Alzheimer's & Dementia最新文献_第4页

Sex-specific brain reserve and progression from mild cognitive impairment to Alzheimer's disease dementia. 性别特异性脑储备和从轻度认知障碍到阿尔茨海默病痴呆的进展。

IF 12.8 1区医学

Alzheimer's & Dementia Pub Date : 2026-10-01 DOI: 10.1002/alz.71913

Xulin Liu, Sterre C M de Boer, Maria Carmela Tartaglia

{"title":"Sex-specific brain reserve and progression from mild cognitive impairment to Alzheimer's disease dementia.","authors":"Xulin Liu, Sterre C M de Boer, Maria Carmela Tartaglia","doi":"10.1002/alz.71913","DOIUrl":"10.1002/alz.71913","url":null,"abstract":"Introduction: Sex differences exist in Alzheimer's disease (AD) treatment response, but the role of sex in disease development and progression remains unclear.Methods: We performed multimodal analyses of AD biomarker-positive individuals with mild cognitive impairment (MCI) and AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI; MCI n = 593, AD n = 270) and National Alzheimer's Coordinating Center (MCI n = 436, AD n = 174). Baseline gray matter volume (GMV) was compared by sex. In ADNI, tau positron emission tomography burden and cerebrospinal fluid growth-associated protein 43 (GAP-43) were assessed. Longitudinal analyses examined atrophy and conversion from MCI to dementia.Results: Females with MCI exhibited greater baseline GMV than males primarily in the thalamus, caudate, cerebellum, postcentral gyrus, and middle cingulate gyrus, with no differences at the AD stage. Despite this, females exhibited higher baseline GAP-43, greater tau burden in temporal and parietal regions, and more rapid annual hippocampal atrophy. Conversion rates were similar.Discussion: Findings suggest that females may tolerate greater pathology at early stages but experience faster neurodegeneration later, supporting sex-specific disease trajectories and highlighting the need for sex-informed biomarkers.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 10","pages":"e71913"},"PeriodicalIF":12.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tyrosine kinase inhibitor use and risk of neurodegenerative disease: A Swedish population-based cohort study. 酪氨酸激酶抑制剂的使用和神经退行性疾病的风险：一项基于瑞典人群的队列研究

IF 12.8 1区医学

Alzheimer's & Dementia Pub Date : 2026-10-01 DOI: 10.1002/alz.71916

Felix Wittström, Enoch Yi-Tung Chen, Iris Blotenberg, Torsten Dahlén

{"title":"Tyrosine kinase inhibitor use and risk of neurodegenerative disease: A Swedish population-based cohort study.","authors":"Felix Wittström, Enoch Yi-Tung Chen, Iris Blotenberg, Torsten Dahlén","doi":"10.1002/alz.71916","DOIUrl":"10.1002/alz.71916","url":null,"abstract":"Introduction: Effective disease-modifying therapies remain unavailable for neurodegenerative diseases (NDDs). Tyrosine kinase inhibitors (TKIs) indicated for chronic myeloid leukemia (CML) have been hypothesized to modulate the pathological mechanisms underlying neurodegeneration. Therefore, we aimed to explore the association between initiation of six different TKIs and the subsequent risk of developing NDDs in Swedish nationwide registries (2005-2024).Methods: CML patients ≥50 years at diagnosis initiating TKI therapy were identified, alongside five comparators without CML matched on sex, age, and residence at diagnosis. CML cases and comparators were followed from the initiation date of the respective TKI and could contribute follow-up time to multiple TKI cohorts. A composite measure of NDD diagnosis or death due to NDD was the outcome. Hazard ratios (HRs) were estimated using Cox proportional hazards models, with adjustments for calendar year at follow-up initiation, and relevant comorbidities.Results: A total of 1322 CML cases were included in the study. 1188 initiated imatinib (of which 41 experienced an NDD event), 541 dasatinib (15 events), 390 nilotinib (five events), 174 bosutinib, 71 ponatinib, and 41 asciminib. Adjusted hazard ratios comparing each TKI group to their matched comparator populations were 0.98 (95% confidence interval [CI], 0.71 to 1.36) for imatinib users, 1.18 (95% CI, 0.68 to 2.03) for dasatinib users, and 0.37 (95% CI, 0.15 to 0.90) for nilotinib users. Bosutinib, ponatinib, and asciminib users were too few to conduct comparative analyses.Discussion: Initiation of nilotinib, but not imatinib or dasatinib, was associated with a significantly lower NDD incidence relative to general population comparators.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 10","pages":"e71916"},"PeriodicalIF":12.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Direction-specific biomarker profiles and clinical significance of plasma p-tau217/amyloid PET discordance in cognitively normal adults. 认知正常成人血浆p-tau217/淀粉样蛋白PET不一致的定向特异性生物标志物及其临床意义

