Data_Sheet_1_Apolipoprotein E Genotype Moderation of the Association Between Physical Activity and Brain Health. A Systematic Review and Meta-Analysis.doc

IntroductionPossession of one or two e4 alleles of the apolipoprotein E (APOE) gene is associated with cognitive decline and dementia risk. Some evidence suggests that physical activity may benefit carriers of the e4 allele differently. MethodWe conducted a systematic review and meta-analysis of studies which assessed APOE differences in the association between physical activity and: lipid profile, Alzheimer's disease pathology, brain structure and brain function in healthy adults. Searches were carried out in PubMed, SCOPUS, Web of Science and PsycInfo. ResultsThirty studies were included from 4,896 papers screened. Carriers of the e4 allele gained the same benefit from physical activity as non-carriers on most outcomes. For brain activation, e4 carriers appeared to gain a greater benefit from physical activity on task-related and resting-state activation and resting-state functional connectivity compared to non-carriers. Post-hoc analysis identified possible compensatory mechanisms allowing e4 carriers to maintain cognitive function. DiscussionThough there is evidence suggesting physical activity may benefit e4 carriers differently compared to non-carriers, this may vary by the specific brain health outcome, perhaps limited to brain activation. Further research is required to confirm these findings and elucidate the mechanisms.引言 携带1个或2个载脂蛋白E（apolipoprotein E, APOE）基因e4等位基因与认知衰退及痴呆发病风险显著相关。现有研究证据表明，体力活动对e4等位基因携带者的获益可能与非携带者存在差异。 方法 本研究针对健康成人开展系统综述与荟萃分析，纳入评估体力活动与血脂谱、阿尔茨海默病（Alzheimer's disease）病理、脑结构及脑功能之间的关联中APOE基因差异效应的相关研究。检索数据库涵盖PubMed、SCOPUS、Web of Science及PsycInfo。 结果 本研究从初筛的4896篇文献中最终纳入30项符合标准的研究。在绝大多数结局指标上，e4等位基因携带者与非携带者从体力活动中获得的获益程度相当。但针对脑激活的亚组分析显示，与非携带者相比，e4等位基因携带者在任务相关脑激活、静息态脑激活及静息态功能连接方面，从体力活动中获得的获益更为显著。事后分析揭示了潜在的代偿机制，可帮助e4等位基因携带者维持认知功能。 讨论 尽管现有证据表明，体力活动对e4等位基因携带者与非携带者的获益存在差异，但该差异可能因具体脑健康结局指标的不同而有所区别，或仅局限于脑激活层面。未来仍需开展进一步研究以验证本研究结论，并阐明其潜在生物学机制。