Suzanne A Ligthart1, Eric P Moll van Charante1, Willem A Van Gool2, Edo Richard21Department of General Practice, 2Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsBackground: Over the last decade, evidence has accumulated that vascular risk factors increase the risk of Alzheimer disease (AD). So far, few randomized controlled trials have focused on lowering the vascular risk profile to prevent or postpone cognitive decline or dementia.Objective: To systematically perform a review of randomized controlled trials (RCTs) evaluating drug treatment effects for cardiovascular risk factors on the incidence of dementia or cognitive decline.Selection criteria: RCTs studying the effect of treating hypertension, dyslipidemia, ­hyperhomocysteinemia, obesity, or diabetes mellitus (DM) on cognitive decline or dementia, with a minimum follow-up of 1 year in elderly populations.Outcome measure: Cognitive decline or incident dementia.Main results: In the identified studies, dementia was never the primary outcome. Statins (2 studies) and intensified control of type II DM (1 study) appear to have no effect on prevention of cognitive decline. Studies on treatment of obesity are lacking, and the results of lowering homocysteine (6 studies) are inconclusive. There is some evidence of a preventive effect of antihypertensive medication (6 studies), but results are inconsistent.Conclusion: The evidence of a preventive treatment effect aimed at vascular risk factors on cognitive decline and dementia in later life is scarce and mostly based on secondary outcome parameters. Several important sources of bias such as differential dropout may importantly affect interpretation of trial results.Keywords: cardiovascular risk factors, cognitive decline, dementia, preventio