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Brain atrophy is associated with impairment in cognitive function and learning function. The aim of this study was to determine whether daily physical activity prevents age-related brain atrophy progression.The participants were 381 men and 393 women who had participated in both the baseline and the follow-up surveys (mean duration = 8.2 yr). Magnetic resonance imaging of the frontal and temporal lobes was performed at the time of the baseline and follow-up surveys. The daily physical activities and total energy expenditures of the participants were recorded at baseline with uniaxial accelerometry sensors. Multiple logistic regression models were fit to determine the association between activity energy expenditure, number of steps, and total energy expenditure variables and frontal and temporal lobe atrophy progression while controlling for possible confounders.In male participants, the odds ratio of frontal lobe atrophy progression for the fifth quintile compared with the first quintile in activity energy expenditure was 3.408 (95% confidence interval = 1.205–9.643) and for the number of steps was 3.651 (95% confidence interval = 1.304–10.219). Men and women with low total energy expenditure were at risk for frontal lobe atrophy progression. There were no significant differences between temporal lobe atrophy progression and physical activity or total energy expenditure.The results indicate that physical activity and total energy expenditure are significant predictors of frontal lobe atrophy progression during an 8-yr period. Promoting participation in activities may be beneficial for attenuating age-related frontal lobe atrophy and for preventing dementia.