In this issue of JAMA Internal Medicine, Gray and colleagues1 present findings from an observational analysis that show a higher risk for dementia with the increasing dose and duration of exposure to medications with strong anticholinergic activity. The risk for dementia was consistent when comparing participants with recent and past heavy use of such medications with nonusers, suggesting that the adverse cognitive effects are permanent. Other studies2-4 have consistently shown similar results. However, the question of reversibility of the adverse cognitive effects of medications and the safety risks of discontinuing the use of such medications remain untested in randomized clinical trials (RCTs).