@article {pmid41703264,
year = {2026},
author = {Ma, Y and Li, Y and Wu, G and Liu, L and Tian, M and Han, X and Chen, X and Xuan, X and Zheng, T and Gao, X and Xia, Q and Li, F and Wang, D},
title = {Protective mutations associated with APOE in Alzheimer's disease.},
journal = {Molecular psychiatry},
volume = {},
number = {},
pages = {},
pmid = {41703264},
issn = {1476-5578},
abstract = {Alzheimer' s disease (AD) is a progressive neurodegenerative disorder characterized by a spectrum of cognitive impairments, ranging from mild memory loss to severe cognitive decline and, ultimately, death. The global incidence of AD is projected to increase significantly, with late-onset AD being predominantly sporadic in nature. Over the past three decades, the Apolipoprotein E (APOE) gene has been recognized as the most important single genetic determinant of sporadic AD risk. The APOE4 allele is a major risk factor for AD and is known to exacerbate the pathological process for AD. Identifying protective variants that may reduce the risk or delay the onset of AD is of great significance for the development of effective treatments. This review comprehensively examines the protective effects of APOE and its related protective mutations. It also explores the impact of these unique protective variants at the cellular level during the pathological progression of AD. Furthermore, the review compiles new insights for AD treatment offered by these protective mutations, exploring the potential applications of APOE and its related protective variants in advanced therapeutic strategies, including gene editing, RNA editing, and stem cell therapy.},
}

@article {pmid41703146,
year = {2026},
author = {Yuste, MT and Badillo, E and Galecio, JS and Marín, P},
title = {Selective oestrogen receptor modulators and Alzheimer´s disease: a real-world pharmacovigilance study.},
journal = {European journal of clinical pharmacology},
volume = {82},
number = {3},
pages = {81},
pmid = {41703146},
issn = {1432-1041},
}

@article {pmid41702724,
year = {2026},
author = {Groshkov, AA and Kolotyeva, NA and Tregub, PP and Zhdankina, VI and Komleva, YK and Salmina, AB and Illarioshkin, SN},
title = {Diagnostics of Synucleinopathies by Protein Amplification Methods: Methodological and Bibliometric Analysis.},
journal = {Biochemistry. Biokhimiia},
volume = {91},
number = {1},
pages = {1-16},
doi = {10.1134/S000629792560214X},
pmid = {41702724},
issn = {1608-3040},
mesh = {Humans ; Bibliometrics ; *Synucleinopathies/diagnosis/metabolism ; *alpha-Synuclein/metabolism/analysis ; },
abstract = {Early preclinical diagnostics of neurodegenerative diseases (synucleinopathies, Alzheimer's disease, etc.) can be achieved through the detection of pathological amyloid aggregates in biological fluids. Protein amplification methods (PMCA, RT-QuIC) have become promising diagnostic tools by offering high sensitivity and specificity for detecting α-synuclein oligomers at the early disease stages and studying the fibril formation kinetics and mechanisms of amyloid aggregation. However, these methods have several significant limitations, as they are technically complex and time-consuming and lack standardized protocols, control samples, and substrates. Despite these challenges, protein amplification methods hold potential as the most productive, accessible, and standardizable diagnostic approaches in synucleinopathies. This review presents the results of bibliometric analysis of publications on the use of protein amplification methods in the diagnostics of synucleinopathies. We also provide a comparative analysis of common RT-QuIC protocols, with special focus on the method principles, approaches for its optimization, types of biological materials, key factors influencing the sensitivity and specificity of this technique, and areas for its improvement.},
}

Humans
Bibliometrics
*Synucleinopathies/diagnosis/metabolism
*alpha-Synuclein/metabolism/analysis

@article {pmid41702720,
year = {2026},
author = {Blankenship, HE and Higgs, MH and Harold, KM and Humphries, KM and Beckstead, MJ},
title = {Alzheimer's pathology enhances excitatory synaptic input and integration in VTA dopamine neurons.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1523/JNEUROSCI.2085-25.2026},
pmid = {41702720},
issn = {1529-2401},
abstract = {In Alzheimer's disease (AD) models, ventral tegmental area (VTA) dopamine neurons are intrinsically hyperexcitable, yet release less dopamine and exhibit dysfunctional downstream signaling. Synaptic transmission is broadly disrupted in AD, but it is not known to what extent excitatory and inhibitory inputs to the VTA are altered. Here we describe enhanced synaptic excitation in dopamine neurons from male and female 3xTg-AD mice (an amyloid + tau-driven model). AMPAR-mediated excitatory input was enhanced in a subset of connections, while GABAAR-mediated inhibition decreased as a function of dendritic atrophy. Protein phosphorylation analysis and pharmacology suggested that strengthened excitation depends on both presynaptic protein kinase C activity and postsynaptic enhancement of perisomatic AMPA receptor currents. Biophysical modeling predicted that enhanced excitatory synaptic input in 3xTg-AD dopamine neurons, combined with altered dendritic morphology and intrinsic hypersensitivity, produces increased firing and a steeper input-output relationship. These results suggest that AD pathology is associated with increased sensitivity of single dopamine neurons, which may serve to maintain phasic dopamine signaling in early stages of degeneration.Significance Statement While recent studies describe a suspected role for VTA dopamine neurons in Alzheimer's disease, the influence of excitatory and inhibitory input as well as single neuron morphology is not known. Using single-cell patch-clamp electrophysiology we find that 3xTg-AD dopamine neurons receive enhanced glutamatergic synaptic input and reduced inhibitory GABA input, thus tipping the balance further toward excitation. By combining this with morphological reconstructions, multicompartmental biophysical modeling, and past findings of intrinsic hypersensitivity, we predict that synaptic changes drive increased burst firing and convey a steeper input-output relationship in 3xTg neurons. These modifications likely alter downstream signaling or serve as a compensatory protective mechanism in the face of degenerative pathology in AD.},
}

@article {pmid41702711,
year = {2026},
author = {Michalon, R and Planche, V and Lemoine, M and Keuck, L and Villain, N},
title = {Defining Alzheimer's disease: stipulations and the ethics of diagnostic change.},
journal = {Journal of neurology, neurosurgery, and psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1136/jnnp-2025-337832},
pmid = {41702711},
issn = {1468-330X},
}

@article {pmid41702507,
year = {2026},
author = {Yan, C and Kong, Z and Pan, Y and Fu, Z and Han, K and Zhao, X and Zhang, J and Bo, L and Sun, W and Gao, J and Dong, X and Zheng, Z and Yue, X and Sun, P and Jiang, X and Chen, C},
title = {Anti-CLEC7A nanobody in situ engineering promotes amyloid-β oligomers clearance by CAR-microglia to alleviate Alzheimer's disease pathology in mice.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {114710},
doi = {10.1016/j.jconrel.2026.114710},
pmid = {41702507},
issn = {1873-4995},
abstract = {Chimeric antigen receptor microglia (CAR-M)-mediated amyloid-β oligomers (AβO) phagocytosis shows great promise in Alzheimer's disease (AD) treatment, however, the limited AβO degradation of CAR-M compromises their anti-AβO potency. This work here reports an in situ engineered agonistic anti-C-type lectin domain containing 7 A (CLEC7A) nanobody to accelerate AβO degradation of CAR-M, augmenting their anti-AβO efficacy. Specifically, with the intranasal-delivered microglia-targeting lipid nanoparticles (LNP), this work generates an AβO-specific degradation-potentiated CAR-M by introducing dual mRNAs encoding AβO-specific CAR and anti-CLEC7A nanobody into the cerebral microglia. These data show that these engineered CAR-M exhibited superior phagocytic function and promoted intracellular AβO degradation via activating CLEC7A-spleen tyrosine kinase (SYK) signaling pathway through the local secretion of anti-CLEC7A nanobody. In the APP/PS1 mouse model of AD, these in situ reprogrammed CAR-M significantly reduced cerebral Aβ levels, suppressed neuroinflammation, and restored cognitive function. In sum, these findings demonstrate that potentiating AβO degradation within CAR-M effectively alleviates AD pathology, providing a promising therapeutic strategy for AD with broad application in other neurodegenerative diseases.},
}

@article {pmid41702369,
year = {2026},
author = {Travers-Lesage, V and Crouzier, L and Antonijevic, M and Wang, A and Toublet, FX and Davis, A and Modeste, F and Brazzolotto, X and Nachon, F and Since, M and Maurice, T and Rochais, C and Dallemagne, P},
title = {Access to novel potent pleiotropic prodrugs, targeting both butyrylcholinesterase and serotonin reuptake, with anti-amnesic activities in Alzheimer's disease model.},
journal = {European journal of medicinal chemistry},
volume = {307},
number = {},
pages = {118670},
doi = {10.1016/j.ejmech.2026.118670},
pmid = {41702369},
issn = {1768-3254},
abstract = {The treatment of Alzheimer's disease should undoubtedly be multifactorial and require a polypharmacological approach to be effective. Pleiotropic prodrugs can release, upon inhibition of a primary target, a drug that targets a second protein of therapeutic interest. Here, we describe the design of prodrugs that release a potent serotonin reuptake inhibitor, 7-hydroxysertraline, upon the inhibition of butyrylcholinesterase. Indeed, 7-hydroxysertraline is not only a ligand of the serotonin transporter but also possesses the structural requirements to yield carbamates, able to bind to the catalytic site of butyrylcholinesterase and undergo its carbamylation. This behavior could result in a pseudo-irreversible inhibition of butyrylcholinesterase, followed by release of the serotonin reuptake inhibitor. Several carbamates of 7-hydroxysertraline were synthesized and evaluated in vitro for their acetyl- and butyrylcholinesterase inhibitory activities and their affinity for the serotonin transporter. Structure-activity relationships were then established based on a molecular modelling study. Investigations into cholinesterase inhibition kinetics have been conducted, resulting in the selection of two prodrugs for in vivo evaluation in an Alzheimer's disease mouse model. One of these, compound 8e, provided complete protection against short- and long-term memory deficits induced by intracerebroventricular administration of β-amyloid oligomers. This makes compound 8e a promising candidate for preclinical development as a possible treatment for Alzheimer's disease.},
}

@article {pmid41702332,
year = {2026},
author = {Messak, M and Abdelmageed, A and Khattab, YA and Altalab, G and Mandour, Y and Shaker, O},
title = {α-synuclein monoclonal antibodies in Parkinson's disease: A failed promise or unmet potential?.},
journal = {Journal of the neurological sciences},
volume = {482},
number = {},
pages = {125806},
doi = {10.1016/j.jns.2026.125806},
pmid = {41702332},
issn = {1878-5883},
abstract = {BACKGROUND: Monoclonal antibodies (mAbs) have shown disappointing results in targeting α-synuclein (α-Syn) aggregates in PD, leading us to question whether this therapeutic approach is fundamentally flawed or unrealized potential awaiting better application. This review aims to assess the current evidence, identify key challenges hindering this therapeutic approach, and highlight priorities for future research.

METHODS: A narrative review of the literature was conducted focusing on available evidence with respect to safety, efficacy, pharmacokinetics, CNS exposure, peripheral and central target engagement, emerging biomarkers and PET scan imaging tracers, and lessons from immunotherapy development in Alzheimer's disease.

FINDINGS: Five RCTs, three phase-I and two phase-II trials, testing three different forms of mAb (n = 786) were identified. All studies showed that mAbs were generally safe. They demonstrated low but measurable CSF mAb concentration (CSF:Serum = 0.2-0.5%) with limited evidence regarding central target engagement. Phase-II trials failed to meet their primary efficacy endpoints and showed no significant slowing of disease progression (Cinpanemab 250 mg P-value = 0.7, 1250 mg P-value = 0.78, 3500 mg P-value = 0.7; Prasinezumab 1500 mg P-value = 0.24, 4500 mg P-value = 0.72). These disappointing results are attributed to several factors, including late timing of intervention, poor BBB permeability, heterogeneity in α-Syn pathology, not using sensitive tools to detect central target engagement and Delayed PET scan tracers' development.

CONCLUSION: Although there is strong preclinical evidence supporting the efficacy of mAb in PD, several limitations prevent this from translating into tangible clinical benefit. These limitations do not necessarily indicate a fundamental flaw in the therapeutic concept, but they do highlight the urgent need for future research to prioritize addressing these limitations.},
}

@article {pmid41702051,
year = {2026},
author = {Bartley, MM and St Sauver, JL and Schroeder, DR and Khera, N and Griffin, JM},
title = {Social Determinants of Health and Research Participation Among People Living With Mild Cognitive Impairment and Dementia.},
journal = {Journal of applied gerontology : the official journal of the Southern Gerontological Society},
volume = {},
number = {},
pages = {7334648261425294},
doi = {10.1177/07334648261425294},
pmid = {41702051},
issn = {1552-4523},
abstract = {IntroductionPeople most likely to be affected by Alzheimer's disease and related dementias (ADRD) are underrepresented in clinical research. Identifying and addressing factors which may influence their research participation is important to advance science and promote diversity. We examined the influence of social determinants of health (SDOH) on research participation among people living with ADRD.MethodsWe included those age 55 years and older living with ADRD, followed in our community practice in Rochester, Minnesota, who completed a questionnaire assessing SDOH and had at least one clinic visit between June 1, 2019 and June 1, 2020. Demographic and SDOH factors were examined by research participation.ResultsAmong 3273 people included, research participation was low overall (265/3273; 8.1%). People participating in research were more likely to be socially integrated and of higher educational attainment (p < 0.05).ConclusionPromoting social interaction is a potential area for focus to increase research participation in at risk populations.},
}

@article {pmid41701880,
year = {2026},
author = {Zhang, L and Li, L and Wang, X and Ma, L and Yan, L and Xiang, Q and Cui, Y and Liu, Z},
title = {Neuroinflammation and Cellular Senescence in Brain Aging and Neurodegeneration.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.1538},
pmid = {41701880},
issn = {2152-5250},
abstract = {Against the backdrop of a rapidly aging global population, the incidence of neurodegenerative diseases such as Alzheimer's and Parkinson's continues to rise, imposing a severe socioeconomic burden. Neuroinflammation is recognized as the core mechanism linking physiological brain aging to pathological cognitive decline. This paper aims to systematically elucidate the multi-level activation mechanisms of neuroinflammation during aging and comprehensively evaluate drug intervention strategies targeting this process. Research reveals that the chronicity of neuroinflammation is driven by multiple cellular and molecular events. At the cellular level, aging and dysfunction in microglia and astrocytes lead to their respective transitions toward pro-inflammatory M1 and neurotoxic A1 phenotypes. These changes interact synergistically with blood-brain barrier dysfunction, peripheral immune cell infiltration, and abnormal aggregation of pathological proteins like Aβ and α-synuclein, forming a vicious cycle. At the molecular level, signaling pathways including NLRP3 inflammasome, NF-κB, and JAK/STAT are persistently activated, while epigenetic modifications play crucial regulatory roles. Addressing these mechanisms, this review systematically examines six major intervention strategies: modulating neuroimmune cell function, inhibiting core inflammatory pathways, targeting inflammatory mediators like cytokines, employing senolytics to clear senescent cells, enhancing endogenous anti-inflammatory defenses, and exploring multi-target natural products and drug repurposing. Research indicates that targeting neuroinflammation offers a highly promising new avenue for delaying brain aging and related diseases. However, this field still faces numerous challenges, including target specificity, blood-brain barrier delivery, individual heterogeneity, and difficulties in clinical translation. Future breakthroughs will depend on more precise drug design, innovative delivery technologies, biomarker development, and interdisciplinary collaborative research.},
}

@article {pmid41701875,
year = {2026},
author = {Li, M and Wang, H and Tang, Z and Yang, S and Lin, L},
title = {Dysregulated Lipid Metabolism and Neurovascular Unit Dysfunction: Novel Mechanisms Linking Alzheimer's Disease and Vascular Dementia.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.1464},
pmid = {41701875},
issn = {2152-5250},
abstract = {The neurovascular unit (NVU) represents a multicellular functional ensemble pivotal to the preservation of cerebral homeostasis, encompassing endothelial cells, pericytes, glial cells (astrocytes, microglia, oligodendrocytes), and neurons. This complex orchestrates the regulation of blood-brain barrier (BBB) integrity, cerebral blood flow (CBF), and the metabolic microenvironment requisite for neuronal viability and functional competence. Accumulating lines of evidence have underscored that NVU dysfunction constitutes a critical early pathological event in neurodegenerative disorders, including Alzheimer's disease (AD) and vascular dementia (VaD). The present review summarizes the structural composition and core physiological functionalities of the NVU, with particular emphasis on the emerging role of lipid metabolism dysregulation in mediating NVU impairment-an aberrant process encompassing lipid droplets, apolipoprotein E (APOE), ATPase phospholipid transporting 11B (ATP11B), triggering receptor expressed on myeloid cells 2 (TREM2), and ATP-binding cassette (ABC) transporters. We further delineate the mechanisms by which disrupted lipid homeostasis elicits neuroinflammation, amplifies oxidative stress, impairs amyloid-β (Aβ) clearance, and precipitates BBB breakdown, ultimately culminating in cognitive decline. Simultaneously, this review examines controversies within the field, such as the specific role of apolipoprotein E ε4 allele (APOE4) in disease and highlights the significant pathophysiological differences between preclinical animal models and human diseases. Therapeutic strategies targeting lipid metabolism or the blood-brain barrier still face considerable challenges in clinical translation. Meanwhile, emerging tools such as lipidomics contribute to systematically analyzing the associated dysregulated lipid networks, thereby aiding in the identification of novel therapeutic targets.},
}

@article {pmid41701873,
year = {2026},
author = {Hong, J and Liu, Y and Peng, Q and Mei, Z and Wang, G},
title = {Cuproptosis and Aging: Molecular Mechanisms and Therapeutic Implications.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.1305},
pmid = {41701873},
issn = {2152-5250},
abstract = {With the accelerated pace of global population aging, the number of people suffering from age-related diseases is increasing, posing a serious threat to human health and well-being. Age-related diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), hypertension, atherosclerosis, type 2 diabetes (T2DM), and osteoporosis (OP), are often characterized by physiological function decline and metabolic disorders caused by aging, among which dysregulation of metal ion homeostasis, especially copper homeostasis imbalance, has emerged as a major factor. Copper is an essential enzymatic cofactor whose homeostasis is tightly regulated at systemic, cellular, and subcellular levels. However, during the aging process, the balance between copper uptake and efflux becomes compromised, alongside a reduction in cellular copper-buffering capacity. These alterations may lead to the loss of copper homeostasis and induce cuproptosis, which is a recently elucidated form of regulated cell death (RCD) triggered by copper overload and disrupts mitochondrial metabolism by promoting the aggregation of lipoylated proteins in the tricarboxylic acid cycle (TCA) and destabilizing respiratory chain complexes. Copper homeostasis imbalance and the resulting cuproptosis accelerate the aging process by promoting molecular mechanisms, including telomere attrition, mitochondrial dysfunction, oxidative stress, proteostasis imbalance, epigenetic changes, and chronic inflammation. This review focuses on the reciprocal interactions between aging and copper homeostasis: it elucidates how aging impairs copper homeostatic regulation, and how dysregulated copper metabolism and subsequent cuproptosis accelerate aging and exacerbate age-related diseases. Furthermore, it explores potential therapeutic strategies targeting copper homeostasis and cuproptosis to treat age-related diseases.},
}

@article {pmid41701839,
year = {2026},
author = {Chen, J and Xu, M and Liu, Y and Hadi, F and Xue, S and Chien, S and Zhong, S},
title = {RNA-binding activity of PHGDH drives amyloid-beta production in a human brain organoid model of sporadic Alzheimer's disease.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {8},
pages = {e2532234123},
doi = {10.1073/pnas.2532234123},
pmid = {41701839},
issn = {1091-6490},
support = {DP1DK126138//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; R01GM138852//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01HD107206//HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/ ; F32AG094189//HHS | NIH | National Institute on Aging (NIA)/ ; },
mesh = {*Alzheimer Disease/metabolism/pathology/genetics ; Humans ; *Amyloid beta-Peptides/metabolism/biosynthesis ; *Organoids/metabolism/pathology ; Animals ; *Brain/metabolism/pathology ; Mice ; Amyloid Precursor Protein Secretases/metabolism/genetics ; *Phosphoglycerate Dehydrogenase/metabolism/genetics ; Aspartic Acid Endopeptidases/metabolism/genetics ; eIF-2 Kinase/metabolism/genetics ; Neurons/metabolism ; 3' Untranslated Regions ; Disease Models, Animal ; Eukaryotic Initiation Factor-2/metabolism/genetics ; *RNA-Binding Proteins/metabolism ; Phosphorylation ; Astrocytes/metabolism ; },
abstract = {Pathological progression in sporadic Alzheimer's disease (sAD) initiates with an early rise in soluble amyloid-β (Aβ), preceding plaque formation and neurodegeneration. However, the molecular event triggering this initial accumulation remains unknown. We report that phosphoglycerate dehydrogenase (PHGDH), a consistent biomarker of prodromal sAD, drives Aβ production through a previously unrecognized RNA-binding function. Specifically, PHGDH binds the 3'UTR of EIF2AK1 mRNA, enabling the physical interaction between PHGDH and the EIF2AK1 protein. By facilitating the recruitment of EIF2AK1 to its substrate EIF2α, this complex drives EIF2α phosphorylation, thereby selectively promoting the translation of BACE1, the rate-limiting enzyme for Aβ generation. We demonstrate that PHGDH overexpression elevates BACE1 protein and intracellular Aβ in neurons and astrocytes across mouse models and human brain organoids, independent of its canonical enzymatic or transcriptional roles. Mechanistically, this process requires a specific RNA-binding surface within PHGDH and the EIF2AK1 3'UTR. These findings define a PHGDH-EIF2AK1-EIF2α-BACE1 axis as a key driver of the earliest amyloid pathology in sAD.},
}

*Alzheimer Disease/metabolism/pathology/genetics
Humans
*Amyloid beta-Peptides/metabolism/biosynthesis
*Organoids/metabolism/pathology
Animals
*Brain/metabolism/pathology
Mice
Amyloid Precursor Protein Secretases/metabolism/genetics
*Phosphoglycerate Dehydrogenase/metabolism/genetics
Aspartic Acid Endopeptidases/metabolism/genetics
eIF-2 Kinase/metabolism/genetics
Neurons/metabolism
3' Untranslated Regions
Disease Models, Animal
Eukaryotic Initiation Factor-2/metabolism/genetics
*RNA-Binding Proteins/metabolism
Phosphorylation
Astrocytes/metabolism

@article {pmid41701791,
year = {2026},
author = {Kittle, KR and Cicero, EC and Pelkmans, J and Flatt, JD and Anderson, JG},
title = {Health of Bi+ Dementia Caregivers: Moderation Effects of Minority and Caregiving Stress.},
journal = {American journal of Alzheimer's disease and other dementias},
volume = {41},
number = {},
pages = {15333175251415106},
doi = {10.1177/15333175251415106},
pmid = {41701791},
issn = {1938-2731},
mesh = {Humans ; *Caregivers/psychology/statistics & numerical data ; Male ; Female ; *Stress, Psychological/psychology ; *Dementia/nursing ; Cross-Sectional Studies ; Middle Aged ; *Sexual and Gender Minorities/psychology/statistics & numerical data ; *Quality of Life/psychology ; Aged ; *Health Status ; Adult ; },
abstract = {Despite comprising the largest segment of the sexual minority population and experiencing unique stressors and health disparities, bi+ dementia caregivers remain underrepresented in health and caregiving research. This secondary analysis of cross-sectional survey data from LGBTQ+ dementia caregivers (bi+, n = 125; gay[g]/lesbian[l], n = 161) examined whether associations between minority and caregiving stressors and global health differed by caregiver group. Bi+ caregivers reported significantly higher minority stress and lower family quality of life but better health than g/l caregivers. Moderation analyses revealed: higher perceived stress predicted worse health for bi+ but better health for g/l; higher family quality of life predicted better health for both groups, with a stronger effect among bi+ caregivers; and more lifetime discrimination predicted worse health for both groups, with a stronger effect among bi+ caregivers. Results underscore the need for inclusive, affirming research and interventions addressing bi+ caregiver stress experiences.},
}

Humans
*Caregivers/psychology/statistics & numerical data
Male
Female
*Stress, Psychological/psychology
*Dementia/nursing
Cross-Sectional Studies
Middle Aged
*Sexual and Gender Minorities/psychology/statistics & numerical data
*Quality of Life/psychology
Aged
*Health Status
Adult

