Hypertension and hypothalamo-pituitary-adrenal axis hyperactivity affect frontal lobe integrity

Chronically elevated cortisol levels have been associated with elevated blood pressure, brain atrophy, and cognitive impairments. In this cross-sectional exploratory study, we assessed whether hypertension was related to hypothalamo-pituitary-adrenal axis hyperactivity and whether this may in part explain prefrontal brain atrophy and cognitive impairments in this population. We studied 27 patients with hypertension and 27 normotensive control subjects. Glucocorticoid feedback was assessed using the combined dexamethasone-CRH test. All participants completed a neuropsychological battery and received brain magnetic resonance imaging for volumetric measurement of frontal and medial temporal lobe regions. Hypertension was significantly associated with impaired glucocorticoid feedback control after statistically controlling for age, gender, and body mass index ( P = 0.01). Hypertensive patients also showed a trend toward reductions in frontal lobe volume ( P = 0.09) and had significantly lower scores in one of two tests of executive function ( P = 0.03). Significant correlations were observed between hypothalamo-pituitary-adrenal hyperactivity and frontal lobe atrophy. Our data indicate that impaired glucocorticoid feedback control may partly account for the prefrontal volume reductions present in patients with hypertension. Future studies assessing the impact of hypertension on the brain should include cortisol assessments.