Observational study of brain atrophy and cognitive decline comparing a sample of community-dwelling people taking angiotensin converting enzyme inhibitors and angiotensin receptor blockers over time

Background: Hypertension is an established risk factor for dementia. However, it is unclear whether there are differential effects of angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blockers (ARB) on brain health. In human observational studies, the evidence for superiority of either agent remains unclear.

Objective: To compare brain atrophy and cognitive decline between people treated with ACEi or ARB.

Methods: Participants aged 55-90 years without dementia had brain magnetic resonance imaging and neuropsychological assessments performed at 3 time points. The sample was enriched with people with type 2 diabetes (T2D). Multivariable mixed models were used to examine longitudinal associations of antihypertensive medication class with change in cognition and total brain volume.

Results: Of 565 people with longitudinal data, there were 163 on ACEi (mean age 69.9 years, T2D:64% with) and 125 on ARB (mean age 69.6 years, T2D:62%) at baseline. The baseline characteristics of those taking either an ACEi or ARB were similar with regards to age, sex, blood pressure control, and vascular risk factors. The mean duration of follow up was 3.2 years. The baseline association of ACEi and ARB use with total brain volume was similar in both groups. However, those taking an ARB had a slower rate of brain atrophy than those taking an ACEi (p = 0.031). Neither ACEi nor ARB use was associated with baseline cognitive function or cognitive decline.

Conclusions: These results support the theory that ARB may be preferable to ACEi to reduce brain atrophy. The mechanisms underlying this differential association warrant further investigation.