Modifying effects of race and ethnicity and APOE on the association of physical activity with risk of Alzheimer's disease and related dementias

Abstract

IntroductionWe investigated whether the protective association of physical activity with risk of Alzheimer's disease and related dementias (ADRD) has genetic or behavioral variations.MethodsIn the Multiethnic Cohort, we analyzed moderate or vigorous physical activity (MVPA) reported at ages 45 to 75 among 88,047 participants in relation to 13,039 incident diagnoses of late‐onset ADRD identified in Medicare claims (1999 to 2014), by five racial and ethnic groups, hours sitting, and in a subset (16%), apolipoprotein E (APOE) genotype.ResultsMVPA was inversely associated with ADRD (hazard ratio for ≥14 vs <2.5 hours/week: 0.83, 95% confidence interval [CI]: 0.76 to 0.90 in men; 0.88, 5% CI: 0.81 to 0.95 in women). The association was inverse in all racial and ethnic groups except Black participants (P‐heterogeneity = 0.52), but stronger in individuals with lower levels of sitting duration or those who do not carry the APOE e4 risk allele.DiscussionThe different effects of physical activity by sitting duration and APOE genotype warrant further research.

Ideal vitamin D and handgrip strength counteracts the risk effect of APOE genotype on dementia: a population-based longitudinal study

“…Therefore, the two optimal exposures may jointly interact with dementia related genetic risk. Emerging evidence confirmed that a higher frequency of participation in physical activity can improve handgrip strength and increase vitamin D level, and the interaction between physical and APOE genotype have been reported [ 44 , 45 ]. Brain structural alteration may be another potential mechanism.…”

Reduced GLP-1R availability in the caudate nucleus with Alzheimer’s disease

“…The risk of developing AD is influenced by heritable factors to the extent of 60–80% ( Mez et al, 2016 ; Bao et al, 2022 ; Karlsson et al, 2022 ), and more than 40 genetic risk loci associated with AD have been identified ( Kunkle et al, 2019 ; Sullivan et al, 2022 ; Dato et al, 2023 ; Fominykh et al, 2023 ; Huang et al, 2023 ; Wainberg et al, 2023 ). Among these loci, apolipoprotein E (APOE) alleles exhibit the strongest association with the disease ( Park et al, 2023 ; Polsinelli et al, 2023 ; Sadleir and Vassar, 2023 ). Advanced biomarkers, such as positron emission tomography (PET) scans and plasma assays for aβ and phosphorylated tau, demonstrate significant potential for both clinical and research applications ( Feinkohl et al, 2020 ; Peng et al, 2021 ; Shen et al, 2022 ; Wilson et al, 2022 ; Gonzalez-Ortiz et al, 2023 ; Zhang et al, 2023 ).…”