All the components of the classic renin-angiotensin system (RAS) have been identified in the brain. Today, the RAS is considered to be composed mainly of two axes: the pressor axis, represented by angiotensin (Ang) II/angiotensin-converting enzyme/AT1 receptors, and the depressor and protective one, represented by Ang-(1-7)/ angiotensin-converting enzyme 2/Mas receptors. Although the RAS exerts a pivotal role on electrolyte homeostasis and blood pressure regulation, their components are also implicated in higher brain functions, including cognition, memory, anxiety and depression, and several neurological disorders. Overactivity of the pressor axis of the RAS has been implicated in stroke and several brain disorders, such as cognitive impairment, dementia, and Alzheimer or Parkinson's disease. The present review is focused on the role of the protective axis of the RAS in brain disorders beyond its effects on blood pressure regulation. Furthermore, the use of drugs targeting centrally RAS and its beneficial effects on brain disorders are also discussed.

Background:Several studies have examined the links between hypertension, vascular damage, and cognitive impairment. The functions most commonly involved seem to be those associated with memory and executive function.Aims:1) to report the cognitive evolution in a cohort of hypertensive patients, 2) to identify the affected domains, and 3) to correlate the results obtained with blood pressure measurements.Materials and Methods:Observational 6-year follow-up cohort study including both males and females aged ≥65 and ≤80 years, and hypertensive patients under treatment. Patients with a history of any of the following conditions were excluded: stroke, transient ischemic attack, diabetes mellitus, atrial fibrillation, cardiac surgery, dementia, or depression. Four neurocognitive evaluations were performed (at baseline and every 2 years). The tests used evaluated memory and executive function domain. Blood pressure was measured on every cognitive evaluation.Results:Sixty patients were followed for 76.4 ± 2.8 months. The average age at baseline was 72.5 ± 4.2 and 77.9 ± 4.6 at 6 years (65% were women). Two patients were lost to follow up (3.3%) and 8 patients died (13.3%).The density incidence for dementia was 0.6% patients per year (pt/y) (n = 3) and for depression was 1.6% pt/y (n = 12). No changes were observed in either memory impairment or the Mini Mental State Examination (MMSE) results (p = ns) during follow-up. A progressive impairment of the executive function was shown regardless of the blood pressure measurements.Conclusion:1) the incidence of dementia doubled to general population, 2) the initial memory impairment did not change during the evaluation period, 3) cognitive impairment worsened in the areas related to executive function (prefrontal cortex) regardless of the adequacy of anti-hypertensive treatment and blood pressure values.

The aim of this study was to investigate the cognitive state in women and its relation to menopause and hypertension (HTN). The authors included 1034 women aged 47.13±15.71 years. The prevalence of HTN was 47.1%, with 67.8% of patients treated and 48.6% controlled. Cognitive impairment was higher among hypertensive menopausal (mini‐Boston Naming Test: 7.4±3.1 vs 8.5±2.4, P<.001; Clock‐Drawing Test: 5.2±2 vs 5.6±1.6, P<.01). Using logistic regression adjusted by age and education level, statistical differences were found in the results from the mini‐Boston Naming Test between menopausal hypertensive vs menopausal normotensive women (odds ratio, 1.48; 95% confidence interval, 1.06–2.07; P=.021), and no difference between nonmenopausal hypertensive vs menopausal normotensive women (odds ratio, 0.89; 95% confidence interval, 0.51–1.57; P=.697). The P interaction between both groups was significant (P=.038). The possibility of alteration in cortical functions in menopausal hypertensive woman showed a relative increment of 48% (P=.021). The association between HTN and menopause increases the possibility of compromising the semantic memory by 50%.

Vascular risk factors are shared by heart and brain. Vascular brain injury (small vessel disease, stroke) alone or combined with neurodegenerative pathology (β-amyloid depositions) brings about either cognitive decline and vascular dementia or Alzheimer’s disease. Long-term exposure to vascular risk factors precedes the onset of neurocognitive diseases by one or two decades. Early detection and control of modifiable vascular risk factors seem to be the only current strategies to prevent cognitive impairment and dementia.