@article {pmid41701728,
year = {2026},
author = {Morita, K and Ihashi, S and Okamura, E and Goto, K and Yoshihara, T and Honda, A and Ema, M and Asano, M},
title = {Highly efficient production of transgenic rats with long DNA insertions using piggyBac transposase mRNA and piezo-assisted microinjection.},
journal = {PloS one},
volume = {21},
number = {2},
pages = {e0339406},
doi = {10.1371/journal.pone.0339406},
pmid = {41701728},
issn = {1932-6203},
mesh = {Animals ; *Microinjections/methods ; *Transposases/genetics/metabolism ; Rats ; Rats, Transgenic ; *RNA, Messenger/genetics ; Female ; Zygote/metabolism ; Male ; Transgenes ; *DNA/genetics ; },
abstract = {In the conventional method of producing transgenic (Tg) animals, donor DNA is microinjected into the pronuclei of zygotes using a sharp glass needle. However, this approach is generally inefficient as it requires highly skilled microinjection techniques to ensure zygote survival and the transgene is incorporated into only a small proportion of the offspring. In contrast, methods based on piggyBac transposase (PBase) enables more efficient insertion of DNA into the genome and generation of Tg animals. The use of piggyBac transposase have also been examined in rats→ However, this method has not yet been fully optimized or properly characterized. In this study, we examined the microinjection of PBase mRNA and donor plasmid DNA into the pronuclei of rat zygotes using piezo-assisted microinjection. This approach resulted in high survival rates and enabled the efficient generation of Tg rats, even with long donor DNA. When the zygotes were microinjected using Piezo, over 70% were viable, and after embryo transfer, over 80% of the pups carried the transgene. Furthermore, we confirmed germline transmission to the F1 and F2 generations. We also attempted to generate a rat model of Alzheimer's using this method→ However, the protein was not detected despite mRNA expression, and the phenotype was not observed in behavioral tests. Although the generation of Alzheimer's disease model remains a challenge, our findings show that piggyBac transposase mRNA combined with piezo-assisted microinjection represents a simple and efficient method for producing Tg rats, even with long donor DNA.},
}

Animals
*Microinjections/methods
*Transposases/genetics/metabolism
Rats
Rats, Transgenic
*RNA, Messenger/genetics
Female
Zygote/metabolism
Male
Transgenes
*DNA/genetics

@article {pmid41701723,
year = {2026},
author = {Li, R and Jiang, S and Pi, Z and Chen, G},
title = {Early diagnosis of Alzheimer's Disease: Graph theoretical analysis of cerebellar network features based on 18F-AV45 PET.},
journal = {PloS one},
volume = {21},
number = {2},
pages = {e0342738},
doi = {10.1371/journal.pone.0342738},
pmid = {41701723},
issn = {1932-6203},
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/diagnosis ; *Positron-Emission Tomography/methods ; Male ; Aged ; Female ; *Cerebellum/diagnostic imaging/pathology ; Early Diagnosis ; Cognitive Dysfunction/diagnostic imaging ; *Ethylene Glycols ; Aged, 80 and over ; Aniline Compounds ; Plaque, Amyloid/diagnostic imaging/pathology ; Machine Learning ; },
abstract = {Pathological and neuroimaging changes in the cerebellum of Alzheimer's disease (AD) patients have been well documented. However, the changes in cerebellar amyloid plaque deposition connectivity networks during AD progression based on positron emission tomography (PET) imaging remain unclear. We selected 18F-florbetapir PET (18F-AV45 PET) imaging data from the Alzheimer's disease neuroimaging initiative (ADNI) dataset (n = 612) and employed graph theoretical analysis to examine amyloid plaque deposition connectivity, comparing the connectivity differences across cognitively normal (CN), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and AD groups. In addition, we combined graph theoretical features with the standardized uptake value ratio (SUVR) of regions of interest and applied them to machine learning models for the early diagnosis of AD. As cognitive decline progressed, significant changes in cerebellar network connectivity were observed across groups. Regarding local connectivity, changes in betweenness centrality were evident in multiple cerebellar regions at different cognitive stages. Cerebellar amyloid networks revealed early changes in amyloid plaque deposition connectivity. The machine learning model achieved an area under the curve (AUC) of 0.950 for distinguishing AD from CN, 0.995 for CN vs. EMCI, 0.964 for EMCI vs. LMCI and 0.632 for LMCI vs. AD. These findings provide new insights into the cerebellar pathological features of AD and highlight the potential of this approach for early identification and prediction of AD progression.},
}

Humans
*Alzheimer Disease/diagnostic imaging/diagnosis
*Positron-Emission Tomography/methods
Male
Aged
Female
*Cerebellum/diagnostic imaging/pathology
Early Diagnosis
Cognitive Dysfunction/diagnostic imaging
*Ethylene Glycols
Aged, 80 and over
Aniline Compounds
Plaque, Amyloid/diagnostic imaging/pathology
Machine Learning

@article {pmid41701678,
year = {2026},
author = {Deng, Y and Liu, Y and Hao, H and Xu, K and Zhu, Q and Li, H and Ma, T and Steenland, K},
title = {The role of comorbidities in the associations between air pollution and Alzheimer's disease: A national cohort study in the American Medicare population.},
journal = {PLoS medicine},
volume = {23},
number = {2},
pages = {e1004912},
doi = {10.1371/journal.pmed.1004912},
pmid = {41701678},
issn = {1549-1676},
mesh = {Humans ; *Alzheimer Disease/epidemiology/etiology/diagnosis ; United States/epidemiology ; Aged ; Medicare ; *Air Pollution/adverse effects ; Female ; Male ; *Particulate Matter/adverse effects ; Comorbidity ; Aged, 80 and over ; Cohort Studies ; Risk Factors ; *Environmental Exposure/adverse effects ; Incidence ; Air Pollutants/adverse effects ; },
abstract = {BACKGROUND: Air pollution and several common comorbidities-such as hypertension, stroke, and depression-are established risk factors for Alzheimer's disease (AD). However, whether these comorbidities mediate or amplify the effects of fine particulate matter (PM2.5) on AD remains unclear. We aimed to investigate whether these conditions modify or mediate the association between PM2.5 exposure and incident AD.

METHODS AND FINDINGS: We conducted a nationwide cohort study including 27.8 million US Medicare beneficiaries aged 65 years and older from 2000 to 2018. Exposure to PM2.5 was assessed using high-resolution air pollution datasets. Cox proportional hazards models were applied to estimate the associations between exposure to PM2.5, incident AD, and comorbidities. The potential for comorbidities to modify and mediate the association between PM2.5 and AD was evaluated by stratified analyses and mediation analysis. We identified approximately 3.0 million incident AD cases. PM2.5 exposure (5-year moving average prior to AD onset) was associated with increased risk of AD in the overall population (hazard ratio [HR]) per interquartile range [IQR, 3.8 µg/m3] increase: 1.085 (95% CI: 1.078, 1.091]. This association was slightly stronger in individuals with stroke (HR per IQR increase: 1.105; 95% CI: 1.096, 1.114), but there was little effect modification for hypertension and depression. PM2.5 exposure was also significantly associated with higher risks of hypertension, depression, and stroke, all of which were also linked to increased AD risk. However, mediation effects were minimal, with 1.6% of the association between PM2.5 and incident AD mediated by hypertension, 4.2% by stroke, and 2.1% by depression. Study limitations include use of administrative claims data and potential exposure misclassification from area-level PM2.5 estimates.

CONCLUSIONS: Our findings suggest that PM2.5 exposure was associated with increased AD risk, primarily through direct rather than comorbidity-mediated pathways. Stroke may modestly increase susceptibility. These findings highlight the need for air quality interventions as part of dementia prevention strategies in aging populations, especially those facing overlapping environmental and clinical vulnerabilities.},
}

Humans
*Alzheimer Disease/epidemiology/etiology/diagnosis
United States/epidemiology
Aged
Medicare
*Air Pollution/adverse effects
Female
Male
*Particulate Matter/adverse effects
Comorbidity
Aged, 80 and over
Cohort Studies
Risk Factors
*Environmental Exposure/adverse effects
Incidence
Air Pollutants/adverse effects

@article {pmid41701639,
year = {2026},
author = {Macomber, A and Zouridakis, A and Lubbat, V and Minogue, G and Kawles, A and Keszycki, R and Nelson, C and Gill, N and Gutstein, D and Castellani, R and Jamshidi, P and Grant, R and Mesulam, MM and Geula, C and Gefen, T},
title = {Vulnerability of anterior cingulate Von Economo neurons to FTLD-tauopathies in behavioral variant frontotemporal dementia.},
journal = {Cerebral cortex (New York, N.Y. : 1991)},
volume = {36},
number = {2},
pages = {},
doi = {10.1093/cercor/bhag011},
pmid = {41701639},
issn = {1460-2199},
support = {P30AG013854/AG/NIA NIH HHS/United States ; P30 AG072977/AG/NIA NIH HHS/United States ; R01 AG062566/AG/NIA NIH HHS/United States ; F31AG076318/AG/NIA NIH HHS/United States ; T32AG020506/AG/NIA NIH HHS/United States ; R01 NS085770/NS/NINDS NIH HHS/United States ; T32 NS047987/NS/NINDS NIH HHS/United States ; DGE-1842165//National Science Foundation's Graduate Research Fellowship/ ; //Karen Toffler Charitable Trust/ ; },
mesh = {Humans ; *Gyrus Cinguli/pathology ; Male ; Female ; Aged ; *Frontotemporal Dementia/pathology ; *Neurons/pathology ; Middle Aged ; *Tauopathies/pathology ; Aged, 80 and over ; tau Proteins/metabolism ; },
abstract = {Von Economo neurons (VENs) are unique spindle-shaped neurons that primarily reside in the anterior cingulate (ACC) and fronto-insular (FI) cortices. They are more numerous in species with affiliative behaviors and may support social-emotional functions. VENs are reduced in the ACC and FI of individuals with behavioral variant frontotemporal dementia (bvFTD), marked by personality changes and socially inappropriate behavior. Neuropathologies underlying bvFTD include frontotemporal lobar degenerations (FTLD) with tauopathy (FTLD-tau) or TDP-43 (FTLD-TDP). This study examined VEN density across three FTLD-tau subtypes: the 4R tauopathies of corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), and the 3R tauopathy known as Pick's disease (PiD). Twenty-six right-handed bvFTD-FTLD-tau cases were identified from the Northwestern University Alzheimer's Disease Research Center brain bank (PiD n = 9; CBD n = 11; PSP n = 6). Paraffin sections were cresyl violet-stained to visualize VENs in the ACC and analyzed using unbiased stereology. Wilcoxon rank-sum tests showed significantly lower VEN density in PiD than CBD (P < 0.05). No significant differences were found between PiD and PSP or CBD and PSP. Across isoforms, VEN density was over fourfold higher in 4R than 3R cases (P < 0.01). Overall, stereology indicates VENs are more vulnerable to 3R PiD than 4R CBD, both causes of bvFTD. The clinical implications of this differential vulnerability warrant further study.},
}

Humans
*Gyrus Cinguli/pathology
Male
Female
Aged
*Frontotemporal Dementia/pathology
*Neurons/pathology
Middle Aged
*Tauopathies/pathology
Aged, 80 and over
tau Proteins/metabolism

@article {pmid41701587,
year = {2026},
author = {Zhang, H and Wang, L and Zhao, Y and Xie, J and Fang, T and Song, R and Zhang, W},
title = {Heterophily-Aware Spectral GCN for Population-Level Brain Disorder Prediction.},
journal = {IEEE journal of biomedical and health informatics},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/JBHI.2026.3665521},
pmid = {41701587},
issn = {2168-2208},
abstract = {Integrating resting-state functional magnetic resonance imaging (rs-fMRI) and phenotypic data is a promising way to build a comprehensive population graph for the prediction of brain disorders using graph neural networks (GNNs). However, existing GNN-based methods face two limitations: the complexity of relationships between subjects poses challenges in constructing a well-defined population graph, and the inherent node heterophily within the population graph is often overlooked. To address them, we propose a population graph with a phenotypic encoder, which leverages rs-fMRI and phenotypic data to model complex relationships between subjects and enables GNN to learn population-level features. We also design a heterophily-aware spectral graph convolution network that incorporates local similarity-based learning to assess node homophily and addresses the heterophily issue. Experiments demonstrate that our method performs well in classifying both Alzheimer's Disease and Autism Spectrum Disorder. In addition, it can distinguish between progressive and stable mild cognitive impairment, facilitating timely interventions for the diseases.},
}

@article {pmid41701517,
year = {2026},
author = {Ejiofor, T and Oluwafunmilayo J, O and Kala, A and Ephraim, AD and Apochi, OO},
title = {Structural Brain Correlates With Appetite and Eating Disturbances Across the Alzheimer Disease Spectrum.},
journal = {Alzheimer disease and associated disorders},
volume = {},
number = {},
pages = {},
doi = {10.1097/WAD.0000000000000719},
pmid = {41701517},
issn = {1546-4156},
abstract = {INTRODUCTION: Neuropsychiatric symptoms are integral features of Alzheimer disease (AD) and may precede cognitive impairment. Appetite and eating disturbances are common across the AD spectrum.

METHODS: We analyzed 7223 participants from the National Alzheimer's Coordinating Center with Uniform Data Set assessments and MRI. Appetite and eating disturbances were assessed using the Neuropsychiatric Inventory Questionnaire. Cross-sectional associations with brain volumes were examined using multivariable regression. Longitudinal analyses among participants without baseline appetite disturbance used discrete-time survival models.

RESULTS: Appetite disturbances were present in 9.4% of participants and were associated with greater neuropsychiatric burden and disease severity. Cross-sectionally, lower global gray matter volume showed the most robust association, while regional effects were attenuated after neuropsychiatric adjustment. Longitudinally, baseline brain structure predicted incident appetite disturbance only among cognitively normal participants (OR per SD decrease=0.87).

DISCUSSION: Appetite disturbances may reflect diffuse neurodegenerative vulnerability and represent early behavioral markers of Alzheimer-related brain aging.},
}

@article {pmid41701420,
year = {2026},
author = {Koundal, A and Chodhary, N and Kumar, H and Vashisht, K and Ashawat, MS and Kushawaha, SK},
title = {Ganaxolone as a promising therapeutic agent for Alzheimer's disease: signaling pathways and mechanistic insights-a narrative review.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41701420},
issn = {1568-5608},
}

@article {pmid41701395,
year = {2026},
author = {Nisar, A and Akhter, N and Chauhdary, Z and Anjum, F and Saleem, F and Sana, S and Rafiq, I and Mustafa, A},
title = {Investigating the Neuroprotective Effects of Saw Palmetto Fruit Extract Against D-Galactose and Aluminum Chloride Induced Alzheimer's Disease: In Vivo Study.},
journal = {Neurochemical research},
volume = {51},
number = {2},
pages = {76},
pmid = {41701395},
issn = {1573-6903},
}

@article {pmid41701084,
year = {2026},
author = {Shir, D and Lachner, C},
title = {Alzheimer's disease: a clinical update on diagnosis and treatment.},
journal = {Neurologia i neurochirurgia polska},
volume = {},
number = {},
pages = {},
doi = {10.5603/pjnns.109190},
pmid = {41701084},
issn = {0028-3843},
abstract = {INTRODUCTION: Alzheimer's disease (AD) is the leading cause of dementia, characterized by progressive cognitive and functional decline. As the population ages, the prevalence of AD is expected to increase significantly, imposing a growing burden on patients, caregivers, and healthcare systems. Advances in our understanding of AD pathophysiology and biomarker-based diagnosis have redefined clinical practice, introducing challenges in early detection, accurate diagnosis, and effective treatment.

STATE OF THE ART: Current AD diagnostic frameworks incorporate clinical assessment alongside biomarkers of amyloid and tau pathology, cerebrovascular contributions, and neurodegeneration. Imaging modalities and fluid biomarker analyses enable more precise diagnosis, although accessibility remains limited in many settings. Recent therapeutic advancements in the form of anti-amyloid monoclonal antibodies offer disease-modifying potential but are accompanied by implementation challenges, such as patient selection, monitoring for adverse events, and cost considerations.

CLINICAL IMPLICATIONS: Integrating biomarker testing into routine clinical practice requires a careful review of individual risks and benefits for each patient, balancing diagnostic accuracy with practical considerations like testing consequences, test availability, pretest probability, and patient preferences. Shared decision-making is pivotal when discussing treatment options, weighing potential clinical benefits against risks and the overall burden of care.

FUTURE DIRECTIONS: Enhancing the delivery of anti-amyloid antibodies and advancing research into tau-targeted therapies represent promising therapeutic avenues. Incorporating scalable, non-invasive biomarkers, e.g., plasma-based biomarkers, into clinical practice has the potential to transform diagnostic workflows, provided they are applied in appropriate clinical contexts. Bridging the gap between research innovations and real-world implementation will require coordinated, multidisciplinary collaboration across healthcare systems.},
}

@article {pmid41700962,
year = {2026},
author = {Hanson, HG and Arias, JJ and Wurtz, HM and Manchester, M and Scipion, C and Federman, AD},
title = {Primary Care Physician Perspectives on Artificial Intelligence for Dementia Screening: A Qualitative Study.},
journal = {AJOB empirical bioethics},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/23294515.2026.2632089},
pmid = {41700962},
issn = {2329-4523},
abstract = {BACKGROUND: Automated approaches to cognitive impairment screening may soon achieve sufficient levels of accuracy for clinical implementation but they present potentially serious ethical challenges. Overcoming such challenges for successful implementation of automated screening may depend on the perspective of the clinicians who are its intended users.

METHODS: We conducted a qualitative study of internal medicine, geriatrics and family medicine physicians recruited from ambulatory practices in New York City, NY to identify ethical challenges of implementing automated CI screening (n = 22). In four focus groups, we explored attitudes and beliefs about routine manual screening for cognitive impairment and automated screening based in machine learning models of data from electronic medical records (EMR) or patient audio recordings, using hypothetical scenarios. Focus group recordings were transcribed and analyzed using grounded theory.

RESULTS: Participants reported routine screening for cognitive impairment only in the context of the Medicare annual wellness visit and generally avoided routine screening because of limited treatment options to support patients, such as poor access to geriatrics/neuropsychiatric services. Thematic analysis revealed several perceived benefits: enhanced clinical efficiency, engagement in cognitive healthcare of their patients, and expanded access to cognitive care. They identified several potential challenges with ethics implications: concerns about accuracy of the technology, bias, difficulty communicating the technology and results to patients and caregivers that could impact their ability to provide informed consent, and risks to patients (privacy, stigmatization and insurability). They noted that without more health system infrastructure to support patients with dementia, the benefits of automated screening would be limited.

CONCLUSIONS: Physicians identified several critical ethical challenges to automated CI screening. Health systems will need to address these challenges to ensure benefit for and the safety, autonomy and privacy of patients and ultimately, the successful implementation of such technology.},
}

@article {pmid41700920,
year = {2026},
author = {Zhong, Y and Wei, L and Xue, R},
title = {GSK126 mitigates oxidative stress in Alzheimer disease models via an enhancer of Zeste homolog 2-H3 lysine 27 trimethylation-superoxide dismutase 1 axis.},
journal = {Journal of neuropathology and experimental neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnen/nlag008},
pmid = {41700920},
issn = {1554-6578},
support = {2022ZD02//Key Research Project of Xi'an International Medical Center Hospital/ ; },
abstract = {Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and neuronal loss and with limited effective therapies. Oxidative stress, driven by disrupted redox balance and excessive reactive oxygen species (ROS), is believed to be a key pathogenic driver. This study aimed to explore the role and mechanism of the selective enhancer of Zeste homolog 2 (EZH2) methyltransferase inhibitor GSK126 in alleviating AD-related OS in AD models. Using Aβ1-42-induced AD model rats, we conducted Morris water maze tests, histologic and immunohistochemical staining, CCK-8/Annexin V-PI assays, Western blot, quantitative Reverse Transcription PCR (qRT-PCR), and Chromatin Immunoprecipitation quantitative Real-Time PCR (ChIP-qPCR). GSK126 shortened escape latency, reduced hippocampal pathology/apoptosis, upregulated Superoxide dismutase 1 (SOD1), and lowered ROS/malondialdehyde/protein carbonyls, thereby increasing antioxidant capacity in the AD model rats. In okadaic acid-treated SH-SY5Y cells, GSK126 enhanced viability, reduced apoptosis by downregulating Bax/c-Cas3 and upregulating Bcl-2 and upregulated SOD1 by inhibiting EZH2-mediated H3 lysine 27 trimethylation (H3K27me3) enrichment at the SOD1 promoter. SOD1 overexpression antagonized EZH2-induced damage. These results suggest that GSK126 could alleviate AD-related pathologic alterations in these models via the EZH2-H3K27me3-SOD1 axis, thereby suggesting a potential therapeutic target for AD.},
}

@article {pmid41700788,
year = {2026},
author = {Bafail, DA},
title = {The cognitive neutrality of common antidiabetic medications in older adults: A propensity score-matched cohort analysis from the National Alzheimer's Coordinating Center database.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251410210},
doi = {10.1177/13872877251410210},
pmid = {41700788},
issn = {1875-8908},
abstract = {BackgroundType 2 diabetes mellitus (T2DM) affects about 25% of adults aged 65 years and older in the United States. It is linked to faster cognitive decline and nearly double the risk of dementia. However, the long-term cognitive effects of different diabetes medications are not well understood, as observational studies are often impacted by various biases.ObjectiveThis study aims to compare cognitive changes over time among older adults with T2DM who are taking different diabetes medications.MethodsWe examined data from 54,631 participants (204,031 observations) in the National Alzheimer's Coordinating Center (NACC) database from 2005 to 2019. We applied propensity score matching to reduce bias and create balanced groups for medication comparisons. We used linear mixed-effects models to assess rates of cognitive decline in 18 areas, including overall cognition, memory, executive function, language, and daily functioning. We also ran sensitivity, mediation, and moderation analyses, applying corrections for multiple testing using the domain-specific false discovery rate (FDR).ResultsOut of 86 comparisons between medication and cognitive outcomes, 96.5% (83 out of 86) found no meaningful differences in rates of cognitive decline. The only exception was a sharper decline in functional abilities (CDR judgment, community affairs, home/hobbies) for insulin-sulfonylurea combinations compared to insulin-metformin combinations (p < 0.05; Cohen's d = 0.52-0.59; NNT = 23-32). Metformin did not show any cognitive benefit compared to no medication, sulfonylurea, or insulin alone. The length of time a person has had diabetes turned out to be a stronger predictor of cognitive decline than any specific medication (p < 0.001). These results were consistent through additional analyses and corrections for multiple testing.ConclusionsThe choice of diabetes medication has little effect on cognitive changes in older adults with T2DM, as 96.5% of comparisons showed no significant differences. The duration of the disease, rather than the type of medication chosen, has a bigger impact on cognitive outcomes. This suggests that starting and maintaining good blood sugar control is more important than the specific cognitive effects of different medications.},
}

@article {pmid41700444,
year = {2026},
author = {Khan, B and Kong, Y and Luo, XQ and Ahmad, K and Iqbal, MK and Lu, JC and Huang, YL and Li, QF and Zhao, YF and Shi, QD and Supratik, K and Wang, YZ and Chi, XD and Sui, AR and Li, S},
title = {A low dose of the γ-secretase inhibitor DAPT improves learning and memory by regulating the NaV1.6/Notch axis in C57BL/6 male mice.},
journal = {British journal of pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bph.70369},
pmid = {41700444},
issn = {1476-5381},
support = {2023ZD0507100//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; 82401823//National Natural Science Foundation of China/ ; 82471464//National Natural Science Foundation of China/ ; LJ222510161002//Leading Talent Team Project of the Education Department of Liaoning Province/ ; },
abstract = {BACKGROUND AND PURPOSE: Cognitive impairment poses a major challenge in neurodegenerative diseases and inflammatory brain disorders due to limited treatment options. The voltage-gated sodium channel NaV1.6 is associated with synaptic plasticity and cognitive decline in APP/PS1 mice. DAPT, a γ-secretase inhibitor that blocks Notch signalling, has variable cognitive effects depending on dosage. This study investigates the dose-dependent effects of DAPT on cognition in C57BL/6 male mice, elucidating its mechanisms through NaV1.6 channels, Notch signalling, synaptic plasticity, and neurogenesis.

