Antihypertensive therapy and cerebral hemodynamics in executive mild cognitive impairment: results of a pilot randomized clinical trial.
OBJECTIVE
To compare the effects of three antihypertensive medications on cerebral hemodynamic and cognitive function in hypertensive individuals with executive dysfunction.


METHODS
Double-blind randomized clinical trial.


METHODS
Community.


METHODS
Fifty-three individuals aged 60 and older with hypertension and executive dysfunction.


METHODS
Lisinopril, candesartan, or hydrochlorothiazide for 1 year.


METHODS
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).


CONCLUSIONS
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.
Division of Geriatric, Hospital, and General Internal Medicine, Department of Medicine, University of Southern California, Los Angeles, CA 90033, USA. ihajjar@usc
Ihab
I
Hajjar
Meaghan
M
Hart
Yu-Ling
YL
Chen
Wendy
W
Mack
Vera
V
Novak
Helena
H
C Chui
Lewis
L
Lipsitz
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects*; D060825:Cognitive Dysfunction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan