Antihypertensive Therapy and Cerebral Hemodynamics in Executive Mild Cognitive Impairment: Results of a Pilot Randomized Clinical Trial

OBJECTIVES: To compare the effects of three antihypertensive medications on cerebral hemodynamic and cognitive function in hypertensive individuals with executive dysfunction. DESIGN: Double-blind randomized clinical trial. SETTING: Community. PARTICIPANTS: Fifty-three individuals aged 60 and older with hypertension and executive dysfunction. INTERVENTION: Lisinopril, candesartan, or hydrochlorothiazide for 1 year. MEASUREMENTS: Cerebral blood flow velocity (BFV; transcranial Doppler ultrasonography during rest, sitting, standing, hypercapnia, and hypocapnia), cognition, and blood pressure were measured at baseline and after 6 and 12 months. Linear mixed models were used to compare the three groups. RESULTS: Of the 53 participants, 47 had successful insonation (mean age 72; 70% white; 57% women). There was a tendency toward an increase in BFV in the candesartan group and a decrease in the lisinopril and hydrochlorothiazide groups (between-group P = .57) that was significant in those with low BFV at baseline (<median 27.6 cm/s, between-group P = .03). The candesartan group also had the greatest improvement in executive function (Trail Making Test Part B improved by 17.1 seconds, vs hydrochlorothiazide improved by 4.2 seconds and lisinopril worsened by 14.4 seconds, P = .008). Carbon dioxide vasoreactivity and vasomotor range declined significantly in the lisinopril (within-group P = .001 for vasoreactivity and .02 for vasomotor range) and hydrochlorothiazide groups (within-group P = .10 and .009, respectively) but not in the candesartan group (within-group P = .25 and .38, respectively; between-group P = .30 and .46, respectively). CONCLUSION: Angiotensin receptor blockers may preferentially preserve cerebral hemodynamics and executive function in individuals with executive dysfunction. These findings warrant further investigation in a larger trial.