Renin Angiotensin Aldosterone System Inhibition in Controlling Dementia-Related Cognitive Decline

With the rising prevalence of cognitive impairment worldwide, clinicians are facing important challenges managing dementia, particularly Alzheimer's disease, the most prevalent dementia subtype. Given that current treatments mainly offer symptomatic improvement, without altering disease progression, the challenge now is to identify and integrate new therapeutic strategies. Hypertension is increasingly recognized as a modifiable risk factor for mild cognitive impairment (MCI), the precursor of dementia. The renin angiotensin aldosterone system (RAAS) is central to blood pressure regulation and medications targeting RAAS inhibition are associated with reduced rates of both cognitive and functional decline in those with MCI and dementia. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are widely prescribed anti-hypertensives acting on the RAAS, and there is growing evidence that they act centrally, possibly exerting their effects independent of their blood pressure lowering properties. The relationship is complex however, and given the risks associated with hypotension particularly in older adults, treatment with these agents may not benefit all. Additionally, current evidence is limited to preclinical and observational studies such that there is now a pressing need to confirm preliminary studies with properly conducted randomized control trials. Here, we review some of the salient and complex aspects of these observations to date.