A systematic review on the potential role of APOE genotype as a moderator in the relationship between physical activity, brain health and dementia risk

Abstract

AbstractBackgroundPhysical activity (PA) has been associated with decreased dementia risk, reduced Alzheimer’s disease (AD) neuropathological burden, and cognitive decline. On the other hand, the strongest genetic risk factor for AD is the Apolipoprotein E (APOE) ε4 allele, which increases AD‐risk in a dose‐dependent manner. Over the past two decades, researchers around the world have tried to unveil whether APOE ε4 carriage moderates the relationship between PA, brain health and dementia risk (Figure 1). Nevertheless, at present, this findings within this field remain inconsistent.MethodPubmed and Web of Science were searched for entries following the criteria specified in Table 1. The PRISMA guidelines for systematic reviews were followed throughout the process. A final set of 33 studies were considered after abstracts and full‐text articles were screened by two independent researchers. These included studies addressing the protective effect of PA on dementia risk (19 publications) and different markers of brain pathology (14 publications, see Figure 2).ResultStudies with shorter follow‐up periods found PA reduced dementia risk generally found that in both genotype groups; however, studies with longer follow‐ups showed varying results. Midlife PA seems to exert a greater impact on ε4 non‐carriers. Conversely, in neuroimaging studies, mainly ε4 carriers or both groups showed benefits, particularly when group sizes were large. Additionally, the association between PA and amyloid burden is stronger among ε4 carriers.ConclusionAlthough available data appears inconclusive, a close‐up look into the different study designs, methodologies and outcomes utilized can clarify the relationship between dementia and PA. More randomized clinical trials as well as longitudinal neuroimaging studies are need in order to fully elucidate relationship between PA, brain health and dementia risk.