Effects of centrally acting angiotensin converting enzyme inhibitors on functional decline in patients with Alzheimer's disease

J Alzheimers Dis. 2014;40(3):595-603. doi: 10.3233/JAD-131694.


Background: Centrally acting angiotensin converting enzyme inhibitors (CACE-Is) are associated with reduced rates of cognitive decline in patients with dementia. CACE-Is may also improve exercise tolerance in functionally impaired older adults with normal cognition, suggesting that CACE-Is may positively influence activities of daily living (ADL) in dementia.

Objective: To compare rates of decline in patients with mild to moderate Alzheimer's disease (AD) receiving CACE-Is to those not currently treated with CACE-Is (NoCACE-I), included in the Doxycycline and Rifampicin for Alzheimer's Disease study (n = 406).

Methods: Patients were included if baseline and end-point (twelve months apart) scores were available for measures including the Standardized Alzheimer's Disease Assessment Scale - Cognitive Subscale; Quick Mild Cognitive Impairment screen; Clinical Dementia Rating Scale (CDR-SB), and Lawton-Brody ADL Scale.

Results: There was a significant, 25% difference (median one-point) in the 12-month rate of decline in ADL scores in patients taking CACE-Is (n = 91), compared to the NoCACE-I group (n = 274), p = 0.024. This remained significant after adjusting for age, gender, education, and blood pressure, p = 0.034. When individual CACE-Is were compared to the NoCACE-I group, a significant reduction in the rate of decline in ADLs (median one versus four points), were only observed for perindopril, p = 0.01. The CDR-SB was also reduced (median one-point) for the perindopril compared to the NoCACE-I group, p = 0.04.

Conclusion: This observational study suggests that CACE-Is, and potentially perindopril in particular, are associated with a reduced rate of functional decline in patients with AD, without an association with mood or behavior. This suggests that CACE-Is may slow disease progression in AD.

Keywords: ACE inhibitors; Alzheimer's disease; cognitive; dementia; function; psychological decline.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications
  • Alzheimer Disease / drug therapy*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Double-Blind Method
  • Doxycycline / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Outcome Assessment, Health Care
  • Psychiatric Status Rating Scales
  • Retrospective Studies
  • Rifampin / therapeutic use*


  • Angiotensin-Converting Enzyme Inhibitors
  • Doxycycline
  • Rifampin

Grant support