cell lymphoma-2 [BCL-2]), mitochondrial balance, and ultimately led to the neuronal rescue. Molecular docking simulations support the possibility of the SA1-4 modulatory effect within the active binding site of SIRT1. Importantly, in silico predictions of pharmacokinetic profiles suggested that the synthetic compounds possessed preferable drug-like properties, good oral bioavailability, and safety profiles. Network pharmacology also revealed the involvement of SA1-4 and key targets-regulated SIRTs in neurodegeneration, including non-amyloidogenic cascade, tau phosphorylation, calcium homeostasis, insulin-mediated glucose uptake, and neuroinflammation. Therefore, SA1-4 exert promising multi-target therapeutic strategies against oxidative damage, potentially offering alternative anti-Alzheimer candidates for further clinical neurodegenerative and anti-aging therapeutics.},
}

Humans
*Sirtuins/metabolism
*Alzheimer Disease/drug therapy/metabolism
*Forkhead Box Protein O3/metabolism
*Sulfonamides/pharmacology/chemistry/therapeutic use
*Network Pharmacology/methods
Molecular Docking Simulation
*Neuroprotective Agents/pharmacology
*ortho-Aminobenzoates/pharmacology/therapeutic use
Signal Transduction/drug effects
Cell Line, Tumor
Animals

@article {pmid41713755,
year = {2026},
author = {Liu, S and Dang, B and Kang, Z and Wei, R and Yang, Z and Guo, X and Shao, F and Li, Z and Xing, L and Hu, J and Chen, X},
title = {Discovery of tetrahydroisoquinoline derivatives as selective histone deacetylase 6 inhibitors with neurite outgrowth-promoting activities and neuroprotective activities.},
journal = {Bioorganic & medicinal chemistry letters},
volume = {},
number = {},
pages = {130593},
doi = {10.1016/j.bmcl.2026.130593},
pmid = {41713755},
issn = {1464-3405},
abstract = {Recently, histone deacetylase 6 (HDAC6) has attracted considerable attention for its potential in treating neurodegenerative disorders. In this paper, a series of tetrahydroisoquinoline derivatives were designed and synthesized as selective HDAC6 inhibitors. 4-((7-chloro-3, 4-dihydroisoquinolin-2(1H)-yl)methyl)-3-fluoro-N-hydroxybenzamide (8g), the most promising compound, potently inhibited HDAC6 (IC50 = 7.0 nM) and exhibited >2000 ~ fold selectivity over HDAC1. Molecular simulation indicated its molecular basis of HDAC6 inhibition. In vitro, 8g showed no significant toxicity on rat dopaminergic pheochromocytoma PC-12 cells. Furthermore, we demonstrated that 8g induced neurite outgrowth and showed good neuroprotective activity in PC-12 cells. Our research provided a new promising structure for the development of HDAC6is against Alzheimer's disease.},
}

@article {pmid41713678,
year = {2026},
author = {Li, A and Xing, Y and Xie, S and Meng, W and Wu, Z and Wu, N and Wang, Z and Zhu, W and Shi, X and Xie, B and Yin, Y and Mi, Y and Wei, T and Qiao, Y and Wei, J and Zhang, G and Tang, Y},
title = {Simulated Default Mode Network Electric Fields are Associated with Cognitive Response to Transcranial Alternating Current Stimulation in Mild Alzheimer's Disease.},
journal = {Brain stimulation},
volume = {},
number = {},
pages = {103056},
doi = {10.1016/j.brs.2026.103056},
pmid = {41713678},
issn = {1876-4754},
}

@article {pmid41713416,
year = {2026},
author = {Xu, YKT and Bush, A and Musheyev, E and Umans, J and Zhang, L and Kim, AA and Zhang, S and Eugenin von Bernhardi, J and Yan, Y and Sulam, J and Bergles, DE},
title = {Brain-wide mapping of oligodendrocyte organization, oligodendrogenesis, and myelin injury.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2026.01.025},
pmid = {41713416},
issn = {1097-4172},
abstract = {Insulating sheaths of myelin accelerate neuronal communication in the mammalian brain. Oligodendrocytes that produce myelin are generated throughout life to gradually increase myelin coverage, but these dynamics have not been defined brain-wide across the lifespan. We developed a cellular mapping pipeline involving tissue clearing, lightsheet microscopy, and AI-assisted analysis to identify the precise location of millions of oligodendrocytes and assess regional myelin density in the mouse brain. These atlases revealed the diversity of oligodendrocyte patterning, which was consistent between brain hemispheres, individuals, and sexes but displayed both age- and region-specific differences. Integration of these atlases with transcriptomic and ultrastructural datasets highlighted underlying mechanisms that may control this patterning. In models of demyelination and disease, we identified regions of enhanced oligodendrocyte resilience and vulnerability and white matter injury near β-amyloid plaques, demonstrating the utility of this pipeline for defining brain-wide oligodendrocyte dynamics in both health and disease.},
}

@article {pmid41713415,
year = {2026},
author = {Bieri, G and Pratt, KJB and Fuseya, Y and Aghayev, T and Sucharov, J and Horowitz, AM and Philp, AR and Fonseca-Valencia, K and Chu, R and Phan, M and Remesal, L and Wang, SJ and Yang, AC and Casaletto, KB and Villeda, SA},
title = {Liver exerkine reverses aging- and Alzheimer's-related memory loss via vasculature.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2026.01.024},
pmid = {41713415},
issn = {1097-4172},
abstract = {Blood factors transfer the benefits of exercise to the aged brain independent of physical activity. Here, we show that the liver-derived exercise factor (exerkine) glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (GPLD1), a GPI-degrading enzyme, reverses aging- and Alzheimer's-related memory loss by targeting the brain vasculature. GPLD1 has the potential to cleave over 100 putative GPI-anchored proteins, necessitating the identification of downstream targets that mediate cognitive rejuvenation for translational application. We identified GPI-anchored tissue-nonspecific alkaline phosphatase (TNAP) on the brain vasculature as a GPLD1 substrate. Mimicking age-related increases in cerebrovascular TNAP impaired blood-brain transport and cognition in young mice and mitigated GPLD1-induced cognitive benefits in aged mice. Inhibiting TNAP recapitulated the benefits of GPLD1 in old age, restoring youthful hippocampal transcriptional signatures and rescuing cognition. In an Alzheimer's disease model, increasing GPLD1 or inhibiting TNAP ameliorated Aβ pathology and improved cognitive deficits. We thus identify brain vasculature as a mediator of the cognitive benefits of a liver-to-brain exercise axis.},
}

