APOE ε4, modifiable risk factors, and dementia in community-based older Japanese adults

Apolipoprotein E (APOE) ε4 is a major genetic risk factor for dementia. We examined whether APOE ε4 genotype modified the associations between a modifiable risk factor (mRF) score and dementia in older Japanese adults.

This cross-sectional study included 9605 community-dwelling Japanese individuals aged ≥65 years. APOE ε4 genotype and mRF scores were assessed. Dementia was clinically diagnosed. Brain magnetic resonance imaging (MRI) measures were available in a subset.

The odds ratio (OR) for dementia increased with the number of APOE ε4 alleles. A low mRF score was associated with lower ORs for prevalent dementia in non-carriers and heterozygotes but not in homozygotes. On MRI, low mRF scores were associated with preserved brain structure in non-carriers and heterozygotes, but not in homozygotes.

Favorable risk factor profiles were associated with lower dementia risk and preserved brain structure in APOE ε4 non-carriers and heterozygotes, but not in homozygotes, supporting genotype-tailored prevention strategies.