Angiotensin Receptor Blockers Are Associated With a Lower Risk of Progression From Mild Cognitive Impairment to Dementia

Abstract

Background: Previous studies found that antihypertensive medications (AHMs) acting on the renin-angiotensin system had the potential to reduce the progression from mild cognitive impairment to dementia. However, it remains unclear whether this association differs between ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers. methods: We conducted a retrospective cohort study in the Alzheimer’s Disease Neuroimaging Initiative among 403 participants with hypertension and mild cognitive impairment at baseline. Information on AHMs received during the follow-up period, including angiotensin receptor blockers, ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics, were self-reported. Cox proportional hazards models adjusted for potential confounders were used in the time to event analysis with progression to dementia as outcome. Results: Of the 403 participants, the mean (SD) age was 74.0 (7.3) years, 152 (37.7%) were female, 158 (39.2%) progressed to dementia over a median follow-up time of 3.0 years. Angiotensin receptor blockers were associated with a lower risk of progression to dementia as compared to ACE inhibitors (adjusted hazard ratio=0.45 [95% CI, 0.25–0.81]; P =0.023), other classes of AHMs (beta-blockers, calcium channel blockers, diuretics; adjusted hazard ratio, 0.49 [95% CI, 0.27–0.89]; P =0.037), and none of AHMs (adjusted hazard ratio, 0.31 [95% CI, 0.16–0.58]; P =0.001). Conclusions: In patients with hypertension and mild cognitive impairment, angiotensin receptor blockers were associated with a lower risk of progression to dementia compared with ACE inhibitors and other classes of AHMs. Our findings may have important implications for clinical practice but still warrant further investigations in larger prospective cohorts or clinical trials.

Diverse biological functions of the renin‐angiotensin system

“…[90][91][92] A 2022 study found that ARBs are associated with a lower risk of progression to dementia in hypertensive patients with mild cognitive impairment as a baseline. 93 Similar results are found for the neurodegenerative Parkinson's disease. A recently concluded 10-year observational study of patients with ischemic heart disease found that using ARBs that can penetrate the blood-brain barrier significantly reduced the risk of Parkinson's, suggesting a protective effect.…”

Autonomic nervous system and cardiac neuro-signaling pathway modulation in cardiovascular disorders and Alzheimer’s disease

“…In line with our hypothesis of a link between heart and brain dysfunction, recent clinical investigations, as well as studies in animal models, have highlighted the beneficial effects promoted by different cardioprotective drugs (i.e., Beta-blockers, Angiotensin Converting Enzyme (ACE) inhibitors, sartans, and Aldosterone receptor antagonists) in Alzheimer’s disease and cognitive dementia. The cardioprotective drugs, in addition to providing preventive effects ( Carey and Fossati, 2022 ), also appear to prevent the neuronal accumulation of Aβ aggregates and result in a significant improvement in memory impairment in some clinical studies as well as in multiple animal models ( Chen et al, 2020 ; Lee et al, 2020 ; Drews et al, 2021 ; Ouk et al, 2021 ; Wang et al, 2021 ; Beaman et al, 2022 ; Deng et al, 2022 ; Mehdipour et al, 2022 ). This evidence points to the possibility that combination therapies containing these compounds may have efficacy for the treatment and prevention of both cardiac diseases and dementia in older adults.…”

Angiotensin Receptor Blockers and Dementia Prevention: Do Not RAS to a Conclusion Yet

“…Angiotensin Receptor Blockers and Dementia Prevention: Do Not RAS to a Conclusion Yet Sevil Yasar , Whitney Wharton I n this issue of Hypertension, Deng et al 1 investigate the longitudinal effect of antihypertensive medications acting via the renin-angiotensin system. They examine the effects of both angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin 1 receptor blockers (AT1RB) in participants with hypertension and mild cognitive impairment on all-cause dementia risk and cognitive function.…”

“…The study by Deng et al 1 fills part of this knowledge gap. It is the first study evaluating the impact of ATR1B medications on progression from mild cognitive impairment to dementia in people with hypertension accounting for Alzheimer’s disease biomarkers.…”