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

IF 11.1 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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白质损伤、血浆阿尔茨海默病和社区老年人认知能力下降的神经退行性生物标志物:一项为期10年的纵向研究
本研究旨在探讨白质损伤、阿尔茨海默病和神经退行性病理对老年人长期认知能力下降和痴呆风险的协同影响。方法:我们纳入262名无痴呆的参与者,进行基线和随访访谈(2010-2021年)。基线时,通过扩散张量成像评估骨架化平均扩散率(PSMD)的峰宽。采用单分子免疫阵列法测定血浆磷酸化tau217 (p-tau217)和神经丝轻链(NfL)。认知功能评估采用简易精神状态检查(MMSE)和特定领域的认知测试。结果:高水平PSMD、p-tau217和NfL患者的MMSE下降最快(β = - 0.30),痴呆发病率最高,为3.54/100人年。结合年龄、性别、教育程度和载脂蛋白E的三种标记物的组合模型对痴呆具有较好的预测价值(曲线下面积= 0.93,95%可信区间= 0.86,0.99)。联合病理标志物可以识别出认知能力下降的高风险个体。骨化平均扩散率(PSMD)峰宽与长期认知能力下降相关,这种相关性被血浆磷酸化tau (p-tau)217和神经丝轻链(NfL)修饰。PSMD、p-tau217和NfL水平高的参与者表现出最快的认知能力下降和最高的痴呆风险。在10年的随访期间,这三种标志物的组合对痴呆的发生有很好的预测价值。
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来源期刊
Alzheimer's & Dementia
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.
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