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A decrease in brain volume (ie, brain atrophy) is a marker of cognitive health in older adults. Insufficient weekly accumulation of moderate and vigorous physical activity (MVPA) has been associated with lower brain volume. As this association has been established for a small number of brain areas and structures and atrophy rates seem to be nonuniform between them, more comprehensive analyses are warranted. We compared the volume of 71 brain areas and structures in 45 older adults who met and did not meet objectively measured MVPA recommendations. In addition, we used multiple regression models to determine whether cardiorespiratory fitness (VO2PEAK), MVPA, and health-related risk factors could affect the atrophy of brain areas and structures. An accelerometer (GT9-X ActiGraph) was worn for 7 days. Participants were then classified into 2 groups: <150 minutes MVPA (<150′MVPA; n  = 20) and ≥150 minutes MVPA (≥150′MVPA; n  = 25) per week. Older adults who accumulated ≥150′MVPA per week had significantly higher absolute and relative (% of intracranial volume) volumes of 39 and 9 brain areas and structures, respectively, than those who accumulated <150′MVPA per week. Higher VO2PEAK seems to be a key predictor of the atrophy of brain areas and structures. In conclusion, meeting weekly physical activity recommendations seems to have a widespread effect on preserving the volume of more than 30 brain areas and structures in older adults. VO2PEAK seems to be the most frequent and important predictor of brain volume preservation. [ABSTRACT FROM AUTHOR]