Angiotensin II represents a key molecule in hypertension and cerebrovascular pathology. By promoting inflammation and oxidative stress, enhanced Ang II levels accelerate the onset and progression of cell senescence. Sustained activation of RAS promotes end-stage organ injury associated with aging and results in cognitive impairment and dementia. The discovery of the angiotensin-converting enzyme ACE2-angiotensin (1–7)-Mas receptor axis that exerts vasodilator, antiproliferative, and antifibrotic actions opposed to those of the ACE-Ang II-AT1 receptor axis has led to the hypothesis that a decrease in the expression or activity of angiotensin (1–7) renders the systems more susceptible to the pathological actions of Ang II. Given the successful demonstration of beneficial effects of increased expression of ACE2/formation of Ang1–7/Mas receptor binding and modulation of Mas expression in animal models in containing cerebrovascular pathology in hypertensive conditions and aging, one could reasonably hope for analogous effects regarding the prevention of cognitive decline by protecting against hypertension and cerebral microvascular damage. Upregulation of ACE2 and increased balance of Ang 1–7/Ang II, along with positive modulation of Ang II signaling through AT2 receptors and Ang 1–7 signaling through Mas receptors, may be an appropriate strategy for improving cognitive function and treating dementia. 1. Cognition and Dementia Cognition is a general term that refers to all mental processes, such as perception, thinking, memory, movement, attention, emotions, ability to understand the intentions and thoughts of other people, decision making, and self-awareness. Anecdotal evidence of age-related decline in cognitive functions is amply supported by a wealth of objective data. Mild cognitive impairment (MCI) is a widely used term to indicate a syndrome characterized by a mild memory or cognitive impairment that cannot be accounted for by any recognized medical or psychiatric conditions [1]. The general criteria for MCI require a subjective complaint of memory loss, an objective impairment of memory function for age and education (1 or 2 SD below the mean score of the examined sample) assessed by formal neuropsychological testing, with no evidence of dementia, but preservation of intact activities of daily living and other cognitive domains [1]. In contrast to MCI, a diagnosis of dementia is made when cognitive impairment is greater than that found in normal aging and it affects two or more cognitive domains that comprise orientation, attention, verbal linguistic
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