Physical activity modifies associations between cerebrospinal fluid tau measures and executive function

IF 6.8 Q1 CLINICAL NEUROLOGY Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-04-15 DOI:10.1002/trc2.70085

Ryan J. Dougherty, Anja Soldan, Corinne Pettigrew, Barry Greenberg, Adam P. Spira, Abhay Moghekar, Marilyn Albert

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Abstract

BACKGROUND

Alzheimer's disease (AD) is characterized by the abnormal accumulation of amyloid-beta (Aβ) and tau that can be quantified in vivo through cerebrospinal fluid (CSF) sampling. Physical activity has emerged as a possible modifier of AD risk; however, its impact on CSF biomarkers and cognitive function is not yet fully understood. We examined whether higher levels of physical activity modifies associations between AD CSF biomarkers and cognitive function.

METHODS

One hundred and seventeen adults free of dementia from the BIOCARD study (mean age 72.2 ± 8.0 years, 70% women) wore a wrist accelerometer for 1 week, underwent lumbar puncture to collect CSF, and completed a comprehensive neuropsychological exam. Multivariable linear regression analyses were used to examine whether physical activity (total activity counts over the 10 most active hours of the day) moderates the association between AD CSF biomarkers [Aβ42/40, phosphorylated tau (p-tau181), and total tau] and cognitive composite scores (episodic memory, executive function).

RESULTS

There were significant interactions between physical activity and p-tau181 (p = 0.016) as well as between physical activity and total tau (p = 0.004) in relation to the executive function composite score. Among participants with higher levels of physical activity, the adverse relationship between CSF-measured tau and executive function was diminished. In contrast, there were no significant interactions for episodic memory, and physical activity did not interact with Aβ42/40 (all interactions p > 0.05).

CONCLUSION

A physically active lifestyle may provide protection against AD-related cognitive decline by reducing the impact of tau pathology.

Highlights

Older age was associated with lower levels of physical activity, worse CSF biomarker profiles, and poorer cognition.
Physical activity moderates the impact of tau pathology on executive function but shows no significant effect on amyloid-beta pathology.
Physical activity may enhance cognitive reserve, thereby attenuating the influence of accumulating AD pathology on cognition.

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体力活动改变脑脊液tau测量和执行功能之间的关联

阿尔茨海默病（AD）的特征是淀粉样蛋白- β (Aβ)和tau蛋白的异常积累，可以通过脑脊液（CSF）取样在体内量化。体育活动已成为阿尔茨海默病风险的可能调节因素；然而，其对脑脊液生物标志物和认知功能的影响尚不完全清楚。我们研究了高水平的体育活动是否会改变阿尔茨海默病脑脊液生物标志物与认知功能之间的关系。方法来自BIOCARD研究的117名无痴呆的成年人（平均年龄72.2±8.0岁，70%为女性）佩戴手腕加速度计1周，行腰椎穿刺收集脑脊液，并完成全面的神经心理检查。使用多变量线性回归分析来检查身体活动（总活动量超过一天中最活跃的10个小时）是否调节AD CSF生物标志物[Aβ42/40，磷酸化tau （p-tau181）和总tau]与认知综合评分（情景记忆，执行功能）之间的关联。结果体力活动与p-tau181之间存在显著交互作用（p = 0.016），体力活动与总tau之间存在显著交互作用（p = 0.004）。在体力活动水平较高的参与者中，csf测量的tau与执行功能之间的不利关系减弱。相比之下，情景记忆没有显著的相互作用，体育活动与Aβ42/40没有相互作用(所有相互作用p >；0.05)。结论积极运动的生活方式可能通过减少tau病理的影响，对ad相关的认知能力下降提供保护。年龄越大，体力活动水平越低，脑脊液生物标志物谱越差，认知能力越差。体育活动调节tau病理对执行功能的影响，但对淀粉样蛋白病理无显著影响。体育活动可以增强认知储备，从而减弱AD病理积累对认知的影响。

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来源期刊

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Medicine-Psychiatry and Mental Health

CiteScore

10.10

自引率

2.10%

发文量

134

审稿时长

10 weeks

期刊介绍： Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.