Vascular factors and cognition: toward a prevention of dementia?

High blood pressure is a known risk factor for stroke and dementia. However, very little is known about the prevention of dementia by lowering blood pressure. Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) was designed to determine the effects of an angiotensin-converting enzyme (ACE) inhibitor-based blood pressure-lowering regimen on the risk of stroke among individuals with a prior stroke or transient ischaemic attack (TIA). One of the important aims of the study was to test the hypothesis that treatment would reduce the incidence of dementia and cognitive decline. A total of 6105 patients were randomized to active treatment or placebo. Active treatment comprised perindopril for all participants, and indapamide for those with neither a specific indication for, nor a contraindication to, a diuretic. Dementia was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Cognitive decline was defined as a drop of 3 points or more on the Mini-Mental State Examination (MMSE) between baseline and final follow-up. During a median follow-up of 3.9 years, dementia was diagnosed in 410 patients and cognitive decline in 610. Active treatment reduced the risk of cognitive decline (risk reduction [RR] 19%; 95% confidence interval [CI], 4-32; P = 0.01] but there was no clear reduction in the risk of dementia (RR, 12%; 95% CI, -8-28; P = 0.2]). The RR for cognitive outcomes preceded by a recurrent stroke was 34% (95% CI, 3-55; P = 0.03) for dementia and 45% (95% CI, 21-61; P = <0.001) for cognitive decline. Among individuals with a history of stroke or TIA, blood pressure-lowering treatment reduced the risk of cognitive decline by about one fifth. Cognitive decline and dementia associated with recurrent stroke during follow-up were each reduced by between one third and one half. These findings provide further support for the recommendation that blood pressure lowering with perindopril and indapamide be considered for all patients with cerebrovascular disease.