EXPERIMENTAL APPROACH: Mice received unilateral stereotactic injections in the right hemisphere of low-dose DAPT (1 μg·μl[-1]), high-dose DAPT (2 μg·μl[-1]), or DMSO (control). Cognitive abilities were evaluated using the Morris Water Maze and Y-maze, western blots, immunofluorescence, and RT-qPCR analysed NaV1.6, synaptic proteins, NMDA/AMPA receptors, and neuroinflammatory markers. Neurogenesis was assessed via Nissl and doublecortin (DCX) staining. Primary neuron experiments examined DAPT effects on NaV1.6 interactions.

KEY RESULTS: Low-dose DAPT significantly improved cognition, suppressed Notch pathway genes, reduced NaV1.6, and up-regulated synaptic proteins, NMDA/AMPA receptors, and neuronal markers in vivo/in vitro. In primary culture neurons, DAPT reduced Notch-1/NICD with TTX but not ATX-II. Inflammatory markers/cytokines were unchanged. In vitro, 5-μM DAPT decreased NaV 1.6, increased Notch receptors and reduced Notch-1/HES-1 mRNA. Low-dose DAPT enhanced neurogenesis (increased dentate gyrus DCX[+] cells). Molecular docking confirmed favourable DAPT- NaV 1.6 interactions.

CONCLUSION AND IMPLICATIONS: Low-dose DAPT improved cognitive function in C57BL/6 male mice, by modulating the NaV 1.6/Notch axis and enhancing neurogenesis, indicating its potential as a therapeutic strategy for Alzheimer's-related cognitive decline.},
}

@article {pmid41700389,
year = {2026},
author = {Fariñas Lucas, IDM and Al-Hilaly, YK and Lutter, L and Xue, WF and Serpell, LC},
title = {The supramolecular architecture of amyloid fibrils formed by a human tau-derived hexapeptide VQIVYK.},
journal = {Nanoscale},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5nr04317d},
pmid = {41700389},
issn = {2040-3372},
abstract = {The sequence 306VQIVYK311 is an aggregation-prone region of the tau protein implicated in driving the assembly of tau into paired helical filaments. These filaments accumulate as intraneuronal neurofibrillary tangles in Alzheimer's disease and a range of tauopathies. Prolonged incubation of VQIVYK results in highly ordered fibrillar structures that give rise to unusually detailed and highly oriented X-ray fibre diffraction patterns. These mature fibrils provided the opportunity to use a novel integrative approach that combined X-ray fibre diffraction analysis with 3D contact point reconstruction atomic force microscopy (CPR-AFM) of individual filaments to determine molecular and supramolecular details. X-ray diffraction analysis resulted in a molecular model consistent with an X-ray crystallography structure, which could be further optimised to give rise to a highly twisted filamentous protofilament architecture. Analysis of individual fibril envelopes by CPR-AFM revealed a diverse polymorphous population with a major fibril morphology of apparently smooth, cylindrical fibrils, and morphological subpopulations of fibrils with clear left-handed twisting patterns, while X-ray diffraction suggests that the protofilament core structure remains consistent between the polymorphs. Here, we reveal that VQIVYK amyloid fibrils form a polymorphous amyloid population by assembly of highly ordered protofilaments. The combined approach provides novel molecular and supramolecular information regarding the structure of highly twisted amyloid fibrils.},
}

@article {pmid41700307,
year = {2026},
author = {Benussi, A and Cantoni, V and Palacino, F and Altomare, D and Moretti, DV and Manganotti, P and Borroni, B},
title = {EEG network reorganization across Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70275},
pmid = {41700307},
issn = {2352-8729},
abstract = {INTRODUCTION: Electroencephalography (EEG) provides a temporally precise index of neural dysfunction, capturing changes in oscillatory activity, connectivity, and network organization. While spectral slowing is well documented in Alzheimer's disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB), less is known about how these alterations extend to large-scale networks.

METHODS: We studied 173 participants: 56 AD, 59 FTD, 26 DLB, and 32 healthy controls (HC). Resting-state EEG was analyzed to quantify spectral power and amplitude-envelope correlation-based connectivity across frequency bands.

RESULTS: AD showed canonical slowing with delta/theta increases and posterior alpha loss. FTD exhibited preserved alpha but frontal beta reductions, while DLB displayed delta/theta excess, posterior alpha attenuation, and uniquely reduced gamma. Connectivity analyses revealed syndrome-specific patterns of network reorganization with distinct frequency-dependent signatures.

DISCUSSION: EEG network metrics capture distinct disease signatures and may inform mechanistic models of dementia.},
}

@article {pmid41700306,
year = {2026},
author = {Giacomucci, G and Tabbì, SMR and Ingannato, A and Bagnoli, S and Padiglioni, S and Crucitti, C and Sensi, C and Sanesi, S and Moschini, V and Morinelli, C and Galdo, G and Berti, V and Nacmias, B and Bessi, V},
title = {Refining Alzheimer's disease biological diagnosis with plasma biomarkers: Resolving p-tau217 "gray zone" with p-tau181 integration.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70285},
pmid = {41700306},
issn = {2352-8729},
abstract = {BACKGROUND: Blood-based biomarkers offer a less invasive and more scalable alternative to cerebrospinal fluid (CSF) analysis and amyloid-positron emission tomography (PET) for the biological diagnosis of Alzheimer's disease (AD). Among blood-based biomarkers (BBMs), plasma phosphorylated tau217 (p-tau217) has shown the highest accuracy, although intermediate ("gray zone") values remain challenging to interpret.

METHODS: In this study, 401 individuals across the Alzheimer's Disease (AD) continuum (Subjective Cognitive Decline, Mild Cognitive Impairment, and AD dementia) underwent clinical and biomarker assessment. Plasma p-tau217, p-tau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were measured. Core1 status was defined through CSF or amyloid-PET.

RESULTS: Plasma p-tau217 demonstrated the strongest discrimination of Core1 positivity (area under the curve [AUC] = 0.95) and showed the steepest increase with disease progression. A two-cutoff strategy improved diagnostic accuracy (94%), though 18% of patients fell into the gray zone. Within this subgroup, p-tau181 was the only predictor of Core1 status and correctly reclassified 77.4% of indeterminate cases.

DISCUSSION: These findings support a sequential plasma biomarkers approach for reliable AD detection.},
}

@article {pmid41700142,
year = {2026},
author = {Ackley, SF and Flanders, MD and Murchland, A and Chen, R and Wang, J and Shah, SJ and Huey, ED and Glymour, MM},
title = {Evaluation of amyloid change as a surrogate for cognitive decline: demonstration in individual-level data from the A4 study of solanezumab.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {1},
pages = {e70205},
pmid = {41700142},
issn = {2352-8737},
abstract = {BACKGROUND: Differential amyloid change has served as a surrogate outcome in Alzheimer's disease trials, allowing accelerated approval of aducanumab and lecanemab. Individual-level data from the A4 study support the demonstration of novel methods to evaluate amyloid's validity as a surrogate for cognitive decline.

METHODS: In 812 participants, cognitive change was measured using the Clinical Dementia Rating Sum of Boxes (CDR-SB) score. Instrumental-variable analysis estimated the effect of amyloid change; mediation analysis quantified proportion of cognitive effects mediated by amyloid change.

RESULTS: Each 10-Centiloid reduction in amyloid due to randomization to treatment was associated with a 0.026 higher CDR-SB score (95% confidence interval [CI]: -0.013, 0.065). Amyloid reduction mediated 14.6% of solanezumab's effect on cognition (95% CI: -122%, 208%).

DISCUSSION: Near-zero effect estimates for amyloid change on cognitive decline in the A4 study suggest minimal impact of limited amyloid change reduction in populations with little disease progression. The broader question of validity of amyloid as a surrogate outcome cannot be conclusively answered in data from the A4 study due to study-intrinsic limitations. Replication in anti-amyloid trials with larger treatment effects will evaluate whether amyloid is an appropriate surrogate outcome.

HIGHLIGHTS: This study evaluated amyloid change's validity as a surrogate for cognitive and functional decline in AD drug trials.Newly available individual-level trial data from the A4 study enabled the application of epidemiologic and econometric methods to assess amyloid's impact on cognition.IV and causal mediation analyses estimated the effect of amyloid change on cognitive outcomes.Amyloid change mediated 15% of solanezumab's cognitive effect, though estimates were imprecise due to limited disease progression in the sample and solanezumab's minimal amyloid removal.Applying the same methods to data from trials of more effective anti-amyloid drugs could validate amyloid as a surrogate outcome, guide related regulatory decisions, and influence treatment strategy.},
}

@article {pmid41700119,
year = {2026},
author = {Kim, HK and Lee, JH and Chun, JH and Kim, YJ and Park, M and West, T and Kirmess, KM and Verghese, PB and Connell, D and Braunstein, JB and Ryu, YH and Cho, H and Lyoo, CH},
title = {Plasma p-tau217 predicts PET-based pathological staging for precision Alzheimer disease assessment.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71199},
doi = {10.1002/alz.71199},
pmid = {41700119},
issn = {1552-5279},
support = {RS-2025-18362970//Ministry of Science and ICT, South Korea/ ; RS-2020-KH106683//Korea Health Industry Development Institute/Republic of Korea ; RS-2023-00247986//Ministry of Education/ ; 6-2024-0109//Yonsei University College of Medicine/ ; },
mesh = {Humans ; *tau Proteins/blood ; *Alzheimer Disease/pathology/diagnostic imaging/blood/diagnosis ; *Positron-Emission Tomography ; Female ; Male ; Biomarkers/blood ; Aged ; Amyloid beta-Peptides/blood ; Aged, 80 and over ; Phosphorylation ; Brain/pathology/diagnostic imaging ; },
abstract = {INTRODUCTION: While positron emission tomography (PET) is the standard for pathological staging, its limited availability necessitates accessible alternatives. We evaluated plasma biomarkers for detecting PET-based stages using single-axis (Thal/Braak) and integrated A/T composite models.

METHODS: We enrolled 237 AD spectrum participants undergoing multimodal assessments including amyloid/tau PET and plasma biomarker analysis (phosphorylated tau [p-tau] 217, %p-tau217, and amyloid beta [Aβ] 42/40 ratio). Detecting and discriminative performance was assessed using receiver operating characteristics (ROC) analysis and probability-based stage prediction.

RESULTS: Plasma p-tau217-based biomarkers showed excellent detecting performance for early amyloid (Thal I-II; area under the curve values > 0.96) and intermediate tau (Braak III-IV; area under the curve values > 0.92). Probability-based prediction identified therapeutic window thresholds of 1.895-5.077 pg/mL. Notably, integrated A/T composite staging yielded highly consistent thresholds (< 3% variance).

DISCUSSION: Plasma p-tau217-based biomarkers accurately reflect PET-based staging across frameworks. The convergent therapeutic window thresholds demonstrate robust biological transitions, enabling accessible identification of optimal candidates for disease-modifying therapies.},
}

Humans
*tau Proteins/blood
*Alzheimer Disease/pathology/diagnostic imaging/blood/diagnosis
*Positron-Emission Tomography
Female
Male
Biomarkers/blood
Aged
Amyloid beta-Peptides/blood
Aged, 80 and over
Phosphorylation
Brain/pathology/diagnostic imaging

@article {pmid41700075,
year = {2026},
author = {Benejam, B and McCarron, M and Carmona-Iragui, M and Dunne, P and Maure-Blesa, L and Altuna, M and Arranz, J and Barroeta, I and Bejanin, A and Soriano, LDH and Fernández, S and Giménez, S and Lleó, A and Lynch, L and McCallion, P and Mulryan, N and Pertierra, L and Rebillat, AS and Rodríguez-Baz, Í and Hernández, AS and Vaqué-Alcázar, L and Videla, L and Wormald, A and Fortea, J and McGlinchey, E},
title = {Factors impacting survival in individuals with Down syndrome-associated Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71156},
doi = {10.1002/alz.71156},
pmid = {41700075},
issn = {1552-5279},
support = {//Instituto de Salud Carlos III through the Río Hortega Fellowship "CM23/00291" and co-funded by the European Union./ ; CP24/00112//Universidad Carlos III de Madrid/ ; 2326 - GRT-2024A//Fondation Jérôme Lejeune/ ; GBHI_ALZ-18-543740//Global Brain Health Institute/ ; //Ajuntament de Barcelona, in collaboration with Fundació La Caixa/ ; AACSF-25-1486364/ALZ/Alzheimer's Association/United States ; //Fondo de Investigaciones Sanitario/ ; //Instituto de Salud Carlos III and co-funded by the European Union through the Miguel Servet grant/ ; IIBSP-DOW-2020-151//Fundación Tatiana Pérez de Guzmán el Bueno/ ; SLT006/17/00119//Departament de Salut, Generalitat de Catalunya/ ; 1R01AG056850-01A1/NH/NIH HHS/United States ; R21AG056974/NH/NIH HHS/United States ; R01AG061566/NH/NIH HHS/United States ; 1R01AG081394-01/NH/NIH HHS/United States ; 1R61AG066543-01 to J.F./NH/NIH HHS/United States ; Program 1//Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas/ ; CD23/00235 Sara Borrell postdoctoral fellowship//Instituto de Salud Carlos III/ ; IDS-TILDA-2021-001/HRBI_/Health Research Board/Ireland ; IDS-TILDA 2018-001/HRBI_/Health Research Board/Ireland ; },
mesh = {Humans ; *Down Syndrome/mortality/complications ; *Alzheimer Disease/mortality ; Female ; Male ; Ireland/epidemiology ; Middle Aged ; Spain/epidemiology ; Aged ; Adult ; Epilepsies, Myoclonic/epidemiology/mortality ; Kaplan-Meier Estimate ; },
abstract = {INTRODUCTION: Adults with Down syndrome (DS) are at high risk for Alzheimer's disease (AD), the leading cause of death in this population. Survival in DS after AD diagnosis appears shorter than in sporadic AD; however, the factors influencing survival remain poorly understood.

METHODS: We analyzed 157 adults with DS from Spain and Ireland who died of AD between 2012 and 2024. Clinical, genetic, and care predictors were examined using Kaplan-Meier curves and Cox regression.

RESULTS: Mean survival after AD diagnosis was 4.8 years (SD 3.5). Those in specialist intellectual disability dementia care had a longer survival time (mean 9.5 years) than other settings (mean 3.4 to 4.1 years; p < 0.001). Late-onset myoclonic epilepsy in DS (LOMEDS) was linked to a threefold higher risk of death after onset (p < 0.001).

DISCUSSION: Specialist care settings and LOMEDS timing significantly shape survival in DS-associated AD, highlighting the importance of tailored services and proactive epilepsy treatment.},
}

Humans
*Down Syndrome/mortality/complications
*Alzheimer Disease/mortality
Female
Male
Ireland/epidemiology
Middle Aged
Spain/epidemiology
Aged
Adult
Epilepsies, Myoclonic/epidemiology/mortality
Kaplan-Meier Estimate

@article {pmid41700069,
year = {2026},
author = {Yamane, T},
title = {[PET in Neurology: Imaging Pathology, Metabolism, and Disease Progression].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {2},
pages = {147-155},
doi = {10.11477/mf.188160960780020147},
pmid = {41700069},
issn = {1881-6096},
mesh = {Humans ; *Positron-Emission Tomography/methods ; Disease Progression ; *Nervous System Diseases/diagnostic imaging/metabolism/pathology ; Neurology ; Alzheimer Disease/diagnostic imaging ; },
abstract = {Anti-amyloid-β therapies for Alzheimer's disease-lecanemab (Leqembi approved in September 2023) and donanemab (Kisunla®; approved in September 2024)-have been authorized in Japan and are now in clinical use. In parallel, amyloid positron emission tomography (PET) is now reimbursed by the national health insurance for determining treatment eligibility and three amyloid PET radiopharmaceuticals are currently approved. Amyloid PET images interpretation relies primarily on visual reads, which require dedicated training, and clinicians with limited PET imaging experience may find some cases challenging. Although quantitative approaches (e.g., standardized uptake value ratio and Centiloid metrics) are available, their accurate application likewise necessitates appropriate training. Moreover, the availability of tau PET, which images cerebral tau deposition, is also expanding. Additional PET relevant to neurological diseases include those assessing glucose metabolism, oxygen metabolism, amino acid transport, and dopaminergic systems. When used appropriately, these modalities enable a noninvasive, multidimensional assessment of the pathology, metabolism, and disease burden, thereby allowing for a more refined characterization of neurological disorders.},
}

Humans
*Positron-Emission Tomography/methods
Disease Progression
*Nervous System Diseases/diagnostic imaging/metabolism/pathology
Neurology
Alzheimer Disease/diagnostic imaging

@article {pmid41700061,
year = {2026},
author = {Cao, H and Zheng, Z and Zhou, X and Kikuchi, M and Wong, HY and Cheng, EYL and Wong, BWY and Lo, RMN and Shoai, M and Chong, JR and Chan, ALT and Chen, C and Lam, LCW and Mok, VCT and Kwok, TCY and , and , and Chen, Y and Ip, FCF and Mok, KY and Miyashita, A and Ikeuchi, T and Hardy, J and Fu, AKY and Ip, NY},
title = {Ethnic-specific effects of the LILRB2-LILRB5 locus and newly identified risk loci for Alzheimer's disease in the East Asian population.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71219},
doi = {10.1002/alz.71219},
pmid = {41700061},
issn = {1552-5279},
support = {FIF20RD01//Fidelity Foundation/ ; C6027-19GF//Research Grants Council of Hong Kong Collaborative Research Fund/ ; T13-605/18W//Research Grants Council of Hong Kong Theme-Based Research Scheme/ ; HKUST16103122//Research Grants Council of Hong Kong General Research Fund/ ; HKUST16104624//Research Grants Council of Hong Kong General Research Fund/ ; HKUST16102824//Research Grants Council of Hong Kong General Research Fund/ ; AoE/M-604/16//Areas of Excellence Scheme of the University Grants Committee/ ; //InnoHK Initiative of the Innovation and Technology Commission of the HKSAR Government/ ; ITCPD/17-9//Innovation and Technology Fund for State Key Laboratory/ ; JLFS/M-604/24//SIAT-HKUST Joint Laboratory for Brain Science/ ; 2023B1212120004//Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders/ ; 2019B1515130004//Guangdong Provincial Fund for Basic and Applied Basic Research/ ; MOH-000707-00//National Medical Research Council Singapore Translational Research Investigator Award/ ; JP25dk0207060//AMED/ ; 25K02262//JSPS Grant-in-Aid for Scientific Research/ ; },
mesh = {Humans ; *Alzheimer Disease/genetics/ethnology ; *Genetic Predisposition to Disease/genetics ; *Receptors, Immunologic/genetics ; Genome-Wide Association Study ; *Asian People/genetics ; Male ; Female ; Polymorphism, Single Nucleotide/genetics ; *Membrane Glycoproteins/genetics ; Aged ; White People/genetics ; Genetic Loci ; East Asian People ; },
abstract = {INTRODUCTION: Genome-wide association studies have identified numerous Alzheimer's disease (AD) susceptibility loci in European populations. However, the genetic architecture of AD in non-European populations remains underinvestigated.

METHODS: We performed a genetic association study in East Asians (N = 8514) to validate known AD loci and identify new susceptibility loci.

RESULTS: We identified LILRB2-LILRB5 as an AD susceptibility locus with ethnic-specific effects between Europeans and East Asians. The lead variant, rs587709-T, was associated with decreased AD risk and increased LILRB5 expression in Europeans. Conversely, in East Asians, the same allele was associated with increased AD risk and increased LILRB2 expression. Furthermore, genome-wide analysis identified TTC3 and FAM135A as candidate susceptibility loci for AD or cognition.

DISCUSSION: The results establish LILRB2-LILRB5 as a cross-ancestry AD-associated locus with ethnic-specific genetic mechanisms and reveal new susceptibility loci, extending the understanding of the genetic etiology of AD.},
}

Humans
*Alzheimer Disease/genetics/ethnology
*Genetic Predisposition to Disease/genetics
*Receptors, Immunologic/genetics
Genome-Wide Association Study
*Asian People/genetics
Male
Female
Polymorphism, Single Nucleotide/genetics
*Membrane Glycoproteins/genetics
Aged
White People/genetics
Genetic Loci
East Asian People

@article {pmid41700028,
year = {2026},
author = {Zhang, X and Bao, H and Hu, J and Ren, W and He, Z and Yu-Taeger, L and Wu, A and Li, J},
title = {Neuropeptide-GPCR Regulation of the Neuroimmune Axis in Neurodegeneration: Mechanisms and Translation.},
journal = {Bioconjugate chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.bioconjchem.5c00637},
pmid = {41700028},
issn = {1520-4812},
abstract = {Chronic neuroinflammation and dysfunction of the neuro-glial-vascular unit (NGVU) are central mechanisms driving the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Neuropeptides, as key regulatory signaling molecules in the central nervous system (CNS), bind to specific G protein-coupled receptors (GPCRs) on the surfaces of microglia, astrocytes, oligodendrocytes, and cerebrovascular elements. Through cell type-specific biased signaling, they precisely regulate the threshold for inflammatory activation, coordinate phagocytosis and autophagy, maintain metabolic homeostasis, and support the function of the blood-brain barrier. This review systematically analyzes the immune-regulatory roles of key neuropeptides, including neuropeptide Y (NPY), vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide (VIP/PACAP), substance P (SP), and calcitonin gene-related peptide (CGRP). We focus on how these systems contribute to CNS homeostasis and disease-relevant processes, including myelin repair and neuroinflammatory regulation. Integrating evidence from preclinical models and human samples, it clarifies the pathological mechanisms linking these neuropeptides to disease progression. The review also outlines a translational research pathway focused on ligand structure engineering, targeted delivery, and biomarker-guided patient stratification, emphasizing receptor subtype selectivity and CNS permeability for precise therapy. By integrating the neuropeptide-mediated neuro-immune network, this work offers new insights into immune pathology in neurodegenerative diseases and provides a foundation for next-generation immune regulation.},
}

@article {pmid41699945,
year = {2026},
author = {Majuri, T and Silvan, J and Tolppanen, AM and Hartikainen, S and Huotari, T and Rautio, N and Miettunen, J and Nordström, T and Jääskeläinen, E and Haapea, M},
title = {Characteristics and predictors of antipsychotic medication off-label use among community-dwelling older people.},
journal = {Nordic journal of psychiatry},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/08039488.2026.2631597},
pmid = {41699945},
issn = {1502-4725},
abstract = {BACKGROUND: Concerns have been raised regarding the common off-label use of antipsychotic (AP) medications among older adults. However, comprehensive knowledge of the determinants of AP off-label use in this population remains limited.

METHODS: We examined characteristics and predictors of AP off-label use in a nationwide Finnish cohort of community-dwelling older adults with psychiatric morbidity-but without Alzheimer's disease-using longitudinal register data on sociodemographic and illness-related factors. The sample comprised four groups: those prescribed APs off-label (n = 20,563), those with non-psychotic mental disorders without off-label APs (CG1, n = 22,891), those with psychosis or bipolar disorder with APs (CG2, n = 8,966), and those with psychosis or bipolar disorder without APs (CG3, n = 4,585). Sociodemographic and illness-related factors were compared between the off-label and the comparison groups using logistic regression.

RESULTS: Compared to comparison groups, individuals with off-label use more frequently had cardiovascular diseases and strokes. Compared to CG1 and CG3, individuals with AP off-label use were more often female, had a lower prevalence of asthma/chronic obstructive pulmonary disease, and a higher use of psychotropic medications and opioids. Compared to CG2, individuals with off-label use were more often male and had a lower prevalence of diabetes, epilepsy, as well as a lower use of psychotropic medications and a higher use of opioids. Risperidone (43%) and quetiapine (39%) were the most used APs off-label.

