Ten-year longitudinal effects of physical activity and apolipoprotein E ..4 genotype on precuneus atrophy in Japanese older adults.

Left precuneus volume declined significantly over 10 years regardless of MVPA level or APOE ε4 genotype.

• The study followed 295 community-dwelling older adults (154 men and 141 women; age ≥65 years) over 10 years.
• Left precuneus volume decline was statistically significant for all subgroups (each p < 0.0001).
• Brain volumes were assessed using longitudinal magnetic resonance imaging.
• Decline occurred irrespective of physical activity intensity level or APOE ε4 carrier status.

Among APOE ε4 carriers, greater time spent in MVPA was associated with a slower rate of left precuneus volume decline.

• The MVPA × APOE ε4 × year interaction effect was observed specifically in women's left precuneus.
• The three-way interaction was significant in unadjusted models but did not survive false discovery rate (FDR) correction across 16 models.
• The finding is characterized as exploratory.
• No similar attenuation effect of MVPA on precuneus decline was observed in men.

Physical activity was measured objectively using accelerometers and analyzed by intensity level at baseline.

• Baseline physical activity was quantified using accelerometers.
• Activity was analyzed according to intensity, including moderate-to-vigorous physical activity (MVPA).
• Participants were categorized as APOE ε4 carriers or non-carriers.
• Sex-stratified linear mixed models were used, adjusting for relevant covariates.

No significant interaction between physical activity and APOE ε4 status on posterior cingulate cortex volume changes was reported.

• Both the precuneus and posterior cingulate cortex volumes were assessed using longitudinal MRI.
• The APOE ε4 allele is associated with early atrophy in both the precuneus and posterior cingulate cortex.
• Significant findings were limited to the left precuneus in women, with no comparable effects noted for the posterior cingulate cortex.
• 16 models total were tested, necessitating FDR correction.

The APOE ε4 allele is described as a major genetic risk factor for Alzheimer's disease associated with early precuneus and posterior cingulate cortex atrophy.

• APOE ε4 is identified as a major genetic risk factor for Alzheimer's disease.
• The allele is associated with early atrophy in the precuneus and posterior cingulate cortex.
• The study examined whether physical activity can mitigate this atrophy in high-risk APOE ε4 carriers.
• Participants were community-dwelling older adults aged ≥65 years from Japan in a 10-year longitudinal design.