Abstract
BACKGROUND: Studies of hypertension and cognition variously report adverse, null, and protective associations. We evaluated evidence supporting three potential explanations for this variation: an effect of hypertension duration, an effect of age at hypertension initiation, and selection bias due to dependent censoring. METHODS: The Normative Aging Study is a prospective cohort study of men in the greater Boston area. Participants completed study visits, including hypertension assessment, every 3-5 years starting in 1961. Seven hundred fifty-eight of 1,284 men eligible at baseline completed cognitive assessment between 1992 and 2005; we used the mean age-adjusted cognitive test Z score from their first assessment to quantify cognition. We estimated how becoming hypertensive and increasing age at onset and duration since hypertension initiation affect cognition. We used inverse probability of censoring weights to reduce and quantify selection bias. RESULTS: A history of hypertension diagnosis predicted lower cognition. Increasing duration since hypertension initiation predicted lower mean cognitive Z score (-0.02 standard units per year increase [95% confidence interval= -0.04 to -0.001]), independent of age at onset. Comparing participants with and without hypertension, we observed noteworthy differences in mean cognitive score only for those with a long duration since hypertension initiation, regardless of age at onset. Age at onset was not associated with cognition independent of duration. Analyses designed to quantify selection bias suggested upward bias. CONCLUSIONS: Previous findings of null or protective associations between hypertension and cognition likely reflect the study of persons with short duration since hypertension initiation. Selection bias may also contribute to cross-study heterogeneity.