Candesartan and cognitive decline in older patients with hypertension: a substudy of the SCOPE trial

Hypertension is associated with impaired cognitive function but the effect of antihypertensive treatment on cognitive function is unclear.

We investigated the effect of treatment of hypertension on cognition with the angiotensin-receptor-blocker, candesartan, in a placebo-controlled, double-blind, randomized controlled trial at one center participating in the Study on Cognition and Prognosis in the Elderly. A total of 257 older adults with hypertension (mean age 76 years, blood pressure 165 +/- 8/88 +/- 7 mm Hg) were recruited from general practice and treated with 8-16 mg candesartan or placebo once daily, for a mean follow-up period of 44 months. Additional antihypertensive therapy was permitted in both groups to achieve treatment targets. Cognitive function was measured using the Cognitive Drug Research computerized assessment battery, trail-making tests, and verbal fluency. Data from annual assessments were used to calculate individual coefficients of decline by regressing composite test scores over time for five cognitive domains.

The blood pressure difference between groups at study close was 8/3 mm Hg. The candesartan group showed less decline in attention (0.004 vs -0.036, p = 0.04) and episodic memory (0.14 vs -0.22, p = 0.04) compared to placebo, a similar trend for speed of cognition (-2.3 vs -17.4, p = 0.15), but no differences in working memory (0.0014 vs 0.0010, p = 0.90) or executive function (-0.0031 vs -0.0023, p = 0.95). Effect sizes were in the small-to-moderate range.

The potential for blood pressure-lowering with angiotensin-receptor-blockers to reduce the rate of decline of specific areas of cognitive function in older patients with hypertension warrants further investigation to determine clinical efficacy.