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.
From the aDepartment of Epidemiology, Harvard School of Public Health, Boston, MA; bDepartment of Environmental Health, Harvard School of Public Health, Boston, MA; cDepartment of Biostatistics, Harvard School of Public Health, Boston, MA; dVeterans Affairs Normative Aging Study, Boston, MA; and 5Department of Medicine, Boston University School of Medicine, Boston, MA.
The Normative Aging Study is supported by the Cooperative Studies Program/ERIC of the US Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center. M.C.P. is funded by an NIA F31 Predoctoral Training Grant (F31 AG038233), and this work was supported by NIH R01ES005257. D.S. is the recipient of a Research Career Scientist award from the VA Clinical Science Research & Development Service. The researchers are independent of the study funders. The funding sources had no role in the study design, collection, analysis, and interpretation of data, writing of the report, or in the decision to submit the article for publication.
All authors declare no conflicts of interest.
Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com). This content is not peer-reviewed or copy-edited; it is the sole responsibility of the author.
Correspondence: Melinda C. Power, Harvard School of Public Health, EOME, Landmark Center, 3rd Floor East, PO BOX 15697, Boston, MA 02215. E-mail: firstname.lastname@example.org.
Received October 23, 2012
Accepted June 11, 2013