Journal of Alzheimer's Disease最新文献

{"title":"Role of ezrin-radixin-moesin proteins in the regulation of inflammatory cytokine expression in activated microglia.","authors":"Ayane Nakano, Shogo Maekawa, Takanori Murakami, Ayaka Fujimaki, Shinnosuke Takizawa, Junya Murata, Kazuki Ohuchi, Hisaka Kurita, Kazuyuki Takata, Masatoshi Inden","doi":"10.1177/13872877251378462","DOIUrl":"https://doi.org/10.1177/13872877251378462","url":null,"abstract":"<p><p>The ERM protein family, comprising ezrin, radixin, and moesin, mediates membrane-cytoskeleton interactions, regulating key cellular functions. This study investigated the expression of ERM proteins in microglia surrounding amyloid plaques in <i>App^NL-F</i> knock-in mice and their role in inflammatory responses. Moesin was predominantly localized to plaque-associated microglia, and in vitro knockdown experiments revealed distinct roles of ERM proteins in cytokine regulation. These findings suggest that each ERM protein contributes to microglial function through distinct mechanisms. Further elucidating the roles of individual ERM proteins in microglial function may lead to the identification of novel therapeutic targets for neurodegenerative diseases.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251378462"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Route-following deficits in amnestic mild cognitive impairment: Is the dual encoding of route-following strategies impaired?","authors":"Otmar Bock, Ju-Yi Huang, Maike Wigge, Chiara Bieche, Christina Kehm, Nils Richter, Gereon R Fink, Oezguer A Onur","doi":"10.1177/13872877251378658","DOIUrl":"https://doi.org/10.1177/13872877251378658","url":null,"abstract":"<p><p>BackgroundOne of the earliest signs of amnestic mild cognitive impairment (MCI) and neurodegenerative dementia (ND) is spatial disorientation, e.g., getting lost on previously familiar routes. Healthy individuals often follow routes by combining two strategies, serial recall of directions and cue-direction associations, but the integration of these two strategies may be degraded in amnestic MCI and ND.ObjectiveTo evaluate whether impaired integration of the two strategies (dual encoding) contributes to the route-following deficits in amnestic MCI.MethodsTwenty-five patients with amnestic MCI and 25 age-matched healthy controls (HC) followed routes through virtual mazes that allowed the use of the serial order strategy only (maze S), the associative cue strategy only (maze A), or both strategies (maze SA).ResultsFor longer routes, accuracy in maze SA exceeded that in mazes S and A, confirming the existence of a dual encoding benefit. The magnitude of this benefit was comparable in both groups. In contrast, performance on an additional dual-task test was poorer in MCI than in HC.ConclusionsWe attribute the dissociation between preserved dual encoding and impaired dual-tasking in amnestic MCI not to fundamental differences in the underlying mechanisms, but rather to the different ecological validity of the two experimental paradigms. Our findings suggest that spatial orientation training in amnestic MCI need not target dual encoding.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251378658"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of monoclonal antibody therapies on depression in Parkinson's disease and Alzheimer's disease: Systematic review and meta-analysis.","authors":"Guy Gitlin-Leigh, Jack Wilson, Rebecca Howard, Robert Howard, Harry Costello","doi":"10.1177/13872877251378156","DOIUrl":"https://doi.org/10.1177/13872877251378156","url":null,"abstract":"<p><p>BackgroundDepression in Alzheimer's disease (AD) and Parkinson's disease (PD) is common, disabling and difficult to treat. Pathological protein deposition in PD and AD has been associated with late-life depression, and inflammatory and vascular changes have been proposed as key mechanisms underlying depression in neurodegenerative disorders. Monoclonal antibody therapies (mAbs) effectively clear pathological protein aggregates in PD and AD but are associated with cerebral inflammation and microvascular damage.ObjectiveWe conducted a systematic review and meta-analysis to determine whether mAb treatment influences the risk or severity of depression in AD and PD.MethodsCochrane, Ovid