The brain shrinks with age, but the timing of this process and the extent of its malleability are unclear. We measured changes in regional brain volumes in younger (age 20-31) and older (age 65-80) adults twice over a 6 months period, and examined the association between changes in volume, history of hypertension, and cognitive training. Between two MRI scans, 49 participants underwent intensive practice in three cognitive domains for 100 consecutive days, whereas 23 control group members performed no laboratory cognitive tasks. Regional volumes of seven brain structures were measured manually and adjusted for intracranial volume. We observed significant mean shrinkage in the lateral prefrontal cortex, the hippocampus, the caudate nucleus, and the cerebellum, but no reliable mean change of the prefrontal white matter, orbital-frontal cortex, and the primary visual cortex. Individual differences in change were reliable in all regions. History of hypertension was associated with greater cerebellar shrinkage. The cerebellum was the only region in which significantly reduced shrinkage was apparent in the experimental group after completion of cognitive training. Thus, in healthy adults, differential brain shrinkage can be observed in a narrow time window, vascular risk may aggravate it, and intensive cognitive activity may have a limited effect on it.