Relationship Between Antihypertensive Medications and Cognitive Impairment: Part II. Review of Physiology and Animal Studies

Abstract

Purpose of ReviewThere is an established association between hypertension and increased risk of poor cognitive performance and dementia including Alzheimer’s disease; however, associations between antihypertensive medications (AHM) and dementia risk are less clear. An increased interest in AHM has resulted in expanding publications; however, none of the recent reviews provide comprehensive review. Our extensive review includes 24 mechanistic animal and human studies published over the last 5 years assessing relationship between AHM and cognitive function.Recent FindingsAll classes of AHM showed similar result patterns in animal studies. The mechanism by which AHM exert their effect was extensively studied by evaluating well-established pathways of AD disease process, including amyloid beta (Aβ), vascular, oxidative stress and inflammation pathways, but only few studies evaluated the blood pressure lowering effect on the AD disease process.SummaryMethodological limitations of the studies prevent comprehensive conclusions prior to further work evaluating AHM in animals and larger human observational studies, and selecting those with promising results for future RCTs.

Drug interactions with dementia‐related pathophysiological pathways worsen or prevent dementia

“…By diminishing the intracellular calcium levels through the blockade of neuronal calcium channels, CCBs could prevent cognitive decline (Rouch et al, ) because an increase in cytosolic calcium could trigger the production of Aβ1‐42 and induce neuronal death. CCBs also improve the regional cerebral blood flow and angiogenesis and decrease oxidative stress markers (R. Peters, Schuchman, Peters, Carlson, & Yasar, ).…”

“…Thus, the modulation of RAS by ARBs and ACE‐Is is noteworthy. ACE‐Is also diminished ROS generation and enhanced CF (R. Peters et al, ) probably through the inhibition of cerebral ACE. However, according to (Fournier et al, ), ACE‐Is only exert short‐term protective effects, and chronic exposure to ACE‐Is could lead to an increased Aβ42 brain burden and cognitive decline.…”

“…In a mouse model of AD, losartan normalized cerebrovascular reactivity (R. Peters et al, ), which is impaired in AD patients. These beneficial effects on memory have been well established, but the effects on the cerebral levels of Aβ1‐42 remain unclear (R. Peters et al, ). However, losartan could counteract the deleterious effect induced by angiotensin II (Ang‐II).…”

“…Among the ARBs, losartan and telmisartan are the most studied (R. Peters et al, 2016). In a mouse model of AD, losartan normalized cerebrovascular reactivity (R. Peters et al, 2016), which is impaired in AD patients.…”

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

“…Results from human observational studies and secondary observations in clinical trials of populations with high cardiovascular morbidity generally favour a beneficial effect of antihypertensive medications (AHM) on reducing dementia risk [2] but are not conclusive [3]. These studies report a wide variation in the magnitude of treatment effect [2,4]. One possible explanation for this may be that various classes of AHM have differential effects on brain health independent of their blood pressure lowering effect [2,4,5].…”