Discontinuation of Antihypertensive Medication, Cognitive Complaints, and Incident Dementia

To evaluate whether discontinuation of antihypertensive medication in community-dwelling older people is associated with a reduction in memory complaints and/or incident dementia.

Prospective observational cohort study within the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial.

Community-dwelling participants (aged 70-78 years at baseline) who underwent 2-yearly assessments during 6-8 years of follow-up.

Cox regression analyses of the relation between discontinuation of antihypertensive medication during the study and change in subjective memory complaints, incident dementia, and mortality.

Dementia occurred more often in participants discontinuing antihypertensive treatment (13.4% vs 6.2%, P = .02); mortality was similar (16.5% vs 13.9%, P = .52). Discontinuation of antihypertensive medication was associated with a double dementia hazard [hazard ratio (HR) (95% confidence interval) = 2.15 (1.15-4.03)], which somewhat attenuated after adjustment for sex, blood pressure, number of antihypertensives and other medications [HR = 1.92 (1.01-3.65)], and additionally for stroke, cardiovascular disease, diabetes, smoking, memory complaints, and MMSE score [HR = 1.79 (0.93-3.44)]. Antihypertensive discontinuation was associated with an approximately 50% higher hazard of dementia and/or mortality combined [HR = 1.58 (1.04-2.40); model 2: HR = 1.64 (1.07-2.51); model 3: HR = 1.49 (0.96-2.30)]. Antihypertensive discontinuation was not associated with change in memory complaints [odds ratio (95% confidence interval) = 0.96 (0.55-1.67)]. Subgroup and sensitivity analyses addressing possible sources of bias and confounding gave similar results.

Our results suggest that antihypertensive withdrawal in community-dwelling older people does not preserve cognition and may in fact increase dementia risk. This is not due to reduced mortality as competing risk. Additional analyses suggest results are unlikely to be explainable by confounding, reverse causality, or observational biases. Studies with person-specific reasons for antihypertensive discontinuation may be able to exclude reverse causality completely. Given the beneficial effects of antihypertensive medication on cardiovascular risk, observational data may be the best currently obtainable on the pressing issue of when withdrawal of antihypertensives in older people is acceptable and what consequences need to be weighed.