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Midlife and Late-Life Obesity and the Risk of Dementia: Cardiovascular Health Study
Open accessAbstract
BACKGROUND: While high adiposity in middle age appears to be related to greater dementia risk, studies exploring this association in the elderly are conflicting. OBJECTIVE: To evaluate associations between midlife and late-life obesity and risk of dementia. DESIGN: Prospective study with mean follow-up of 5.4 years (1992-1994 through 1999). SETTING: Community-dwelling sample in 4 US sites recruited from Medicare eligibility files. PARTICIPANTS: A total of 2798 adults without dementia (mean age, 74.7 years; 59.1% women) participating in the Cardiovascular Health Study who underwent magnetic resonance imaging were measured for height and weight at baseline at age 65 years or older (late life), and self-reported weight at age 50 years (midlife). Body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) was calculated at both times. MAIN OUTCOME MEASURES: Dementia, Alzheimer disease, and vascular dementia classified by a multidisciplinary committee using standardized criteria. RESULTS: Classification resulted in 480 persons with incident dementia, 245 with Alzheimer disease (no vascular dementia), and 213 with vascular dementia (with or without Alzheimer disease). In evaluations of midlife obesity, an increased risk of dementia was found for obese (BMI >30) vs normal-weight (BMI 20-25) persons, adjusted for demographics (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.03-1.87) and for cardiovascular risk factors (1.36; 0.94-1.95). The risk estimates were reversed in assessments of late-life BMI. Underweight persons (BMI <20) had an increased risk of dementia (1.62; 1.02-2.64), whereas being overweight (BMI >25-30) was not associated (0.92; 0.72-1.18) and being obese reduced the risk of dementia (0.63; 0.44-0.91) compared with those with normal BMI. CONCLUSION: These results help explain the "obesity paradox" as differences in dementia risk across time are consistent with physical changes in the trajectory toward disability.
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“High waist-hip ratio strengthened the association with hypertension and dementia in the highest quartile of waist-hip ratio.”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [322]
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“It is unclear what confounding factors were taken into account in these analyses.322”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [322]
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“Studies suggest that midlife and late-life central obesity increases the risk of cognitive impairment but that high late-life obesity (as assessed by BMI) may be protective.71–73”
From Defining Optimal Brain Health in Adults: A Presidential Advisory From the American Heart Association/American Stroke Association (2017) · cites this paper as [73]
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“Obesity,71–73 dyslipidemia,74–77 and high BP78,79 are also major contributors to vascular brain health.”
From Defining Optimal Brain Health in Adults: A Presidential Advisory From the American Heart Association/American Stroke Association (2017) · cites this paper as [73]
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“In contrast, late-life obesity 114 and hypertension onset after age 80 115 are associated with decreased risk of dementia.”
From 2023 Alzheimer's disease facts and figures (2023) · cites this paper as [114]
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“In the Framingham Offspring Study, higher waist-hip ratio was associated with lower cognitive function, which was measured 12 years later.”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [322]
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“obesity has been linked with increased risk for neurological changes, including Alzheimer’s disease, vascular dementia, as well as brain atrophy.4,5 Indeed, obese persons also exhibit impairments on formal cognitive testing, including on tasks of attention, executive function, and memory.6,7”
From Cognitive Function After Bariatric Surgery: Evidence for Improvement 3 Years After Surgery (2014) · cites this paper as [4]
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Self-citation
Metadata
- Authors
- Fitzpatrick, A. L., Kuller, L. H., Lopez, O. L., Diehr, P., O’Meara, E. S., Longstreth, W. T., & Luchsinger, J. A.
- Affiliations
- University of Washington (US)
- University of Pittsburgh (US)
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2009-03-01
- Volume
- 66
- Issue
- 3
- Pages
- 336-42
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC3513375
- OpenAlex
- W2077468399
- Cited by
- 796
- References
- 42
- Citations by year
- 2026: 43 · 2025: 42 · 2024: 55 · 2023: 48 · 2022: 54 · 2021: 52 · 2020: 49 · 2019: 55 · 2018: 41 · 2017: 48 · 2016: 47 · 2015: 45 · 2014: 51 · 2013: 50 · 2012: 38
- FWCI
- 23.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc045133-001, n01hc085079-024, n01hc015103-009, n01hc085084-005, n01hc085085-011, n01hc085083-027, n01hc085080-026, n01hc085086-022, n01hc55222-0-0-0, n01hc075150-004, n01hc035129-010)
- National Institute on Aging (5R01 AG 15928-02, R01AG015928)
- National Heart, Lung, and Blood Institute (N01-HC-85081, N01HC85085, N01 HC085086, N01HC-85083, N01HC15103, N01 HC085079, N01 HC085083, N01HC85082, N01HC‐75150, N01 HC85086, N01 HC085080, N01 HC035129, N01HC85080, N01 HC015103, N01 HC55222, U01HL080295, N01 HC055222, N01 HC085081, N01 HC075150, N01 HC045133, N01-HC85079, N01-HC85084)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Keywords
- obesity, dementia, midlife obesity, body mass index, Alzheimer's disease, vascular dementia, obesity paradox, underweight, cardiovascular risk factors, aging
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Anthropometry, Evaluation Studies as Topic, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Obesity, Prospective Studies, Risk, Dementia, Vascular, Body Mass Index, Survival Analysis
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