Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease

Arch Intern Med. 2003 May 12;163(9):1069-75. doi: 10.1001/archinte.163.9.1069.


Background: High blood pressure and stroke are associated with increased risks of dementia and cognitive impairment. This study aimed to determine whether blood pressure lowering would reduce the risks of dementia and cognitive decline among individuals with cerebrovascular disease.

Methods: The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, double-blind, placebo-controlled trial conducted among 6105 people with prior stroke or transient ischemic attack. Participants were assigned to either active treatment (perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). The primary outcomes for these analyses were dementia (using DSM-IV criteria) and cognitive decline (a decline of 3 or more points in the Mini-Mental State Examination score).

Results: During a mean follow-up of 3.9 years, dementia was documented in 193 (6.3%) of the 3051 randomized participants in the actively treated group and 217 (7.1%) of the 3054 randomized participants in the placebo group (relative risk reduction, 12% [95% confidence interval, -8% to 28%]; P =.2). Cognitive decline occurred in 9.1% of the actively treated group and 11.0% of the placebo group (risk reduction, 19% [95% confidence interval, 4% to 32%]; P =.01). The risks of the composite outcomes of dementia with recurrent stroke and of cognitive decline with recurrent stroke were reduced by 34% (95% confidence interval, 3% to 55%) (P =.03) and 45% (95% confidence interval, 21% to 61%) (P<.001), respectively, with no clear effect on either dementia or cognitive decline in the absence of recurrent stroke.

Conclusions: Active treatment was associated with reduced risks of dementia and cognitive decline associated with recurrent stroke. These findings further support the recommendation that blood pressure lowering with perindopril and indapamide therapy be considered for all patients with cerebrovascular disease.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Cerebrovascular Disorders / complications*
  • Cerebrovascular Disorders / etiology
  • Cognition / drug effects*
  • Cognition Disorders / etiology
  • Cognition Disorders / prevention & control*
  • Dementia / etiology
  • Dementia / prevention & control*
  • Diuretics / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Indapamide / administration & dosage
  • Indapamide / therapeutic use*
  • Male
  • Middle Aged
  • Perindopril / administration & dosage
  • Perindopril / therapeutic use*
  • Risk
  • Treatment Outcome


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Diuretics
  • Indapamide
  • Perindopril