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Cited by 797Dementia and Cognitive Impairment ResearchMenopause: Health Impacts and TreatmentsCancer Risks and Factors

Midlife and Late-Life Obesity and the Risk of Dementia: Cardiovascular Health Study

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Fitzpatrick, Annette L., Kuller, Lewis H., Lopez, Oscar L., Diehr, Paula, O’Meara, Ellen S., Longstreth, W. T., Luchsinger, José A.·2009·Archives of Neurology
DOI 10.1001/archneurol.2008.582PMC PMC3513375
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Abstract

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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Crossref · 10.1001/archneurol.2008.582

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  • High waist-hip ratio strengthened the association with hypertension and dementia in the highest quartile of waist-hip ratio.

    “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]

    The Results (page unavailable) report no significant association between late-life waist–hip ratio and dementia. The Discussion (page unavailable) likewise states that the authors found no association for waist–hip ratio in old age; it does not report a strengthened hypertension–dementia association in the highest waist–hip-ratio quartile. (LLM, conf=0.78)

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  • It is unclear what confounding factors were taken into account in these analyses.

    “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]

    The Methods section explicitly states which factors were included in the adjusted models, including demographics, cardiovascular and dementia risk factors, smoking, physical activity, and ApoE genotype. The claim that it is unclear which confounding factors were taken into account is therefore contrary to the cited paper's account. (LLM, conf=0.89)

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  • Late-life obesity and hypertension onset after age 80 are associated with decreased risk of dementia.

    “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]

  • In the Framingham Offspring Study, higher waist-hip ratio was associated with lower cognitive function measured 12 years later.

    “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]

    The Methods describe the Cardiovascular Health Study, not the Framingham Offspring Study. The Results address late-life waist-to-hip ratio and dementia, but do not report cognitive function measured 12 years later in Framingham. Searches for “Framingham Offspring Study” and “12 years cognitive function waist hip ratio” found no passage addressing the claim. (LLM, conf=0.76)

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  • Obesity is linked to neurological changes such as Alzheimer's disease, vascular dementia, and brain atrophy, and obese persons show impairments on cognitive tests of attention, executive function, and memory.

    “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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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)
ORCID
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)
DOI
10.1001/archneurol.2008.582
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
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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