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Cited by 197Dementia and Cognitive Impairment ResearchCancer Risks and FactorsObesity, Physical Activity, Diet

Overweight in midlife and risk of dementia: a 40-year follow-up study

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Hassing, L B, Dahl, A K, Thorvaldsson, V, Berg, S, Gatz, M, Pedersen, N L, Johansson, B·2009·International Journal of Obesity
DOI 10.1038/ijo.2009.104PMC PMC3025291
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Abstract

Objective:This study examines whether overweight in midlife increases dementia risk later in life.Methods:In 1963 body mass index was assessed in 1152 participants of The Swedish Twin Registry, at the age of 45–65 years. These participants were later screened for dementia in a prospective study with up to 40 years follow-up. A total of 312 participants were diagnosed with dementia.Results:Logistic regression analyses adjusted for demographic factors, smoking and alcohol habits, indicated that men and women categorized as overweight in their midlife had an elevated risk of dementia (OR=1.59; 95% CI: 1.21–2.07, P=0.002), Alzheimer's disease (OR=1.71; 95% CI: 1.24–2.35, P=0.003), and vascular dementia (OR=1.55; 95% CI: 0.98–2.47, P=0.059). Further adjustments for diabetes and vascular diseases did not substantially affect the associations, except for vascular dementia (OR=1.36; 95% CI: 0.82–2.56, P=0.116), reflecting the significance of diabetes and vascular diseases in the etiology of vascular dementia. There was no significant interaction between overweight and APOE ɛ4 status, indicating that having both risk factors does not have a multiplicative effect with regard to dementia risk.Conclusions:This study gives further support to the notion that overweight in midlife increases later risk of dementia. The risk is increased for both Alzheimer's disease and vascular dementia, and follows the same pattern for men and women.

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Crossref · 10.1038/ijo.2009.104

Cites

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Claims the paper makes

0 of 25 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Additional adjustment for diabetes and vascular diseases reduced the association between midlife overweight and vascular dementia to non-significance (OR 1.36, 95% CI 0.82-2.56, p=.116).

    “except for vascular dementia (OR = 1.36; 95% CI: 0.82 to 2.56, p = .116)”
    • Also stated in: § Risk of dementia in relation to midlife BMI · plain
      “However, the risk was substantially reduced in Model II by including diabetes and vascular diseases (OR = 1.36; p = .162), reflecting the significance of these factors in the aetiology of VaD.”
    Quote in the paperSubstantial claim
  • Findingown data

    When analysed separately by sex, the link between midlife overweight and dementia risk appeared similar in men and women.

    “The sex stratified analyses on BMI and dementia risk showed the same pattern among men and women, therefore, these results will not be presented separately.”
    • Also stated in: § Discussion · hedged
      “Finally, the sex stratified analyses indicated the same pattern for men and women.”
    Quote in the paperNot a substantial claim
  • Findingown data

    APOE ε4 carrier status was associated with increased dementia risk (OR 3.99, 95% CI 2.96-5.38, p<.001).

    “For APOE ε4 status the OR was 3.99 (95% CI = 2.96 to 5.38, p < .001), confirming the well established role of APOE e4 as a risk factor for dementia.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Additional adjustment for diabetes and vascular diseases did not substantially change the association between midlife overweight and all-cause dementia.

    “Further adjustments for diabetes and vascular diseases did not substantially affect the associations, except for vascular dementia (OR = 1.36; 95% CI: 0.82 to 2.56, p = .116), reflecting the significance of diabetes and vascular diseases in the aetiology of vascular dementia.”
    • Also stated in: § Risk of dementia in relation to midlife BMI · plain
      “Further adjustments for diabetes and vascular diseases in Model II did not substantially change this association.”
    Quote in the paperSubstantial claim
  • Findingown data

    There was no statistically significant interaction between midlife overweight and APOE ε4 status on dementia risk (p=.781).

    “There was no significant interaction between overweight and APOE ε4 status, indicating that having both risk factors does not have a multiplicative effect concerning dementia risk.”
    • Also stated in: § Risk of dementia in relation to midlife BMI · plain
      “The interaction between BMI and APOE ε4 was not statistically significant (p = .781), indicating that having both risk factors does not have a multiplicative effect on dementia risk but rather an additive effect (see Table 4).”
    Quote in the paperSubstantial claim
  • May combine two claims. 14
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 12

  • May combine two claims.