CONCLUSION: Alternative treatments are needed to curb off-label AP use among community-dwelling older adults, given the high prevalence of cardiovascular disease and stroke. Monitoring guidelines are needed to promote safer prescribing practices.},
}

@article {pmid41699900,
year = {2026},
author = {Mulhall, S and Gibson, D and Longley, WA and D'Cunha, NM},
title = {Improving Access to Cognitive Interventions for People With Dementia in Australian Community-Based Settings.},
journal = {Australasian journal on ageing},
volume = {45},
number = {1},
pages = {e70140},
doi = {10.1111/ajag.70140},
pmid = {41699900},
issn = {1741-6612},
mesh = {Humans ; *Dementia/psychology/therapy/diagnosis/rehabilitation/physiopathology ; Australia ; *Health Services Accessibility/organization & administration ; *Cognition ; *Community Health Services/organization & administration ; Quality of Life ; *Cognitive Behavioral Therapy ; *Health Services for the Aged/organization & administration ; Treatment Outcome ; },
abstract = {Cognitive interventions, including cognitive stimulation therapy, cognitive rehabilitation and cognitive training, are increasingly recommended as key components of non-pharmacological post-diagnostic support for people with dementia. Cognitive interventions may help delay cognitive decline, enhance goal-directed functional abilities and improve quality of life. Despite inclusion in clinical guidelines and recommendations, guidance on the delivery of these interventions within Australian community settings remains limited and is underutilised. This article addresses a critical translation gap in cognitive interventions for people with dementia, synthesises the evidence through an Australian practice and policy lens, examines current uptake in community settings and identifies barriers, enablers and delivery models to inform implementation strategies. Community settings are defined as memory clinics, primary care, hospital outpatient services, allied health providers, community aged care and non-government providers. Current evidence indicates cognitive interventions have varying benefits across different outcomes, including cognitive function, social engagement, everyday functioning, quality of life and goal attainment. International practices related to implementation are explored, along with future directions for expanding access through technology, flexible delivery models, group-based approaches and integrating these interventions into existing care structures. Addressing the gap between recommendations and current practices requires building community awareness, improving access to professional education and training, and careful resource allocation. Cognitive interventions should be part of comprehensive rehabilitation and can be personalised to individual needs and goals. Expanding access and improving the availability of a range of cognitive interventions in community settings is crucial to ensure people with dementia receive best practice post-diagnostic support.},
}

Humans
*Dementia/psychology/therapy/diagnosis/rehabilitation/physiopathology
Australia
*Health Services Accessibility/organization & administration
*Cognition
*Community Health Services/organization & administration
Quality of Life
*Cognitive Behavioral Therapy
*Health Services for the Aged/organization & administration
Treatment Outcome

@article {pmid41699754,
year = {2026},
author = {Kanda, A and Mazumder, A and Das, S and Singh, A and Prabhakar, V},
title = {Bioactive-Guided Isolation and Optimization of Luffa Acutangula Nanoemulsion for In vitro, In vivo, and In silico Cholinesterase Inhibition for Alzheimer's Disease Management.},
journal = {Chemistry & biodiversity},
volume = {23},
number = {2},
pages = {e02600},
doi = {10.1002/cbdv.202502600},
pmid = {41699754},
issn = {1612-1880},
mesh = {*Alzheimer Disease/drug therapy/metabolism ; Animals ; *Cholinesterase Inhibitors/chemistry/isolation & purification/pharmacology ; Emulsions/chemistry/pharmacology ; Mice ; Molecular Docking Simulation ; Acetylcholinesterase/metabolism ; Particle Size ; Male ; Scopolamine ; *Plant Extracts/chemistry/isolation & purification/pharmacology ; *Neuroprotective Agents/isolation & purification/chemistry/pharmacology ; Maze Learning/drug effects ; },
abstract = {Alzheimer's disease (AD) progressively impairs memory and cognition. Luffa acutangula (LA), rich in triterpenoids, fatty acids, and iridoid glycosides, exerts anti-Alzheimer's effects by inhibiting acetylcholinesterase (AChE). This study aims to isolate bioactive compounds from LA fruits, formulate and optimize a nanoemulsion to improve brain targeting, and assess its anti-Alzheimer efficacy through in vitro, in vivo, and in silico approaches. LA was extracted using a 1:1 hydro-ethanol mixture and subsequently underwent chromatographic isolation to yield four major constituents: oleanolic acid, stearic acid, cucurbitacin H, and acutoside C. A multiple nanoemulsion (containing a mixture of isolated constituents) was formulated using Box-Behnken design and characterized for particle size, viscosity, entrapment efficiency, and FTIR compatibility. In vivo studies were conducted in scopolamine-induced memory-impaired mice using Hebb-William's Maze (HWM) and Cook's pole climbing tests. AChE activity was biochemically assessed, followed by histopathological brain analysis. Molecular docking was used to predict ligand-AChE binding affinities. The optimized L. acutangula loaded multiple nanoemulsion (LAMN) exhibited an average particle size of 142.1 nm, viscosity of 60 cP, and entrapment efficiency (EE) of 96.8 %. It decreased learning scores in the HWM and shortened latency time in Cook's pole-climbing test in memory-impaired mice. AChE levels were significantly reduced in LAMN-treated groups, correlating with histological evidence of hippocampal protection. Molecular docking revealed strong AChE binding, particularly by oleanolic acid (-10.5 kcal/mol), comparable to donepezil (-10.7 kcal/mol). LAMN offers a promising phytopharmaceutical intervention for AD, with multitargeted neuroprotective effects mediated through AChE inhibition and improved drug delivery across the blood-brain barrier. The findings support further clinical development of LA-based nanoformulations for AD management.},
}

*Alzheimer Disease/drug therapy/metabolism
Animals
*Cholinesterase Inhibitors/chemistry/isolation & purification/pharmacology
Emulsions/chemistry/pharmacology
Mice
Molecular Docking Simulation
Acetylcholinesterase/metabolism
Particle Size
Male
Scopolamine
*Plant Extracts/chemistry/isolation & purification/pharmacology
*Neuroprotective Agents/isolation & purification/chemistry/pharmacology
Maze Learning/drug effects

@article {pmid41699702,
year = {2026},
author = {Chung, TD and Liang, L and Wang, L and Kim, EG and Gupta, S and Pandey, I and Searson, PC},
title = {Mutations associated with Alzheimer's disease and aged serum synergistically elicit blood-brain barrier dysfunction in a tissue-engineered model.},
journal = {Fluids and barriers of the CNS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12987-026-00773-x},
pmid = {41699702},
issn = {2045-8118},
support = {R33HL154252/GF/NIH HHS/United States ; },
}

@article {pmid41699650,
year = {2026},
author = {Tang, PA and Ruiz-Pastor, MJ and Lewis, AE and Fladmark, KE and Kobro-Flatmoen, A and Halskau, Ø and Lal, P},
title = {Cetoleic acid and other long-chain unsaturated fatty acids as neuroprotective nutraceuticals.},
journal = {Lipids in health and disease},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12944-026-02876-8},
pmid = {41699650},
issn = {1476-511X},
abstract = {Long-chain monounsaturated fatty acids such as erucic acid, cetoleic acid and gondoic acid, are 20-22-carbon fatty acids with a double bond in their ω-9, ω-11 and ω-9 positions, respectively. Recent experimental research suggests that these lipids may provide benefits related to cardiovascular, but also brain health. Research on cetoleic acid using cell lines suggests that this fatty acid may positively affect neurological health. Also, in limited doses, erucic acid and gondoic acid have been reported to have a neuroprotective effect through action on peroxisome proliferator-activated receptors, and monounsaturated fatty acids generally are able to influence these receptors. Herein, we review the current state of knowledge of monounsaturated fatty acids effect on health, with an emphasis on erucic acid and cetoleic acid and their possible neuroprotective effects. Research has not progressed far regarding the direct neuroprotective effects of cetoleic acid, and mechanisms underlying such effects. However, both erucic and cetoleic acid influence the availabilities of docosahexaenoic and eicosapentaenoic acids, that do confer several health benefits, including neuroprotective effects. We highlight knowledge gaps related to metabolism, putative neuroprotective mechanisms, and briefly review animal model systems suitable for investigating these gaps.},
}

@article {pmid41699609,
year = {2026},
author = {Zhu, T and Zhou, C and Zhou, H and Shen, F and Wang, S and Zhou, Y and Jin, G and Zu, J and Yang, X and Shi, H and Cui, G and Hua, F},
title = {Overexpression of PGRMC2 in astrocytes improved cognitive function in a mouse model of Alzheimer's disease by modulating neuroinflammation.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-07862-3},
pmid = {41699609},
issn = {1479-5876},
support = {82171420//National Natural Science Foundation of China/ ; },
}

@article {pmid41699585,
year = {2026},
author = {Zhang, R and Chen, D and Qin, Y and Han, H and Yu, H},
title = {Longitudinal multi-modal data prediction model for mild cognitive impairment by deep survival analysis.},
journal = {BMC medical informatics and decision making},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12911-026-03387-3},
pmid = {41699585},
issn = {1472-6947},
}

@article {pmid41699438,
year = {2026},
author = {Yamazaki, A and Mishina, M and Sakamoto, Y and Suda, S},
title = {Time From Initial Community-Based Dementia Consultation to Confirmed Diagnosis: A Retrospective Analysis.},
journal = {Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society},
volume = {26},
number = {2},
pages = {e70148},
doi = {10.1111/psyg.70148},
pmid = {41699438},
issn = {1479-8301},
mesh = {Humans ; Female ; Retrospective Studies ; Male ; Aged ; Japan ; *Referral and Consultation/statistics & numerical data ; *Dementia/diagnosis ; *Delayed Diagnosis/statistics & numerical data ; Aged, 80 and over ; *Cognitive Dysfunction/diagnosis ; Time Factors ; *Alzheimer Disease/diagnosis ; },
abstract = {BACKGROUND: With the launch of anti-amyloid beta antibody drugs, physicians face the need to quickly diagnose dementia. In prehospital consultation services in Japan, the duration from memory-related consultations to confirmed diagnosis has not been sufficiently investigated. Therefore, this study investigated the duration from initial community-based dementia consultation to confirmed diagnosis and the factors associated with diagnostic delays across dementia subtypes.

METHODS: This retrospective observational study included patients who consulted the Community Consultation Center for Citizens with Mild Cognitive Impairment and Dementia (CCCCMD) and subsequently received a confirmed dementia diagnosis at Nippon Medical School Musashi Kosugi Hospital between 2010 and 2024. Time to diagnosis was defined as the number of days from the initial CCCCMD consultation to diagnostic confirmation. We classified those who were diagnosed with dementia during outpatient visits amongst the consultees as Alzheimer disease (AD) or non-Alzheimer disease (non-AD). Diagnostic delay was further divided into pre-hospital interval and in-hospital phase. Group comparisons and multivariable Cox proportional hazards and logistic regression analyses were performed to identify factors associated with diagnostic delay.

RESULTS: A total of 739 patients were included: 504 with AD and 235 with non-AD dementias. Time to diagnosis was shorter in the AD group than in the non-AD group. This difference was primarily attributable to prolonged delays during the pre-hospital interval amongst patients with non-AD; however, delays during the in-hospital diagnostic process were small and largely overlapping between the groups. Diagnosis of AD, older age, and the presence of a primary care physician were associated with a shorter time to diagnosis, whereas higher cognitive scores at the initial community consultation were associated with longer diagnostic delays.

CONCLUSION: Diagnostic delay differed substantially by dementia subtype. These findings highlight the importance of community-based consultation pathways as key targets for reducing diagnostic delays, particularly for patients with non-AD dementias.},
}

Humans
Female
Retrospective Studies
Male
Aged
Japan
*Referral and Consultation/statistics & numerical data
*Dementia/diagnosis
*Delayed Diagnosis/statistics & numerical data
Aged, 80 and over
*Cognitive Dysfunction/diagnosis
Time Factors
*Alzheimer Disease/diagnosis

@article {pmid41699413,
year = {2026},
author = {Shaldam, MA and Carradori, S and Balaha, M and Guglielmi, P and Diomede, F and D'Agostino, I and Tawfik, HO},
title = {Patents involving monoamine oxidase (MAO): a comprehensive update (2022-2025) on its inhibitors and applications.},
journal = {Expert opinion on therapeutic patents},
volume = {},
number = {},
pages = {},
doi = {10.1080/13543776.2026.2633345},
pmid = {41699413},
issn = {1744-7674},
abstract = {INTRODUCTION: Monoamine oxidases (MAOs) A and B are key enzymes for the oxidative deamination of monoamine neurotransmitters, including dopamine, serotonin, norepinephrine, and tyramine. Selective MAO-B inhibitors are clinically employed as adjuvant therapies for neurodegenerative disorders, whereas selective MAO-A inhibitors are mainly considered third-line options in the treatment of depression. However, due to their function in regulating synaptic activity and exogenous monoamine metabolism, research in this field is continually expanding.

AREAS COVERED: This review summarizes patents on MAO inhibitors between 2022 and 2025. For the most investigated chemotypes (14 synthetic cores along with compounds from natural sources), biological activities were analyzed. The compounds are divided into two main categories, naturally occurring molecules and newly synthesized derivatives, with a total of 114 compounds discussed. To provide a more comprehensive perspective on the therapeutic potential of these inhibitors, additional treatment alternatives are also outlined.

EXPERT OPINION: Recently patented MAO inhibitors show notable properties, including significant isoform selectivity and therapeutic potential toward other diseases, such as fibromyalgia, CDKL5-deficient disorder, neuropathic pain, and Alzheimer's disease.},
}

@article {pmid41699353,
year = {2026},
author = {Casciati, A and Colantoni, E and Camera, F and Fratini, E and Casula, EP and Mencarelli, L and Di Lorenzo, F and Bonnì, S and Koch, G and Tanno, B and Merla, C},
title = {Deregulation of Synaptic Plasticity-Related MicroRNAs After Repetitive Transcranial Magnetic Stimulation in Alzheimer's Disease.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {442},
pmid = {41699353},
issn = {1559-1182},
support = {Regione Lazio POR FESR Lazio 2014-2020 n. A0375-2020-36546//Regione Lazio/ ; },
abstract = {Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-invasive therapeutic approach to slow down cognitive and functional decline in Alzheimer's disease (AD), potentially through plasticity-related mechanisms. MicroRNAs (miRNAs) play a crucial role in synaptic plasticity, and their deregulation contributes to AD-related cognitive impairment. In the present study, we first used a dosimetric model to translate rTMS field applied in AD patients to an in vitro system, identifying miRNAs as potential biomarkers responsive to rTMS. We found that rTMS induced in vitro deregulation of miR-26b, miR-125b, miR-181c, and miR-146a. Then, we investigated the effects of rTMS over precuneus during a 3-week, randomized, sham-controlled trial in AD patients. In patient serum, miR-26b, miR-30b, and miR-125b were significantly modulated in AD patients compared to healthy controls, though no significant modulation emerged between sham and rTMS groups before or after stimulation. Subsequently, the correlation analyses, which incorporated patients' cognitive scores, revealed that reduced miR-25 levels were significantly associated with cognitive improvement. However, no significant differences emerged between Real- and sham-rTMS correlation coefficients, likely due to the limited sample size, indicating that miR-25 may represent a general prognostic marker rather than a treatment-specific indicator. Furthermore, the ability of this miRNA to discriminate responders from non-responders, shown by ROC analysis, highlights its potential as a promising predictor of rTMS treatment efficacy to be validated in a larger patient cohort. Altogether, our findings suggest, for the first time, that rTMS may modulate specific miRNAs in AD patients, with miR-25 representing a pivotal key target for future validation studies.},
}

@article {pmid41699331,
year = {2026},
author = {Ercin, N and Besli, N and Beker, M and Celik, U},
title = {Non-canonical cell death in neurodegeneration: emerging mechanisms and therapeutic Frontiers.},
journal = {Apoptosis : an international journal on programmed cell death},
volume = {31},
number = {3},
pages = {72},
pmid = {41699331},
issn = {1573-675X},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/pathology/metabolism/genetics ; *Cell Death/drug effects ; Animals ; Necroptosis/drug effects ; Ferroptosis/drug effects ; Neuroprotective Agents/therapeutic use/pharmacology ; Pyroptosis/drug effects ; Oxidative Stress ; },
abstract = {Neurodegenerative diseases, specifically Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are defined by progressively increased neuronal loss that lacks curative therapies. Increasing evidence supports that non-canonical regulated cell death pathways including ferroptosis, necroptosis, pyroptosis, and parthanatos, are implicated in pathological mechanisms of neuroinflammation, and oxidative stress, and mitochondrial dysfunction, likely impacting neurodegenerative pathologies. In this review, we summarize the existing literature on the molecular pathways and potential pathogenic implications of these cell death pathways in neurodegenerative diseases, highlighting their upstream triggers, regulatory proteins, and downstream effectors. We also briefly describe representative pharmacological agents, including ferrostatin-1, necrostatin-1, MCC950 and PARP-inhibitors, that have shown neuroprotective effects in experimental studies. Experimental studies provide valuable information, but translation to clinical treatments presents barriers including overlapping regulated cell death mechanisms, constraints of bloodbrain barrier penetrance and concern for safety. Future development may come through concepts such as biomarker-based patient stratification strategies, multivalent interventions, and improved translational models. Identifying these new regulated cell death pathways may eventually provide new avenues to slow the progression of neurodegeneration and develop more targeted therapies.},
}

Humans
*Neurodegenerative Diseases/drug therapy/pathology/metabolism/genetics
*Cell Death/drug effects
Animals
Necroptosis/drug effects
Ferroptosis/drug effects
Neuroprotective Agents/therapeutic use/pharmacology
Pyroptosis/drug effects
Oxidative Stress

@article {pmid41699298,
year = {2026},
author = {Monroe, KM and Hong, S and Lewcock, JW and Yang, AC},
title = {Therapeutic targeting of neuroimmune mechanisms in neurodegeneration.},
journal = {Nature reviews. Drug discovery},
volume = {},
number = {},
pages = {},
pmid = {41699298},
issn = {1474-1784},
abstract = {Effective treatments for age-related chronic neurodegenerative diseases such as Alzheimer's disease remain limited, in part because the molecular drivers of cognitive decline are still not fully understood. Human genetic studies, together with detailed analysis of disease pathology, indicate that the immune system has an important influence on disease progression. Research to date has focused largely on microglia - specialized innate immune cells that reside within the central nervous system (CNS) - as functional studies combined with deep transcriptional profiling have improved our understanding of this innate immune cell type in neurodegeneration and have identified several potential therapeutic targets. Increasing evidence now shows that microglia coordinate diverse CNS and peripheral cell populations to shape disease outcomes. In this Review, we discuss these neuroimmune interactions, which reveal a more intricate framework for how the central and peripheral immune systems may influence neurodegeneration. These insights could redirect future drug discovery efforts towards immune targets that complement existing therapies aimed at core pathological features. We also outline how this knowledge suggests new therapeutic strategies and highlight a critical need for disease-specific neuroimmune biomarkers.},
}

@article {pmid41699292,
year = {2026},
author = {Nagai, M and Dote, K and Dasari, TW},
title = {Increased blood pressure variability - A risk of Alzheimer's disease?.},
journal = {Hypertension research : official journal of the Japanese Society of Hypertension},
volume = {},
number = {},
pages = {},
pmid = {41699292},
issn = {1348-4214},
}

@article {pmid41698644,
year = {2026},
author = {Xu, Z and Li, X and Wang, S and Lyu, J and Zhu, S and Chen, S and Li, Y and Zhang, Y and Wang, F and Duan, R},
title = {Diminazene attenuates astrocytic oxidative stress and neuronal ferroptosis via miR-10b-3p/NOX4 axis in Alzheimer's Disease Model.},
journal = {Neuropharmacology},
volume = {},
number = {},
pages = {110880},
doi = {10.1016/j.neuropharm.2026.110880},
pmid = {41698644},
issn = {1873-7064},
abstract = {PURPOSE: Diminazene (DIZE), an agonist of the Ang-(1-7) system, has been proven to suppress astrocytic neuroinflammatory responses in Alzheimer's disease (AD). NADPH oxidase 4 (NOX4) is abundantly expressed in astrocytes and critically mediates oxidative stress damage and ferroptosis. However, the mode of DIZE in AD-related NOX4 overactivation and ferroptosis remains to be revealed.

METHODS: Male APP/PS1 mice received DIZE and the ferroptosis inhibitor Liproxstatin-1 (LIP) treatment. Behavioral tests, Nissl staining, Western blotting, ELISA and immunofluorescence were performed to evaluate the effects of DIZE on neuronal loss, synaptic damage, inflammation and iron accumulation. Astrocytes from APP/PS1 mice were underwent high-throughput miRNA sequencing to identity the most differentially expressed miRNAs after DIZE administration. Subsequently, the role of this miRNA in DIZE's anti-ferroptosis impact within primary astrocytes was explored.

RESULTS: DIZE markedly reduced iron accumulation while lowering oxidative stress and inflammation in APP/PS1 mice. Simultaneously, DIZE significantly mitigated cognitive deficits and synaptic injury in APP/PS1 mice. DIZE suppressed the expression level of NOX4 and upregulated miR-10b-3p. Importantly, miR-10b-3p levels were notably elevated in astrocytes of APP/PS1 mice administered DIZE, targeting the NOX4 protein. Inhibition of miR-10b-3p expression significantly reversed the therapeutic effect of DIZE.

CONCLUSION: These findings indicate that DIZE suppresses astrocytic oxidative stress and neuronal ferroptosis via miR-10b-3p/NOX4 axis in AD model.},
}

@article {pmid41698629,
year = {2026},
author = {Patwekar, F and Patwekar, M and Wei, LS and Rather, GA and Mohammed, A and Hussain, MS and Gupta, G and Fuloria, S and Fuloria, NK},
title = {Marine-Derived bioactive compounds from Aquaculture: Receptor-Mediated neuroprotection in neurodegenerative disorders.},
journal = {Brain research},
volume = {},
number = {},
pages = {150208},
doi = {10.1016/j.brainres.2026.150208},
pmid = {41698629},
issn = {1872-6240},
abstract = {Neurodegenerative diseases, like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and ischemic stroke (IS), are a major global health challenge because of their complex, multifactorial pathology, and the lack of effective disease-modifying therapies. In recent years, aquaculture-derived marine bioactive molecules like fucoidan, phlorotannins, fucoxanthin, laminarin, alginate oligosaccharides, and C-phycocyanin have developed as promising agents for neuroprotection with their structural diversity and multi-target biological activity. This review showcase predominantly preclinical evidence, including in silico molecular docking analyses, in vitro functional assays, and in vivo animal models, to critically understand the receptor-mediated mechanisms with the neuroprotective actions of marine bioactives originated from aquaculture systems. Available studies shows these compounds can modulate large neuro-receptor systems, like cholinergic, dopaminergic, GABAergic, glutamatergic, toll-like, and nuclear receptors, leading in attenuation of oxidative stress, lowering of neuro-inflammation, regulation of neurotransmission, and conservation of mitochondrial and synaptic function. However, the positive approach of mechanistic evidence varies across compounds and receptor classes, with large interactions assisted by functional outcomes instead of direct receptor-binding validation. The review even discusses emerging and enabling technologies like brain organoids, multi-electrode array platforms, omics-based profiling, and artificial intelligence assisted drug discovery, which are increasingly utilized to refine mechanistic understanding and optimize marine-derived products. Importantly, current evidence stay largely preclinical, with little human studies and a lack of validated receptor-specific biomarkers. Overall, this review provides a well-balanced, evidence-based assessment of aquaculture-derived marine bioactive as potential neurotherapeutic agents.},
}

@article {pmid41698556,
year = {2026},
author = {Zavala-Ocampo, LM and Mendoza-Franco, G and Aparicio-Bautista, DI and López-Camacho, PY and García-Sierra, F and Basurto-Islas, G},
title = {Petiveria alliacea L. Methanolic Extract Inhibits Amyloid-β Aggregation and Enhances Cell Viability in SH-SY5Y Cells: In Vitro and In Silico Evidence.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {121381},
doi = {10.1016/j.jep.2026.121381},
pmid = {41698556},
issn = {1872-7573},
abstract = {Petiveria alliacea L. is a member of the Petiveriaceae botanical family, distributed in America and some Asian countries, and is used as a medicinal plant to enhance memory. Pharmacological studies have demonstrated that it reduces oxidative damage and regulates the cholinergic function in the brain, exhibiting a significant memory-enhancing potency.

AIM OF THE STUDY: This study evaluated the effect of P. alliacea by inhibiting polymerization and disassembly of amyloid β (Aβ) oligomers in SH-SY5Y cells.

MATERIAL AND METHODS: SH-SY5Y cells were incubated with Aβ peptide oligomers and treated with either methanol (PMF) or hexane fraction (PHF) of P. alliacea at different time points. Cellular viability and toxicity were assessed by MTT assay. Inhibition of Aβ polymerization in cells was assessed using the thioflavin T (ThT) assay and immunofluorescence. The chemical profile of P. alliacea was analyzed by GC-MS. Bioinformatic data analysis was performed using the STITCH database, and PPIs were identified using STRING.