IF 12.8 1区医学

Alzheimer's & Dementia Pub Date : 2026-10-01 DOI: 10.1002/alz.71922

Yanlu Huang, Lin Huang, Liang Cui, Fengfeng Pan, Fang Xie, Hongbo Guo, Qihao Guo

{"title":"Direction-specific biomarker profiles and clinical significance of plasma p-tau217/amyloid PET discordance in cognitively normal adults.","authors":"Yanlu Huang, Lin Huang, Liang Cui, Fengfeng Pan, Fang Xie, Hongbo Guo, Qihao Guo","doi":"10.1002/alz.71922","DOIUrl":"10.1002/alz.71922","url":null,"abstract":"Introduction: Plasma phosphorylated tau (p-tau)217 is increasingly used to triage amyloid testing, but the biological and clinical meaning of discordant plasma p-tau217 and amyloid positron emission tomography (PET) results in cognitively normal adults remains uncertain.Methods: We analyzed cognitively normal participants from the Chinese Preclinical Alzheimer's Disease Study (CPAS; n = 594) and the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 475). Amyloid PET positivity was defined as Centiloid ≥ 20. Cohort-specific p-tau217 positivity was defined using PET-anchored cutoffs with ≥ 0.90 specificity, yielding four p-tau/PET groups. Linear models assessed cross-sectional biomarker and cognitive differences; mixed-effects and Cox models assessed ADNI longitudinal Centiloid accumulation, cognitive trajectories, and clinical progression.Results: In cross-sectional analyses, compared to p-tau-/PET-, p-tau+/PET- had higher glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) levels across cohorts; p-tau-/PET+ showed a lower plasma amyloid beta 42/40 ratio in ADNI; and p-tau+/PET+ showed the broadest multimodal abnormalities. In ADNI, both p-tau+ groups had higher clinical progression risk and faster decline in selected cognitive domains; both PET+ groups showed faster Centiloid accumulation. Faster Centiloid accumulation in p-tau+/PET- was observed only at lower specificity thresholds.Discussion: Discordant plasma p-tau217 and amyloid PET results should be interpreted according to both the positivity pattern and the p-tau217 cutoff applied. Distinguishing these patterns may aid risk stratification and longitudinal monitoring. Different p-tau217 operating points may support risk enrichment and prioritization for confirmatory amyloid testing, but require validation before clinical use.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 10","pages":"e71922"},"PeriodicalIF":12.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Network‐dependent remote effects and local tau burden jointly shape neuronal dysfunction in Alzheimer's disease 网络依赖的远程效应和局部tau负担共同塑造阿尔茨海默病的神经元功能障碍

IF 14 1区医学

Alzheimer's & Dementia Pub Date : 2026-10-01 DOI: 10.1002/alz.71914

Lukas Frontzkowski,Sebastian Roemer‐Cassiano,Johannes Gnörich,Daniel Janowitz,Hannah Eyob,Katharina Probst,Dario Dhoqina,Anna Dewenter,Anna Steward,Zeyu Zhu,Madleen Klonowski,Fabian Hirsch,Davina Biel,Melina Paulus,Jonathan Vöglein,Sonja Schönecker,Boris‐Stephan Rauchmann,Carolin Kurz,Carolin Koriath,Jan Häckert,Sophia Stöcklein,Carla Palleis,Robert Perneczky,Johannes Levin,Katharina Buerger,Rudolf A. Werner,Günter Höglinger,Matthias Brendel,Nicolai Franzmeier