MEDLINE/PubMed, PsycINFO and Embase databases were searched for articles published from inception to 8 April 2025. Randomized controlled trials of mAbs for PD or AD reporting a validated measure of depressive symptoms, or depression incidence were included and meta-analyzed.ResultsWe identified 13 studies including 8603 participants (treatment arm: n = 4690, placebo arm: n = 3913). All studies reported depression incidence as an adverse event, but none assessed changes in depressive symptom severity using standardized mood scales. Meta-analysis revealed no significant difference in the incidence of depression with mAb therapy (log risk ratio: -0.24, 95% CI (-0.52, 0.04), p = 0.09).ConclusionsWe observed no significant association between mAb therapy and risk of depression in PD or AD. However, the absence of validated symptom assessments in these trials represents a critical gap in outcome reporting. Future trials should incorporate standardized depressive symptom measures as outcomes to evaluate the potential neuropsychiatric risks of these therapies.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251378156"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of vitamins in dementia prevention and cognitive health: A comprehensive review.","authors":"Adeel Ahmed, Hamid Khan, Syed Shahab Ud Din Shah, Mubin Mustafa Kiyani, Fawaz Al-Hussain, Shahid Bashir, Xiaoqin Fu, Peijun Li","doi":"10.1177/13872877251379700","DOIUrl":"https://doi.org/10.1177/13872877251379700","url":null,"abstract":"<p><p>Dementia is a progressive neurodegenerative disorder characterized by cognitive decline that interferes with daily functioning, particularly in the elderly. As one of the leading causes of disability among older adults, dementia remains a significant public health concern. Emerging evidence suggests that certain vitamins may play a crucial role in the prevention and management of cognitive impairment. This review explores the potential impact of key micronutrients specifically water-soluble vitamins such as vitamin C and B-complex (B1, B2, B3, B5, B6, B9, B12), and fat-soluble vitamins A, D, E, and K on dementia pathogenesis and cognitive function. Vitamin B deficiencies have been associated with brain atrophy, an early indicator of cognitive decline, and supplementation has shown promise in enhancing memory and slowing brain shrinkage. Similarly, vitamin C exhibits antioxidative properties that may protect against neurodegeneration. While nutritional support, particularly through micronutrient intake, is increasingly considered a viable strategy for cognitive preservation, findings from epidemiological and clinical studies remain mixed. These inconsistencies highlight the need for further research to determine optimal dosing, efficacy, and long-term impact of vitamin supplementation in dementia prevention. A well-balanced diet rich in essential vitamins may support brain health, but individual variability suggests the importance of personalized nutritional interventions. This review underscores the potential role of vitamins in maintaining cognitive health and calls for continued investigation into their therapeutic utility in delaying or preventing dementia.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251379700"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-dependent effect of amyloidosis on functional network 'hub' topology is associated with downregulated neuronal gene signatures in the APP<i>swe</i>/PSEN1dE9 double transgenic mouse.","authors":"Zachary D Simon, Karen N McFarland, Todd E Golde, Paramita Chakrabarty, Marcelo Febo","doi":"10.1177/13872877251378778","DOIUrl":"10.1177/13872877251378778","url":null,"abstract":"<p><p>BackgroundExtracellular amyloid-β (Aβ) impairs brain-wide functional connectivity, although mechanisms linking Aβ to broader functional network connectivity remain elusive.ObjectiveHere, we evaluated the effect of Aβ on fear memory and functional connectome measures in mice.MethodsMiddle-aged (9-11 months of age) double transgenic APP-PS1 mice and age and sex-matched controls were evaluated on a fear conditioning protocol and then imaged at 11.1 Tesla. Brains were harvested and processed for analysis of Aβ plaques and Iba1 immunolabeling in cortex, hippocampus, and