RESULTS: PMF inhibited polymerization and induced disassembly of Aβ oligomers, leading to a possible neuroprotective effect in SH-SY5Y cells. A total of 73 compounds were identified in PHF and 70 in PMF; among these, 14 were associated with Aβ activity based on bioinformatic analyses. Bioinformatic analysis identified that several metabolites from P. alliacea may interact with proteins involved in neuroinflammatory pathways.

CONCLUSIONS: P. alliacea demonstrates substantial anti-amyloidogenic capabilities and protects SH-SY5Y cell viability in an Aβ-induced cytotoxicity model. Our findings suggest that P. alliacea is a promising candidate for the development of novel therapeutic interventions for neurodegenerative diseases such as Alzheimer's disease.},
}

@article {pmid41698553,
year = {2026},
author = {Pocevičiūtė, D and Roth, B and Olofsson, A and Hansson, O and Wennström, M},
title = {APOE isotype-dependent regulation of IgG and IgA levels against different IAPP epitopes.},
journal = {Immunology letters},
volume = {},
number = {},
pages = {107152},
doi = {10.1016/j.imlet.2026.107152},
pmid = {41698553},
issn = {1879-0542},
abstract = {The efficient clearance of IAPP oligomers (IAPPo) by autoantibodies is crucial as increased plasma levels of IAPPo can induce microvascular alterations and Alzheimer's disease (AD)-characteristic amyloid-β deposition in the brain. We have recently demonstrated that plasma immunoglobulin (Ig) A levels against IAPPo, but not IgG, are reduced in an Apolipoprotein E (APOE) ε4 allele dose-dependent manner. In this study, we aimed to investigate if this APOE genotype-dependent impact can be explained by differences in IAPP epitope recognition by IgA and IgG. We found that the specificity for IAPP epitopes does not differ between IgG and IgA autoantibodies and that IgG and IgA autoantibodies are directed foremost against the C-terminus of the IAPP. However, IgG autoantibody levels against the N-terminus and midportion of IAPP increased significantly in AD patients with APOE44 compared to controls with APOE33, while the opposite was seen in IgA autoantibody levels. We propose that the IgG and IgA levels against different IAPP epitopes are APOE isotype-dependent, possibly due to differences in cytokine profile between various APOE genotypes or the need for different effector functions of IgG or IgA.},
}

@article {pmid41698489,
year = {2026},
author = {Bloch, L and Borys, K and Nensa, F and Friedrich, CM and , },
title = {MRI-based Radiomics and volumetrics for predicting the onset of Alzheimer's Disease with explainable machine learning.},
journal = {NeuroImage},
volume = {},
number = {},
pages = {121813},
doi = {10.1016/j.neuroimage.2026.121813},
pmid = {41698489},
issn = {1095-9572},
abstract = {The detection of Alzheimer's Disease (AD) using structural Magnetic Resonance Imaging (MRI) and Machine Learning (ML) often focuses on late-stage atrophy patterns. End-to-end deep learning models address this by considering MRI signal intensities. However, their explainability components typically focus on attention regions, neglecting underlying patterns. This work overcomes both problems by training and explaining time-to-event models utilizing Radiomics features. SHapley Additive exPlanations (SHAP) and high-level explanations were combined to interpret the effects of MRI texture, shape, and volumes, as well as neuro-psychological and cognitive tests, and socio-demographic features on the AD risk score. All models were trained and internally validated on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. External validation was performed on the Australian Imaging Biomarkers and Lifestyle flagship study of Ageing (AIBL) and the Open Access Series of Imaging Studies version 3 (OASIS-3). The results demonstrate that Radiomics features add value to models trained on cognitive tests, socio-demographics, genetics, and MRI volumes, particularly for long-term AD predictions. On average, the Radiomics-based models slightly outperformed the comparison models by between 0.11% points and 3.02% points in terms of Brier scores for the eight-year prediction. Despite varying data distributions during external validation, the models demonstrate moderate to high reproducibility. The analysis of Radiomics features uncovered complex associations with AD, including tissue with complex texture in the left entorhinal cortex, an irregular shape of the right amygdala, and a fine-granular texture of the left middle temporal gyrus. All models showed reasonable concordance with the Voxel-Based Morphometry (VBM).},
}

@article {pmid41698287,
year = {2026},
author = {Bengs, B and Swerdlow, RH and Burns, J and Slawson, C and , and McCoy, M and Sardiu, ME},
title = {Digital siblings unveil distinct molecular and clinical subtypes in Alzheimer's disease via omics-driven profiling.},
journal = {Journal of the neurological sciences},
volume = {482},
number = {},
pages = {125812},
doi = {10.1016/j.jns.2026.125812},
pmid = {41698287},
issn = {1878-5883},
abstract = {Alzheimer's Disease (AD) is a multifactorial neurodegenerative disorder marked by extensive biological and clinical heterogeneity, complicating prognosis and personalized treatment strategies. Because of this, data-driven methods that characterize patient similarity and subgroup-specific molecular signatures are essential for advancing precision medicine in AD. We applied manifold learning techniques to fuse proteomic, demographic, and clinical data from 438 AD patients, enabling the identification of "digital siblings"-patients with closely related molecular and clinical profiles within a learned latent space. This framework enabled robust clustering and stratification of patient subgroups, revealing distinct pathway enrichments associated with clinical traits such as age, alcohol use, and comorbidities. Moreover, structural and network analyses of key protein interactions within these subgroups provided insights into the molecular mechanisms potentially driving disease heterogeneity. While this approach primarily clustered patients based on comprehensive molecular patterns, it lays critical groundwork for developing predictive models that incorporate longitudinal progression and intervention outcomes. Overall, our results underscore the potential of "digital sibling"-based stratification to refine patient subgroup characterization and serve as a foundation for future dynamic modeling in AD.},
}

@article {pmid41698243,
year = {2026},
author = {Khan, F and Pandit, D and Lalan, S and Rane, MR},
title = {Comprehensive multimodal prediction of Alzheimer's disease.},
journal = {Biomedical physics & engineering express},
volume = {},
number = {},
pages = {},
doi = {10.1088/2057-1976/ae4630},
pmid = {41698243},
issn = {2057-1976},
abstract = {Alzheimer's disease (AD) classification using machine learning has increasingly relied on multimodal inputs such as Magnetic Resonance Imaging (MRI), cognitive assessments, and biological markers. This study evaluates whether integrating these sources enhances predictive performance compared to using them independently. Neural networks were trained on data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to classify subjects into Cognitively Normal (CN), Mild Cognitive Impairment (MCI), and AD categories using unimodal, bimodal, and trimodal input configurations. Contrary to expectations, multimodal models did not consistently outperform unimodal ones. The highest test accuracy (81%) was achieved by both the cognitive-only and trimodal models, with the former also demonstrating superior class-wise performance. These findings suggest that neuropsychological features may carry greater diagnostic value than imaging or fluid biomarkers, underscoring the importance of more targeted data fusion strategies. Furthermore, the inclusion of biological markers did not significantly improve early MCI detection, likely due to their limited dimensionality and the model's constrained ability to extract meaningful patterns from such inputs.},
}

@article {pmid41697960,
year = {2026},
author = {Hupalo, D and McCauley, JL and Gomez, L and Griswold, AJ and Hoher, G and Konidari, I and Lorenzo, J and Parker, GS and Pascual, J and Sandford, AR and Whitehead, PL and Davis, DA and Garamszegi, S and Gultekin, SH and Sun, X and Vontell, RT and Chatigny, M and Chernicky, D and Constant, MM and Darling, IG and Ennulat, DJ and Esposito, JM and Morris, K and Lawton, ES and Morakabati, NR and Oduor, P and Rodgers, AP and Sang, LA and Sullivan, KM and Tabit, CJ and Turpin, T and Zeabi, A and Zheng, T and Berretta, S and Klengel, T and Ruzicka, WB and Oakley, DH and Blanchard, T and Ho, E and Johnson, R and LeFevre, A and Bustamante, M and Haroutunian, V and Marino, C and Purohit, DP and Wysocki, M and Glausier, JR and Lewis, DA and Nagra, RM and Alba, C and Martin, J and Rice, E and Rosenberger, J and Smith, G and Sukumar, G and Tompkins, M and Wilkerson, MD and Dalgard, CL and Scott, WK},
title = {The NeuroBioBank whole-genome catalogue of human brain donors with central nervous system disorders.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag057},
pmid = {41697960},
issn = {1460-2156},
abstract = {CNS diseases are a prevailing cause of morbidity and mortality worldwide, and are influenced by environmental and biological factors, including genetic risk. Here, we generated genome-wide genetic data on a large cohort of brain tissue donors with in-depth clinical and neuropathological phenotyping, allowing for broad investigations into the risk and mechanisms of these neurological, neurodevelopmental, and psychiatric conditions. This resource consists of 9,663 donors with array-based genotyping and 9,543 donors with whole-genome sequencing completed. The clinical diagnoses of these donors include 148 central nervous system diseases clustered into 15 broad categories by International Classification of Diseases-10 (ICD-10) coding. These donors were collected by six repositories comprising the National Institutes of Health NeuroBioBank, with an average participant age of 60 years. While primarily older individuals of European descent, the cohort also contains younger donors and individuals from non-European backgrounds. Variants were detected in whole-genome sequencing (WGS), normalized and annotated to describe their functional impact, resulting in 171,121,209 unique variants and 1,078,774 non-silent variants. These raw and normalized data have been made available as a neurogenomics resource in the National Institute of Mental Health Data Archive (NIMH NDA) (nda.nih.gov), combined with donor-matched deep demographic and phenotypic data from the NeuroBioBank Portal (neurobiobank.nih.gov). To illustrate applications, we replicated the strong association observed in previous studies between pathogenic CAG nucleotide repeat expansions in the HTT gene with the clinical diagnosis of Huntington's disease, as well as associations of the APOE gene with Alzheimer's disease, and examined the association of polygenic risk scores with the three most common disease diagnoses in the cohort.},
}

@article {pmid41697952,
year = {2026},
author = {Jamuna, NA and Arumugam, D and Mandal, S},
title = {Hydration Shell of PEO-PPO-PEO Block Copolymer Assembly Controls the Modulation of Protein Aggregation: Synergistic Inhibition of Fibrillation Using Trehalose and Protection from Cu[2+]-Induced Fibrillation.},
journal = {ACS applied bio materials},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsabm.5c02236},
pmid = {41697952},
issn = {2576-6422},
abstract = {Amyloid aggregation is a key process involved in many neurodegenerative diseases including Alzheimer's disease. It affects the brain and peripheral tissues, where different types of protein aggregates are accumulated. Pluronic PEO-PPO-PEO block copolymer self-assemblies are widely used as nanocarriers for the brain-targeted delivery of therapeutic agents. Elucidating protein aggregation at these polymer interfaces can provide critical insights into how macromolecular crowding and protein-polymer interactions influence the kinetics of protein aggregation. Here, we investigate the roles of two pluronic copolymers, namely, P123 and F127, which have a similar size of hydrophobic PPO block but different PEO block length on protein aggregation using hen egg white lysozyme (HEWL) as a model protein. Our study reveals that the more hydrated F127 self-assemblies with thicker PEO hydration shells accelerate the onset of protein-aggregation yet moderately retard the extent of overall fibril formation. On the other hand, the less hydrated P123 self-assemblies with compact hydration shells significantly delay the onset of protein aggregation and efficiently inhibit fibril formation. The binding of protein within the hydrated and longer PEO corona of F127 micelles favors accelerated kinetics of β-rich oligomers and fibril formation without a delay phase through soft-chemical interactions. For the less hydrated P123 micellar assemblies, the hydrophobic interactions and strong excluded volume effects probably contribute to stabilization of the protein. The addition of the widely used osmolyte trehalose further delays the protein aggregation and significantly retards the fibril formation through the synergistic inhibitory effects of trehalose and polymer assemblies. The trehalose-bearing pluronic micelles can, therefore, emerge as a potentially efficient inhibitor with great promise in therapeutic applications. The pluronic self-assemblies are also found to be highly effective in protecting the protein from toxicity associated with Cu[2+] induced enhanced amyloid fibrillation. The binding of Cu[2+] within the hydrated PEO corona makes them inaccessible to protein interactions and fibril formation.},
}

@article {pmid41697903,
year = {2026},
author = {Muniz-Perez, A and Meyer-Acosta, KK and Boyana, S and Ponnala, V and McMahon, CL and Aruk, A and Elizalde, A and Hsieh, J},
title = {Modest neurodevelopment impacts of APOE4 in a human brain organoid model of low-grade SARS-CoV-2 infection.},
journal = {Developmental neuroscience},
volume = {},
number = {},
pages = {1-15},
doi = {10.1159/000550957},
pmid = {41697903},
issn = {1421-9859},
abstract = {INTRODUCTION: The long-term neurological consequences of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, are an area of growing concern, particularly for prenatally exposed individuals. Prior research has shown that APOE4, the leading genetic risk factor for late-onset Alzheimer's disease, is associated with increased COVID-19 severity and enhanced SARS-CoV-2 neurotropism. However, whether the interaction between APOE4 and SARS-CoV-2 infection leads to adverse neurodevelopmental outcomes remains unclear. Using human induced pluripotent stem cell derived cortical and ganglionic eminence organoids (COs and GEOs) to model neurodevelopment, we have previously reported that SARS-CoV-2 preferentially infects glial cells, and that APOE4 promotes gliogenesis in COs and accelerates GABAergic neuron differentiation in GEOs. Here, we build upon our previous work by using COs and GEOs to examine how APOE4 modifies cellular responses to SARS-CoV-2 during late gestational development.

METHODS: Using low viral titers to better mimic natural infection, COs and GEOs were infected at 220-270 DIV, aligning with the third trimester, and were analyzed 7 days post infection.

RESULTS: We observed region-specific, APOE4-dependent changes. In infected COs, APOE4 elevated immature astrocyte marker, suggesting a genotype-dependent glial response. Additionally, infected GEOs exhibited reduced marker expression for mature neurons within both genotypes. Notably, APOE4 and infection interacted to modulate immature neuron expression in a region-specific manner.

CONCLUSION: Taken together, this study suggests that APOE4 modulates region-specific responses to low-grade SARS-CoV-2 infection, underscoring the importance of exploring how genetic risk factors alter neurodevelopmental vulnerability to prenatal viral infection.},
}

@article {pmid41697767,
year = {2026},
author = {De Oliveira, RL and Pinz, MP and Voss, GT and Da C Rodrigues, K and Vogt, AG and Dos S Barboza, V and De A Vaucher, R and Giongo, JL and Lima, AS and Alves, D and Quines, CB and Fidelis, EM and Pinton, S and Savegnago, L and Luchese, C},
title = {Redox modulation contributes to the antidepressant-like and neuroprotective effects of 7-chloro-4-(phenylselanyl)quinoline in an Alzheimer's disease model.},
journal = {Redox report : communications in free radical research},
volume = {31},
number = {1},
pages = {2626641},
doi = {10.1080/13510002.2026.2626641},
pmid = {41697767},
issn = {1743-2928},
mesh = {Animals ; *Alzheimer Disease/drug therapy/metabolism/chemically induced ; Mice ; Male ; *Neuroprotective Agents/pharmacology/therapeutic use ; Disease Models, Animal ; *Antidepressive Agents/pharmacology/therapeutic use ; *Quinolines/pharmacology/therapeutic use ; Oxidation-Reduction/drug effects ; Amyloid beta-Peptides ; Depression/drug therapy ; Lipid Peroxidation/drug effects ; Acetylcholinesterase/metabolism ; Corticosterone/blood ; Hippocampus/drug effects/metabolism ; },
abstract = {OBJECTIVES: Alzheimer's disease (AD) is characterized by cognitive impairment and neuropsychiatric disturbances, including depression, both tightly linked to redox imbalance and neuroinflammatory activation. This study investigated whether the selenium-containing compound 7-chloro-4-(phenylselanyl)quinoline (4-PSQ) mitigates behavioral and biochemical alterations in a β-amyloid (Aβ)-induced mouse model of AD through modulation of redox-regulated pathways.

METHODS: Male Swiss mice received intracerebroventricular Aβ (25-35) or saline (3 µL/site) and were treated orally for seven days with 4-PSQ (1 mg/kg), paroxetine (1 mg/kg), or donepezil (1 mg/kg). Depressive-like behavior and memory performance were assessed, followed by determination of plasma corticosterone, reactive species levels, lipid peroxidation, antioxidant enzyme activities, neuroinflammatory mediators, and acetylcholinesterase (AChE) activity in the hippocampus and prefrontal cortex of mice.

RESULTS: 4-PSQ significantly reversed Aβ-induced depressive behavior and memory impairment. The compound normalized plasma corticosterone levels, reduced reactive species and lipid peroxidation, and restored antioxidant enzyme activity. It also decreased the expression of inflammatory markers while regulating AChE activity, indicating concomitant modulation of redox, neuroimmune, and cholinergic pathways.

CONCLUSION: By restoring redox homeostasis and attenuating neuroinflammatory responses, 4-PSQ effectively counteracted behavioral and biochemical disruptions associated with Aβ toxicity. These findings support 4-PSQ as a promising selenium-based therapeutic candidate targeting redox-driven features of AD, including comorbid depression and cognitive decline.},
}

Animals
*Alzheimer Disease/drug therapy/metabolism/chemically induced
Mice
Male
*Neuroprotective Agents/pharmacology/therapeutic use
Disease Models, Animal
*Antidepressive Agents/pharmacology/therapeutic use
*Quinolines/pharmacology/therapeutic use
Oxidation-Reduction/drug effects
Amyloid beta-Peptides
Depression/drug therapy
Lipid Peroxidation/drug effects
Acetylcholinesterase/metabolism
Corticosterone/blood
Hippocampus/drug effects/metabolism

@article {pmid41697669,
year = {2026},
author = {Coughlan, GT and Ourry, V and Townsend, D and Klinger, H and Brown, JA and Cuppels, M and Betthauser, T and Langhough, R and Cody, K and Seto, M and Birkenbihl, C and Li, A and Farrell, M and Thibault, E and Kivisäkk Webb, P and Arnold, S and Rissman, RA and Properzi, M and Schultz, A and Johnson, K and Langford, O and Donohue, MC and Villeneuve, S and Johnson, SC and Yang, HS and Manson, JE and Sperling, R and Buckley, RF and , },
title = {Sex Differences in P-Tau217, Tau Aggregation, and Cognitive Decline.},
journal = {JAMA neurology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaneurol.2025.5670},
pmid = {41697669},
issn = {2168-6157},
abstract = {IMPORTANCE: Among individuals with high levels of amyloid-β (Aβ), women exhibit higher insoluble tau burden and accumulation than age-matched men. It remains unclear whether this sex difference is influenced by soluble phosphorylated tau (p-tau), a biomarker that changes early in Alzheimer disease.

OBJECTIVE: To investigate whether sex and aggregated Aβ synergistically predict plasma phosphorylated tau 217 (p-tau217) levels and whether levels of p-tau217 predict cross-sectional and longitudinal tau aggregation in a sex-specific manner (as measured by positron emission tomography [PET]).

This longitudinal study analyzed data between September 7, 2024, and October 29, 2025, from 1 clinical trial cohort and 4 observational study cohorts including men and women without cognitive impairment who had undergone multiple assessments via tau PET (18F-flortaucipir or 18F-MK-6240) and plasma p-tau217 assay at baseline. Cognitive performance was measured with the Preclinical Alzheimer Cognitive Composite. Data on cognitive performance were available from 3 of the 5 cohorts for a mean of 4.6 years (SD, 3.1 years). Across the 5 cohorts, the mean follow-up for tau PET was 3.6 years (SD, 1.7 years).

EXPOSURES: Self-reported sex (male or female), tau PET, and p-tau217 assay.

MAIN OUTCOMES AND MEASURES: The primary analyses used linear and mixed-effects models to assess baseline and longitudinal sex × p-tau217 interactions for 9 tau PET regions. The secondary analyses assessed sex × p-tau217 interactions for cognitive change using the Preclinical Alzheimer Cognitive Composite.

RESULTS: Across the 5 cohorts, there were a total of 1292 participants (63.6% women; mean age, 70.6 [SD, 6.4] years) with tau PET assessments. Compared with men, women had significantly higher baseline p-tau217 levels at higher aggregated Aβ Centiloid levels (β, -0.21 [95% CI, -0.37 to -0.05], P = .009; highest interaction was found in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration [A4/LEARN] cohort). The sex × p-tau217 interactions at baseline were significant for 1 tau PET region in the Harvard Aging Brain Study (HABS) cohort, for 2 tau PET regions in the A4/LEARN cohort, for 6 tau PET regions in the Wisconsin Registry of Alzheimer's Prevention (WRAP) cohort, and for 4 tau PET regions in the Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) cohort. Longitudinal interactions were significant for 4 tau PET regions in the A4/LEARN cohort, for 5 tau PET regions in both the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort and the WRAP cohort, and for 2 PET regions in both the HABS cohort and the PREVENT-AD cohort. Compared with men, women displayed greater tau deposition and accumulation at higher p-tau217 levels. Use of a secondary model showed women with higher p-tau217 levels also exhibited faster rates of cognitive decline relative to men in the both the WRAP cohort and the ADNI cohort.

