Laura DeFina of the Cooper Institute in Dallas and colleagues analyzed data involving about 20,000 middle-aged people over a 24-year period.
"With increasing cardiorespiratory fitness levels, there was decreased development of all-cause dementia in later life," DeFina said in a statement.
For example, people in the fittest 20 percent around age 50 were 36 percent less likely than those in the least-fit 20 percent to be diagnosed with dementia after age 65, the study found.
DeFina noted other studies found better blood flow in brains of fitter people.
The study was published in the Annals of Internal Medicine.