basolateral amygdala. Additional RNA sequencing data from separate age, strain, and sex matched mice were analyzed for differentially expressed genes (DEGs) and weighted gene co-expression networks.ResultsIn both male and female mice, we observed increased functional connectivity in a dorsal striatal/amygdala network due to Aβ. Increased functional connectivity within this network was matched by increases in AβPP gene expression, Aβ and Iba1 immunolabeling, and an upregulated cluster of DEGs involved in the immune response. Conversely, the network measure representing node 'hubness', eigenvector centrality, was increased in prefrontal cortical brain regions, but only in female APP-PS1 mice. This female specific-effect of amyloid was associated with downregulation of a cluster of DEGs involved in cortical and striatal GABA transmission, anxiogenic responses, and motor activity, in female APP-PS1 mice, but not males.ConclusionsOur results contribute to a growing literature linking between Aβ, immune activation and functional network connectivity. Furthermore, they reveal effects of Aβ on gene expression patterns in female mice that may contribute to amyloidosis-induced dysregulation of non-cognitive circuitry.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251378778"},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tau seeding activity in Alzheimer's disease: Characteristics, factors, and applications.","authors":"Yajie Liu, Yuxiong Chen, Ziyi Chen, Hao Wan, Chengsi Wu","doi":"10.1177/13872877251378772","DOIUrl":"https://doi.org/10.1177/13872877251378772","url":null,"abstract":"<p><p>The prion-like seeding activity (SA) of misfolded microtubule-associated protein tau (MAPT, tau) drives neuropathological progression in Alzheimer's disease (AD), offering a dynamic biomarker beyond static quantitative measures. Recent advances in biomarker research have highlighted the importance of tau seeding activity (TSA), a prion-like propagation mechanism, in the early diagnosis and monitoring of AD. TSA reflects the dynamic process of pathological tau aggregation and spread across brain regions, offering a potential tool for predicting disease progression and differentiating AD from other tauopathies. This article reviews the structural and functional characteristics of tau, the mechanisms underlying its SA, and the impact of post-translational modifications on tau propagation. We also discuss the limitations of current diagnostic methods, which rely on static quantitative measures of tau levels, and propose that tau SA could serve as a more comprehensive biomarker for early diagnosis and risk assessment in asymptomatic individuals. Furthermore, we explore the translational potential of TSA in precision medicine, emphasizing the need for standardized detection methods and clinical validation. By integrating TSA with neuroimaging and fluid biomarkers, a multi-dimensional predictive framework could be established to guide individualized therapeutic strategies and improve diagnostic accuracy in AD and related tauopathies.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251378772"},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The feasibility, acceptability, and effects of the adapted 6-month Otago exercise program on cognitive, physical, and psychological function in people living with dementia in residential care facilities: The ENABLED randomized controlled trial.","authors":"Deborah A Jehu, Charmi Patel, Andre Soares, Jennifer L Waller, Ryan M Carrick, Colleen Hergott, Lufei Young, William Hall, Dawnchelle Robinson-Johnson, Crystal Allen, Richard Sams, Mark Hamrick, Ying Huang, Haidong Zhu, Yanbin Dong","doi":"10.1177/13872877251378670","DOIUrl":"https://doi.org/10.1177/13872877251378670","url":null,"abstract":"<p><p>BackgroundPeople living with dementia (PWD) have poor executive function, which impacts their independence and fall risk. Exercise is a promising strategy but needs to be adapted for PWD in residential care settings. Thus, the feasibility, acceptability, and efficacy of adapted exercise on executive function need to be established.ObjectiveThe purpose of the 6-month assessor-blinded strENgth And BaLance exercise on Executive function in people living with Dementia (ENABLED) randomized