Modifiable risk factor profiles moderate the effect of β-amyloid pathology on cognition in aging

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging Pub Date : 2025-05-15 DOI:10.1016/j.neurobiolaging.2025.05.001

Mohini Bhade , Stefania Pezzoli , Joseph Giorgio , Tyler J. Ward , Joseph R. Winer , Theresa M. Harrison , Susan M. Landau , William J. Jagust

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Abstract

Although modifiable risk factors may account for around 40 % of population variability in dementia risk, the effect of risk factor interrelationships on pathology-cognition relationships is poorly understood. Using risk factor data from a cohort of 203 cognitively normal older adults (73 ± 6.4 years, 56 % female), we used k-means clustering to assign participants to one of three risk-related profiles; namely, positive-active (physical/cognitive activity, education), positive-affective (sleep, depression, personality), and negative multi-domain clusters. Linear mixed-effects models showed an attenuated effect of β-amyloid on non-memory cognition decline in positive profiles (positive-active: β=3.7, p = 0.008, positive-affective: β=3.7, p = 0.007) compared to the negative profile. While a significant entorhinal tau x time effect (p < 0.001) was observed in a model predicting episodic memory decline, cluster membership did not modify this relationship. These findings suggest that different risk profiles moderate pathology-cognition relationships, and highlight the role of groups of modifiable resilience factors in mitigating the effects of β-amyloid deposition.

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可改变的危险因素谱调节β-淀粉样蛋白病理对衰老认知的影响

尽管可改变的风险因素可能占痴呆症风险人群变异性的40%左右，但风险因素相互关系对病理认知关系的影响尚不清楚。使用来自203名认知正常老年人（73 ± 6.4岁，56%为女性）队列的风险因素数据，我们使用k-means聚类将参与者分配到三个风险相关概况之一；即积极-主动（身体/认知活动，教育），积极-情感（睡眠，抑郁，个性）和消极多域集群。线性混合效应模型显示，与阴性谱相比，阳性谱中β-淀粉样蛋白对非记忆认知衰退的影响减弱（阳性-活跃：β=3.7, p = 0.008，阳性-情感：β=3.7, p = 0.007）。虽然在预测情景记忆衰退的模型中观察到显着的内嗅tau x时间效应（p <； 0.001），但聚类成员并没有改变这种关系。这些发现表明，不同的风险特征调节了病理-认知关系，并强调了可改变的弹性因子组在减轻β-淀粉样蛋白沉积影响中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurobiology of Aging 医学-老年医学

CiteScore

8.40

自引率

2.40%

发文量

225

审稿时长

67 days

期刊介绍： Neurobiology of Aging publishes the results of studies in behavior, biochemistry, cell biology, endocrinology, molecular biology, morphology, neurology, neuropathology, pharmacology, physiology and protein chemistry in which the primary emphasis involves mechanisms of nervous system changes with age or diseases associated with age. Reviews and primary research articles are included, occasionally accompanied by open peer commentary. Letters to the Editor and brief communications are also acceptable. Brief reports of highly time-sensitive material are usually treated as rapid communications in which case editorial review is completed within six weeks and publication scheduled for the next available issue.