Angiotensin-Converting Enzyme Inhibitors and Alzheimer’s Disease Progression in Older Adults : Results from the Reseau sur la Maladie d’Alzheimer Français Cohort

OBJECTIVES: To assess whether angiotensin-converting enzyme inhibitor (ACE-I) treatment is associated with less cognitive decline in older adults with Alzheimer's disease (AD) than in those using other hypertensive or no drugs. DESIGN: Four-year prospective multicenter cohort study with a biannual assessment. SETTING: Memory clinics from 16 university hospitals in France. PARTICIPANTS: Community-dwelling older adults with mild to moderate AD (N = 616). MEASUREMENTS: Participants were stratified into four groups according to type and duration of antihypertensive drug treatment. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE). Linear mixed-effects models were used to assess differences in decline in MMSE score between the four groups. Hypertension at each visit was included in the model. RESULTS: Sixty-one participants had used ACE-Is continuously, 57 had used them intermittently, 189 had used other antihypertensive drugs, and 309 never used any antihypertensive drugs. Continuous ACE-Is users had a 4-year decline in MMSE of 6.4 ± 1.6 points (P < .001), intermittent ACE-Is users of 7.9 ± 1.1 points (P < .001), continuous or intermittent users of other antihypertensive drugs of 8.8 ± 0.7 points (P < .001), and never-users of 10.2 ± 0.6 points (P < .001). MMSE decline between the four groups was significantly different (adjusted P = .02). In subgroup analysis, the 118 (19.2%) participants who had continuously or intermittently used ACE-Is had a significant difference in 4-year MMSE decline from the 498 (80.8%) who had never used ACE-Is (7.5 ± 0.9 vs 9.7 ± 0.4; P = .03). CONCLUSION: The use of ACE-Is in older adults with AD is associated with a slower rate of cognitive decline independent of hypertension. Future research is needed to explore the role of ACE-Is in long-term AD progression.