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

J Am Geriatr Soc. 2013 Feb;61(2):194-201. doi: 10.1111/jgs.12100. Epub 2013 Jan 25.

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Benzimidazoles / administration & dosage*
  • Biphenyl Compounds
  • Blood Pressure / drug effects
  • Cerebrovascular Circulation / drug effects*
  • Cognition / drug effects*
  • Cognitive Dysfunction / complications
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / physiopathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Pilot Projects
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology*
  • Tetrazoles / administration & dosage*
  • Treatment Outcome

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Benzimidazoles
  • Biphenyl Compounds
  • Tetrazoles
  • candesartan

Associated data

  • ClinicalTrials.gov/NCT00605072