@article {pmid41713294,
year = {2026},
author = {Guerrero, S and Hassan, N and Salas-Huenuleo, E and Moglia, I and Prades, R and Massa, S and Teixido, M and Guzman, F and Giralt, E and Albericio, F and de Oliveira, E and Araya, E and Kogan, MJ},
title = {Apolipoprotein E-enriched protein corona enhances the blood-brain barrier transport of β-sheet-breaker peptide-functionalized gold nanoparticles.},
journal = {Colloids and surfaces. B, Biointerfaces},
volume = {262},
number = {},
pages = {115538},
doi = {10.1016/j.colsurfb.2026.115538},
pmid = {41713294},
issn = {1873-4367},
abstract = {The transient, heterogeneous nano-bio interface defined by the protein corona in biological environments dictates the biodistribution, immune recognition, metabolism, and clearance of nanomaterials. Far from being a drawback, this corona can be harnessed for targeted nanodrug delivery when its composition is predictably tuned or deliberately modulated. We hypothesized that preloading apolipoprotein E (ApoE), previously identified as a constituent of the corona of β-sheet-breaker peptide-functionalized gold nanoparticles (AuNPs), would enhance transport across the blood-brain barrier (BBB) and increase brain uptake. To test this, we synthesized AuNPs (approximately 12 nm) functionalized (AuNP-f) with CLPFFD or THRPPMWSPVWPCLPFFD peptides, both containing the β-sheet-breaker motif LPFFD, which recognizes β-amyloid aggregates implicated in Alzheimer's disease. After incubation with human plasma, hard-corona proteins were profiled by 2D IEF/SDS-PAGE and LC-MS/MS. Proteins were ranked based on their roles in nanoparticle trafficking and BBB transcytosis, and ApoE was selected for deliberate enrichment due to its recurrent presence. ApoE-decorated AuNP-f were evaluated in an in vitro BBB model and in vivo biodistribution assays using Sprague-Dawley rats. Brain accumulation was assessed ex vivo. Preloading ApoE onto AuNP-f significantly enhanced nanoparticle transport across the BBB in vitro and increased brain accumulation in rats. These results demonstrate that rational corona enrichment with ApoE improves BBB transit and brain accumulation without altering nanoparticle surface chemistry. Corona engineering thus offers a pragmatic route to brain-targeted nanodrug delivery and may be extended to other protein-receptor axes for organ-specific targeting.},
}

@article {pmid41712998,
year = {2026},
author = {Pavilek, B and Hajduová, D and Bortňák, D and Milata, V},
title = {Kynurenic acid derivatives in treatment for Alzheimer's disease.},
journal = {Bioorganic & medicinal chemistry},
volume = {136},
number = {},
pages = {118601},
doi = {10.1016/j.bmc.2026.118601},
pmid = {41712998},
issn = {1464-3391},
abstract = {This review provides a comprehensive overview of kynurenic acid (KYNA) derivatives with specific focus on KYNA amides as an emerging class of multi-target directing drugs (MTDDs) for the treatment of Alzheimer's disease (AD). It highlights the urgent need for novel AD therapies, discusses the key structural and pharmacological attributes that position KYNA as a promising candidate for this role, outlines laboratory synthesis for KYNA scaffold. Furthermore, the review summarizes the most promising KYNA derivatives reported in the literature, critically evaluates the results from conducted bioassays, and establishes future prospectives for KYNA MTDDs. Overall, eleven leading structures (compounds 1-11) were identified whose MTDD profiles usually combine the neuroprotective and anti-inflammatory features of KYNA with neurotransmitter modulation, anti-amyloid-beta (Aβ) aggregation activity, and, less frequently, antioxidant properties and the maintenance of ion homeostasis. Comparative analysis of the bioassay data identifies compounds 2 and 6 as MTDDs with superior translational validity, evidenced by their demonstrated efficacy in vivo models (Caenorhabditis elegans). Conversely, compounds 7 and 8 emerged as the candidates with the highest potency and broadest pharmacological scope. These derivatives effectively modulated five distinct pathological hallmarks of AD: Aβ accumulation, oxidative stress, neurotransmitter imbalance, and neuroinflammation. Notably, they exhibit disease-modifying potential by functioning not only as neuroprotective agents but also as promoters of neurogenesis. Synthetically, amidation represents the predominant strategy for achieving an MTDD profile, facilitating the efficient modification of pharmacological activity in a single step via the incorporation of bioactive amines.},
}

@article {pmid41712850,
year = {2026},
author = {Piyaamornpan, N and Srisuwannanukorn, S and Tangthamrongthanawat, K and Mekhasingharak, P and Rattanabannakit, C and Hunnangkul, S and Wongkom, N and Senanarong, V},
title = {Web-Based Application for Cognitive and Functional Assessments in Dementia Screening: Mixed Methods, User-Centered Development Approach.},
journal = {JMIR human factors},
volume = {13},
number = {},
pages = {e85454},
doi = {10.2196/85454},
pmid = {41712850},
issn = {2292-9495},
mesh = {Humans ; Female ; *Dementia/diagnosis ; Aged ; Male ; Thailand ; *Internet ; *Mass Screening/methods ; Aged, 80 and over ; Middle Aged ; Neuropsychological Tests ; User-Centered Design ; Cognitive Dysfunction/diagnosis ; },
abstract = {BACKGROUND: Digital health technologies offer new opportunities for cognitive screening and monitoring among older adults. In Thailand, where dementia prevalence is rising, accessible web-based cognitive tools remain limited despite their potential to facilitate early detection and community-based assessment. Understanding usability and validity is critical to ensure successful implementation in real-world contexts.

