White matter injury, plasma Alzheimer's disease, and neurodegenerative biomarkers on cognitive decline in community-dwelling older adults: A 10-year longitudinal study

IF 13 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2025-02-12 DOI:10.1002/alz.14594

Qili Hu, Xiaowen Zhou, Zhenxu Xiao, Qianhua Zhao, Ding Ding, Jun Zhang

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Abstract

INTRODUCTION

This study aimed to investigate the synergistic impact of white matter injury, Alzheimer's disease, and neurodegenerative pathology on long-term cognitive decline and dementia risk in older adults.

METHODS

We included 262 dementia-free participants with baseline and follow-up interviews (2010–2021). At baseline, peak width of skeletonized mean diffusivity (PSMD) was assessed from diffusion tensor imaging. Plasma phosphorylated tau 217 (p-tau217) and neurofilament light chain (NfL) were measured using a single-molecule immune-array assay. Cognitive function was evaluated using Mini-Mental State Examination (MMSE) and domain-specific cognitive tests.

RESULTS

Participants with high-level PSMD, p-tau217, and NfL showed the fastest decline of MMSE (β = −0.30) and the highest dementia incidence of 3.54/100 person-years. A combination model with three markers demonstrated a good predictive value for dementia, incorporating age, sex, education, and apolipoprotein E (area under the curve = 0.93, 95% confidence interval = 0.86, 0.99).

DISCUSSION

Combining co-pathology markers may identify individuals with a high risk of cognitive decline.

Highlights

Peak width of skeletonized mean diffusivity (PSMD) was correlated with long-term cognitive decline, and this correlation was modified by plasma phosphorylated tau (p-tau)217 and neurofilament light chain (NfL).
Participants with high levels of PSMD, p-tau217, and NfL showed the fastest cognitive decline and the highest risk of dementia.
A combination of the three markers exhibited a good predictive value of incident dementia over a 10-year follow-up period.

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.