Purpose of review: The recent advances in our understanding of Alzheimer's disease pathophysiology and the renin angiotensin system pathways suggest that angiotensin receptor blockers (ARBs) are ideal drugs to explore for Alzheimer's disease therapy.
Recent findings: New evidence suggests that the brain renin angiotensin system has two opposing pathways: a damaging pathway and a neuro-protective pathway. Both pathways are involved in the amyloid hypothesis (Aβ cascades) and vascular mechanisms of Alzheimer's disease. Studies in animal models suggest that ARBs have cognitive protective effects that are related to their ability to decrease production and oligomerization and increase degradation of Aβ and their vascular effects (improve blood–brain barrier, restore endothelial function, decrease inflammation, and increase cerebral blood flow). Human observational studies have further suggested that ARB use is associated with decreased risk of Alzheimer's disease and protection against future cognitive decline. Our work has suggested that ARB use is associated with decreased amyloid deposition in the brain in Alzheimer's disease and can provide cognitive protection in those with mild cognitive impairment, a prodromal state for Alzheimer's disease, and dementia.
Summary: To date, no robust clinical trial of ARBs in Alzheimer's disease has been performed. All things being equal, it is reasonable to consider ARBs in those with cognitive risks.