Supplementary Material for: Sex Differences in the Impact of <b><i>BDNF</i></b> Genotype on the Longitudinal Relationship between Physical Activity and Cognitive Performance

<b><i>Background:</i></b> Physical activity may preserve cognitive function in older adults, but benefits vary by sex and genetic factors. <b><i>Objective:</i></b> We tested the longitudinal association between physical activity and cognitive performance to de termine whether a common genetic polymorphism for brain-derived neurotrophic factor <i>(BDNF</i> Val66Met<i>)</i> moderated this effect. <b><i>Methods:</i></b> In a 12-year longitudinal population-based sample of older adults (<i>n</i> = 2,218), we used growth curve modeling to investigate whether the benefits of physical activity on cognitive preservation differed by <i>BDNF</i> genotype and sex across multiple cognitive domains including processing speed, attention, working memory, and episodic verbal memory. <b><i>Results:</i></b> The relationship between physical activity and cognitive performance was dependent on <i>BDNF</i> carrier status in males (Δχ² [Δdf] = 12.94 [4], <i>p</i> = 0.01), but not in females (Δχ² [Δdf] = 4.38 [4], <i>p</i> = 0.36). Cognition benefited from physical activity in male <i>BDNF</i> <i>met</i> noncarriers, but not <i>met</i> carriers, whereas cognition was not statistically significantly related to physical activity in females regardless of genotype. <b><i>Conclusion:</i></b> We observed longitudinal, but not cross-sectional, effects of physical activity on cognitive performance. Our study highlights the importance of longitudinal follow-up and consideration of sex differences in the relationships between physical activity, <i>BDNF</i> genotype, and cognitive decline. The findings contribute to understanding gene-lifestyle interactions in promoting cognitive health.<b><i>研究背景：</i></b> 体力活动或可维持老年人的认知功能，但其获益程度存在性别与遗传因素层面的差异。<b><i>研究目的：</i></b> 本研究旨在探究体力活动与认知表现之间的纵向关联，以明确脑源性神经营养因子（brain-derived neurotrophic factor, BDNF）Val66Met常见基因多态性是否对该效应存在调节作用。<b><i>研究方法：</i></b> 本研究针对一项为期12年的社区老年人群纵向队列（n=2218），采用增长曲线模型，分析体力活动对认知维持的获益情况是否因BDNF基因型与性别而异，涉及加工速度、注意力、工作记忆及言语情景记忆等多个认知维度。<b><i>研究结果：</i></b> 体力活动与认知表现之间的关联在男性群体中受BDNF携带者状态影响（Δχ²(Δdf)=12.94(4), p=0.01），但在女性群体中无此显著关联（Δχ²(Δdf)=4.38(4), p=0.36）。具体而言，男性BDNF Met等位基因非携带者的认知功能可从体力活动中获益，而Met等位基因携带者则无此获益；女性群体中，无论基因型如何，认知表现与体力活动均无统计学意义上的显著关联。<b><i>研究结论：</i></b> 本研究发现体力活动对认知表现存在纵向效应，而非横断面效应。本研究强调了纵向随访以及在体力活动、BDNF基因型与认知衰退的关联中考虑性别差异的重要性。本研究结果有助于深入理解基因-生活方式交互作用对认知健康的促进作用。