OBJECTIVE: This study aimed to develop and validate a web-based application, Healthy Brain Test, for cognitive and functional assessments in dementia screening among older Thai adults. Specific objectives were to (1) design user-centered cognitive modules covering key cognitive domains and (2) evaluate correlations between the web-based assessments and conventional clinical tools to determine diagnostic cutoffs for cognitive impairment.

METHODS: We designed Healthy Brain Test as a self-administered web application suitable for older users and their caregivers. The platform includes digital versions of the Thai Mental State Examination (e-TMSE), a clock drawing test, and a category verbal fluency test, along with electronic versions of the short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-16) and cognitive instrumental activities of daily living (IADLs). Participants completed both web-based and paper-based assessments. Correlations between modalities were analyzed, and receiver operating characteristic (ROC) curves were generated to determine sensitivity and specificity. Data were analyzed using SPSS for Windows, version 30.0 (IBM Corp) and MedCalc Statistical Software (MedCalc Software Ltd).

RESULTS: A total of 198 older adults participated (women: 137/198, 69.2%; median age 69.4 years), with 57.1% (113/198) having more than 6 years of education. Of the 198 participants, 44 were diagnosed with major neurocognitive disorder, 58 were diagnosed with mild neurocognitive disorder, and 96 were cognitively normal. The e-TMSE showed strong agreement with the traditional TMSE (r=0.837; P<.001). Category verbal fluency, IQCODE-16, and IADL modules also demonstrated significant correlations (P<.001). The e-TMSE achieved an area under the ROC curve of 0.84 (bootstrapped 95% CI 0.78-0.89); a cutoff ≤23 provided 88.6% sensitivity and 70.1% specificity for identifying major neurocognitive disorder. Participants reported high ease of use and engagement during pilot testing.

CONCLUSIONS: Healthy Brain Test demonstrated strong validity and usability as a web-based cognitive and functional assessment platform for dementia screening. Its integration of established cognitive measures into a digital interface enables remote, accessible, and user-friendly evaluation for older adults and caregivers. Future research should assess long-term feasibility, user adherence, and integration with clinical workflows to support large-scale screening initiatives.},
}

Humans
Female
*Dementia/diagnosis
Aged
Male
Thailand
*Internet
*Mass Screening/methods
Aged, 80 and over
Middle Aged
Neuropsychological Tests
User-Centered Design
Cognitive Dysfunction/diagnosis

@article {pmid41712108,
year = {2026},
author = {Grasso, M and Fidilio, A and L'Episcopo, F and Recupero, M and Barone, C and Lovino, M and Alboni, S and Bacalini, MG and Caruso, G and Greco, D and Buono, S and De La Torre, R and Tascedda, F and Blom, JM and Benatti, C and Caraci, F},
title = {Searching for New Possible Peripheral Biomarkers of Cognitive Decline in Down Syndrome: The Role of IL-18 Pathway and its Interaction with TGF-β1 and TNF-α.},
journal = {Neuromolecular medicine},
volume = {28},
number = {1},
pages = {12},
pmid = {41712108},
issn = {1559-1174},
support = {GR-2019-12369983//Ministero della Salute/ ; GR-2019-12369983//Ministero della Salute/ ; grant agreement no. 899986//European Union's Horizon 2020 research and innovation program/ ; },
mesh = {Humans ; *Interleukin-18/blood/physiology ; Biomarkers/blood ; Adult ; Male ; Female ; *Down Syndrome/blood/complications/psychology ; *Transforming Growth Factor beta1/blood/physiology ; Young Adult ; *Tumor Necrosis Factor-alpha/blood/physiology ; *Cognitive Dysfunction/blood/etiology ; Middle Aged ; Alzheimer Disease/blood/diagnosis ; Signal Transduction ; Aged ; },
abstract = {Down syndrome (DS) represents one of the most common genetic disorders attributable to a partial or complete trisomy of chromosome 21 that affects about 1 in 700 individuals at birth. The diagnosis of Alzheimer's Disease (AD)-correlated cognitive decline in this population requires new approaches and new biomarkers that comprehensively assess health status and early cognitive decline. In this observational study, we explored for the first time the relation of IL-18, a cytokine member of IL-1 family involved in both innate and acquired immune responses, with DS associated cognitive decline. We observed that plasma total IL-18, in subjects with DS over 35 with and without AD-related cognitive decline, and plasma concentrations of its binding protein in subjects with DS (19-35 years) were correlated with lower plasma concentrations of Transforming Growth Factor (TGF-β1), which are linked to an increased rate of cognitive decline in adults with DS. In addition, we found a significant association between low baseline concentrations of Free IL-18, the active form of the cytokine, and an increased rate of cognitive decline at 12 months, calculated as delta of the Test for Severe Impairment (dTSI), in individuals with DS (19-35 years). Finally, we demonstrated a reduction of Free IL-18/TNF-α ratio, considered as a new possible double biomarker, in both young and older adult DS subjects without AD-related cognitive decline (area under the receiver operating curve (AUC) was 0.82 and 0.71, respectively), suggesting the advantage of the composite biomarkers in the discrimination of patients from healthy people over single biomarkers.},
}

Humans
*Interleukin-18/blood/physiology
Biomarkers/blood
Adult
Male
Female
*Down Syndrome/blood/complications/psychology
*Transforming Growth Factor beta1/blood/physiology
Young Adult
*Tumor Necrosis Factor-alpha/blood/physiology
*Cognitive Dysfunction/blood/etiology
Middle Aged
Alzheimer Disease/blood/diagnosis
Signal Transduction
Aged

@article {pmid41712029,
year = {2026},
author = {Ahmad, HA and Zafar, M and Khan, T and Khan, MI},
title = {Current progress in pathway-targeted therapeutics for Alzheimer's disease: mechanistic insights and windows of opportunity.},
journal = {Molecular and cellular biochemistry},
volume = {},
number = {},
pages = {},
pmid = {41712029},
issn = {1573-4919},
}

@article {pmid41711970,
year = {2026},
author = {Pham, HB and Tong, MT and Tran, NTL and Tran, TT and Phan, TL and Ching, CTS and Huynh, CK and Ha, TTH and Tran, CT},
title = {Development and human samples validation of a plasma pTau‑217 electrochemical sensor for Alzheimer's detection in Vietnamese patients.},
journal = {Mikrochimica acta},
volume = {193},
number = {3},
pages = {170},
pmid = {41711970},
issn = {1436-5073},
support = {B2024-28-06//Vietnam National University HoChiMinh City (VNU-HCM)/ ; },
}

@article {pmid41711262,
year = {2026},
author = {Keshavan, A and Wiltshire, K and Wee, R and Belio, IG and Tucker, K and Hart, M and Lunn, MP and David, MCB and Rizzo, L and Sadeghi-Alavijeh, O and Wilson, P and Gale, DP and Heslegrave, AJ and Zetterberg, H and Fox, NC and Malhotra, P and Schott, JM},
title = {The Alzheimer's Disease Diagnosis and Plasma Phospho-Tau217 (ADAPT) study stage 1: Validating clinical cut-points against CSF and amyloid PET.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71147},
doi = {10.1002/alz.71147},
pmid = {41711262},
issn = {1552-5279},
support = {ARUK-BBC2023-002//Blood Biomarker Challenge/ ; },
mesh = {Humans ; *Alzheimer Disease/diagnosis/cerebrospinal fluid/blood/diagnostic imaging ; *tau Proteins/blood/cerebrospinal fluid ; *Positron-Emission Tomography ; Male ; Female ; Aged ; Biomarkers/blood/cerebrospinal fluid ; Phosphorylation ; Sensitivity and Specificity ; Amyloid beta-Peptides/cerebrospinal fluid ; Middle Aged ; Aged, 80 and over ; Cohort Studies ; },
abstract = {INTRODUCTION: We validated plasma phosphorylated tau (p-tau)217 cut-points for Alzheimer's disease (AD) diagnosis using two commercial assays in two biomarker-defined cohorts and examined influences of pre-analytical factors and chronic kidney disease (CKD) on p-tau217 concentrations.

METHODS: Lumipulse (Fujirebio) and ALZpath (Quanterix) assays quantified plasma p-tau217 in symptomatic patients (AD status definition cerebrospinal fluid [CSF] n = 257; amyloid positron emission tomography [PET] n = 76). Receiver operating characteristic (ROC) analyses established ≥ 95% sensitivity/specificity cut-points. In separate cohorts we evaluated the impact of pre-analytical handling/transport variations (n = 40/10) and cognitively normal (CN)-CKD individuals (n = 58).

RESULTS: Diagnostic accuracy was similar (area under the ROC Lumipulse 0.947; ALZpath 0.940). Lumipulse p-tau217 achieved 95% sensitivity and 97% specificity using dual cut-points (0.153/0.422 pg/mL), producing indeterminate results in 19.4% (CSF defined) and 34.2% (PET defined). P-tau217 concentrations were stable across handling conditions and kit lots, and mostly in the low-to-intermediate range in CN-CKD.

DISCUSSION: Lumipulse plasma p-tau217, now available in our United Kingdom Accreditation Service-accredited clinical National Health Service laboratory, will be used in a randomized trial of p-tau217 result disclosure in memory services.},
}

Humans
*Alzheimer Disease/diagnosis/cerebrospinal fluid/blood/diagnostic imaging
*tau Proteins/blood/cerebrospinal fluid
*Positron-Emission Tomography
Male
Female
Aged
Biomarkers/blood/cerebrospinal fluid
Phosphorylation
Sensitivity and Specificity
Amyloid beta-Peptides/cerebrospinal fluid
Middle Aged
Aged, 80 and over
Cohort Studies

@article {pmid41711160,
year = {2026},
author = {Zerbini, E and Riva, D and Maffioli, E and Tedeschi, G and Sacchi, S and Pollegioni, L},
title = {Post-translational regulation of human D-3-phosphoglycerate dehydrogenase in Alzheimer's disease.},
journal = {Protein science : a publication of the Protein Society},
volume = {35},
number = {3},
pages = {e70505},
doi = {10.1002/pro.70505},
pmid = {41711160},
issn = {1469-896X},
support = {PRIN 2017 (2017H4J3AS)//Ministero dell'Università e della Ricerca/ ; },
mesh = {Humans ; *Alzheimer Disease/enzymology/genetics/metabolism ; *Phosphoglycerate Dehydrogenase/metabolism/chemistry/genetics ; *Protein Processing, Post-Translational ; Female ; Male ; Phosphorylation ; Acetylation ; Hippocampus/enzymology ; Aged ; },
abstract = {Emerging evidence suggests that sex-specific differences in L-serine (L-Ser) metabolism play a key role in Alzheimer's disease (AD). While disruptions in amino acid balance are well known, recent findings point to a dimorphic regulation of the serine biosynthetic pathway. To explore this, we examined post-translational modifications (PTMs) of D-3-phosphoglycerate dehydrogenase (PHGDH)-the rate-limiting enzyme for de novo L-Ser synthesis-as a potentialmechanism underlying this difference. PHGDH was immunoprecipitated from hippocampal tissue of healthy and AD-affected males and females and analyzed by mass spectrometry. Five phosphorylation sites (S55, T60, T78, S383, and S473) were shared across all groups, but a unique deacetylation at K289 appeared exclusively in AD males. Functional assays using recombinant PHGDH variants revealed that changes at solvent-exposed sites (K289, S383, and S473) reduced solubility, while phosphomimetic substitutions at S55 and T78 within the catalytic cleft strongly impaired activity. Notably, mimicking acetylation at K289 improved protein stability. Overall, these PTMs act both as subtle modulators and as on/off switches, fine-tuning PHGDH function and potentially contributing to sex-dependent metabolic vulnerability in AD.},
}

Humans
*Alzheimer Disease/enzymology/genetics/metabolism
*Phosphoglycerate Dehydrogenase/metabolism/chemistry/genetics
*Protein Processing, Post-Translational
Female
Male
Phosphorylation
Acetylation
Hippocampus/enzymology
Aged

@article {pmid41711094,
year = {2026},
author = {Gaugler, JE and Albers, EA and Birkeland, RW and Urbanski, DP},
title = {A mixed methods evaluation of the Residential Care Transition Module.},
journal = {Aging & mental health},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/13607863.2026.2631437},
pmid = {41711094},
issn = {1364-6915},
abstract = {OBJECTIVES: A post-hoc, mixed methods analysis of a randomized controlled trial of a 12-month psychosocial and psychoeducational telehealth intervention to support dementia caregivers of cognitively impaired relatives living in residential long-term care settings (the Residential Care Transition Module/RCTM) was conducted to identify and test potentially new mechanisms and outcomes of the RCTM.

