BACKGROUND Previous studies have suggested that the association between APOE ɛ4 and dementia is moderated by physical activity (PA), but the results remain inconclusive and longitudinal data on cognitive decline is missing. In this study we examine whether there is a gene-environment interaction between APOE and PA on cognitive decline in older adults using 9-year follow-up data of three cohort studies. METHODS We followed 7176 participants from three longitudinal cohort studies: Longitudinal Aging Study Amsterdam (LASA), InCHIANTI and Rotterdam Study for 9 years. PA was assessed with self-reported questionnaires and was categorized in low, moderate and high PA. Cognitive function was assessed with the Mini-Mental State Examination (MMSE) and cognitive decline was defined as a decrease of 3 points or more on the MMSE during 3 years follow-up. We fitted logistic regression models using Generalized Estimating Equations adjusting for age, sex, education, depressive symptoms and number of chronic disease. Interaction between APOE and PA was tested on multiplicative and additive scale. RESULTS Cohorts were similar in most aspects but InCHIANTI participants were on average older and had lower education. APOE ɛ4 carriers had higher odds of cognitive decline (OR=1.46, 95% CI (1.29-1.64)) while PA was not significantly associated with cognitive decline overall (Moderate PA: OR 0.87(0.67-1.13); High PA: OR 0.71(0.36-1.40)). There was no evidence for an interaction effect between PA and APOE ɛ4 in cognitive decline in older adults (APOE*Moderate PA: p=0.83; APOE*High PA: p=0.90). CONCLUSIONS Previous claims of a gene-environment interaction between APOE ɛ4 and PA in cognitive decline are not supported by our results.

中文翻译：

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体力活动是老年人APOE与认知能力下降之间联系的调节剂：三项纵向队列研究的结果。

背景技术先前的研究表明，APOEɛ4与痴呆之间的关联可以通过体育活动（PA）进行调节，但结果尚无定论，并且缺乏有关认知能力下降的纵向数据。在这项研究中，我们使用三项队列研究的9年随访数据，研究了APOE和PA之间在老年人认知能力下降方面是否存在基因-环境相互作用。方法我们追踪了来自三个纵向队列研究的7176名参与者：阿姆斯特丹的纵向老龄化研究（LASA），印第安纳州和鹿特丹研究长达9年。PA用自我报告的问卷进行评估，并分为低，中和高PA。认知功能通过迷你精神状态检查（MMSE）进行评估，认知能力下降定义为在3年的随访期间MMSE下降3分以上。我们使用广义估计方程拟合了逻辑回归模型，该方程针对年龄，性别，教育程度，抑郁症状和慢性病数量进行了调整。APOE和PA之间的相互作用在乘法和加法尺度上进行了测试。结果队列在大多数方面相似，但InCHIANTI的参与者平均年龄较大，文化程度较低。APOEɛ4携带者认知功能下降的几率更高（OR = 1.46，95％CI（1.29-1.64）），而PA与整体认知功能下降没有显着相关（中度PA：OR 0.87（0.67-1.13）；高PA：OR 0.71 （0.36-1.40））。没有证据表明PA和APOEɛ4在老年人认知下降中有相互作用作用（APOE *中度PA：p = 0.83； APOE *高PA：p = 0.90）。