    Findingown data

    Midlife overweight was associated with an increased risk of vascular dementia after adjustment for demographics, smoking, and alcohol, but the association was not statistically significant (OR 1.55, 95% CI 0.98-2.47, p=.059).

    “vascular dementia (OR = 1.55; 95% CI: 0.98 to 2.47, p = .059)”
    • Also stated in: § Risk of dementia in relation to midlife BMI · plain
      “Concerning VaD, the risk associated with higher BMI fell short out of significance in Model I, (OR = 1.55; p = .059).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    In the study sample of 1152 Swedish twins aged 45-65 in 1963, midlife overweight (BMI ≥26.5, top 25%) was associated with an increased risk of all-cause dementia in later life after adjustment for demographics, smoking, and alcohol (OR 1.59, 95% CI 1.21-2.07, p=.002).

    “Logistic regression analyses, adjusted for demographic factors, smoking and alcohol habits, indicated that men and women categorized as overweight in their midlife had an elevated risk of dementia (OR = 1.59; 95% CI: 1.21 to 2.07, p = .002)”
    • Also stated in: § Risk of dementia in relation to midlife BMI · plain
      “Model I (adjusted for demographics, smoking, and alcohol use) showed that midlife overweight was associated with greater risk of dementia, such that those with a BMI above the third quartile had a 59% greater risk of getting dementia in old age as compared with those with lower BMI.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the fully adjusted model for vascular dementia, congestive heart failure and stroke were significant predictors (ORs 1.98 and 6.97), while diabetes was marginally significant (OR 1.65, p=.067).

    “In this model, congestive heart failure (OR = 1.98), and stroke (OR = 6.97) were significantly related to risk of VaD (ps < .05), whereas diabetes was marginally significant (OR = 1.65; p = .067).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Compared with controls, dementia cases were more often women, older, less educated, had shorter survival, more often abstained from alcohol, and had higher rates of congestive heart failure, stroke, APOE ε4 carriage, and BMI (ps < .05).

    “There were statistically significant differences between controls and cases, such that the dementia group had more women, were older, had fewer years of education, had shorter survival, comprised more individuals who did not use alcohol, had more prevalent congestive heart failure, stroke, and APOE ε4 carriers, and a higher BMI (ps < .05).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Compared with the normal weight group, the overweight group included more people with hypertension, congestive heart failure, and diabetes (ps < .05).

    “There were statistically significant differences between the normal weight group and the overweight group, such that the overweight group had fewer years of education, comprised more individuals who did not use alcohol, hade more individuals with hypertension, congestive heart failure, and diabetes (ps < .05).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Dementia diagnoses in this study came from a detailed clinical assessment, giving high confidence in the outcome classification.

    “In our study the dementia diagnoses were made through a thorough clinical procedure, resulting in a highly confident outcome diagnosis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductcitation

    Self-reported height and weight data are valid and reliable, as shown by correlations of 0.97 for height and 0.95 for weight between self-reported and measured values in SATSA.

    “However, analyses completed in the SATSA comparing self-reported and measured information on heights and weights (within a one year period) resulted in a correlation of 0.97 for height and 0.95 for weight20.”
    • Also stated in: § Discussion · hedged
      “However, correlational analyses conducted on SATSA20, comparing self reported and measured data on heights and weights, resulted in correlation of 0.97 for height and 0.95 for weight, supporting a notion of valid and reliable self reported data.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Stunkard AJ, Harris JR, Pedersen NL, McClearn GE . The body-mass index of twins who have been reared apart. N Engl J Med 1990; 322: 1483–1487. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Diabetes and vascular diseases are important causal factors in vascular dementia.

    “reflecting the significance of diabetes and vascular diseases in the aetiology of vascular dementia”
    • Also stated in: § Risk of dementia in relation to midlife BMI · plain
      “reflecting the significance of these factors in the aetiology of VaD”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Midlife overweight raises the risk of both Alzheimer's disease and vascular dementia.

    “The risk is increased for both Alzheimer’s disease and vascular dementia, and follows the same pattern for men and women.”
    • Also stated in: § Discussion · plain
      “Further, the risk was increased for both AD and VaD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The combined presence of midlife overweight and APOE ε4 does not multiply dementia risk; their effects add together.