CONCLUSION AND RELEVANCE: These findings add to growing evidence that women have a differential tau response to Aβ that may emerge at the point of p-tau secretion. These findings have implications for the therapeutics and diagnostics of preclinical Alzheimer disease.},
}

@article {pmid41697625,
year = {2026},
author = {Günsel, A and Karanlık, CC and Taslimi, P and Günsel, H and Taskin-Tok, T and Bilgiçli, AT and Özden, EM and Gülçin, İ and Erdoğmuş, A and Yarasir, MN},
title = {Water-soluble phthalocyanines with non-peripheral naphthoxy-sulfonate substituents: computational docking, biological and sono-photochemical investigations.},
journal = {Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology},
volume = {},
number = {},
pages = {},
pmid = {41697625},
issn = {1474-9092},
abstract = {This study reports the synthesis of a novel ligand, sodium 6-(2,3-dicyanophenoxy)naphthalene-2-sulfonate (1), and the corresponding non-peripherally substituted metallophthalocyanines (MPcs) [M = Zn(II) (2), Ga(III) (3); X = Cl, In(III) (4); X = Cl]. These compounds were functionalized with 6-naphthoxy-2-sulfonic acid sodium salt groups. Given the limitations of conventional photodynamic therapy (PDT), we investigated the potential of sonophotodynamic therapy (SPDT), a dual-modality approach combining light and ultrasound, to enhance singlet oxygen ([1]O2) production. Among the synthesized metallophthalocyanines, the zinc(II) complex (2) shows the highest [1]O2 production in both organic and aqueous media under both photochemical and sonophotochemical conditions, showing promise for SPDT applications. Furthermore, the inhibitory effects of these complexes on acetylcholinesterase (AChE) and human carbonic anhydrase isoenzymes (hCA I and II), important targets for Alzheimer's disease, glaucoma, and epilepsy, were evaluated. The compounds showed strong inhibition with Ki values ranging from 130.31 ± 6.18 to 157.47 ± 9.37 µM for hCA I (compared to AZA: 177.41 ± 11.40 µM), 99.18 ± 8.13 to 106.72 ± 8.50 µM for hCA II (compared to AZA: 143.51 ± 9.94 µM) and 0.31 ± 0.03 to 1.21 ± 0.01 µM for AChE (compared to TAC: 1.24 ± 0.21 µM). Molecular docking revealed strong binding affinities: In(III)-Pc (4) showed the highest affinity for AChE (BE: -26.96 kcal/mol), while Ga(III)-Pc (3) preferentially bound to hCA I and II (BE: -13.90 and - 15.39 kcal/mol, respectively). These findings position the synthesized MPcs as multifunctional agents for SPDT and enzyme-targeted therapies.},
}

@article {pmid41697572,
year = {2026},
author = {Liu, R and Deng, Q and Gong, L and Yang, L},
title = {Role Shift of Glial Cells from Physiology to Pathology in Alzheimer's Disease: The Regulatory Impact of Exercise.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {41697572},
issn = {1995-8218},
abstract = {Alzheimer's disease (AD) is a widespread neurodegenerative condition with cognitive and behavioral decline. Astrocytes and microglia, the primary glial cells in the central nervous system, are deeply involved in AD development. Their functional impairments, such as astrocytic shifts in phenotype, blood-brain barrier breakdown, and glymphatic failure, along with microglial "dual phagocytic dysfunction", including impaired amyloid-beta (Aβ) clearance and overactive phagocytosis of healthy synapses, imbalanced inflammation, and metabolic abnormalities, are key drivers of disease progression. Growing research indicates that physical activity, as a non-drug intervention, exerts significant regulatory effects on glial cell function. Exercise regulates the polarization of both astrocytes and microglia, enhances their phagocytic abilities, improves mitochondrial metabolism, and alleviates neuroinflammatory responses. This review outlines the normal physiological roles of astrocytes and microglia, details their pathological alterations in AD, and explores how exercise targets these glial cells to alleviate AD pathology, offering valuable perspectives for potential therapeutic approaches.},
}

@article {pmid41697348,
year = {2026},
author = {Mohammadi, S and Ghorbandaiepour, T and Zahmatkesh, M and Karimi-Zandi, L and Mirzakhani, A},
title = {Potential Role of Extrapineal Melatonin as a Neurohormone in the Pathophysiology of Alzheimer's Disease: Unanswered Questions.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00401},
pmid = {41697348},
issn = {1948-7193},
abstract = {Melatonin, the pineal gland hormone, is produced in various extrapineal tissues as well, and its reduction has been reported in sporadic Alzheimer's disease (AD). The exact reason for tissue melatonin synthesis, despite the pineal source of melatonin, is not well understood, although the melatonin decline in the biological fluids of AD patients is a reasonable justification for melatonin therapy in cognitive impairment. However, the effectiveness of melatonin administration in AD patients was insignificant. Additionally, there is evidence of alterations in local melatonin synthesis in pathological situations, and little is known regarding its physiological or pathological modulators. Recently, the decline in the hippocampal enzyme of melatonin synthesis has been reported in amyloid-β neurotoxicity. It has been shown that reduced hippocampal melatonin synthesis by siRNA has been associated with cognitive decline. This review has included AD studies that noticed the impacts of melatonin prescription on memory and cognitive function in both animal research and randomized controlled trials, while also reviewing the available data regarding the alterations in brain tissue melatonin synthesis. This review highlights the role of brain (extrapineal) tissue melatonin synthesis in cognitive function in AD pathophysiology. Understanding the induction pattern of extrapineal melatonin synthesis, dosing optimization of exogenous administration, noting gender-specific differences, and clarifying microbiota-melatonin interactions point toward new approaches that may enhance the effectiveness of melatonin-based interventions for preventing or delaying AD progression.},
}

@article {pmid41697185,
year = {2026},
author = {Cottrell, S and Yoon, S and Wei, X and Dickson, A and Wei, GW},
title = {Computational Drug Repurposing for Alzheimer's Disease via Sheaf Theoretic Population-Scale Analysis of snRNA-Seq Data.},
journal = {Journal of medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jmedchem.5c02862},
pmid = {41697185},
issn = {1520-4804},
abstract = {Single-cell and single-nucleus RNA sequencing are used to reveal heterogeneity in cells, showing a growing potential for precision and personalized medicine. Nevertheless, sustainable drug discovery must be based on a population-level understanding of molecular mechanisms, which calls for a population-scale analysis of this data. This work introduces a sequential target-drug selection model for drug repurposing against Alzheimer's Disease (AD) targets inferred from snRNA-seq data of AD progression- involving hundreds of thousands of nuclei from multipatient and multiregional studies. We utilize Persistent Sheaf Laplacians (PSL) to facilitate a Protein-Protein Interaction (PPI) analysis inferred from disease related differential gene expression (DEG). We then use an ensemble of machine learning models to predict repurpose-able compounds. We screen the efficacy of different small compounds and further examine their central nervous system relevant ADMET properties, resulting in a list of potential molecular targets as well as pharmaceutical lead candidates for AD treatment.},
}

@article {pmid41697144,
year = {2026},
author = {Lee, WT and Wang, JT and Tsai, MH and Fang, YW},
title = {GLP-1 receptor agonists reduce dementia and Alzheimer disease risk in diabetic Patients with CKD.},
journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association},
volume = {},
number = {},
pages = {},
doi = {10.1093/ndt/gfag032},
pmid = {41697144},
issn = {1460-2385},
abstract = {BACKGROUND: Patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) are at increased risk of developing dementia and Alzheimer's disease due to vascular dysfunction, insulin resistance, and chronic inflammation. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown neuroprotective properties; however, their impact on dementia risk in diabetic patients with CKD remains uncertain. This study evaluated the association between GLP-1RAs use and dementia risk in patients with CKD stage 3 or later, compared to dipeptidyl peptidase-4 inhibitors (DPP4is).

METHODS: This retrospective cohort study analyzed data from the TriNetX global research network, comprising electronic medical records from 67 healthcare organizations in the US Collaborative Network. We identified patients with CKD stage 3 or later and T2DM who were newly prescribed GLP-1RAs or DPP4is between January 1, 2015, and December 31, 2020. Patients with prior GLP-1RAs or DPP4is use, a dementia diagnosis within 12 months before the index date, or recent hospitalization were excluded. The primary outcome was the incidence of dementia, Alzheimer's disease, vascular dementia, frontotemporal dementia, Parkinson's disease, extrapyramidal and movement disorders, and dementia with Lewy bodies, assessed over a follow-up period ranging from 90 days to 5 years. Statistical analyses included Kaplan-Meier survival curves and Cox proportional hazards models.

RESULTS: GLP-1RAs use was associated with a significantly lower risk of dementia (HR: 0.80, 95% CI: 0.71-0.91, p = 0.001) and Alzheimer's disease (HR: 0.76, 95% CI: 0.59-0.98, p = 0.033) compared to DPP4is use. However, no significant differences were observed in vascular dementia, frontotemporal dementia, Parkinson's disease, extrapyramidal and movement disorders, or dementia with Lewy bodies.

CONCLUSIONS: GLP-1RAs therapy may reduce the risk of dementia and Alzheimer's disease in patients with CKD stage 3 or later, offering potential neuroprotective benefits beyond glycemic control. Research is needed to confirm these findings and optimize treatment strategies for this vulnerable population.},
}

@article {pmid41696979,
year = {2026},
author = {Shergill, JK and Azarnia Tehran, D},
title = {Endocytic scaffolds at the crossroads of Alzheimer's disease and neuronal aging.},
journal = {Biological chemistry},
volume = {},
number = {},
pages = {},
pmid = {41696979},
issn = {1437-4315},
abstract = {More than a century after Alois Alzheimer's neuropathological description, the mechanisms driving Alzheimer's disease (AD) remain only partially understood, and the failure of most clinical trials underscores the need to identify and target alternative pathogenic pathways. Recent genetic, biochemical, and cellular studies support the view that AD is characterized by early alterations in the endolysosomal system and implicate multiple endocytic scaffold proteins as key drivers of AD progression. In this review, we summarize the current knowledge of five endocytic scaffold proteins, CALM, AP-2, BIN1, CD2AP, and ITSN1, which have been identified as AD risk factors by genome-wide association studies. We describe how, under physiological conditions, they couple membrane remodeling to intracellular signaling, whereas in AD they influence amyloid precursor protein trafficking, amyloid-β (Aβ) generation, tau pathology, and synaptic integrity. Finally, we propose a model in which cell type-specific and age-dependent dysfunction of endocytic scaffolds defines a pathogenic hotspot of proteostasis failure and offers new entry points for therapeutic intervention.},
}

@article {pmid41696940,
year = {2026},
author = {Li, H and Li, M and Li, C and Liu, D and Kang, Y and Tang, Y and Feng, P and Qian, C},
title = {A Preventable Alzheimer's Disease Microneedle Patch with Synaptic Protection and NLRP3 Inflammasome Suppression in Microglia during Smoking Cessation.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.6c00812},
pmid = {41696940},
issn = {1936-086X},
abstract = {Long-term smoking elevates the risk of Alzheimer's disease (AD), yet it is overlooked that nicotine replacement therapy (NRT) inadvertently exacerbates tau pathology during smoking cessation. Here, we mimicked the nicotine replacement patch to design a microneedle patch for the prevention of Alzheimer's disease (PADM), capable of regulating microglia with synaptic protection and NLRP3 inflammasome suppression during smoking cessation. We first demonstrated that nicotine (NIC) transiently preserved synaptic integrity by upregulating the "do not eat me" signal SIRPα on microglia, reducing aberrant synaptic pruning and enhancing amyloid-β (Aβ) clearance in early AD. However, the NLRP3 inflammasome of microglia was activated after NIC intervention and exhibited tau hyperphosphorylation in neurons in late pathology of AD. To address this, we further integrated a natural NLRP3 inhibitor, resveratrol (RES), with NIC into a bilayer microneedle patch. The tip layer enabled sustained low-dose NIC release for smoking cessation, while the backing gel reservoir slowly released RES to suppress neuroinflammation. In APP/PS1 mice, early smoking cessation intervention improves cognition and reduces Aβ burden, and continuous RES delivery prevented late-stage tau pathology. The PADM patch offers a safe prophylactic approach to AD during smoking cessation in high-risk populations.},
}

@article {pmid41696896,
year = {2026},
author = {Jubair, H},
title = {Glial cells in dementia: From cellular dysfunction to therapeutic frontiers.},
journal = {Cell transplantation},
volume = {35},
number = {},
pages = {9636897251414216},
doi = {10.1177/09636897251414216},
pmid = {41696896},
issn = {1555-3892},
mesh = {Humans ; *Neuroglia/metabolism/pathology ; *Dementia/pathology/therapy/metabolism ; Animals ; },
abstract = {Neurodegenerative dementias, including Alzheimer's disease and vascular dementia, have long been viewed through a neuron-centric lens. However, growing evidence highlights the indispensable and multifaceted roles of glial cells, astrocytes, microglia, and oligodendrocytes in both the onset and progression of these disorders. While prior reviews have cataloged glial dysfunction in isolation, this review offers a novel, integrative framework that maps the interconnected roles of glial subtypes across molecular, cellular, and circuit-level pathology in dementia. We critically synthesize recent advances in single-cell RNA sequencing, spatial transcriptomics, and glial imaging to redefine glial heterogeneity and function in disease states. Special emphasis is placed on the dynamic cross talk between glial populations and the feedback loops that govern their dual roles in neuroprotection and neurodegeneration. Furthermore, we examine emerging therapeutic strategies targeting glial-specific pathways, including NF-κB, JAK/STAT, CSF1R, and TREM2 signaling, as well as remyelinating agents and stem cell-based interventions. By integrating glial biology with therapeutic innovation, this review positions glial cells not as supporting actors but as central regulators and potential gatekeepers of dementia pathogenesis and treatment.},
}

Humans
*Neuroglia/metabolism/pathology
*Dementia/pathology/therapy/metabolism
Animals

@article {pmid41696700,
year = {2025},
author = {Ji, X and Lin, Y and Chen, X and Jiang, X and Wang, Q and Cui, X and Wang, K},
title = {The burden of neurological diseases in G7 countries from 1990 to 2021 and projections for the next 30 years: a Global Burden of Disease study.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1632773},
pmid = {41696700},
issn = {2296-2565},
mesh = {Humans ; *Global Burden of Disease/trends ; Male ; *Nervous System Diseases/epidemiology/mortality ; Female ; Middle Aged ; Disability-Adjusted Life Years ; Aged ; Adult ; Incidence ; *Global Health/statistics & numerical data ; Forecasting ; Adolescent ; Child ; *Cost of Illness ; Infant ; Prevalence ; Aged, 80 and over ; Young Adult ; Child, Preschool ; },
abstract = {BACKGROUND: Neurological disorders have become a significant global public health challenge due to their high rates of disability and mortality. This study analyzed epidemiological trends of neurological disorders in G7 countries from 1990 to 2021 based on Global Burden of Disease (GBD) 2021 data and predicted the disease burden for the next 30 years.

METHODS: Using the Joinpoint regression model and the Nordpred Age-Period-Cohort (APC) model, the study evaluated indicators such as incidence, mortality, and Disability-Adjusted Life Years (DALYs) of neurological disorders. It also analyzed the impact of gender, age, and social factors on the disease burden.

RESULTS: The overall burden of neurological disorders in G7 countries is lower than the global level, but there are significant gender differences. Women have a higher prevalence rate, which may be related to migraine and hormonal fluctuations, while men have more prominent Years of Life Lost (YLL) due to premature death, except in Japan and Italy. Regarding age distribution, the risk of disease gradually increases for individuals over 10 years old, and the mortality rate rises sharply after 70 years old. The association between aging and neurodegenerative diseases (such as Alzheimer's disease) is particularly significant. Historical trend analysis from 1990 to 2021 shows that the global age-standardized incidence and mortality rates have remained stable overall. However, male mortality rates have increased significantly in the United States, Japan, and Germany. Predictions for the next 30 years indicate that despite stabilizing age-standardized rates, the number of neurological disease cases in G7 countries will continue to increase due to population growth and aging.

CONCLUSION: The study untangles the unique challenges faced by G7 countries in preventing and controlling neurological disorders. It emphasizes the need to develop precise intervention strategies that consider age, gender, and social factors, providing valuable insights for developing countries.},
}

Humans
*Global Burden of Disease/trends
Male
*Nervous System Diseases/epidemiology/mortality
Female
Middle Aged
Disability-Adjusted Life Years
Aged
Adult
Incidence
*Global Health/statistics & numerical data
Forecasting
Adolescent
Child
*Cost of Illness
Infant
Prevalence
Aged, 80 and over
Young Adult
Child, Preschool

@article {pmid41696648,
year = {2026},
author = {Hamilton, LJ and Coleman, ME and Sprecher, A and Rutter, LA},
title = {Dementia stigma in the United States: variation by target gender, degree of impairment, and respondent characteristics.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70260},
pmid = {41696648},
issn = {2352-8729},
abstract = {INTRODUCTION: The rising prevalence of Alzheimer's disease and related dementias (ADRD) poses major public health concerns. Public knowledge about ADRD diverges from scientific consensus, and consequently, public stigma presents barriers to diagnosis and care.

METHOD: This study addresses ADRD stigma in the United States using the well-established vignette approach. A stratified quota sample of 1115 adults matching national demographics were randomly assigned to one of six vignettes. Symptoms of the vignette character mirrored the presentation of ADRD and were reviewed by geriatric neuropsychologists for accuracy.

RESULTS: Apart from small vignette effects, stigma was shaped by respondent characteristics. Higher stigma was predicted by less knowledge, being male, non-White race, and living in counties with higher ADRD prevalence. Surprisingly, personal contact showed no effect.

DISCUSSION: Rehumanizing individuals with ADRD and enhancing ADRD knowledge should be public health priorities. Stigma reduction efforts need to address informational deficits and narratives that perpetuate negative perceptions.},
}

@article {pmid41696647,
year = {2026},
author = {Johnson, AS and Houlihan, H and Ziaggi, G and Maldonado, A and Smith, AC and Heuer, LB and Guzmán, DS and Okafor, A and Sanchez, T and Palacios, C and Huey, ED and Talmasov, D and Provenzano, F and Lee, S and Kreisl, WC and Lao, PJ and , },
title = {Hallucinations and delusions are associated with elevated tau PET signal independent of age, clinical severity, and amyloid burden.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70264},
pmid = {41696647},
issn = {2352-8729},
abstract = {INTRODUCTION: Psychosis in Alzheimer's disease (AD) is associated with worse outcomes, yet no established biomarkers exist for early diagnosis and intervention. We compared tau positron emission tomography (PET) burden across older individuals with and without psychotic symptoms.

METHODS: [18F]AV1451 tau PET binding was compared between 32 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects with psychotic symptoms (delusions and/or hallucinations) and 32 ADNI subjects without psychotic symptoms, matched for age, sex, race/ethnicity, and clinical severity. Tau was assessed in a priori regions of interest (ROIs) and in voxelwise analyses, both corrected for amyloid PET burden.

RESULTS: Tau was greater in individuals with psychotic symptoms in the amygdala, hippocampus, frontal cortex, and early, middle, and late Braak stage regions in primary analyses. When considering subgroups, tau binding was greatest in those with concurrent delusions.

DISCUSSION: Greater than expected tau burden for age, clinical severity, and amyloid burden may be relevant for psychotic symptoms in older adults.

HIGHLIGHTS: Tau positron emission tomography (PET) was elevated in individuals with psychosisElevated tau was independent of Alzheimer's disease (AD) clinical severity and amyloid burdenThere was variability in the regional distribution depending on psychosis type.},
}

@article {pmid41696646,
year = {2026},
author = {Jasim, N and Shatnawi, E and Vasquez, FS and Ali, Y and Phillipson, L and Oliveira, D and Dao-Tran, TH and Steiner-Lim, GZ and Karamacoska, D},
title = {Validation of the Arabic Dementia Diagnosis Attitude Scale (A-DDAS).},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70262},
pmid = {41696646},
issn = {2352-8729},
abstract = {INTRODUCTION: Culturally appropriate scales are needed to efficiently assess stigma among Arabic-speaking communities. This study aimed to validate the Arabic version of the Dementia Diagnosis Attitude Scale (A-DDAS).

METHODS: The translated A-DDAS underwent pre-testing with native speakers in Australia. The final version of the scale was tested with Arabic-speaking adults aged ≥ 18 residing in Australia. The sample (N = 266) was randomly split such that one half (n = 133) underwent exploratory factor analysis and the other half (n = 133) underwent confirmatory factor analysis. Internal consistency reliability was assessed via Cronbach α.

RESULTS: The final 10-item scale consisted of two factors with five items each: "fear of labelling" (α = 0.88) and "fear of discrimination" (α = 0.85), with inter-factor correlation r = 0.51 and high reliability (α = 0.87).

DISCUSSION: The A-DDAS yielded good validity and reliability scores, confirming its suitability for use with Arabic-speaking Australians in stigma studies, educational interventions, and clinical settings.},
}

@article {pmid41696319,
year = {2026},
author = {Sánchez-Mendoza, AV and Vázquez-García, RA and Castaño, V and Torres-Ramos, MA and Juárez-Solano, AH and Camarillo-López, RH and Rosales-Hernández, MC},
title = {Design and Evaluation of Quinoline-derived Fluorophores for Labeling Amyloid Beta 1-42 in Alzheimer's Disease.},
journal = {ACS omega},
volume = {11},
number = {5},
pages = {7343-7358},
pmid = {41696319},
issn = {2470-1343},
abstract = {Amyloid beta (Aβ) is a key biomarker in Alzheimer's disease, driving the formation of senile plaques that contribute to neuronal death within a complex etiology. Typically, most treatments begin at advanced stages, when irreversible brain atrophy has already occurred; therefore, early diagnosis is essential for effective intervention. Several probes based on the conventional donor-π-acceptor (D-π-A) structural motif have been developed as diagnostic tools, yet few have reached clinical trials. Alternatively, quinoline-based fluorescent compounds with push-pull structures and aggregation-induced emission properties show enhanced fluorescence in the aggregated state due to restricted intramolecular motion (RIM). Accordingly, four quinoline derivatives(?)2QnCN, 3QnCN, 3QnB, and 4QnBB(?)were synthesized using standard methods, including benzoxazole segments and a cyano (-CN) group. They were chemically and optically characterized, and their photophysical properties were calculated. Theoretical analyses include band gap estimation and visualization of intramolecular charge transfer. Molecular docking was also performed to assess binding with the Aβ1-42 pentamer (PDB: 2BEG), identifying 3QnCN as the most promising candidate with a binding energy of-11.9 kcal/mol. Cytotoxicity was tested using the MTT assay to determine the optimal working concentration. The fluorescence intensity of 3QnCN in PC12 cells was quantified, and confocal microscopy confirmed its effectiveness in labeling Aβ1-42.},
}

@article {pmid41696300,
year = {2026},
author = {Bajaj, S and Mahesh, R},
title = {Galantamine-Escitalopram Combination Therapy in Alzheimer's Comorbid Depression Model in Mice: Role of BDNF/KYN Pathways, Neuroinflammation, and Oxidative Stress.},
journal = {ACS omega},
volume = {11},
number = {5},
pages = {7396-7414},
pmid = {41696300},
issn = {2470-1343},
abstract = {Alzheimer's disease (AD) is the most prevalent form of dementia, accounting for more than two-thirds of cases in older adults. AD is associated with neuropsychiatric symptoms such as depression, anxiety, and sleep disturbances. The coexistence of AD with depression, in particular, poses serious challenges and often results in suboptimal outcomes with conventional therapies. The present study therefore aimed to investigate the therapeutic potential of escitalopram (ESC; SSRI) in combination with galantamine (GAL; AChE inhibitor) on key pathological pathways, including the neurotrophic system, hypothalamic-pituitary-adrenal (HPA) axis, kynurenine pathway, inflammation, and oxidative stress, in an animal model of AD comorbid with depression. Swiss albino mice were subjected to chronic mild stress (CMS) for 21 days and received intrahippocampal administration of amyloid-β peptide to mimic AD-depression comorbidity. Subsequently, ESC (10 mg/kg) combined with GAL (5 mg/kg) was administered orally for 20 days alongside the CMS protocol, followed by behavioral, biochemical, and histopathological assessments. The combined GAL + ESC treatment significantly alleviated depressive symptoms and improved working and spatial memory in CMS and amyloid-β-exposed mice. Furthermore, the therapy normalized hippocampal levels of BDNF, proinflammatory cytokines (IL-6, TNF-α), kynurenine metabolites (3-HK, QUIN), and oxidative stress markers toward those observed in the sham group. Histopathological analysis further confirmed the preservation of hippocampal integrity with combined therapy. Overall, the findings highlight the potential of ESC as an adjunct to GAL in ameliorating depressive symptoms and cognitive deficits, underscoring its promise for further clinical evaluation in the management of AD comorbid with depression.},
}

@article {pmid41696228,
year = {2026},
author = {de Araújo, AB and S Azul, FVC and Carneiro, YC and de Sousa, CNS and de Vasconcelos, SMM and Rios, FJ and Leal, LKAM},
title = {Neuroinflammation and Oxidative Stress in Parkinson's Disease, Alzheimer's Disease, and COVID-19: Microglia-Neutrophil Interaction.},
journal = {ACS omega},
volume = {11},
number = {5},
pages = {6922-6938},
pmid = {41696228},
issn = {2470-1343},
abstract = {Abnormal activation of the immune system and oxidative stress are crucial factors in neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease. Microglia, neutrophils, oxidative stress mediators such as reactive oxygen species (ROS), lipid peroxidation products (e.g., malondialdehyde), and nitrosative stress markers (e.g., nitrite and nitrate) play important roles in neuroinflammatory mechanisms. Microglial cells acquire a proinflammatory phenotype through interactions with endogenous or exogenous compounds, including cell debris, abnormally modified proteins (including Aβ species and alpha-synuclein), and pathogens (e.g., SARS-CoV-2). They produce many inflammatory mediators and promote the activation of adjacent brain cells and leukocyte infiltration, including polymorphonuclear neutrophils. Accumulation of neutrophils in the central nervous system (CNS) leads to the secretion of more proinflammatory mediators, such as cytokines, proteases, and oxidants, and the formation of neutrophil extracellular traps (NETs). These processes are associated with the pathological activation of microglial cells, cell death, consequent influence on neuronal functions, or even neuronal death, which is a hallmark of CNS disorders. In this review, we address the importance of inflammatory mechanisms and oxidative stress in the CNS associated with Parkinson's disease, Alzheimer's disease, and the neuronal effects observed in coronavirus disease 2019 (COVID-19), as observed by the abnormal activation of central and peripheral immune cells, such as microglia and neutrophils. We also discuss emerging evidence linking SARS-CoV-2 infection to neuroinflammatory mechanisms that could contribute to neurodegenerative complications.},
}

@article {pmid41696149,
year = {2026},
author = {Fang, W and Zhao, J and Li, L and Wang, Y and Xu, ZP and Zhang, L},
title = {An anti-inflammatory neuroenhancer mitigates amyloid-β pathology to improve Alzheimer's disease therapy.},
journal = {Materials today. Bio},
volume = {37},
number = {},
pages = {102874},
pmid = {41696149},
issn = {2590-0064},
abstract = {β-amyloid (Aβ) inhibition significantly attenuates the early-stage Alzheimer's disease (AD) progression, but the improvement in cognitive function remains limited by neuroinflammation. Here, we developed a bioinspired neuroenhancer that concurrently targets both Aβ aggregation and neuroinflammation. Rutin and small interfering RNA targeting beta-site amyloid precursor protein cleaving enzyme 1 (siBACE1) were co-loaded into the calcium phosphate core, which was further coated with lipid bilayers and Angiopep-2/rabies virus glycoprotein 29 peptides to form the multifunctional neuroenhancer (RB@LCP-AR). RB@LCP-AR not only releases siBACE1 to silence BACE1 expression and block Aβ production from the cleavage of amyloid precursor protein, but also releases Rutin to suppress the Aβ aggregation. Moreover, the released Rutin of RB@LCP-AR directly alleviates Aβ-induced mitochondria dysfunction and intracellular ROS production in neuronal cells. Notably, the targeting of RB@LCP-AR to neurons and the inhibition of Aβ reduce the microgliosis and astrogliosis, further alleviating neuroinflammation and synapse loss. Consequently, AD mice receiving RB@LCP-AR treatment efficiently recovered their memory and cognition. Our study thus provides a coordinated targeting of Aβ and neuroinflammation inhibition, holding considerable potential to promote the recovery of memory and cognition in AD.},
}

@article {pmid41696081,
year = {2026},
author = {Muhammad Saqib, S and A Alkhattabi, M and Khan, MA and Mazhar, T and Iqbal, M and Saudagar, AKJ and Tariq Paracha, W and Hamam, H},
title = {Explainable bidirectional encoder representations from image transformers for Alzheimer's disease prediction.},
journal = {Digital health},
volume = {12},
number = {},
pages = {20552076261416823},
pmid = {41696081},
issn = {2055-2076},
abstract = {BACKGROUND: People who have Alzheimer's disease (AD) experience a progressive decline in their neurological function, which leads to mental deterioration and diminished memory abilities, and altered behaviors that affect both patients and their care providers severely. Diagnosis of the disease at an early stage and with precision helps ensure appropriate intervention strategies.

