Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland.
Department of Psychology, Psychological Methods, Evaluation, and Statistics, University of Zurich, Zurich, Switzerland.
Ann Neurol. 2022 Sep;92(3):451-463. doi: 10.1002/ana.26417. Epub 2022 Jun 14.
Evidence on associations of lifestyle factors with Alzheimer's pathology and cognition are ambiguous, potentially because they rarely addressed inter-relationships of factors and sex effects. While considering these aspects, we examined the relationships of lifestyle factors with brain amyloid burden and cognition.
We studied 178 cognitively normal individuals (women, 49%; 65.0 [7.6] years) and 54 individuals with mild cognitive impairment (women, 35%; 71.3 [8.3] years) enrolled in a prospective study of volunteers who completed F-Flutemetamol amyloid positron emission tomography. Using structural equation modeling, we examined associations between latent constructs representing metabolic/vascular risk, physical activity, and cognitive activity with global amyloid burden and cognitive performance. Furthermore, we investigated the influence of sex in this model.
Overall, higher cognitive activity was associated with better cognitive performance and higher physical activity was associated with lower amyloid burden. The latter association was weakened to a nonsignificant level after excluding multivariate outliers. Examination of the moderating effect of sex in the model revealed an inverse association of metabolic/vascular risk with cognition in men, whereas in women metabolic/vascular risk trended toward increased amyloid burden. Furthermore, a significant inverse association between physical activity and amyloid burden was found only in men. Inheritance of an APOE4 allele was associated with higher amyloid burden only in women.
Sex modifies effects of certain lifestyle-related factors on amyloid burden and cognition. Notably, our results suggest that the negative impact of metabolic/vascular risk influences the risk of cognitive decline and Alzheimer's disease through distinct paths in women and men. ANN NEUROL 2022;92:451-463.
关于生活方式因素与阿尔茨海默病病理和认知之间关联的证据存在不确定性，这可能是因为它们很少涉及因素之间的相互关系和性别效应。在考虑这些方面的同时，我们研究了生活方式因素与大脑淀粉样蛋白负担和认知之间的关系。
我们研究了 178 名认知正常的个体（女性占 49%；65.0[7.6]岁）和 54 名轻度认知障碍个体（女性占 35%；71.3[8.3]岁），他们均参加了一项志愿者前瞻性研究，这些志愿者完成了 F-Flutemetamol 淀粉样蛋白正电子发射断层扫描。使用结构方程模型，我们研究了代表代谢/血管风险、身体活动和认知活动的潜在结构与整体淀粉样蛋白负担和认知表现之间的关联。此外，我们还研究了该模型中性别因素的影响。
总体而言，较高的认知活动与更好的认知表现相关，较高的身体活动与较低的淀粉样蛋白负担相关。后者的关联在排除多元异常值后减弱至无统计学意义。在模型中检查性别调节作用的结果显示，代谢/血管风险与男性的认知呈负相关，而在女性中，代谢/血管风险与淀粉样蛋白负担呈正相关趋势。此外，仅在男性中发现身体活动与淀粉样蛋白负担之间存在显著的负相关。载脂蛋白 E4 等位基因的遗传仅在女性中与较高的淀粉样蛋白负担相关。
性别改变了某些与生活方式相关的因素对淀粉样蛋白负担和认知的影响。值得注意的是，我们的结果表明，代谢/血管风险的负面影响通过女性和男性不同的途径影响认知衰退和阿尔茨海默病的风险。神经病学年鉴 2022；92：451-463。
