Dougherty Ryan J, Soldan Anja, Pettigrew Corinne, Greenberg Barry, Spira Adam P, Moghekar Abhay, Albert Marilyn
Department of Kinesiology and Health Rutgers University New Brunswick New Jersey USA.
Department of Neurology Johns Hopkins School of Medicine Baltimore Maryland USA.
Alzheimers Dement (N Y). 2025 Apr 15;11(2):e70085. doi: 10.1002/trc2.70085. eCollection 2025 Apr-Jun.
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.
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).
There were significant interactions between physical activity and p-tau181 ( = 0.016) as well as between physical activity and total tau ( = 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 > 0.05).
A physically active lifestyle may provide protection against AD-related cognitive decline by reducing the impact of tau pathology.
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.
阿尔茨海默病(AD)的特征是β淀粉样蛋白(Aβ)和tau蛋白异常积聚,可通过采集脑脊液(CSF)在体内进行定量分析。身体活动已成为AD风险的一种可能调节因素;然而,其对脑脊液生物标志物和认知功能的影响尚未完全明确。我们研究了较高水平的身体活动是否会改变AD脑脊液生物标志物与认知功能之间的关联。
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)佩戴腕部加速度计1周,接受腰椎穿刺以采集脑脊液,并完成全面的神经心理学检查。多变量线性回归分析用于检验身体活动(一天中最活跃的10小时内的总活动计数)是否会调节AD脑脊液生物标志物[Aβ42/40、磷酸化tau蛋白(p-tau181)和总tau蛋白]与认知综合评分(情景记忆、执行功能)之间的关联。
就执行功能综合评分而言,身体活动与p-tau181(P = 0.016)以及身体活动与总tau蛋白(P = 0.004)之间存在显著交互作用。在身体活动水平较高的参与者中,脑脊液检测的tau蛋白与执行功能之间的不良关系减弱。相比之下,情景记忆方面没有显著交互作用,且身体活动与Aβ42/40之间没有交互作用(所有交互作用P>0.05)。
积极的生活方式可能通过减少tau蛋白病理的影响来预防与AD相关的认知衰退。
年龄较大与身体活动水平较低、脑脊液生物标志物状况较差以及认知能力较差有关。身体活动可调节tau蛋白病理对执行功能的影响,但对β淀粉样蛋白病理无显著影响。身体活动可能增强认知储备,从而减轻累积的AD病理对认知的影响。