Effects of angiotensin II receptor blockers on dementia

Abstract

The renin-angiotensin system (RAS) is involved in pathological mechanisms of target organ damage as well as the induction of hypertension; therefore, blockade of the RAS has been expected to prevent cardiovascular and cerebrovascular diseases beyond its antihypertensive effects. In spite of the well-characterized role of angiotensin (Ang) II receptor blockers (ARBs) in preventing the onset and recurrence of stroke, the clinical evidence for an effect of ARBs on dementia has not been definitive. However, preliminary experiments raise the possibility that treatment using ARBs may prevent ischemic brain damage and cognitive impairment. Moreover, recent reports have shown that some ARBs prevent amyloid b deposition in the brain and attenuate cognitive impairment in Alzheimer disease models. Furthermore, recent cohort studies indicate that lower incidence of Alzheimer disease is observed in elderly individuals treated with ARBs. These results indicate a beneficial role for ARBs in cognitive impairment associated with vascular disease, Alzheimer disease, metabolic syndrome and other neurodegenerative diseases. Here, we review the effects of ARBs on the brain with a focus on dementia and future therapeutic approaches for elderly people suffering from disabilities. Hypertension Research (2009) 32, 738-740; doi:10.1038/hr.2009 Keywords: dementia; neuroinflammation; neuroprotective; renin-angiotensin system; stroke INTRODUCTION Dementia is a common but serious health problem. An estimated 33 million elderly persons around the world suffer from dementia, and this number is expected to reach 81.1 million by 2040. 1 Dementia impairs quality of life and is associated with a profound disease burden, morbidity and mortality, not only in patients but also in caregivers. 2,3 Therefore, prevention of dementia is a critical need for advanced countries to address. Life style-related disorders, such as hypertension, diabetes mellitus and obesity have been reported to be related to dementia. For example, large prospective cohort studies indicate that midlife hypertension increases the risk of dementia, 4 suggesting that the blood pressure-lowering effects of antihypertensive drugs may reduce the incidence of dementia. Moreover, recent clinical studies and basic research have suggested several ways in which antihypertensive drugs can prevent target organ damage independently of their antihypertensive effect. In particular, the tissue reninangiotensin system (RAS) (the so-called local RAS) is involved not only in the vasculature but also in the brain. Accumulating evidence from large clinical trials suggests that blockade of the RAS by angiotensin (Ang) II type 1 (AT 1 ) receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors is more effective at inhibiting target organ (such as heart and kidney) damage than other hypertensive agents. 5 Here, we overview the accumulating evidence and suggest possible mechanisms by which ARBs prevent brain damage and dementia.

High plasma aldosterone concentration is a novel risk factor of cognitive impairment in patients with hypertension

“…[16][17][18][19][20][21] In addition, as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and potassium sparing diuretics have an advantage in preventing CI, activation of the renin-angiotensin system or low potassium concentration has been suggested to be involved in CI through possible contributors to CI pathogenesis, including oxidative stress, inflammation, platelet aggregation and vasoconstriction. [22][23][24][25][26][27][28][29] Aldosterone, a crucial factor downstream of the renin-angiotensinaldosterone system, has also been shown to cause target organ damage independent of its effects on blood pressure and to be a potent cerebrovascular risk factor. In this study, we showed that increased PAC is associated with CI.…”

Oxidative stress in the cardiovascular center has a pivotal role in the sympathetic activation in hypertension

“…It is also suggested that AT1 blockers may have neuroprotective effects, reducing the incidence of stroke and improving cognition function. 85,86 In addition, renal afferent nerves may also contribute to the blood pressure elevation according to the recent findings of the renal nerve ablation in patients with resistant hypertension. 8,10 Renal afferent nerves project directly to many areas in the central nervous system controlling the sympathetic nervous system activity such as the NTS and hypothalamus.…”

Effects of telmisartan on the cerebral circulation of hypertensive patients with chronic-stage stroke

“…25 Kume et al 26 demonstrated that telmisartan improved cognitive function in Alzheimer's disease patients with hypertension more than amlodipine, although the difference was not significant, whereas Imabayashi et al 27 found that it controlled declining glucose metabolism in the olfactory tract of patients with Alzheimer's disease. The present study did not undertake a detailed investigation of cognitive and other higherorder brain functions.…”