{"title":"Network‐dependent remote effects and local tau burden jointly shape neuronal dysfunction in Alzheimer's disease","authors":"Lukas Frontzkowski,Sebastian Roemer‐Cassiano,Johannes Gnörich,Daniel Janowitz,Hannah Eyob,Katharina Probst,Dario Dhoqina,Anna Dewenter,Anna Steward,Zeyu Zhu,Madleen Klonowski,Fabian Hirsch,Davina Biel,Melina Paulus,Jonathan Vöglein,Sonja Schönecker,Boris‐Stephan Rauchmann,Carolin Kurz,Carolin Koriath,Jan Häckert,Sophia Stöcklein,Carla Palleis,Robert Perneczky,Johannes Levin,Katharina Buerger,Rudolf A. Werner,Günter Höglinger,Matthias Brendel,Nicolai Franzmeier","doi":"10.1002/alz.71914","DOIUrl":"https://doi.org/10.1002/alz.71914","url":null,"abstract":"Abstract BACKGROUND Tau pathology in Alzheimer's disease (AD) propagates along the brain's connectome, yet the mechanisms by which tau drives neuronal dysfunction remain unclear. We hypothesized that dysfunction primarily emerges in regions close to tau‐harboring epicenters. METHODS One hundred thirty‐one amyloid‐positive individuals underwent dynamic [ 18 F]PI‐2620 tau positron emission tomography. Kinetic modeling yielded distribution volume ratios (DVRs) and perfusion (R1). Tau epicenters were defined as top 10% DVR regions. Connectivity‐based distance to epicenters was derived from normative resting‐state functional connectivity. RESULTS At the individual level, hypoperfusion was more closely related to distance from tau epicenters than to local tau deposition, particularly in early AD, consistent with diaschisis‐like disconnection. With advancing biological disease severity, local tau deposition increasingly converged with hypoperfusion. Critically, hypoperfusion mediated the relationship between tau accumulation and cognitive decline. DISCUSSION Tau epicenters shape the brain‐wide pattern of neuronal dysfunction, while local tau burden determines the degree of damage driving cognitive decline.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"4 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Brains for dementia research at 18: Commitment to impact the value of human post-mortem tissue.

IF 12.8 1区医学

Alzheimer's & Dementia Pub Date : 2026-10-01 DOI: 10.1002/alz.71956

Keeley J Brookes, Nicola Barnett, Johanna S Jackson, Emma J Kidd, Debra J Lett, Jillian Madine, Ben Middlehurst, Laura E Palmer, Laura Parkkinen, Andrew C Robinson, Rebecca Sims, Lindsey Sinclair, Alexandra Stolzing, Philip Tinkler, Claire Troakes, Lauren Walker, Alan Thomas, Patrick G Kehoe

引用次数: 0

The value of timely treatment with anti‐amyloid therapy for Alzheimer's disease 抗淀粉样蛋白及时治疗阿尔茨海默病的价值

IF 14 1区医学

Alzheimer's & Dementia Pub Date : 2026-10-01 DOI: 10.1002/alz.71819

Jack M. Chapel,Bryan Tysinger,Hossein Pourmand,Dana Goldman,Paul Aisen,for the Alzheimer's Disease Neuroimaging Initiative

{"title":"The value of timely treatment with anti‐amyloid therapy for Alzheimer's disease","authors":"Jack M. Chapel,Bryan Tysinger,Hossein Pourmand,Dana Goldman,Paul Aisen,for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/alz.71819","DOIUrl":"https://doi.org/10.1002/alz.71819","url":null,"abstract":"Abstract INTRODUCTION Anti‐amyloid therapies can slow Alzheimer's disease (AD) progression; diagnostic and treatment delays might reduce their value. METHODS Using dynamic microsimulation, we estimated the gross societal value of anti‐amyloid treatment for Americans with early symptomatic AD. A treatment scenario slowed the rate of clinical progression by 29% over individuals’ remaining lifetime (baseline mean age: 73.0); earlier treatment initiated 2 years earlier. RESULTS Treatment generated $104,885 (95% CI: $99,291, $110,479) in gross societal value over an individual's lifetime, including quality‐of‐life gains, reduced caregiving burden, and medical cost offsets driven by reduced nursing home use and Medicaid spending. Earlier treatment increased value 32%; this rose to 71% if treatment effects are also stronger (36% slowing) in earlier AD stages. Scenarios with 4‐year effect duration yielded $49,122 (treatment) and $56,385 (earlier treatment). DISCUSSION Timely treatment consistently increased long‐term societal value. The findings provide a benchmark against which treatment implementation costs can be weighed.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"13 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The right temperature at the right time: A framework for understanding thermoregulatory pathophysiology in Alzheimer's disease. 正确的温度在正确的时间：理解阿尔茨海默病的温度调节病理生理的框架。

