Use of Antihypertensives, Blood Pressure, and Estimated Risk of Dementia in Late Life
Authors: Lennon Matthew J. , Lam Ben Chun Pan , Lipnicki Darren M. , Crawford John D. , Peters Ruth , Schutte Aletta E. , Brodaty Henry , Thalamuthu Anbupalam , Rydberg-Sterner Therese , Najar Jenna , Skoog Ingmar , Riedel-Heller Steffi G. , Röhr Susanne , Pabst Alexander , Lobo Antonio , De-la-Cámara Concepción , Lobo Elena , Bello Toyin , Gureje Oye , Ojagbemi Akin , Lipton Richard B. , Katz Mindy J. , Derby Carol A. , Kim Ki Woong , Han Ji Won , Oh Dae Jong , Rolandi Elena , Davin Annalisa , Rossi Michele , Scarmeas Nikolaos , Yannakoulia Mary , Dardiotis Themis , Hendrie Hugh C. , Gao Sujuan , Carrière Isabelle , Ritchie Karen , Anstey Kaarin J. , Cherbuin Nicolas , Xiao Shifu , Yue Ling , Li Wei , Guerchet Maëlenn M. , Preux Pierre-Marie , Aboyans Victor , Haan Mary N. , Aiello Allison E. , Ng Tze Pin , Nyunt Ma Shwe Zin , Gao Qi , Scazufca Marcia , Sachdev Perminder S. S. 
Published: September 2023

Importance

The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested.

Objectives

To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age &amp;gt;60 years) with dementia and the moderating factors of age, sex, and racial group.

Data Source and Study Selection

Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece).

Data Extraction and Synthesis

Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines.

Main Outcomes and Measures

The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group.

Results

The analysis included 17 studies with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses.

Conclusions and Relevance

This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls.