Midlife cardiovascular risk factors and risk of dementia in late life
Abstract
OBJECTIVE: To evaluate if midlife cardiovascular risk factors are associated with risk of late-life dementia in a large, diverse cohort. METHOD: The authors conducted a retrospective cohort study of 8,845 participants of a health maintenance organization who underwent health evaluations from 1964 to 1973 when they were between the ages of 40 and 44. Midlife cardiovascular risk factors included total cholesterol, diabetes, hypertension, and smoking. Diagnoses of dementia were ascertained by medical records from January 1994 to April 2003. RESULTS: The authors identified 721 participants (8.2%) with dementia. Smoking, hypertension, high cholesterol, and diabetes at midlife were each associated with a 20 to 40% increase in risk of dementia (fully adjusted Cox proportional hazards model: HR 1.24, 95% CI 1.04 to 1.48 for hypertension, HR 1.26, 95% CI 1.08 to 1.47 for smoking, HR 1.42, 95% CI 1.22 to 1.66 for high cholesterol, and HR 1.46, 95% CI 1.19 to 1.79 for diabetes). A composite cardiovascular risk score was created using all four risk factors and was associated with dementia in a dose-dependent fashion. Compared with participants having no risk factors, the risk for dementia increased from 1.27 for having one risk factor to 2.37 for having all four risk factors (fully adjusted model: HR 2.37, 95% CI 1.10 to 5.10). CONCLUSION: The presence of multiple cardiovascular risk factors at midlife substantially increases risk of late-life dementia in a dose dependent manner.
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Part of the risk factors for cardiovascular disease are in common with Alzheimer's disease, including hypertension, dyslipidemia, diabetes, obesity, dietary factors, smoking, and physical activity.
“This could explain why part of the risk factors for cardiovascular disease are in common with AD, including hypertension, dyslipidemia, diabetes, obesity, dietary factors, smoking, and physical activity (Figure 1B).”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [100]
Cardiovascular damage is a risk factor for neurodegenerative diseases, and a healthy cardiovascular system can be considered neuroprotective.
“Cardiovascular damage is a risk factor for neurodegenerative diseases, and since the brain is supplied by a large network of blood vessels, a healthy cardiovascular system can be considered neuroprotective [100].”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [100]
Lifestyle is an important risk factor, where intellectual, physical, and social activities, as well as diet, may help to prevent Alzheimer's disease.
“Thus, lifestyle is also an important risk factor, where intellectual, physical, and social activities, as well as diet, may help to prevent AD [1,22,100,101,102,103].”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [100]
Increased brain cholesterol levels and dyslipidemias overall have been linked to Alzheimer's disease incidence.
“Increased brain cholesterol levels and dyslipidemias overall have been linked to AD incidence [49,55,100,107].”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [100]
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- Authors
- Whitmer, R. A., Sidney, S., Selby, J., Johnston, S. C., & Yaffe, K.
- Affiliations
- Kaiser Permanente (US)
- Venue
- Neurology
- Published
- 2005-01-25
- Volume
- 64
- Issue
- 2
- Pages
- 277-281
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W1999664376
- Cited by
- 1,238
- References
- 3
- Citations by year
- 2026: 29 · 2025: 49 · 2024: 52 · 2023: 49 · 2022: 57 · 2021: 96 · 2020: 81 · 2019: 70 · 2018: 79 · 2017: 61 · 2016: 56 · 2015: 55 · 2014: 64 · 2013: 72 · 2012: 61
- FWCI
- 26.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (1 K12 AR47659, K12AR047659)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Risk Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- dementia, cardiovascular risk factors, midlife, late-onset dementia, hypertension, smoking, hypercholesterolemia, diabetes mellitus, cardiovascular risk score, dose-response relationship
- MeSH terms
- Adult, Aged, California, Cardiovascular Diseases, Dementia, Diabetes Mellitus, Female, Humans, Hypercholesterolemia, Hypertension, Male, Middle Aged, Retrospective Studies, Risk, Risk Factors, Smoking, Cohort Studies, Comorbidity, Proportional Hazards Models, Age of Onset
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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