METHOD: Two hundred and forty caregivers were randomly assigned to the RCTM treatment condition or to usual care as the control group and were administered quarterly surveys. Participants in the treatment condition provided qualitative data on perceptions of intervention benefits on follow-up surveys and semi-structured interviews conducted after the 12-month intervention (n = 30). New mechanisms and outcomes identified in the qualitative analysis were mapped onto existing items and scales (e.g. single items from the Short Sense of Competence Questionnaire) and re-analyzed quantitatively using general linear models.

RESULTS: The mixed methods analysis suggested that dementia caregivers in the RCTM group were more confident in their ability to obtain information about and arrange services (e.g. legal and financial planning, long-term care ombudsman) than controls and were less likely to report annoyance with care recipients' behaviors.

CONCLUSION: The mixed methods results advance our understanding of the RCTM's potential efficacy, and the adoption of similar methodologies may yield greater insights into how and why dementia care interventions are beneficial, even in the face of initial null findings.},
}

@article {pmid41711012,
year = {2026},
author = {Sheibani, N and Yadollahikhales, G and Simpkins, AN},
title = {Guidelines in Action: Cognitive Outcomes and Blood Pressure Control.},
journal = {Stroke},
volume = {},
number = {},
pages = {},
doi = {10.1161/STROKEAHA.125.053501},
pmid = {41711012},
issn = {1524-4628},
}

@article {pmid41710946,
year = {2026},
author = {Schwab, D and Hofmann, C and Justies, N and Dickerson, DS and Keshavarz, A and van Iersel, T and Martens, K and Bittner, B},
title = {Bioequivalence Between a Gantenerumab Disposable Syringe and an Autoinjector: A Randomized Controlled Trial in Healthy Volunteers.},
journal = {Clinical pharmacology in drug development},
volume = {15},
number = {2},
pages = {e70038},
doi = {10.1002/cpdd.70038},
pmid = {41710946},
issn = {2160-7648},
support = {//F. Hoffmann-La Roche/ ; },
mesh = {Humans ; Therapeutic Equivalency ; Male ; Female ; Adult ; Healthy Volunteers ; Syringes ; Middle Aged ; Injections, Subcutaneous ; Area Under Curve ; *Antibodies, Monoclonal, Humanized/administration & dosage/pharmacokinetics/adverse effects ; Young Adult ; Disposable Equipment ; },
abstract = {Gantenerumab, a monoclonal antibody targeting amyloid beta plaques in the brain, reduces plaque accumulation and was developed to slow Alzheimer's disease progression. Results from the pivotal GRADUATE I and II studies evaluating gantenerumab in people with early Alzheimer's disease were announced in 2022. The studies did not meet their primary endpoint of slowing clinical decline. This study evaluated the pharmacokinetics, immunogenicity, and safety of a high concentration liquid formulation of gantenerumab administered subcutaneously as a single dose using an autoinjector (AI) or a disposable syringe (DS). The DS was employed in pivotal clinical trials, while the AI was developed in parallel to ease SC administration. The study aimed to demonstrate bioequivalence (BE) between AI and DS administration in healthy participants, defined by 90% confidence intervals (CIs) for geometric least square (LS) mean ratios being within the 0.80-1.25 range for maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC). Among the 266 healthy participants, 135 received 255 mg gantenerumab via AI and 131 received 255 mg via DS in a parallel group design. BE between AI and DS SC administration was demonstrated with geometric LS mean ratios (90% CIs) for Cmax, AUC0-inf, and AUC0-last of 1.078 (1.006, 1.155), 1.053 (0.986, 1.124), and 1.054 (0.992, 1.121), respectively, all within the 0.80-1.25 BE range. Safety findings were consistent with the known safety profile of gantenerumab.},
}

Humans
Therapeutic Equivalency
Male
Female
Adult
Healthy Volunteers
Syringes
Middle Aged
Injections, Subcutaneous
Area Under Curve
*Antibodies, Monoclonal, Humanized/administration & dosage/pharmacokinetics/adverse effects
Young Adult
Disposable Equipment

@article {pmid41710892,
year = {2026},
author = {Peng, L and Zhang, Z and Hu, Y and Chen, H and Tian, Y and Ling, H},
title = {Regulating the crosstalk between Bifidobacterium and the brain: a potential therapeutic strategy for Alzheimer's disease.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1706811},
pmid = {41710892},
issn = {1664-3224},
mesh = {Humans ; *Alzheimer Disease/therapy/microbiology/metabolism ; *Bifidobacterium/physiology/immunology ; *Gastrointestinal Microbiome ; *Brain/metabolism/microbiology ; *Probiotics/therapeutic use ; Animals ; },
abstract = {Alzheimer's disease (AD) is a common dementia in the elderly population, typically manifested through symptoms of cognitive impairment (CI) and memory loss. Pathologically, it is characterized by abnormally elevated levels of amyloid-β (Aβ) deposition and tau phosphorylation. Given the rapid rate of population aging, many scientists are investigating AD, focusing on its pathogenic mechanisms and potential treatments. Unfortunately, to date, no highly effective therapeutic strategies have emerged. Intriguingly, multiple studies have revealed alterations in the gut microbiome of individuals with AD, suggesting it may serve as a novel avenue for investigating AD pathogenesis. Bifidobacterium, a pivotal probiotic in the gastrointestinal tract, is crucial in upholding the equilibrium of gut flora. Notably, marked deficiencies in Bifidobacterium have been observed in the guts of AD patients, underscoring the potential of further inquiry into the impact of Bifidobacteria on AD via the gut-microbe-brain axis. However, current research on the mechanisms through which Bifidobacteria can alleviate AD is limited, warranting further investigation. This review examines Bifidobacterial alterations in Alzheimer's disease patients and the underlying mechanisms, with the aim of evaluating their potential as a therapeutic strategy for Alzheimer's disease.},
}