OBJECTIVES: Modern artificial intelligence (AI) technology is promising in medical use for imaging and diagnostic work, specifically involving AD detection and classification. This study aims to develop and evaluate an explainable transformer-based framework that leverages Bidirectional-Encoder representations from Image Transformers (BEiT) to automatically classify AD stages from magnetic resonance imaging (MRI) brain scans.

METHOD: The proposed framework employs BEiT as a feature extractor on a dataset of 8511 MRI brain images categorized into three diagnostic groups (mild, moderate, and no impairment). Class imbalance is addressed through a Wasserstein generative adversarial network with gradient penalty-based oversampling strategy that generates synthetic MRI images for minority classes, and these images are combined with the original scans to form a balanced training set.

RESULTS: The experiments showed outstanding accuracy levels reaching 96%, while the F1-scores indicated 0.94, 1.00, and 0.95 for mild, moderate, and no AD group classifications. Performance evaluation metrics from the study demonstrate strong outcomes with a mean absolute error reaching 0.0727 and Cohen's kappa equaling 0.9451, while Matthews correlation coefficient reached 0.9455 and Hamming loss remained at 0.0365.},
}

@article {pmid41695973,
year = {2026},
author = {Zhang, Q and Ma, L and Zhao, L and Zhu, S and Qi, H and Pan, Z and Zhou, J},
title = {Network analysis of optimal deep or machine learning strategies for classification and detection of Alzheimer's disease based on MRI scanning.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1644480},
pmid = {41695973},
issn = {1662-4548},
abstract = {BACKGROUND: Alzheimer's disease (AD) presents a significant global health challenge, with its prevalence projected to increase substantially by 2050. Despite its widespread impact, the underlying causes and mechanisms remain incompletely understood, complicating efforts toward effective diagnosis and treatment. Pathologically, AD is marked by the accumulation of senile plaques and neurofibrillary tangles, but the relationship between these factors and disease progression is complex and heterogeneous.

OBJECTIVE: The present study aimed to compare the efficacy of different deep/machine learning models based on MRI scanning.

METHODS: The study follows rigorous systematic review protocols, adhering to the Cochrane Handbook of Systematic Reviews and Interventions and the PRISMA guidelines. A comprehensive search strategy was employed across multiple databases, including PubMed, Web of Science, Cochrane, Medline, and EMBASE. Advanced statistical methods were used for data synthesis and analysis, incorporating network meta-analysis and machine learning techniques to evaluate the accuracy and efficacy of different diagnostic models.

RESULTS: The meta-analysis included 11 studies that met the predefined inclusion criteria. The studies employed various machine learning algorithms, including CNN, ResNet, and DenseNet, to classify AD and distinguish it from mild cognitive impairment (MCI) and healthy controls. The results indicate that CNN and ResNet consistently outperform other models in terms of classification accuracy. Additionally, the integration of nanotechnology and AI-driven diagnostics demonstrates significant potential in enhancing the diagnostic process.

CONCLUSION: Despite challenges such as data heterogeneity and the interpretability of AI-driven models, the study highlights the transformative potential of computational techniques and advanced imaging technologies in AD diagnosis and management. The integration of network-based analyses and machine learning approaches offers promising avenues for future research, aiming to revolutionize the understanding and approach to Alzheimer's disease.},
}

@article {pmid41695753,
year = {2026},
author = {Salvadores, N},
title = {Biomedical research in Alzheimer's disease in a Latin American developing country: challenges in the informed consent process.},
journal = {Brain communications},
volume = {8},
number = {1},
pages = {fcag011},
pmid = {41695753},
issn = {2632-1297},
abstract = {Alzheimer's disease (AD) is a significant global health issue, impacting 50 million individuals with dementia worldwide, a number projected to triple by 2050. Although research has been conducted for decades, there is no effective prevention, treatment, or early diagnostic method for AD. Research on AD in Latin America (LatAm) faces unique challenges compared to developed countries due to socioeconomic, cultural, and infrastructural factors. While the prevalence of dementia is rapidly increasing in LatAm due to demographic shifts, the region is underrepresented in research, diagnostics and care. The informed consent process, a critical aspect of research, becomes particularly complex with individuals who have cognitive impairments. It requires a balance between protecting vulnerable individuals and advancing research for their benefit. By developing and implementing best practices, ethical research can be conducted with this population, ensuring they receive appropriate care. This review provides an update on informed consent for AD research in Chile.},
}

@article {pmid41695624,
year = {2026},
author = {Sun, Y and Liu, B and Tong, J and Shi, D and Zhu, X and Jiang, T and Yang, Y and Sun, X},
title = {Analysis of comorbid characteristics, molecular mechanisms between mild cognitive impairment and Alzheimer's disease with interventions in a community-based population in Shanghai.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1765285},
pmid = {41695624},
issn = {1664-2295},
abstract = {BACKGROUND: Mild cognitive impairment (MCI) is a critical early stage of Alzheimer's disease (AD). Elucidating the comorbidity characteristics, influencing factors, and molecular mechanisms between MCI and AD in community-based populations is crucial for early intervention in cognitive impairment.

METHODS: 2,234 elderly individuals aged 50 years or older from 14 communities in Pudong New District, Shanghai, were enrolled in this study. The Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) were used to divide individuals into a control group (n = 1,160) and an MCI group (n = 1,074). The associations of demographic characteristics, lifestyle, and psychological status with MCI were analyzed. Transcriptome data from GSE140829 (training set) and GSE63060 (validation set) were obtained from the GEO database. Weighted gene co-expression network analysis (WGCNA) was used to identify MCI signature genes. KEGG pathway analysis was combined with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway to elucidate mechanisms of comorbidity. Targeted intervention agents were screened based on the DSigDB database. Molecular docking (MD) was used to evaluate the binding ability between small molecules and target proteins.

RESULTS: The prevalence of AD in the MCI group (30.17%) was significantly higher than that in the control group (p < 0.001), and MCI and AD were significantly positively correlated. Age, gender, smoking, living arrangements, mobile phone use, pet ownership, stress, anxiety, and depression were key influencing factors for MCI (p < 0.05). The proportion of individuals living with children and grandchildren (57.45%) in the MCI group was significantly higher than that in the control group (16.29%) (p < 0.001). WGCNA identified 273 MCI signature genes. KEGG pathway analysis showed that these genes were significantly enriched in neurodegenerative disease pathways, including AD pathways (with the AD pathway ranking first in the "Human Diseases" category). Targeted intervention screening identified the natural compounds boldine (comprehensive score 961.58) and piceatannol (comprehensive score 358.46) as potential drug candidates (p < 0.05), both of which have strong binding ability to target proteins.

CONCLUSION: MCI patients in the community are at high risk of AD, and their comorbidity characteristics are affected by multidimensional lifestyle and psychological factors. Boldine and piceatannol may be potential natural compounds for the intervention of cognitive impairment. The results of this study can provide a theoretical basis for the early prevention and precise intervention of cognitive impairment in the community.},
}

@article {pmid41695614,
year = {2026},
author = {Kara, B and Kelly, IM and Beck, JS and Kuhn, N and Mufson, EJ and Vega, IE and Kanaan, NM and Counts, SE},
title = {Pretangle tau pathology accrual in the default mode network during the progression of Alzheimer's disease.},
journal = {Molecular neurodegeneration advances},
volume = {2},
number = {1},
pages = {13},
pmid = {41695614},
issn = {3059-4944},
abstract = {UNLABELLED: Alzheimer's disease (AD) is a secondary tauopathy characterized by the accumulation of aggregated amyloid-beta (Aβ) peptides as extracellular neuritic and diffuse plaques, alongside hyperphosphorylated tau aggregates forming intracellular neurofibrillary tangles (NFTs). Although NFT pathology is strongly linked to neurodegeneration and cognitive decline in AD, growing evidence suggests that soluble "pretangle" aggregates of tau, formed prior to NFT development, are the primary neurotoxic species driving disease progression and cognitive impairment. We quantified pretangle tau moieties in postmortem tissues of the default mode network (DMN), a resting state connectome that mediates episodic memory and falters early in AD, to determine the association between DMN tau pathology and antemortem cognitive status. To accomplish this, we assayed postmortem fixed and frozen tissue from frontal cortex (FC), posterior cingulate cortex (PCC), and precuneus (PreC) DMN hubs obtained from participants of the Rush Religious Orders Study (RROS). Immunohistochemical and biochemical quantification was performed using site-specific tau antibodies recognizing pathological pretangle epitopes pS422 (phosphorylation at tau residue serine 422), TOC1 (tau oligomers), and TNT2 (N-terminal tau misfolding), as well as the mid-stage NFT marker TauC3 (C-terminal tau truncation). Pretangle tau profiles included neuropil threads and neuronal inclusions as early as Braak stage III, with significant increases from Braak stage IV to V across the DMN hubs. There was a step-wise increase in the pretangle markers in subjects who died with no cognitive impairment (NCI) to mild cognitive impairment (MCI) to AD. The increase in pretangle tau pathology accrual correlated with poorer antemortem neuropsychological tests, including episodic memory, semantic memory, and a global cognitive z score calculated for each RROS participant. Pretangle tau accrual also correlated with postmortem neuropathological diagnostic measures of AD severity. In addition, we found that the PCC displayed greater tau pathology compared to the PreC, suggesting selective vulnerability within DMN hubs. Collectively, our findings are a first of its kind cellular and protein quantitative analysis to demonstrate neurotoxic pre-tangle tau accumulation within the DMN connectome that highly correlated with cognitive decline in MCI and AD, underscoring pretangle tau as a potential early driver of disease progression and a target for therapeutic intervention.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s44477-026-00019-y.},
}

@article {pmid41695579,
year = {2026},
author = {Fu, Y and Pan, Q and van Dijl, JM},
title = {Fimbriae potentiate Aggregatibacter actinomycetemcomitans for periodontal disease.},
journal = {Current research in microbial sciences},
volume = {10},
number = {},
pages = {100566},
pmid = {41695579},
issn = {2666-5174},
abstract = {Aggregatibacter actinomycetemcomitans is a major contributor to aggressive periodontitis and has been increasingly implicated in systemic conditions, such as rheumatoid arthritis and Alzheimer's disease. Among its diverse virulence mechanisms, fimbriae have emerged as central factors driving colonization, immune evasion, and pathogenicity. This review highlights recent findings showing that fimbriae not only facilitate adhesion and biofilm formation, but also contribute to maintaining bacterial cell envelope integrity. The transition from rough (fimbriated) to smooth (non-fimbriated) colony phenotypes upon in vitro culturing is associated with significant changes in virulence, including increased release of outer membrane vesicles (OMVs) and extracellular cytoplasmic proteins (ECPs). These changes suggest a trade-off between surface structure expression and secretion-based virulence. Importantly, fimbriae-rich strains are clinically relevant and more virulent in host models. The combined evidence implies that fimbriae and key virulence factors, such as leukotoxin A, act cooperatively in pathogenesis, as fimbriae-mediated adhesion and persistence will enhance local toxin delivery, killing of immune cells and immune evasion. Together, these insights point to fimbriae as key targets for novel therapeutic and vaccination strategies aimed at controlling periodontal and related systemic diseases.},
}

@article {pmid41695490,
year = {2026},
author = {Lai, R and Shie, F and Chung, R and Hsu, PW and Chen, Y and Lam, K and Juang, J},
title = {Why 11β-HSD1 inhibitors show variable efficacy in Alzheimer's therapy: an APOE4-dependent HSD11B1 mechanism.},
journal = {Theranostics},
volume = {16},
number = {8},
pages = {4113-4127},
pmid = {41695490},
issn = {1838-7640},
mesh = {*11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & inhibitors/genetics/metabolism ; Humans ; *Alzheimer Disease/drug therapy/genetics/pathology/metabolism ; *Apolipoprotein E4/metabolism/genetics ; Animals ; Mice ; Hydrocortisone/blood/metabolism ; Male ; Female ; Brain/pathology/metabolism ; Aged ; },
abstract = {Rationale: Clinical trials for Alzheimer's disease (AD) often yield inconsistent results despite promising preclinical findings. Inhibition of 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), a cortisone reductase, has demonstrated neuroprotective effects in preclinical models. However, clinical outcomes have varied. A potential explanation is the limited representation of apolipoprotein E ε4 (APOE4) carriers in preclinical studies, despite evidence that APOE4 alters stress responses and glucocorticoid regulation. We hypothesized that APOE4 status modulates the efficacy of HSD11B1 inhibition by influencing cortisol metabolism and AD pathology. Methods: We conducted a genetic association study to test whether HSD11B1 variants are linked to plasma cortisol levels, brain atrophy, and AD risk, stratified by APOE4 status. Postmortem human brain tissues and wild-type mice were analyzed for HSD11B1 expression, with emphasis on the entorhinal cortex (EC). Neuroimaging data were examined to assess correlations between cortisol levels and brain volume. In cell models, recombinant APOE4 protein was tested for regulation of HSD11B1 expression via the transcription factor C/EBPβ and its effect on neuronal cortisol production. Results: We identified a functional HSD11B1 variant associated with elevated cortisol, increased AD risk, and accelerated EC atrophy, specifically in APOE4 carriers. HSD11B1 was significantly upregulated in the EC of APOE4-positive brains. Mechanistic studies demonstrated that APOE4, but not APOE3, upregulates HSD11B1 via C/EBPβ, thereby increasing neuronal cortisol. Conclusions: These findings explain the inconsistent efficacy of 11β-HSD1 inhibitors in AD patients by revealing an APOE4-dependent activation of HSD11B1 that promotes early EC pathology. They also support genotype-guided therapeutic strategies targeting local cortisol metabolism.},
}

*11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & inhibitors/genetics/metabolism
Humans
*Alzheimer Disease/drug therapy/genetics/pathology/metabolism
*Apolipoprotein E4/metabolism/genetics
Animals
Mice
Hydrocortisone/blood/metabolism
Male
Female
Brain/pathology/metabolism
Aged

@article {pmid41695418,
year = {2026},
author = {Zareen, W and Ahmed, N and Tokali, FS and Islam, T and Al-Rashida, M and Senol, AM and Ulucay, O and Tawfeek, AM and Taslimi, P and Shafiq, Z and Islam, MS},
title = {Synthesis, multi-target evaluation and DFT analysis of 6-hydroxychromone derived hydrazones with carbonic anhydrase I-II/acetylcholinesterase inhibition and antioxidant activity.},
journal = {RSC advances},
volume = {16},
number = {10},
pages = {8807-8827},
pmid = {41695418},
issn = {2046-2069},
abstract = {Alzheimer's disease seems to be the result of several tumultuous processes such as cholinergic deficits associated with the abnormal metabolic status and oxidative stress that cannot be controlled effectively by single-target molecules. A complex group of agents capable of combining specific enzyme inhibition with antioxidant protection may be seen as an approach toward neuroprotection. The partial synthesis method led to the creation of a new series of chromone hydrazones (3a-p) from substituted hydrazones and 6-hydroxy-chromone. All the newly obtained hydrazones were assayed for their inhibitory activity against acetylcholinesterase (AchE) and human carbonic anhydrases (CA I and II), and their antioxidant potentials were also studied. The chromone-substituted hydrazones 3c, 3e, and 3f exhibited good inhibitory activity against AChE with IC50 values of 0.82 µM, 0.20 µM, and 1.11 µM, respectively. Compound 3e was found to be highly selective for AChE and about six hundred fold more potent as compared to the standard inhibitor, tacrine. Also, these novel chromone derivatives were tested against CA I and II isoenzymes and exhibited IC50 values within the range of 3.16 µM-19.28 µM against CA I and 1.21 µM-14.90 µM against CA II. In addition, in vitro antioxidant assays revealed that compounds 3c, 3e, and 3m exhibited notable radical-scavenging activity, with compound 3e showing superior antioxidant performance (IC50 = 4.17 µg mL[-1] for DPPH and 2.46 µg mL[-1] for ABTS) compared to the reference standard trolox. Furthermore, cytotoxicity studies on HUVEC cells demonstrated that compounds 3c, 3e, and 3m exhibited IC50 values ranging from 52.36 to 60.84 µM. Molecular docking studies described the nature of binding affinities between the synthesized compounds and enzyme targets. DFT-based FMO, MEP, and reactivity analyses demonstrated that the chromone-hydrazone derivatives exhibit narrow HOMO-LUMO gaps and well-defined electrostatic surfaces, supporting their suitability for efficient charge transfer and biological interaction. Moreover, computational simulations and ADME analysis proved that all of the synthesized molecules were druggable with good inhibitory potential.},
}

@article {pmid41695272,
year = {2026},
author = {Xiang, F and Liu, X and Chen, G},
title = {Dynamic trends, spatial clustering, and multi-model projections of the global burden of Alzheimer's disease and other dementias: an analysis of GBD 1990-2021 data to 2050.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1661370},
pmid = {41695272},
issn = {1663-4365},
abstract = {BACKGROUND: Alzheimer's disease and other dementias (ADOD) are a leading causes of disability and mortality among older adults worldwide. While the rising burden is recognized, comprehensive analyses of its dynamic growth rates, spatial clustering patterns, and comparative long-term forecasts remain limited, hindering targeted policy response.

METHODS: Using data from the Global Burden of Disease (GBD) 2021 study for individuals aged ≥60 years across 204 countries (1990-2021), we analyzed six burden indicators. We calculated age-standardized rates (ASR) and estimated annual percentage changes (EAPC) to quantify trends. Spatial clustering of EAPC patterns was performed using hierarchical clustering. Future burden to 2050 was projected using both exponential smoothing (ES) and autoregressive integrated moving average (ARIMA) models, with comparative analysis across sex, age, and Socio-demographic Index (SDI).

RESULTS: From 1990 to 2021, global ADOD burden increased markedly in absolute terms. EAPC analysis revealed accelerated annual growth (>1%) in East Asia and Eastern Europe, surpassing the global average. Spatial clustering identified four distinct geographic archetypes, with rapid-growth clusters spanning middle-income regions in Latin America and Southeast Asia. Women and adults aged ≥80 years, especially those ≥95, bore a disproportionately high and increasing burden. Both ES and ARIMA models projected a continued rise in absolute burden to 2050, forecasting a near-doubling of the disease burden (DALYs) among women.

CONCLUSION: The global ADOD burden is escalating with pronounced dynamic heterogeneity in growth velocity and distinct spatial patterns. Our multi-model projections warn of a mounting crisis, disproportionately impacting women, the oldest-old, and rapidly aging middle-income regions. Public health strategies must evolve from static assessments to dynamic surveillance and geographically tailored interventions, with urgent investment in prevention and care systems in high-growth clusters.},
}

@article {pmid41694909,
year = {2026},
author = {Altuna, M and Rodríguez, E and Núñez, M and Trueba-Saiz, Á and Lizan, L and Díaz-Cerezo, S},
title = {A Systematic Literature Review of the Epidemiological, Diagnostic Workup, Humanistic, and Economic Burden of Alzheimer's Disease in Spain.},
journal = {Cureus},
volume = {18},
number = {1},
pages = {e101581},
pmid = {41694909},
issn = {2168-8184},
abstract = {INTRODUCTION: Alzheimer's disease (AD), the leading cause of dementia, affects over 700,000 individuals in Spain, with prevalence expected to rise due to population aging and improved diagnostic accuracy. Around 40,000 new cases are diagnosed annually, yet early-stage AD dementia remains underdiagnosed, limiting understanding of its full epidemiological, clinical, humanistic, and economic burden in Spain.

METHODS: A systematic literature review (SLR) was conducted on the burden of AD dementia in Spain, focusing on observational studies published from January 2019 to January 2024. Searches were performed in PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE), Medicina en Español (MEDES), and Índice Bibliográfico Español en Ciencias de la Salud (IBECS), following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

RESULTS: Twenty-six publications were included, mainly addressing moderate-to-severe AD dementia, with limited evidence on mild cognitive impairment (MCI) due to AD. Commonly used tools included the Mini-Mental State Examination (MMSE), Barthel Index, and Global Deterioration Scale (GDS). Neurologists were the primary clinicians involved in diagnosis (78.6%), though etiological diagnosis often lacked core AD biomarkers. Most caregivers were informal (mainly women), experiencing significant declines in health-related quality of life (HRQoL). Non-healthcare costs accounted for 84.6%-90.7% of total expenditures, followed by direct healthcare (6.1%-10.0%) and social care costs (2.8%-4.6%). Indirect costs, mostly from reduced working hours, represented 0.5%-0.8%.

CONCLUSIONS: This study highlights the need to improve early diagnosis of AD dementia and to establish reliable health registries to measure its burden. The lack of evidence on practice heterogeneity hinders standardized care strategies. Addressing these gaps is essential to improve patient management, ensure equitable access to timely and accurate diagnosis, and facilitate access to emerging disease-modifying treatments for AD dementia.},
}

@article {pmid41694525,
year = {2026},
author = {Jiang, X and Lv, G and Mendes, ME and Wu, J and Yuan, J and Lu, ZK},
title = {Lifetime cost-effectiveness of lecanemab for early Alzheimer's disease.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1692508},
pmid = {41694525},
issn = {2296-2565},
mesh = {*Alzheimer Disease/drug therapy/economics ; Humans ; *Cost-Benefit Analysis ; *Antibodies, Monoclonal, Humanized/economics/therapeutic use ; Quality-Adjusted Life Years ; United States ; Markov Chains ; Aged ; Male ; Female ; },
abstract = {INTRODUCTION: Lecanemab is the second anti-amyloid-β monoclonal antibody to receive FDA approval for the treatment of early Alzheimer's disease (AD), following aducanumab. Unlike aducanumab, which faced restricted Medicare coverage, lecanemab received traditional approval in 2023, resulting in broader access through Medicare. Despite these developments, the comparative cost-effectiveness of lecanemab and aducanumab has not been fully established. This study aimed to assess whether lecanemab is more cost-effective than aducanumab in the management of early AD.

METHODS: An indirect comparison of cost-effectiveness was performed due to the absence of head-to-head randomized controlled trials. A five-state Markov model was constructed from the perspective of the US healthcare system with a lifetime horizon and a 1-year cycle length. Model outcomes included life-years (LYs), quality-adjusted life-years (QALYs), and costs, all discounted at an annual rate of 3%. Incremental cost-effectiveness ratios (ICERs) were calculated and compared with established willingness-to-pay (WTP) thresholds. One-way sensitivity analyses identified key drivers of model uncertainty, and a probabilistic sensitivity analysis (PSA) with 1,000 Monte Carlo simulations tested the robustness of the findings.

