My understanding is that the hippocampus (and other brain regions) tend to atrophy as we get older, and that a number of studies have show that cardio exercise can stop and/or reverse this process. The research reports I've seen haven't indicated that NOT exercising is the primary cause of the brain shrinking--that seems to be more related to aging. But there probably haven't been many, if any, long-term studies that followed both exercisers and non-exercisers over a long period to see if there are differences in the amount of hippocampus atrophy that could be explained by lack of exercise. It seems reasonable to think that, if exercise can increase the size of the hippocampus once, it can probably do it more than once, but again, I don't know if that's been specifically studied.
Here's a link to an article about the exercise/hippocampus connection:
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