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

Abstract

Cognitive impairment leading to dementia is associated with high prevalence of hypertension, decreased quality of life and poor prognosis. Aldosterone is known as a risk factor for cardiovascular and cerebrovascular diseases. In addition, mineral corticoid receptors are abundantly expressed in the hippocampus, which plays a pivotal role in cognitive function; however, it has not been determined whether plasma aldosterone level is associated with cognitive impairment in patients with hypertension. We enrolled 68 patients with essential hypertension and assessed their cardiovascular risk factors, including blood pressure, hyperlipidemia, diabetes mellitus, obesity, smoking, history of cerebral infarction, renal function, parameters of inflammation, oxidative stress and nitric oxide bioavailability, a parameter of cerebral blood flow and carotid plaque by ultrasound examination, plasma renin activity and plasma aldosterone concentration (PAC). The mini-mental state examination (MMSE) was used to evaluate cognitive function. The relevance of cardiovascular risk factors and MMSE score was statistically evaluated. Multiple regression analysis showed that age (Po0.01), PAC (Po0.01) and history of cerebral infarction (Po0.05) were inversely and independently associated with MMSE score. Mineral corticoid receptor antagonists, including spironolactone and eplerenone, increased MMSE score in seven patients with hypertension, but not in the controls. In conclusion, increased PAC is associated with impaired cognitive function and mineral corticoid receptor blockade may protect against not only cardiovascular mortality, but also cognitive impairment in patients with hypertension.

Phosphodiesterase-4 inhibitors ameliorates cognitive deficits in deoxycorticosterone acetate induced hypertensive rats via cAMP/CREB signaling system

“…These results were found to be in agreement with earlier studies that show significantly higher blood pressure, right kidney weight and heart weight in DOCA salt-induced hypertensive rats as compared to the sham operated rats (Hacioglu et al, 2003). Hypertension is one of the most critical risk factors for cognitive impairment and the renin angiotensin aldosterone system (RAAS) is a key player in hypertension, both in a blood pressure-dependent and-independent manner (Yagi et al, 2011;Yagi et al, 2013). The functional mechanisms of hypertension increasing the risk of cognitive impairment remain ambiguous.…”

Improvement of cognitive impairment in female type 2 diabetes mellitus mice by spironolactone

“…Very recently, Yagi et al reported that high plasma aldosterone concentration becomes a risk factor for cognitive impairment in hypertensives. 17 They also demonstrated that treatment with spironolactone or eplerenone increased mini-mental state examination (MMSE) score in patients with hypertension but not controlled. We did not use eplerenone for this experiment; however, these results indicate that blockade of MR by spironolactone prevents cognitive impairment in female diabetic mice probably as a class effect of MR blockade.…”

Activation of mineralocorticoid receptors in the rostral ventrolateral medulla is involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats

“…[1][2][3] Mineralocorticoid receptor (MR) is recognized as a target for therapeutic intervention in hypertension and heart failure. 4,5 The beneficial effects of the MR antagonist spironolactone or the more specific antagonist eplerenone on end-organ damage have been studied in animal models. [6][7][8][9][10] It has been reported that MRs regulate epithelial Na channels (ENaCs) that are important for the regulation of sodium transport and the maintenance of extracellular fluid volume and arterial pressure (AP) in the kidney.…”