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.

Keywords: B-amyloid; Cognition; Lifestyle; Normal aging; Resilience; Risk factor; Tau.

Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.

尽管可改变的风险因素可能占痴呆症风险人口差异的约40%，但这些风险因素之间的相互关系对病理-认知关系的影响尚不明确。我们使用了一组203名认知正常的老年人（平均年龄73 ± 6.4岁，女性占比56%）的数据，并采用k-means聚类方法将参与者分配到三种与风险相关性状之一：积极活跃型（身体/认知活动、教育）、积极情感型（睡眠、抑郁、性格），以及负面多领域集群。线性混合效应模型显示，在积极的特性组中，β-淀粉样蛋白对非记忆认知下降的影响减弱（积极活跃型：β=3.7, p = 0.008；积极情感型：β=3.7, p = 0.007），而与负面特性组相比则不然。虽然在预测情景记忆下降的模型中观察到了显著的内侧颞叶tau蛋白 x 时间效应（p < 0.001），但聚类成员身份并没有改变这一关系。这些发现表明，不同的风险特征可以调节病理-认知之间的关系，并强调了可调整的韧性因素群体在缓解β-淀粉样蛋白沉积影响中的作用。

关键词： β-淀粉样蛋白； 认知能力； 生活方式； 正常老化； 韧性； 风险因素； Tau 蛋白。