controlled trial was to determine 1) the feasibility and acceptability, and 2) if the adapted physical therapist-led Otago Exercise Program (OEP) plus usual care would improve executive function (primary) and secondary cognitive, physical, and psychological function measures as well as falls compared to usual care only in PWD in residential care facilities.MethodsWe randomized PWD to the exercise (<i>n</i> = 21) or usual care group (n = 21) at two residential care facilities in our parallel, assessor-blinded RCT (1:1) [NCT05488951]. A physical therapist delivered our adapted OEP 3x/week over 6 months. We examined feasibility and acceptability. Participants completed a battery of assessments, with the Color-Word Stroop as our primary outcome.ResultsAttrition (19.0%), exercise adherence (60.2 ± 34.5%; 47/78 sessions), and satisfaction were acceptable (4.2/5 points). We found no differences in the Color-Word Stroop, but better working memory, leg strength, and quality of life following exercise relative to usual care (<i>p</i> < 0.05). No differences in falls emerged.ConclusionsThis feasible and acceptable RCT indicates that exercise improves working memory, leg strength, and quality of life and has implications for the design of therapeutic intervention in PWD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251378670"},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of diagnostic accuracy of Alzheimer's disease cerebrospinal fluid core biomarkers using INNOTEST, Lumipulse G, and Elecsys assays: Insights from the PUMCH dementia cohort study.","authors":"Chenhui Mao, Yutong Zou, Tianyi Wang, Longze Sha, Meiqi Wu, Shanshan Chu, Wei Jin, Bo Li, Yixuan Huang, Yuyue Qiu, Jialu Bao, Wenjun Wang, Yuhan Jiang, Liling Dong, Feng Feng, Li Huo, Charlotte Teunissen, Ling Qiu, Jing Gao","doi":"10.1177/13872877251379084","DOIUrl":"https://doi.org/10.1177/13872877251379084","url":null,"abstract":"<p><p>BackgroundCerebrospinal fluid (CSF) core biomarkers play a pivotal role in the biological diagnosis of Alzheimer's disease (AD). While various commercial assays and kits are available for quantifying these biomarkers, their performance across diverse clinical settings remains insufficiently evaluated.ObjectiveThis study aimed to compare the diagnostic accuracy of AD core biomarkers using four measurement methods in a Chinese population and to establish method-specific cutoff values tailored to different clinical scenarios.MethodsA total of 309 participants were enrolled from the PUMCH dementia cohort, comprising 176 AD, 114 non-AD dementia cases, and 19 cognitively normal controls (CN). For biomarker quantification, we employed one manual immunoassay (INNOTEST, conducted in two independent laboratories) and two fully automated immunoassay platforms (Lumipulse G and Roche Elecsys). These methods were used to measure CSF Aβ_1-40, Aβ_1-42, t-tau, and p-tau₁₈₁, and to calculate three biomarker ratios (Aβ_1-42/Aβ_1-40, t-tau/Aβ_1-42, and p-tau₁₈₁/Aβ_1-42).ResultsOur findings provide method-specific and clinical context-optimized cutoff values for each application scenario including clinically diagnosed AD versus non-AD dementia, amyloid PET-positive versus PET-negative dementia, and AD versus CN. The accuracy of differential diagnosis was higher using biomarker ratios (Aβ_1-42/Aβ_1-40, t-tau/Aβ_1-42, p-tau₁₈₁/Aβ_1-42) than absolute values. Most of the high accuracy was achieved using automated assays especially Lumipulse G rather than manual assays.ConclusionsIn this first comparative study of three immunoassays in a Chinese cohort, automated assays demonstrated superior performance compared to manual assays. We established assay-specific cutoff values tailored to different clinical contexts in a Chinese population.