Apolipoprotein E epsilon 4 genotype and a physically active lifestyle in late life: analysis of gene-environment interaction for the risk of dementia and Alzheimer%26apos;s disease dementia

作者：Luck T^*; Riedel Heller S G; Luppa M; Wiese B; Koehler M; Jessen F; Bickel H; Weyerer S; Pentzek M; Koenig H H; Prokein J; Ernst A; Wagner M; Moesch E; Werle J; Fuchs A; Brettschneider C; Scherer M; Maier W

来源：Psychological Medicine, 2014, 44(6): 1319-1329.

DOI：10.1017/S0033291713001918

• Additive interaction
• apolipoprotein E epsilon 4
• dementia
• gene-environment interaction
• lifestyle
• physical activity

Background. As physical activity may modify the effect of the apolipoprotein E (APOE) epsilon 4 allele on the risk of dementia and Alzheimer%26apos;s disease (AD) dementia, we tested for such a gene-environment interaction in a sample of general practice patients aged 575 years. %26lt;br%26gt;Method. Data were derived from follow-up waves I-IV of the longitudinal German study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). The Kaplan-Meier survival method was used to estimate dementiaand AD-free survival times. Multivariable Cox regression was used to assess individual associations of APOE epsilon 4 and physical activity with risk for dementia and AD, controlling for covariates. We tested for gene-environment interaction by calculating three indices of additive interaction. %26lt;br%26gt;Results. Among the randomly selected sample of 6619 patients, 3327 (50.3%) individuals participated in the study at baseline and 2810 (42.5%) at follow-up I. Of the 2492 patients without dementia included at follow-up I, 278 developed dementia (184 AD) over the subsequent follow-up interval of 4.5 years. The presence of the APOE epsilon 4 allele significantly increased and higher physical activity significantly decreased risk for dementia and AD. The co-presence of APOE epsilon 4 with low physical activity was associated with higher risk for dementia and AD and shorter dementia-and AD-free survival time than the presence of APOE epsilon 4 or low physical activity alone. Indices of interaction indicated no significant interaction between low physical activity and the APOE epsilon 4 allele for general dementia risk, but a possible additive interaction for AD risk. %26lt;br%26gt;Conclusions. Physical activity even in late life may be effective in reducing conversion to dementia and AD or in delaying the onset of clinical manifestations. APOE epsilon 4 carriers may particularly benefit from increasing physical activity with regard to their risk for AD.

• 出版日期2014-4
• 单位上海市精神卫生中心