IF 12.8 1区医学

Alzheimer's & Dementia Pub Date : 2026-10-01 DOI: 10.1002/alz.71847

Esther Blessing

引用次数: 0

Sphingolipid and ceramide associations with tau pathology vary across diverse ethnoracial groups in postmortem brain tissue. 在不同种族的死后脑组织中，神经鞘脂和神经酰胺与tau病理的关系各不相同。

IF 12.8 1区医学

Alzheimer's & Dementia Pub Date : 2026-10-01 DOI: 10.1002/alz.71690

Annalise Schweickart, Richa Batra, Kevin Huynh, Collette Blach, Alexandra Kueider-Paisley, Joseph S Reddy, David A Bennett, Peter J Meikle, Bin Zhang, Philip L De Jager, Laura Heath, Jaclyn Beck, Jo Scanlan, Nicholas T Seyfried, Dennis W Dickson, Nilüfer Ertekin-Taner, Rima Kaddurah-Daouk, Matthias Arnold, Jan Krumsiek

{"title":"Sphingolipid and ceramide associations with tau pathology vary across diverse ethnoracial groups in postmortem brain tissue.","authors":"Annalise Schweickart, Richa Batra, Kevin Huynh, Collette Blach, Alexandra Kueider-Paisley, Joseph S Reddy, David A Bennett, Peter J Meikle, Bin Zhang, Philip L De Jager, Laura Heath, Jaclyn Beck, Jo Scanlan, Nicholas T Seyfried, Dennis W Dickson, Nilüfer Ertekin-Taner, Rima Kaddurah-Daouk, Matthias Arnold, Jan Krumsiek","doi":"10.1002/alz.71690","DOIUrl":"10.1002/alz.71690","url":null,"abstract":"Introduction: Metabolic dysregulation is a hallmark of Alzheimer's disease (AD), with numerous studies characterizing metabolic pathways associated with AD onset and progression. A limitation of these studies has been a focus on non-Hispanic white participants. Despite evidence that AD prevalence, progression, and biomarkers differ across ethnoracial groups, it remains unclear whether previously identified metabolic dysregulation in AD brains generalizes across populations.Methods: We analyzed metabolomics data from 547 postmortem brain tissue samples of Hispanic American, Non-Hispanic African American, and White subjects, providing the largest multiethnic AD brain cohort to date. A metabolome-wide association study examined how relationships between metabolite abundance and AD neuropathology varied by ethnoracial group.Results: Forty-eight metabolites exhibited significant heterogeneity with tau pathology (Braak stage), with enrichment in tricarboxylic-acid-cycle intermediates and sphingolipid-ceramide pathway lipids, and with metabolite-tau associations driven predominantly by the Hispanic American and non-Hispanic White groups.Discussion: These findings reveal ethnoracial-specific metabolic signatures of tau pathology and emphasize the need to evaluate emerging therapeutic targets across diverse groups.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 10","pages":"e71690"},"PeriodicalIF":12.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integration of neuroimaging signatures of aging and Alzheimer's with fluid biomarkers 衰老和阿尔茨海默氏症的神经影像学特征与液体生物标志物的整合

IF 14 1区医学

Alzheimer's & Dementia Pub Date : 2026-10-01 DOI: 10.1002/alz.71889

Mitzi M. Gonzales,Ngoc Huynh Ho,David H. Wang,Tanweer Rashid,Sachintha R. Brandigampala,Mengjin Dong,David Martinez,Sokratis Charisis,Timothy J. Hohman,Sudha Seshadri,Christos Davatzikos,Gladys Maestre,Tiffany F. Kautz,Ashley LaRoche,Vanessa M. Young,Anna Campbell Sullivan,Kristine Yaffe,Jon B. Toledo,Alzheimer's Disease Neuroimaging InitiativeHABS‐HD Study Team,Mohamad Habes