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251379084"},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal neuroimaging related to cerebrospinal fluid biomarkers and cognitive function in Alzheimer's disease.","authors":"Yoshihisa Kitayama, Yoshikazu Nakano, Shigeki Hirano, Satoki Hanayama, Yoshikazu Chishiki, Michiko Izumi, Yume Koizumi, Yutaro Suzuki, Mitsuyoshi Tamura, Kosuke Yamagishi, Ai Ishikawa, Shogo Furukawa, Koichi Kashiwado, Atsuhiko Sugiyama, Masahiro Mori, Satoshi Kuwabara","doi":"10.1177/13872877251376601","DOIUrl":"https://doi.org/10.1177/13872877251376601","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is characterized by amyloid-β (Aβ) and tau protein accumulation, reflected in cerebrospinal fluid (CSF) analysis. However, the interplay among CSF biomarkers, neuroimaging, and cognition remains elusive.ObjectiveTo explore associations among neuroimaging features, CSF biomarkers, and cognitive performance in AD.MethodsSixty patients with clinically diagnosed AD showing Aβ pathology in CSF underwent neuroimaging assessment of gray matter volume using T1-weighted MRI, cerebral blood flow (CBF) using single-photon emission computed tomography, and white matter hyperintensities (WMHs) using T2-weighted or fluid-attenuated inversion recovery images. Partial least square (PLS) regression identified imaging findings related to CSF biomarkers and Mini-Mental State Examination (MMSE) scores. Structural equation modeling (SEM) explored associations between factors with variable importance in projection (VIP) scores above 1.5 in PLS regression.ResultsLateral temporal and occipital gray matter volumes positively correlated with MMSE scores (VIP = 1.95, 1.53), whereas WMHs in parietal and frontal periventricular regions were negatively associated with CSF Aβ₄₂ (VIP = 1.54, 1.58). Lateral temporal CBF was also associated with MMSE scores (VIP = 2.22). SEM analysis showed that reduced CSF Aβ₄₂ was linked to increased WMHs (p = 0.028), which correlated with each region (p < 0.005) and explained the reduced MMSE score (p = 0.013). Lateral temporal CBF correlated with temporo-occipital gray matter volume (p < 0.001) and influenced the MMSE score (p < 0.001).ConclusionsThis study suggests that amyloid pathology via WMHs and neurodegeneration of the lateral temporal lobe independently contribute to cognitive impairment in patients with AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251376601"},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hearing loss, plasma neurodegenerative biomarkers, and cognitive function: Independent and additive effects.","authors":"Semere Bekena, Ramkrishna K Singh, Yiqi Zhu, Carlos Cruchaga, Steven E Arnold, Beau M Ances, Ganesh M Babulal","doi":"10.1177/13872877251378675","DOIUrl":"https://doi.org/10.1177/13872877251378675","url":null,"abstract":"<p><p>BackgroundHearing loss is one of the most prominent modifiable risk factors for dementia, accounting for one of the largest population-attributable risk among midlife exposures according to the Lancet Commission on Dementia. Plasma biomarkers such as neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau-217 (Ptau₂₁₇) have emerged as promising indicators of neurodegeneration and Alzheimer's disease (AD) pathology.ObjectiveTo evaluate whether hearing loss and plasma biomarker concentrations are independently associated with cognitive function in aging adults, and to examine if these associations vary by age group.MethodsThis cross-sectional study used data from 373 participants in the Aging Adult Brain Connectome (AABC) study. Hearing was assessed using the NIH Toolbox Words-in-Noise test, and cognitive function was measured by a Preclinical Alzheimer's Cognitive Composite (PACC). Plasma biomarkers included NfL, GFAP, total tau (tTau), and Ptau₂₁₇. General linear models tested associations with cognition, adjusting for demographic, genetic, and cardiometabolic covariates. Interaction terms assessed modification by age and hearing.ResultsHearing loss was independently associated with lower PACC scores (β = -0.03, p < 0.001), after adjusting for covariates. Higher levels of NfL, GFAP, and Ptau₂₁₇ were each associated with worse cognition. Age significantly moderated these associations, with stronger biomarker-cognition links observed in adults aged 65 and older. No significant interactions were observed between hearing loss and plasma biomarkers.ConclusionsHearing loss and plasma biomarkers reflect distinct, additive pathways of cognitive decline. These findings support integrated dementia risk models and highlight the potential of age- and biomarker-informed cognitive monitoring.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251378675"},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}