Antihypertensive therapy and cerebral hemodynamics in executive mild cognitive impairment: results of a pilot randomized clinical trial

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00605072.

Figure 1

Changes over study period in the three groups in cerebral blood flow velocity in the overall sample (A) and in those with baseline blood flow velocity below the median. Footnote (figure 1): Least square means were adjusted for age. P-values were obtained from the linear mixed model for the visit by group interaction parameter. V0-V1: change from baseline to 6 months; V0–V2: change from baseline to 12 months; V1–V2: change from 6 months to 12 months. BFV: cerebral blood flow velocity. HCTZ: hydrochlorothiazide.