{"title":"Integration of neuroimaging signatures of aging and Alzheimer's with fluid biomarkers","authors":"Mitzi M. Gonzales,Ngoc Huynh Ho,David H. Wang,Tanweer Rashid,Sachintha R. Brandigampala,Mengjin Dong,David Martinez,Sokratis Charisis,Timothy J. Hohman,Sudha Seshadri,Christos Davatzikos,Gladys Maestre,Tiffany F. Kautz,Ashley LaRoche,Vanessa M. Young,Anna Campbell Sullivan,Kristine Yaffe,Jon B. Toledo,Alzheimer's Disease Neuroimaging InitiativeHABS‐HD Study Team,Mohamad Habes","doi":"10.1002/alz.71889","DOIUrl":"https://doi.org/10.1002/alz.71889","url":null,"abstract":"Abstract INTRODUCTION Machine learning algorithms applied to neuroimaging may aid diagnosis and disease monitoring. This study aimed to derive neuroimaging signatures of brain aging (Spatial Pattern of Atrophy for Recognition–Brain Age [SPARE‐BA]) and Alzheimer's disease (SPARE‐AD) in a diverse sample and to examine their associations with plasma biomarkers, diagnosis, and disease progression. METHODS SPARE‐BA and SPARE‐AD were calculated using T1‐images from 1297 participants without dementia. Associations between neuroimaging signatures and plasma biomarkers were assessed with partial correlations. Logistic regression and cox proportional hazard models evaluated diagnostic accuracy and clinical progression. RESULTS SPARE‐AD displayed the strongest association with plasma phosphorylated tau 217, whereas SPARE‐BA correlated most strongly with plasma neurofilament light. The combination of neuroimaging signatures with plasma biomarkers achieved the highest diagnostic discriminability and strongest associations with clinical progression. DISCUSSION Neuroimaging signatures of aging and Alzheimer's disease display distinct associations with plasma biomarkers. Neuroimaging signatures combined with plasma biomarkers may improve the detection and prediction of cognitive impairment.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"87 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Data‑driven cognitive composites predict Aβ‑related decline and progression to MCI: the ADOPIC study. 数据驱动的认知复合预测Aβ相关的下降和MCI的进展：ADOPIC研究

IF 12.8 1区医学

Alzheimer's & Dementia Pub Date : 2026-10-01 DOI: 10.1002/alz.71917

Bhargav Tallapragada, Brook Galna, Rosita Shishegar, Shaun J Markovic, Belinda M Brown, Vincent Dore, Simon M Laws, Tenielle Porter, Samantha Burnham, Yen Ying Lim, Jason Hassenstab, Christopher C Rowe, Liang Jin, Jurgen Fripp, James D Doecke, Duygu Tosun, Michael Weiner, Ralph N Martins, John C Morris, Colin L Masters, Paul Maruff, Hamid R Sohrabi

{"title":"Data‑driven cognitive composites predict Aβ‑related decline and progression to MCI: the ADOPIC study.","authors":"Bhargav Tallapragada, Brook Galna, Rosita Shishegar, Shaun J Markovic, Belinda M Brown, Vincent Dore, Simon M Laws, Tenielle Porter, Samantha Burnham, Yen Ying Lim, Jason Hassenstab, Christopher C Rowe, Liang Jin, Jurgen Fripp, James D Doecke, Duygu Tosun, Michael Weiner, Ralph N Martins, John C Morris, Colin L Masters, Paul Maruff, Hamid R Sohrabi","doi":"10.1002/alz.71917","DOIUrl":"10.1002/alz.71917","url":null,"abstract":"Introduction: Cognitive composites offer greater sensitivity to amyloid beta (Aβ)-related decline compared to individual tests for tracking longitudinal cognitive change. We developed and validated data-driven composites from the harmonized Alzheimer's Dementia Onset and Progression in International Cohorts (ADOPIC) study, addressing gaps in psychometric reporting and multi-cohort validation.Methods: The study included 1964 cognitively unimpaired (CU) participants at baseline (longitudinal subset = 1110). Principal component analysis-derived domain-specific and general cognitive composites were evaluated for psychometric properties, sensitivity to Aβ-related decline, and mild cognitive impairment (MCI) progression prediction compared to the Alzheimer's Disease Cooperative Study - Preclinical Alzheimer's Cognitive Composite (ADCS-PACC).Results: Proposed composites demonstrated good to excellent psychometric properties and sensitivity to differentiating CU Aβ trajectories (p < 0.001). General cognition demonstrated longitudinal sensitivity comparable to the ADCS-PACC (d = -0.20) and equivalent classification performance (area under the receiver operating characteristic curve = 0.70). All composites significantly predicted MCI progression (p < 0.001).Discussion: The composites perform comparably to the ADCS-PACC, developed for CU with Aβ, in longitudinal sensitivity while providing comprehensive psychometric characterization and domain-specific measurement, supporting their utility as outcome measures in preclinical Alzheimer's disease studies.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 10","pages":"e71917"},"PeriodicalIF":12.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0