Abstract：
Objective: Our study aimed to explore whether physical condition might affect the association between genetic predisposition for Alzheimer\'s Disease (AD) and AD incidence. Methods: The sample of participants consisted of 561 community-dwelling adults over 64 years old, without baseline dementia (508 cognitively normal and 53 with mild cognitive impairment), deriving from the HELIAD, an ongoing longitudinal study with follow-up evaluations every 3 years. Physical condition was assessed at baseline through walking time (WT), while a Polygenic Risk Score for late onset AD (PRS-AD) was used to estimate genetic predisposition. The association between WT and PRS-AD with AD incidence was evaluated with Cox proportional hazard models adjusted for age, sex, education years, global cognition score and APOE ε-4 genotype. Then, the association between WT and AD incidence was investigated after stratifying participants by low and high PRS-AD. Finally, we examined the association between PRS-AD and AD incidence after stratifying participants by WT. Results: Both WT and PRS-AD were connected with increased AD incidence (p < 0.05), after adjustments. In stratified analyses, in the slow WT group participants with a greater genetic risk had a 2.5-fold higher risk of developing AD compared to participants with lower genetic risk (p = 0.047). No association was observed in the fast WT group or when participants were stratified based on PRS-AD. Conclusions: Genetic predisposition for AD is more closely related to AD incidence in the group of older adults with slow WT. Hence, physical condition might be a modifier in the relationship of genetic predisposition with AD incidence.
摘要：
目的：我们的研究旨在探讨身体状况是否可能影响阿尔茨海默病（AD）的遗传易感性与AD发病率之间的关系。方法：参与者的样本包括561名64岁以上的社区居住成年人，无基线痴呆（508认知正常和53轻度认知障碍），源于HELIAD，正在进行的纵向研究，每3年进行一次随访评估。通过步行时间（WT）在基线评估身体状况，而晚发性AD的多基因风险评分（PRS-AD）用于估计遗传易感性。使用Cox比例风险模型对WT和PRS-AD与AD发病率之间的关联进行评估，性别,教育年,全球认知评分和APOEε-4基因型。然后，在对参与者进行低PRS-AD和高PRS-AD分层后,研究了WT和AD发病率之间的关联.最后,我们通过WT对参与者进行分层后,研究了PRS-AD与AD发病率之间的关联.结果：WT和PRS-AD均与AD发病率增加有关（p<0.05）。调整后。在分层分析中，在慢WT组中,与遗传风险较低的参与者相比,遗传风险较高的参与者患AD的风险高2.5倍(p=0.047).在快速WT组中或当参与者基于PRS-AD进行分层时没有观察到关联。结论：在WT缓慢的老年人组中，AD的遗传易感性与AD发病率更密切相关。因此，身体状况可能是遗传易感性与AD发病率关系的修饰因素。
