Evidence map›Paper›PMID 42877469›Full record

ArticleJournal of Alzheimer's disease reports

A multivariate plasma pathology-cognition axis reveals biologically anchored residual cognitive heterogeneity across the Alzheimer's disease clinical spectrum.

Wei Han, Shaoyuan Lei, Na Li, Peishen Wang, Wenhao An, Xinye Han, Yihua An, Alzheimer's Disease Neuroimaging Initiative

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Article in Journal of Alzheimer's disease reports. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

8 authors.

Wei HanDepartment of Evidence-Based Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.
Shaoyuan LeiDepartment of Evidence-Based Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.
Na LiBeijing Minde Biotechnology Co, Ltd, Beijing, China.
Peishen WangBeijing Minde Biotechnology Co, Ltd, Beijing, China.
Wenhao AnDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Xinye HanBeijing Minde Biotechnology Co, Ltd, Beijing, China.
Yihua AnBeijing Minde Biotechnology Co, Ltd, Beijing, China.ORCID https://orcid.org/0000-0003-1887-1931
Alzheimer's Disease Neuroimaging Initiative

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
NIA NIH HHS U01 AG024904
6 · The paper itself

Abstract

Background: Alzheimer's disease (AD) pathology does not fully determine clinical expression, as individuals with similar biomarker-defined burden may show substantial differences in cognition. Characterizing cognitive variation beyond pathological burden may improve understanding of clinical heterogeneity in AD. Objective: To develop a multivariate plasma pathology-cognition framework that derives a pathology-anchored residual phenotype capturing cognitive variation beyond circulating pathological burden and to evaluate its clinical and longitudinal relevance. Methods: We analyzed 868 participants from the Alzheimer's Disease Neuroimaging Initiative with plasma p-tau217, glial fibrillary acidic protein, and neurofilament light chain measurements, cognitive assessments, and clinical characterization. Canonical correlation analysis derived a multivariate plasma pathology index and cognitive composite based on memory and language performance. The residual phenotype was defined as the deviation between observed cognition and cognition expected from plasma pathology burden. Clinical correlates and longitudinal trajectories were evaluated using regression and mixed-effects models. Biological validity was assessed by examining associations with amyloid-β and tau positron emission tomography measures. Results: The first canonical correlation between plasma markers and cognition was significant (r = 0.610, permutation p < 0.001). The plasma pathology index correlated with amyloid-β and tau positron emission tomography measures. The resulting pathology-anchored residual phenotype was associated with clinical diagnosis, education, Conclusions: A plasma pathology-anchored residual phenotype captures clinically meaningful cognitive heterogeneity beyond circulating biomarkers and provides a scalable framework for investigating differential clinical manifestations of AD pathology.

Indexed as

Alzheimer's diseasebiomarkersbloodcognitive dysfunction

Identifiers

PMID42877469
PMCPMC13662368

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