Aldosterone, cognitive function, and cerebral hemodynamics in hypertension and antihypertensive therapy

Abstract

Background: Animal studies suggest that the renin-angiotensin-aldosterone system is involved in neurocognitive function and the response to antihypertensive therapy. We investigated the impact of circulating aldosterone and renin activity on cognition and cerebral hemodynamics at baseline and after antihypertensive therapy for 1 year.

Methods: Participants were older adults (n = 47; mean age = 71 years) enrolled in a clinical trial. Routine antihypertensive medications were replaced with the study regimen to achieve a blood pressure <140/90 mm Hg. Executive function, memory, cerebral hemodynamics (blood flow velocity), CO2 vasoreactivity (measured using transcranial Doppler ultrasonography), plasma renin activity, and aldosterone were measured at baseline and at 6 and 12 months after the initiation of treatment.

Results: At baseline, higher levels of circulating aldosterone were associated with lower blood flow velocity (β = -0.02; P = 0.03), lower CO2 vasoreactivity (β = -0.11; P = 0.007), and decreased autoregulation abilities (β = -0.09; P = 0.01). Those with higher levels of aldosterone at baseline demonstrated the greatest improvement in executive function (P = 0.014 for the aldosterone effect) and in CO2 vasoreactivity (P = 0.026 for the aldosterone effect) after 12 months of lowering blood pressure (<140/90 mm Hg). Plasma renin activity was not associated with any of the measures.

Conclusions: Higher levels of aldosterone may be associated with decreased cerebrovascular function in hypertension. Those with higher aldosterone levels may benefit the most from lowering blood pressure. The role of aldosterone in brain health warrants further investigation in a larger trial.

Keywords: aldosterone; blood flow velocity hypertension; blood pressure.; cognition; renin; vasoreactivity.

Figure 1.

Scatter plots and fitted regression lines with the 95% confidence interval band of the cerebral hemodynamics vs. aldosterone levels measure at baseline while off routine antihypertensive therapy. Units of measurements are as follows: orthostatic change in cerebrovascular resistance (DEL-CVR), mm Hg/cm/sec; vasoreactivity, cm/sec/mm Hg per mm Hg P_CO2; blood flow velocity (BFV), cm/sec. P values are testing the null hypothesis that the slope of the fitted line = 0 using the regression analyses.

Figure 2.

Change at 6 and 12 months relative to baseline in Trail Making Test, part B-A, in seconds, and CO₂ vasoreactivity in cm/sec/mm Hg per mm Hg P_CO2 by level of aldosterone at baseline while off antihypertensive therapy. Values are the least square adjusted for age, gender, race, body mass index, and renin levels. For Trail Making Test: between-group P value was 0.014; within-group P values were (low = 0.68, medium = 0.43, high = 0.001). For CO₂ vasoreactivity: between-group P value was 0.026; within group P values were (low = 0.27, medium = 0.88, high = 0.01).