RESULTS: The incremental cost of the lecanemab group compared to the aducanumab group was $30,018.97, with an increase in quality-adjusted life-years (QALYs) of 0.25, resulting in an ICER of $121,678.49 per QALY gained. The result of the one-way sensitivity analysis showed that the utility of the state of mild dementia due to AD had the most important effects on the ICER of the lecanemab group compared to the aducanumab group. The probabilistic sensitivity analysis showed that lecanemab was more cost-effective than aducanumab across various WTP thresholds.

CONCLUSION: Our findings suggest that lecanemab provides greater value than aducanumab; however, at current list prices, neither drug is cost-effective compared with the standard of care. Price reductions are necessary to improve affordability, particularly for lecanemab, which is more widely covered by Medicare. Policy implications remain significant, as under the Inflation Reduction Act (IRA), biologics such as lecanemab are exempt from Medicare price negotiations for 13 years post-approval, limiting short-term opportunities for cost adjustment.},
}

*Alzheimer Disease/drug therapy/economics
Humans
*Cost-Benefit Analysis
*Antibodies, Monoclonal, Humanized/economics/therapeutic use
Quality-Adjusted Life Years
United States
Markov Chains
Aged
Male
Female

@article {pmid41694459,
year = {2025},
author = {Liu, S and Wu, G and Ma, X and Xu, K and Lan, X and Wang, L and Li, H and Gu, D and Wang, M and Liu, J},
title = {Trends and cross-country inequalities in the global burden of Alzheimer's disease and other dementias among adults aged 65+ years, 1990-2021: a population based study with projections into 2050.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1683158},
pmid = {41694459},
issn = {1663-4365},
abstract = {BACKGROUND: Alzheimer's disease and other dementias (ADOD) pose a significant global health challenge, with projected annual increases. The growing elderly population exacerbates burdens, underscoring the need for interventions.

METHODS: Using data from the Global Burden of Disease Study 2021, we analysed global ADOD trends from 1990 to 2021 among adults aged 65+ and projected to 2050. Average annual percentage change (AAPC) in the age-standardised prevalence, mortality and disability-adjusted life years (DALYs) rates of ADOD were calculated to quantify the temporal trends.

RESULTS: Globally, the number of adults aged 65 years or older living with ADOD increased from 18.1 (95% uncertainty interval [UI] 14.4-22.5) million in 1990 to 49.1 (38.7-61.3) million in 2021 (AAPC 0.09%). While mortality rates remained relatively stable (AAPC 0%), DALYs increased by 176% (AAPC 0.02%). Females consistently exhibited a higher age-standardised prevalence (7,603 [95% UI 6,023-9,469] cases per 100,000 population) vs. 5,744 [4,486-7,205]) and mortality (304 [78 to 782] vs. 225 [54-626]) rate compared to males, with notable regional variations. From 1990 to 2021, the age-standardised prevalence of ADOD increased only in East Asia and High-income Asia Pacific (AAPC 0.79% and 0.16%). High fasting plasma glucose, high body-mass index, and smoking were identified as primary risk factors. Projections indicate a 50.1% increase in age-standardised prevalence by 2050, with an estimated 191 (52-330) million cases, and a predicted death toll of 6.8 (2.4-11.3) million.

CONCLUSION: The global number of people living with dementia nearly tripled from 1990 to 2021, mainly due to increases in population ageing and growth. The findings emphasize the need for comprehensive strategies to address ADOD, including prevention, early diagnosis, and effective management, with a focus on gender and regional disparities.},
}

@article {pmid41694229,
year = {2026},
author = {Kushnir, CN and Taylor-Bateman, V and Davies, NM and Anderson, EL},
title = {Assessing the repurposing potential of disease-modifying antirheumatic drug targets to reduce Alzheimer's disease risk: a Mendelian randomization study.},
journal = {Brain, behavior, & immunity - health},
volume = {52},
number = {},
pages = {101185},
pmid = {41694229},
issn = {2666-3546},
abstract = {BACKGROUND: Systemic inflammation plays a key role in the development and progression of Alzheimer's disease (AD). However, the repurposing potential of select anti-inflammatory drug targets for AD treatment remains unclear.

METHODS: Two-sample Mendelian randomization (MR) and colocalization analyses were conducted to estimate the effects of select disease-modifying antirheumatic (DMARD) targets on AD risk. We investigated 9 DMARD targets, using blood protein quantitative trait loci (pQTLs) from the UK Biobank Pharma Proteomics Project (n = 54,219). Outcome associations were extracted from the International Genomics of Alzheimer's Project (ncases = 21,982, ncontrols = 41,944).

RESULTS: Our MR estimates suggest that higher levels of FCGR3B, an etanercept target, increased the risk of AD (OR: 1.10; 95% CI [1.02, 1.19]; p = 0.01). We found little evidence that the remaining DMARD targets affected AD risk. Colocalization analysis provided little evidence that target pQTLs, including FCGR3B, colocalized with AD.

CONCLUSIONS: Our findings suggest a causal effect of FCGR3B on AD risk, but not for the remainder of the analyzed DMARD targets. Further research is recommended to elucidate the causal role of FCGR3B in AD and build upon the current literature on viable AD therapeutic targets.},
}

@article {pmid41693955,
year = {2026},
author = {Fang, L and Zhuang, Y and Zhang, M and Yang, D and Zhang, R and Peng, J and Wang, C},
title = {Dietary and metabolic reprogramming alleviates neurodegeneration: a review of mechanisms and clinical implications.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1706597},
pmid = {41693955},
issn = {2296-861X},
abstract = {Neurodegenerative diseases, characterized by their insidious onset and progressive neuronal degeneration, present significant challenges in the fields of neuroscience and medicine. We elucidate the critical role of nutrition and cellular metabolism in the pathogenesis and progression of these disorders, with a particular focus on Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). We demonstrate that fundamental nutrients such as glucose, lipids, and amino acids are crucial for neuronal bioenergetics, oxidative stress mitigation, and neuroprotective functions. Furthermore, we emphasize the concept of metabolic reprogramming as a key driver in neurodegeneration; this process entails alterations in energy metabolism, mitochondrial dysfunctions, and shifts in nutrient utilization that exacerbate neuroinflammation and oxidative stress. We emphasize the potential advantages of nutritional strategies, especially those involving the Mediterranean dietary pattern, characterized by high antioxidant and omega-3 fatty acid content, to optimize cellular metabolic pathways and attenuate disease manifestations. However, clinical application of nutritional strategies faces several challenges including complexities surrounding nutrient mechanisms, patient adherence issues, and concerns regarding long-term efficacy. To address these obstacles, we advocate for personalized nutrition approaches that integrate metabolomics, genomics, and epigenetics to tailor interventions according to individual metabolic profiles. Additionally, emerging strategies such as probiotics along with synergistic combinations of nutrients and pharmaceuticals offer promising avenues for enhancing therapeutic outcomes. In conclusion, understanding the intricate interplay between nutrition and cellular metabolism is crucial for developing effective treatments for neurodegenerative diseases. Future research should prioritize mechanistic studies alongside precise assessment tools as well as high-quality clinical trials to validate the efficacy of these interventions.},
}

@article {pmid41693920,
year = {2026},
author = {Ebdah, W and Thomas, SD and Eissa, N and Jayaprakash, P and Łażewska, D and Kieć-Kononowicz, K and Sadek, B},
title = {Simultaneous inhibition of cholinesterase and antagonism of histamine H3 receptors alleviates cognitive deficits and mitigates apoptosis in scopolamine-induced amnesia in mice.},
journal = {Frontiers in behavioral neuroscience},
volume = {20},
number = {},
pages = {1722019},
pmid = {41693920},
issn = {1662-5153},
abstract = {INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory deficits. Mounting evidence highlights the role of cholinergic and histaminergic neurotransmissions in the pathophysiology of AD. Hence, developing agents that target multiple neurotransmitter systems may provide improved therapeutic benefits.

METHODS: This study investigated the effects of acute systemic administration of E100, a dual-active cholinesterase inhibitor (ChEI) and histamine H3 receptor (H3R) antagonist, on scopolamine (SCO)-induced memory impairment in male C57BL/6 mice. Behavioral assessments, including the Novel Object Recognition Test (NORT), Y-Maze test (YMT), Three-Chamber Test (TCT), Fear Conditioning test (FCT), and Elevated Plus Maze (EPM), were conducted to assess cognitive performance while biochemical analyses assessed apoptotic markers, oxidative stress, neuroinflammation and acetylcholinesterase activity.

RESULTS: Systemic administration of E100 (10 mg/kg, i.p.) significantly improved memory function in SCO-induced amnesia, as evidenced by enhanced short-term memory (STM) (p < 0.001) and long-term memory (LTM) (p < 0.01) performance in the NORT, as well as improved spatial memory in YMT (p < 0.001) and FCT (p < 0.001; for cued fear memory) and (p < 0.001; for contextual fear memory). Additionally, E100 treatment in the TCT, improved social memory (p < 0.001) and alleviated SCO-induced anxiety-related deficits in the EPM (p < 0.001). Moreover, treatment with E100 (10 mg/kg, i.p.) attenuated SCO-induced neuroinflammation by reducing TNF-α and IL-1β levels and mitigated oxidative stress by increasing GSH and SOD while decreasing MDA levels in the hippocampus and cerebellum (p's < 0.001). E100 also reduced caspase-1 activity (p < 0.001), suggesting its anti-apoptotic effect. Furthermore, E100 attenuated the elevated AChE activity observed in SCO-induced amnesic mice (p < 0.01), providing effects comparable to those of the reference drug Donepezil.

DISCUSSION: These findings provide extensive in vivo evidence of the neuroprotective effects of E100, demonstrating its ability to ameliorate memory deficits, mitigate neuroinflammation and restore oxidative as well as AChE activity balance. By targeting both cholinergic and histaminergic dysfunction in the brain, E100 offers a promising therapeutic strategy for AD and related neurodegenerative disorders. This study highlights the potential role of dual-active ChEIs and H3R antagonists in memory impairment, and addressing multiple neuropathological mechanisms underlying AD.},
}

@article {pmid41693868,
year = {2025},
author = {do Nascimento, ACL and da Paz, EP and Freire, GRLB and Almendra, SCCGE and Almendra, MCCGE and de Lima, LFF and da Silva, LBR and Dos Santos, JFB and de Paiva, BA and Novaes, LESS and de Melo, MM and Sobral, AIGDP},
title = {Assessment of cognitive function in individuals with Down syndrome and dementia: a systematic review.},
journal = {Dementia & neuropsychologia},
volume = {19},
number = {Suppl 1},
pages = {e20250308},
pmid = {41693868},
issn = {1980-5764},
abstract = {UNLABELLED: Individuals with Down syndrome (DS) face a high risk of dementia, particularly Alzheimer's disease (AD). Early diagnosis is complex due to pre-existing cognitive deficits, underscoring the need for specific diagnostic criteria.

OBJECTIVE: To present cognitive and behavioral features of dementia in DS and examine cognitive assessment tools.

METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the databases United States National Library of Medicine (PubMed), Scopus, Web of Science, and Virtual Health Library (BVS) were searched for studies (2014-2024) in English, Portuguese, or Spanish. The quality of the included articles was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria.

RESULTS: Of 254 records screened, 28 studies met the inclusion criteria. Early dementia in DS presents with declines in executive functions, memory, language, attention, and behavioral changes. Behavioral symptoms, including agitation, hallucinations, and apathy, were prominent in AD-DS and prodromal dementia, and may serve as early indicators.

CONCLUSION: Early dementia in individuals with DS is characterized by cognitive and behavioral declines, with behavioral symptoms potentially serving as early diagnostic markers.},
}

@article {pmid41693755,
year = {2026},
author = {Zhai, T and Zhang, W and Ma, C and Ni, L and Paulus, YM and Su, EJ and Murphy, GG and Lawrence, DA and Wang, X},
title = {Multi-parametric longitudinal imaging of cerebral biomarkers in a rodent model of Alzheimer's disease.},
journal = {Photoacoustics},
volume = {48},
number = {},
pages = {100808},
pmid = {41693755},
issn = {2213-5979},
abstract = {This study introduces a method for longitudinally monitoring Alzheimer's disease (AD)-related biomarkers in a rodent model utilizing a dual-modality imaging system combining photoacoustic microscopy (PAM) and confocal fluorescence microscopy (CFM). Using a cranial window transparent to both light and ultrasound, we examined cerebral vasculature, blood flow speed, oxygen saturation (sO2), and amyloid-β (Aβ) deposition with single capillary resolution in genetically modified AD mice longitudinally over three months. Empowered by the high-resolution multimodal imaging, the analysis showed consistent changes of small vessel density decrease and Aβ deposition increase in AD mice compared to the control group. Meanwhile, a decrease in sO2 was observed in AD group near the end of the observation period, highlighting the potential importance of functional imaging of hemodynamics that PAM facilitates. This multimodal system, with its longitudinal imaging capability, could provide valuable insight into the temporal dynamics and interrelationships of multiple biomarkers in neurodegenerative diseases.},
}

@article {pmid41693715,
year = {2026},
author = {Jang, SI and Gomez, CL and Becker, A and Thibault, E and Price, JC and Johnson, KA and El Fakhri, G and Gong, K},
title = {A Cross-modality Transformer Network for MR-guided Low-dose Tau PET Image Denoising.},
journal = {IEEE transactions on radiation and plasma medical sciences},
volume = {10},
number = {2},
pages = {249-257},
pmid = {41693715},
issn = {2469-7311},
abstract = {Tau PET imaging is an essential imaging modality for the diagnosis and monitoring of Alzheimer's disease and related dementias. To enable tau PET imaging-based longitudinal monitoring of disease progression, further reducing the injected dose during each scan is important. In this work, we developed a novel deep learning approach that incorporated cross-modality transformer blocks to integrate both PET and MR prior information to further improve low-dose tau PET imaging. Both spatial and channel information were utilized during the calculation of cross-modality self-attention maps. Performance of the proposed method was evaluated based on the early-frame and late-frame images from 139 dynamic [18]F-MK-6240 tau PET datasets. Results showed that the proposed network can outperform other reference networks which concatenated PET and MR images together as the network input.},
}

@article {pmid41693543,
year = {2026},
author = {Tábuas-Pereira, M and Mano, F and Bernardes, C and Durães, J and Lima, M and DenHaan, K and Paquette, K and Kun-Rodrigues, C and Carmona, S and Tábuas, T and Faustino, P and Coelho, MR and Silva-Spínola, A and Duro, D and Almeida, MR and Malva, J and Baldeiras, I and Brás, J and Guerreiro, R and Santana, I},
title = {Maternal Longevity is Associated With Reduced Risk but an Earlier Onset of Alzheimer's Disease in Offspring.},
journal = {Journal of geriatric psychiatry and neurology},
volume = {},
number = {},
pages = {8919887261424534},
doi = {10.1177/08919887261424534},
pmid = {41693543},
issn = {1552-5708},
abstract = {IntroductionWhile human longevity has increased significantly over the last 2 centuries, the time spent in good physical and cognitive health has not risen proportionately. The incidence of Alzheimer's disease (AD) increases with age, but parental longevity is often associated with better offspring health and lower AD risk. This study aimed to investigate the relationship between parental longevity and AD.MethodsWe included patients with AD and cognitively healthy subjects (over 75 years), collecting family history data, namely maternal and paternal age at death. We performed a logistic regression to evaluate the association of parental longevity and AD risk and linear regression models for the association with age of onset and CSF biomarkers, adjusting for confounders.ResultsWe analyzed 3069 participants from a Portuguese cohort, including 893 AD patients and 2176 cognitively healthy controls. Maternal longevity was inversely associated with AD risk (OR: 0.989, 95%CI = [0.982, 0.997], P = 0.005). In AD patients, higher maternal age of death was associated with an earlier disease onset (β = -0.081, 95%CI = [-0.148, -0.013], P = 0.019). No associations were found between parental longevity and CSF biomarkers.DiscussionMaternal longevity appears protective against AD risk but is linked to an earlier onset in patients. This may indicate that protective factors for AD could become detrimental once AD is triggered. These findings highlight the complex interplay of genetic, environmental, and potentially epigenetic influences on AD.},
}

@article {pmid41693429,
year = {2026},
author = {Shabbir, U and McNulty, H and Hughes, C and Ward, M and Dooley, J and Hoey, L},
title = {B-vitamins, immune function and the ageing brain: A critical review of the evidence, mechanisms and potential role of the gut microbiome.},
journal = {The Proceedings of the Nutrition Society},
volume = {},
number = {},
pages = {1-33},
doi = {10.1017/S0029665126102249},
pmid = {41693429},
issn = {1475-2719},
abstract = {This review aims to explore the potential role of folate and related B-vitamins (B12, B6, and riboflavin) in maintaining cognitive health in ageing, focussing particularly on their interactions with the gut microbiota and inflammation. Low B-vitamin status, common in older adults, is associated with poorer cognitive function and dementia. Furthermore, people with dementia are observed to have increased abundance of pro-inflammatory microbes and concomitant higher concentrations of cytokines in their circulation. Therefore, gut dysbiosis and chronic inflammation have been proposed as contributors of cognitive dysfunction. Although many observational studies report that low B-vitamin status, especially vitamin B6, is associated with a worse inflammatory state, the role of the gut microbiota is much less investigated. Pre-clinical evidence suggests higher B-vitamin intakes may beneficially modulate the gut bacterial profile and its metabolic activity, positively influencing inflammation. The evidence however is inconsistent and the few human intervention studies available are confined to clinical populations, or are limited by small sample size or to a single B-vitamin at high supplementation doses. Of note, one study in rats with Alzheimer's type dementia reported an association of folate and vitamin B12 deficiency with disturbed gut bacterial composition, neuroinflammation and impaired memory. In conclusion, optimising B-vitamin status may help promote cognitive health during ageing through modulation of the gut microbiota and immune function. Well-designed human studies are however required to confirm these relationships and inform evidence-based nutritional strategies for healthy ageing.},
}

@article {pmid41693397,
year = {2026},
author = {Zhang, H and Li, W and Xiao, P and Lu, Z and Tian, Y and Xu, Y},
title = {The immune-metabolism interactome in efferocytosis: a new paradigm for the central nervous system diseases revealed by single-cell sequencing analysis.},
journal = {The Journal of pathology},
volume = {},
number = {},
pages = {},
doi = {10.1002/path.70031},
pmid = {41693397},
issn = {1096-9896},
support = {M1427//345 Talent Project of Shengjing Hospital of China Medical University/ ; 82271294//National Natural Science Foundation of China/ ; 82470923//National Natural Science Foundation of China/ ; },
abstract = {Efferocytosis is a process that maintains tissue homeostasis by removing apoptotic cells (ACs) by professional or non-professional phagocytes. The intricate process can be categorized into recognition of ACs, engulfment of ACs, and degradation of efferosomes. Aberrations in efferocytosis result in inadequate clearance of ACs, leading to prolonged inflammation that is implicated in the development and progression of various human diseases. Most central nervous system (CNS) diseases are associated with dysregulation of inflammatory homeostasis. Microglia, the resident immune cells of the CNS, play a primary role in efferocytosis in the brain, which is essential for maintaining the homeostasis of the internal environment. In this review, we summarize the current knowledge of the basic processes of efferocytosis and its indispensable role in the developing and aging brain. Additionally, we discuss the regulatory role of immune-metabolism crosstalk and the insights from single-cell sequencing analysis in dissecting microglial heterogeneity during efferocytosis. We also focus on recent discoveries regarding the critical role of efferocytosis in several CNS diseases, including cerebral ischemia, intracerebral hemorrhage, traumatic brain injury, major depressive disorder, glioblastoma multiforme, Alzheimer's disease, and Parkinson's disease. Finally, we outline potential therapeutic strategies and existing challenges, emphasizing the need for context-specific targeting to improve CNS disease outcomes. © 2026 The Pathological Society of Great Britain and Ireland.},
}

@article {pmid41693339,
year = {2026},
author = {Tanriverdi, İ and Bilgic, İ and Pasin, O and Oren, C and Irmak, HS and Smith, L and Hajek, A and Soysal, P},
title = {Alzheimer disease knowledge among gerontologists in Turkiye.},
journal = {Gerontology & geriatrics education},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/02701960.2026.2630669},
pmid = {41693339},
issn = {1545-3847},
abstract = {This study aimed to evaluate the level of knowledge about Alzheimer's disease (AD) among graduates of gerontology undergraduate programs in Turkiye and to identify factors associated with their knowledge levels. A cross-sectional study was conducted with 100 gerontology graduates recruited via alumni networks and professional platforms. Data were collected using an online survey including a demographic form and the Turkish version of the Alzheimer's Disease Knowledge Scale (ADKS-TR). Descriptive statistics, Mann-Whitney U, and Kruskal-Wallis tests were used to examine differences in AD knowledge scores across participant characteristics, with significance set at p < .05. The overall mean ADKS-TR score was 22.04 ± 3.44 (IQR:11-29), indicating a moderate level of knowledge. Female graduates scored significantly higher than males (p = .007). Employed participants and those who perceived themselves as knowledgeable also had higher scores (p < .001 and p = .017, respectively). No significant differences were observed based on age, time since graduation, prior AD-specific training, or personal/familial exposure to AD. Participants demonstrated the highest knowledge in the "Assessment and Diagnosis," "Life Impact," and "Symptoms" domains, while "Caregiving" scored lowest. The most common misconceptions concerned functional impairments, prevention strategies, and decision-making abilities, whereas general disease characteristics were correctly identified by most participants. Gerontology graduates in Turkiye possess moderate AD knowledge, with gender, employment status, and self-perceived competence as key correlates. Persistent gaps in practical caregiving and prevention highlight the need for continuous, practice-oriented, and targeted educational programs to improve professional competence in AD care.},
}

@article {pmid41693328,
year = {2026},
author = {Evans, M and Ritchie, C and Trepel, D and Hahn-Pedersen, JH and Kettle, J and Chan, MS and Bray, BD and Clark, A and Ivkovic, M and Wichmann, CA and Edwards, S},
title = {Estimating the Future Health and Social Care Costs of Alzheimer's Disease Dementia in the UK: Impact of Disease Modifying Therapy Efficacy, Uptake, and Care Model - A Scenario Modelling Study.},
journal = {International journal of geriatric psychiatry},
volume = {41},
number = {2},
pages = {e70185},
doi = {10.1002/gps.70185},
pmid = {41693328},
issn = {1099-1166},
support = {//Novo Nordisk/ ; },
mesh = {Humans ; *Alzheimer Disease/economics/therapy/epidemiology ; United Kingdom/epidemiology ; *Health Care Costs/trends ; Aged ; Markov Chains ; Male ; Female ; Aged, 80 and over ; },
abstract = {BACKGROUND: To model scenarios exploring potential impacts of disease-modifying therapies (DMTs) for Alzheimer's disease (AD) dementia on future health and social care costs in the United Kingdom.

METHODS: A cohort Markov model was developed using population projections and published AD epidemiological data. Stage-specific transition rates (mild cognitive impairment due to AD and mild, moderate, severe AD dementia) and health and social care cost data were applied to estimate cost outcomes over 2020-2040. Potential proportion of eligible population receiving treatment (uptake) and follow-up care models (primary vs. specialist care) were elicited from expert opinion. Scenarios combined ranges of DMT efficacy estimates, uptake, and care model. DMT price was excluded due to no UK precedent.

RESULTS: Without DMT access, 1,038,405 people (1.5%) were projected to have AD dementia by 2040. Under the various DMT treatment scenarios, the prevalence of AD dementia by 2040 was projected to be 34,000-98,000 cases lower. Associated cumulative cost offsets were higher, £4.4-12.9billion over 2020-2040, in scenarios where most individuals received primary care follow-up, compared with majority specialist care follow-up (-£2.3billion to +£3.2billion). Assuming DMT efficacy of 25%, 58% uptake and majority primary care follow-up cumulative cost offsets increased from £4.4billion to £10.1billion by 2040 but the UK Health Service would need to diagnose and provide DMT for over a million individuals by 2030 and two million by 2040 to achieve this.

CONCLUSIONS: Potential cost offset from DMT are large but highly dependent on the model of healthcare delivery and the ability of healthcare systems to scale up diagnosis and treatment services.},
}

Humans
*Alzheimer Disease/economics/therapy/epidemiology
United Kingdom/epidemiology
*Health Care Costs/trends
Aged
Markov Chains
Male
Female
Aged, 80 and over