Use of Antihypertensives, Blood Pressure, and Estimated Risk of Dementia in Late Life: An Individual Participant Data Meta-Analysis
Open accessAbstract
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 >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.
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High blood pressure may continue to be a risk in older age, but some people who are developing dementia have lower blood pressure.
“However, an individual participant data (IPD) meta-analysis finds that high blood pressure may continue to be a risk in older age(186) but some people who are developing dementia have a lower blood pressure and therefore the picture is mixed.”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [186]
Untreated hypertension is associated with a 42% higher risk of dementia than healthy controls (HR 1.42, 95% CI 1.15-1.76), but this risk is attenuated or lost with treatment (HR 1.13, 95% CI 0.99-1.28).
“An IPD meta-analysis of 17 studies including people in LMICs and HICs (mean age72.5, follow-up 4.3 years) found that that those with untreated hypertension had a 42% higher risk of dementia than healthy controls (HR 1.42; 1.15-1.76), but this risk was attenuated or lost with treatment (HR 1.13; 0.99-1.28 vs. healthy controls). (186)”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [186]
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Harms of Continued Antihypertensives: An Overview of Reviews
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Management of Hypertension in Adults
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- Authors
- Lennon, M. J., Lam, B. C. P., Lipnicki, D. M., Crawford, J. D., Peters, R., Schutte, A. E., Brodaty, H., Thalamuthu, A., Rydberg-Sterner, T., Najar, J., Skoog, I., Riedel-Heller, S. G., Röhr, S., Pabst, A., Lobo, A., De-la-Cámara, C., Lobo, E., Bello, T., Gureje, O., Ojagbemi, A., Lipton, R. B., Katz, M. J., Derby, C. A., Kim, K. W., Han, J. W., Oh, D. J., Rolandi, E., Davin, A., Rossi, M., Scarmeas, N., Yannakoulia, M., Dardiotis, T., Hendrie, H. C., Gao, S., Carrière, I., Ritchie, K., Anstey, K. J., Cherbuin, N., Xiao, S., Yue, L., Li, W., Guerchet, M. M., Preux, P.-M., Aboyans, V., Haan, M. N., Aiello, A. E., Ng, T. P., Nyunt, M. S. Z., Gao, Q., Scazufca, M., & Sachdev, P. S. S.
- Affiliations
- UNSW Sydney (AU)
- La Trobe University (AU)
- Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Centre for Ageing and Health at the University of Gothenburg, Gothenburg, Sweden
- Sahlgrenska University Hospital (SE)
- Leipzig University (DE)
- Trinity College Dublin (IE)
- Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza, Spain
- Universidad de Zaragoza (ES)
- University of Ibadan (NG)
- Albert Einstein College of Medicine (US)
- Seoul National University (KR)
- Kangbuk Samsung Hospital (KR)
- University of Pavia (IT)
- Fondazione Golgi Cenci (IT)
- National and Kapodistrian University of Athens (GR)
- Harokopio University of Athens (GR)
- University of Thessaly (GR)
- Indiana University Indianapolis (US)
- Université de Montpellier (FR)
- Australian National University (AU)
- Shanghai Jiao Tong University (CN)
- Centre Hospitalier Universitaire de Limoges (FR)
- University of California, San Francisco (US)
- Columbia University (US)
- Ministry of Health (SG)
- National University of Singapore (SG)
- Departamento de Psiquiatria, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- Corresponding author
- Lennon, Matthew J.
- ORCID
- Lennon, Matthew J.
- Lam, Ben Chun Pan
- Lipnicki, Darren M.
- Peters, Ruth
- Schutte, Aletta E.
- Brodaty, Henry
- Thalamuthu, Anbupalam
- Najar, Jenna
- Skoog, Ingmar
- Riedel-Heller, Steffi G.
- Röhr, Susanne
- Pabst, Alexander
- 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
- 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
- Aiello, Allison E.
- Ng, Tze Pin
- Nyunt, Ma Shwe Zin
- Gao, Qi
- Sachdev, Perminder S. S.
- Venue
- JAMA Network Open
- Publisher
- American Medical Association (AMA)
- Published
- 2023-09-12
- Volume
- 6
- Issue
- 9
- Pages
- e2333353
- ISSN
- 2574-3805 (ISSN-L)
- PMC
- PMC10498335
- OpenAlex
- W4386623494
- Cited by
- 100
- References
- 84
- Citations by year
- 2026: 30 · 2025: 45 · 2024: 22 · 2023: 3
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- JAMA Network Open (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- HAL (submittedVersion, cc-by)
- Zaguan (University of Zaragoza Repository) (submittedVersion, cc-by)
- Funders
- Alzheimer's Association (18910276/8/9/2011, IIRG-09-133014)
- Wellcome Trust (GR066133MA, WT079662MF)
- Stiftelsen för Gamla Tjänarinnor
- EU Joint Programme – Neurodegenerative Disease Research
- European Commission
- Agency for Science, Technology and Research (03/1/21/17/214)
- Agence Nationale de la Recherche (ANR‐09‐MNPS‐009‐01, ANR-09-MNPS-0009, ANR-07-LVIE-0004, 009-01, 07LVIE004)
- Institut National de la Santé et de la Recherche Médicale
- Fundação de Amparo à Pesquisa do Estado de São Paulo (98/12727-0)
- AXA Research Fund
- Conseil Régional Languedoc-Roussillon
- Ministerio de Economía y Competitividad (94/1562, 01/0255, 97/1321E, 98/0103, 03/0815, 06/0617, G03/128)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (307579/2019–0)
- Vetenskapsrådet
- Riksbankens Jubileumsfond
- Forskningsrådet om Hälsa, Arbetsliv och Välfärd
- Swedish Brain Power
- Gobierno de Aragón (06/0617, 01/0255, 03/0815, 19/01874, 16/00896, 12/02254, 94/1562, B15_17R, 97/1321E, G03/128, 98/0103)
- National Institutes of Health (2009BAI77B03, 2011-873)
- National Health and Medical Research Council (1093083)
- Instituto de Salud Carlos III (06/0617, 97/1321E, G03/128, 94/1562, 03/0815, 98/0103, 01/0255)
- European Regional Development Fund (B15_17R, 9/2011)
- Biomedical Research Council (03/1/21/17/214)
- National Institute on Aging (P30AG010133, RF1AG057531, P01AG03949, P01AG003949, P30AG072976, R01AG057531)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- antihypertensive medication use, hypertension, dementia risk, blood pressure, older adults, untreated hypertension, systolic blood pressure, diastolic blood pressure, dementia prevention, sex differences, racial differences, age differences, individual patient data meta-analysis, individualized blood pressure targets, antihypertensive efficacy, cognitive aging
- MeSH terms
- Aged, Antihypertensive Agents, Blood Pressure, Dementia, Female, Humans, Hypertension, Longitudinal Studies, Male
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