The Effects of Antihypertensive Treatment on Cognitive Function: Results from the HOPE Study

OBJECTIVES: Hypertension is associated with impaired cognition, but it is unclear whether this impairment is reversible. We sought to evaluate the effect of blood pressure reduction on cognition. DESIGN: A randomized, double-blind trial. SETTING: A single center, with assessments in subjects' domiciles. PARTICIPANTS: Community-screened subjects more than 69 years of age who had median diastolic pressures > 99 mm Hg and systolic pressures > 159 mm Hg or diastolic > 85 mm Hg and systolic > 179 mm Hg with Mini-Mental State Examination scores of 20 to 28. Subjects had not previously received antihypertensive treatment. INTERVENTION: Captopril 12.5 mg twice daily or bendrofluazide 2.5 mg daily for 24 weeks, preceded by a 2-week placebo phase. MEASUREMENTS: Cognition was evaluated by a psychometric test battery comprising Immediate and Delayed Logical Memory, Paired Associates recall, Raven's Progressive Matrices, Halstead Reitan Trail Making A, and the Anomalous Sentences Repetition Test. RESULTS: Eighty-one subjects (28 male, 53 female) were treated (41 captopril, 40 bendrofluazide). At entry, mean age was 76.1 years (range 70-84), mean blood pressure was 191 (160-230) mm Hg systolic, 101 (88-110) mm Hg diastolic, and mean MMSE score 26.1. A total of 69 subjects completed the trial. The 25th, 50th, and 75th percentiles of the difference between pretreatment and Week 24 blood pressures wer 15 mm Hg, 35 mm Hg, and 50 mm Hg (systolic) and 5 mm Hg, 10 mm Hg, and 19 mm Hg (diastolic). There were no significant differences in any psychometric test between captopril and bendrofluazide. The 19 subjects in the quartile that lowered their diastolic blood pressure most ( > or = 19 mm Hg) had improved scores on Anomalous Sentences (P = .012) and Paired Associates (P = .044) compared to the 19 subjects in the least blood pressure responsive quartile (fall < or = 5 mm Hg)s. CONCLUSION: The treatment of hypertension is not hazardous to cognitive function in older people with pre-existing cognitive impairment. Long-term adequate blood pressure control may reverse cognitive impairment associated with pre-existing hypertension.