Humans
*Alzheimer Disease/therapy/microbiology/metabolism
*Bifidobacterium/physiology/immunology
*Gastrointestinal Microbiome
*Brain/metabolism/microbiology
*Probiotics/therapeutic use
Animals

@article {pmid41710720,
year = {2026},
author = {Qiao, Y and Zhou, F and Mao, T and Gao, L},
title = {Revitalizing GIP: Therapeutic Potential in Metabolic and Neurodegenerative Disorders.},
journal = {Diabetes, metabolic syndrome and obesity : targets and therapy},
volume = {19},
number = {},
pages = {559587},
pmid = {41710720},
issn = {1178-7007},
abstract = {Glucose-dependent insulinotropic polypeptide (GIP), once the overlooked sibling of the incretin family, is now experiencing a research renaissance. Historically, its therapeutic development was hindered by a seemingly diminished insulinotropic effect in type 2 diabetes (T2DM), its paradoxical stimulation of glucagon during hyperglycemia, and translational gaps between rodent and human physiology. This review highlights the renewed interest in GIP, driven by a deeper understanding of its pleiotropic actions. GIP stimulates glucose-dependent insulin secretion and, uniquely, also stimulates glucagon secretion during hyperglycemia. Emerging evidence suggests this glucagon release may subsequently enhance insulin secretion through intra-islet α-β cell communication, revealing a more complex role in glucose homeostasis than previously appreciated. Beyond the pancreas, GIP promotes lipid storage in adipose tissue, reduces ectopic fat deposition, modulates bone remodeling, influences cardiovascular lipid metabolism, and exhibits neuroprotective properties. Preclinical and clinical studies indicate that GIP-based therapies can improve glycemic control, alleviate obesity-related inflammation, and enhance insulin sensitivity. Notably, GIP exhibits synergistic effects with GLP-1, exemplified by the dual receptor agonist Tirzepatide, which has demonstrated superior efficacy in clinical trials. Compared to the selective GLP-1 receptor agonist semaglutide (1 mg), the highest dose (15 mg) of tirzepatide achieved a greater reduction in glycated hemoglobin (-2.30 vs -1.86 percentage points) and body weight (an additional 5.5 kg reduction) over 40 weeks. Furthermore, GIP and its analogs show promise in ameliorating pathology and cognitive deficits in neurodegenerative models like Alzheimer's disease, suggesting a potential new therapeutic avenue for central nervous system disorders. This review synthesizes the evolving narrative of GIP from a challenging target to a multifaceted therapeutic agent and identifies key research gaps, particularly in understanding its tissue-specific signaling and optimizing its synergy within multi-agonist therapies for metabolic and neurodegenerative diseases.},
}

@article {pmid41710622,
year = {2026},
author = {Alsalhi, AA and Almazyad, FH and Alharbi, AZ and AlDhuwaihy, A and AlSulaim, YB},
title = {Evaluating the dementia risk associated with anesthesia and surgery: A comprehensive systematic review and meta-analysis.},
journal = {Saudi journal of anaesthesia},
volume = {20},
number = {1},
pages = {156-165},
pmid = {41710622},
issn = {1658-354X},
abstract = {Increasing global life expectancy has expanded the surgical population, raising concerns about postoperative outcomes. Dementia, especially Alzheimer's disease (AD), poses a significant public health challenge. This meta-analysis investigates anesthesia exposure and AD risk. Following PRISMA 2020 guidelines, we systematically searched five databases (2014-2022) for observational studies evaluating dementia risk in adults ≥60 years undergoing surgery with anesthesia. Two reviewers independently screened studies, extracted data, and assessed quality using the Newcastle-Ottawa Scale. Pooled odds ratios were calculated using a random-effects model, with subgroup and publication bias analyses conducted. Significant associations with dementia included hypertension (OR 1.36, 95% CI [1.16, 1.59]), hyperlipidemia (OR 1.19 [1.16, 1.22]), coronary artery disease (OR 2.45 [1.72, 3.50]), depression (OR 1.70 [1.27, 2.27]), and head injury (OR 1.31 [1.14, 1.51]). Subgroup analyses showed mixed results for age, surgery, and medication. Kidney-ureter-bladder surgery increased risk substantially (OR 2.52 [1.10, 5.76]). Publication bias was observed. No statistically significant association was found between general anesthesia and AD risk. However, significant heterogeneity, potential publication bias, inconsistent subgroups, and challenges in isolating anesthesia effects from surgery necessitate cautious interpretation. Large prospective cohort studies with standardized methods, adequate lag time, and rigorous confounder adjustments are imperative. Perioperative care optimization for older adults at risk of cognitive decline is clinically warranted.},
}

@article {pmid41710481,
year = {2026},
author = {Rizvi, SMO and Thakur, A and Sharma, S and Kaur, H and Kaur, S and Dan, P},
title = {Hydroxyapatite nanoparticles as a vehicle for drug delivery approach in Alzheimer's disease.},
journal = {3 Biotech},
volume = {16},
number = {3},
pages = {92},
pmid = {41710481},
issn = {2190-572X},
abstract = {Hydroxyapatite (HAp) nanoparticles are gaining attention as potential drug delivery systems for Alzheimer's Disease (AD) because of their compatibility with biological systems, stability, and adaptable surfaces. Their small size facilitates effective drug encapsulation and controlled release, while surface alterations with ligands or antibodies enable precise targeting of delivery to the blood-brain barrier (BBB) and to areas affected by amyloid-beta (Aβ) plaques and tau accumulations. HAp nanoparticles are capable of transporting anti-amyloid, anti-tau, and neuroprotective drugs, which increases therapeutic levels and reduces systemic adverse effects. Research shows that HAp nanoparticles can pass through the BBB using adsorptive-mediated and receptor-mediated transcytosis, and methods such as temporarily opening tight junctions or modifying surface charges can further improve their permeability. Drugs can be integrated via co-precipitation, adsorption, or encapsulation techniques, often allowing for pH-responsive release in the acidic environment of diseased brain tissue. Nevertheless, there are still obstacles to address regarding the scalability of production, stability and clearance in living organisms, and the long-term compatibility and safety in neural tissue.},
}

@article {pmid41710476,
year = {2026},
author = {Baghel, B and Purohit, P and Roy, B and Pareek, V and Sharma, S and Roy, PK},
title = {Enhanced neuroprotective ability of human cerebellum during ageing: the interplay of neuroplasticity, neurodegeneration and life-time trajectory-a pilot study.},
journal = {3 Biotech},
volume = {16},
number = {3},
pages = {89},
pmid = {41710476},
issn = {2190-572X},
abstract = {The neurodegenerative decline of brain with ageing is an acute global demographic problem, as elderly population surges worldwide. However, ageing effect has not been systematically studied for cerebellum, an autonomous part of brain having motor, cognition, language and memory functions. By magnetic resonance investigation, we study brain-ageing process: 177 normal subjects, aged 20-80, with focus on cerebellum, the first larger-scale analysis as we know. We found that for whole brain, both grey-matter/GM and white-matter/WM) volumes deceases with ageing (by ~ 15%). Contrastingly, these volumes remain unexpectedly stable in ageing cerebellum, indicating neuroprotective ability. To estimate neuroplasticity resilience of brain-tissue, we evaluated GM/WM interrelationship, assessed by GM-volume/WM axial-diffusivity. During ageing, the GM/WM interrelationship is comparatively stable in cerebellum, while in whole brain this relationship is much variable (230% increase). We validated the cerebellar neuroprotective ability by epigenetic tissue ageing analysis (DNA-methylation). Ageing retardation-level (years) of brain-tissue follows the neurodevelopmental caudal-rostral-rhinal axis: cerebellum (maximum retardation/neuroprotection), occipital, frontal, and temporal region (minimum). We log-normally plotted ageing-retardation against phylogenic age of that brain region (million-years ago/MYA), and found linear relationship, implying a quantitative evolutionary behaviour, indicating cerebellum's phylogenic antiquity (Cambrian-era ~ 510MYA), which adapted the cerebellum to withstand degenerative damage. Finally, we investigated cerebellum's neurocognitive resilience, enabling focussed development of coordination, tool-making and language, while present-day humans evolutionarily progressed over Neanderthals. We found that humans show maximal cerebellar expansion and depth. Of seminal significance is that cerebellum is a unique paradoxical brain region with peak neuroprotective behaviour, and may have substantial therapeutic rehabilitative biotechnological implications in neurodegenerative disorders.},
}

@article {pmid41710449,
year = {2026},
author = {MacLennan, RJ and Chapin, BA and Solberg, LM and Clark, DJ},
title = {Cognitive decline in U.S. military veterans: risk factors and clinical implications.},
journal = {Frontiers in dementia},
volume = {5},
number = {},
pages = {1704367},
pmid = {41710449},
issn = {2813-3919},
abstract = {Military veterans have higher aggregate prevalence of risk factors for cognitive decline than non-veterans. This includes risk factors like diabetes, chronic pain, smoking, depression, and more. The disparity in prevalences is due in part to the unique experiences and exposures of their military service. Alzheimer's disease and other dementias are debilitating diseases with large financial and logistical burdens. These burdens are held by the patient, their family, friends, and caregivers, as well as healthcare professionals, and healthcare systems. Standardized screening for these risk factors may be helpful for understanding risk profiles that lead to cognitive decline. Additionally, screening must occur early to encourage early intervention and behavioral modifications and to reduce these burdens. This perspective presents the prevalence of risk factors for cognitive decline in the Veteran and non-veteran populations and proposes an approach to managing risk factors in Veterans.},
}

@article {pmid41710299,
year = {2026},
author = {Anicin, L and Andjelic, S and Markovic Blagojevic, M and Bulaja, D and Zivkovic, M and Zivkovic, T and Antonijevic, M and Bacanin, N},
title = {Metaheuristic-driven dual-layer model for classifying Alzheimer's disease stages.},
journal = {Frontiers in computational neuroscience},
volume = {20},
number = {},
pages = {1731812},
pmid = {41710299},
issn = {1662-5188},
abstract = {INTRODUCTION: Accurate determination of the progression phase of Alzheimer's disease (AD) is crucial for timely clinical decision-making, improved patient management, and personalized therapeutic interventions. However, reliably distinguishing between multiple disease stages using neuroimaging data remains a challenging task.

METHODS: This study proposes an advanced machine learning framework for multi-stage AD classification using magnetic resonance imaging (MRI) data. The architecture follows a two-tier design. In the first stage, convolutional neural networks (CNNs) are employed to extract deep and discriminative feature representations from MRI images. In the second stage, these features are classified using ensemble learning models, specifically XGBoost and LightGBM. Metaheuristic optimization strategies are applied to further enhance model performance. The proposed framework was evaluated using a publicly available Alzheimer's disease dataset under three different experimental configurations.

RESULTS: Experimental results demonstrate that the proposed approach effectively addresses the multi-class classification problem across different AD progression stages. The optimized models achieved a maximum classification accuracy of 89.55%, indicating robust predictive performance and strong generalization capability.

DISCUSSION: To improve transparency and clinical relevance, explainable artificial intelligence (XAI) techniques were incorporated to interpret model predictions and highlight feature importance. The results provide meaningful insights into neuroimaging biomarkers associated with AD progression and support the development of more interpretable and trustworthy diagnostic systems. Overall, the proposed framework contributes to improved data-driven decision support and offers a promising direction for future Alzheimer's disease diagnosis and staging research.},
}

@article {pmid41710159,
year = {2026},
author = {Pang, Y and Yang, J and Liu, J and Xie, Z and Wang, J},
title = {Metabolic interactions in the brain: the crucial roles of neurons, astrocytes, and microglia in health and disease.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1731771},
pmid = {41710159},
issn = {1662-4548},
abstract = {This review provides an in-depth exploration of the intricate energy metabolism pathways within the brain, with a particular focus on the dynamic interplay between neurons, astrocytes, and microglia. Neurons, with their high energy demands, primarily rely on oxidative phosphorylation and the tricarboxylic acid (TCA) cycle to sustain synaptic activity and neurotransmitter synthesis. In contrast, astrocytes predominantly engage in glycolysis, producing lactate and glutathione, which are essential for supporting neuronal function and protecting against oxidative stress. Additionally, microglia, the brain's resident immune cells, exhibit a metabolic flexibility that allows them to shift between oxidative phosphorylation and glycolysis, depending on their activation state, which significantly influences neuroinflammation and synaptic plasticity. The review highlights the critical role of astrocyte-neuron metabolic coupling, particularly through the lactate shuttle and glutathione metabolism, in maintaining neuronal homeostasis and facilitating synaptic function. It also delves into the metabolic underpinnings of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis, illustrating how disruptions in brain energy metabolism contribute to disease progression. By synthesizing recent findings, this review not only underscores the centrality of brain energy metabolism in both normal and pathological conditions but also identifies potential therapeutic targets aimed at modulating these metabolic pathways to mitigate the effects of neurodegenerative disorders. This comprehensive analysis offers valuable insights that could propel further research and innovation in the field of neurology, making it essential reading for experts interested in the molecular mechanisms underlying brain function and disease.},
}

@article {pmid41710117,
year = {2026},
author = {Sergio, J and Price, A and Snyder, PJ and Doster, SA and Durkin, M and Strenger, JR and Thompson, LI and Stradtman, M and Sinoff, S and Alber, J},
title = {The Relationship Between Gait Task Performance and Plasma Biomarkers for Alzheimer's Disease in Cognitively Unimpaired Older Adults and Patients with Mild Cognitive Impairment.},
journal = {Clinical interventions in aging},
volume = {21},
number = {},
pages = {562194},
pmid = {41710117},
issn = {1178-1998},
mesh = {Humans ; Aged ; *Alzheimer Disease/blood/diagnosis/genetics/physiopathology ; *Cognitive Dysfunction/blood/physiopathology/genetics ; Male ; Female ; Biomarkers/blood ; Aged, 80 and over ; *Gait/physiology ; Middle Aged ; Genotype ; Apolipoproteins E/genetics ; Task Performance and Analysis ; },
abstract = {PURPOSE: The Timed Up and Go (TUG) is a 20-foot gait assessment, with TUG-dual task (DT) serial subtractions to determine dual-task cost. Alzheimer's disease (AD) risk is established using plasma biomarkers and APOE genotyping.

METHODS: We investigated: 1) TUG/TUG-DT differences between AD low-risk cognitively unimpaired (CU) older adults (N = 74), AD high-risk CU older adults (N = 87), and mild cognitively impaired (MCI) older adults (N = 33) and 2) the relationship between TUG/TUG-DT performance and plasma biomarkers. One hundred and ninety-four older adults ages 55-80 completed TUG/TUG-DT, a fasting blood draw, and APOE genotyping. Scores on the Clinical Dementia Rating Scale (CU = 0; CI = ≥0.5) and Montreal Cognitive Assessment (CU ≥ 24; CI = ≤23) determined whether participants were placed into the CU low-risk, CU high-risk, or MCI groups. Risk level for CU participants were assessed by APOE genotyping. Those participants who carried at least one copy of the APOE ε4 allele were designated to the high-risk group (n = 87). Participants with no APOE ε4 allele were assigned to the low-risk group (n = 75).

RESULTS: MCI participants took longer to perform the TUG than CU participants (p < 0.001). CU high-risk and MCI group performed similarly on step counts, while the CU low-risk took significantly fewer steps (p<0.001). Speed predicted whether someone was below an AD-risk threshold for pTau217 in CU participants (n = 150). Exploratory generalized additive models showed plasma biomarkers predicted gait metrics in CU groups.

CONCLUSION: Step count may be more sensitive, compared to speed alone, in identifying those in preclinical AD stages. Gait metrics (speed and efficiency) played a key role as a clinical manifestation of early AD pathophysiology determined by blood-based biomarker concentration. Combining these assessments offers a multidimensional, cost-effective approach for preclinical-AD screening and potential early intervention.},
}

Humans
Aged
*Alzheimer Disease/blood/diagnosis/genetics/physiopathology
*Cognitive Dysfunction/blood/physiopathology/genetics
Male
Female
Biomarkers/blood
Aged, 80 and over
*Gait/physiology
Middle Aged
Genotype
Apolipoproteins E/genetics
Task Performance and Analysis

@article {pmid41710069,
year = {2026},
author = {Pronk, NP and Wang, S and Woodard, C and Bhatt, T and Arena, R},
title = {Multilevel prediction of Alzheimer's disease dementia in the United States: An artificial intelligence analysis.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70274},
pmid = {41710069},
issn = {2352-8729},
abstract = {INTRODUCTION: Variables predicting Alzheimer's disease (AD) are not limited to individual-level risk factors. The purpose of this investigation is to assess multilevel predictors of AD prevalence.

METHODS: US county-level datasets incorporating 45 predictor variables were analyzed cross-sectionally using artificial intelligence analytical methods. A Light Gradient-Boosting Machine model was trained to predict county-level AD after which model performance and feature importance were evaluated.

RESULTS: The final model retained 20 features and explained 75% (R [2] = 0.75) of the variance in AD prevalence. Racial and ethnic minority status showed the highest importance value (0.848), far exceeding all other features (e.g., poor sleep ranked second with importance value of 0.153).

DISCUSSION: This study confirmed upstream factors as being significant predictors of AD prevalence and racial and ethnic minority status as being the most important. From a policy perspective, efforts to reduce population levels of AD prevalence should consider addressing racial and ethnic disparities.},
}