    “indicating that having both risk factors does not have a multiplicative effect concerning dementia risk”
    • Also stated in: § Risk of dementia in relation to midlife BMI · hedged
      “indicating that having both risk factors does not have a multiplicative effect on dementia risk but rather an additive effect (see Table 4)”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Whitmer and colleagues reported that overweight raised AD and VaD risk similarly (about twofold), while obesity was linked more strongly to VaD (fivefold) than to AD (threefold).

    “In the study of Whitmer et al.15 overweight (BMI between 25 and 30) increased the risk of AD and VaD to the same extent (approximately a two- fold increased risk), whereas obesity (BMI ≥ 30) was more strongly related to VaD, indicating a five-fold risk, as compared to a three-fold risk of AD.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Whitmer RA, Gunderson EP, Quesenberry Jr CP, Zhou J, Yaffe K . Body mass index in midlife and risk of Alzheimer disease and vascular dementia. Curr Alzheimer Res 2007; 4: 103–109. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Additional models controlled for diabetes and vascular diseases.

    “Further adjustments for diabetes and vascular diseases”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Dementia prevalence in SATSA and OCTO-Twin is similar to that reported in the Kungsholmen study in Sweden and the Framingham study in the U.S.

    “Prevalence rates of dementia in SATSA and OCTO-Twin have been found to resemble other similar studies such as the Kungsholmen study25 in Sweden, and the Framingham study26 in the U.S.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [25] Fratiglioni L, Grut M, Forsell Y, Viitanen M, Grafström M, Holmén K et al. Prevalence of Alzheimer's disease and other dementias in an elderly urban population: relationship with age, sex, and education. Neurology 1991; 41: 1886–1892. source

      Not checked in the free run.

    • cites [26] Bachman DL, Wolf PA, Linn R, Knoefel JE, Cobb J, Belanger A et al. Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study. Neurology 1992; 42: 115–119. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    According to those reviews, significant associations between overweight and dementia came from studies with younger baseline samples and longer follow-up.

    “According to the reviews, the studies that reported significant associations had younger samples at baseline and longer follow-up periods.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [7] Beydoun MA, Beydoun HA, Wang Y . Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis. Obes Rev 2008; 9: 204–218. source

      Not checked in the free run.

    • cites [8] Gorospe EC, Dave JK . The risk of dementia with increased body mass index. Age Ageing 2007; 36: 23–29. source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    In prior work, midlife BMI predicted dementia only in women, while skinfold thickness predicted it in both sexes, suggesting BMI poorly measures adiposity in men.

    “By using midlife assessment of BMI and skinfold thickness3, it was found that midlife BMI predicted dementia among women only, whereas midlife skinfold thickness predicted dementia in both sexes, suggesting that BMI is an inaccurate measure of adiposity in men.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Whitmer RA, Gunderson EP, Barrett-Connor E, Quesenberry Jr CP, Yaffe K . Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study. BMJ 2005; 330: 1360. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Two recent systematic reviews proposed that a high body mass index is independently linked to dementia risk.

    “In two recent systematic review articles 7, 8 on overweight and risk of dementia it was proposed that high body mass index (BMI) is independently associated with risk of dementia.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [7] Beydoun MA, Beydoun HA, Wang Y . Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis. Obes Rev 2008; 9: 204–218. source

      Not checked in the free run.

    • cites [8] Gorospe EC, Dave JK . The risk of dementia with increased body mass index. Age Ageing 2007; 36: 23–29. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Carrying the APOE ε4 allele is an established risk factor for both vascular disease and dementia.

    “APOE ε4 carrier status is a known risk factor for vascular disease and dementia 29, 30.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [29] Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993; 261: 921–923. source

      Not checked in the free run.

    • cites [30] Schmechel DE, Saunders AM, Strittmatter WJ, Crain BJ, Hulette CM, Joo SH et al. Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci USA 1993; 90: 9649–9653. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Overweight may confer a greater dementia risk in women than in men.

    “Studies that have addressed potential sex differences in the association between overweight and dementia risk indicate that overweight may be a stronger risk factor for women as compared to men 3, 14.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [3] Whitmer RA, Gunderson EP, Barrett-Connor E, Quesenberry Jr CP, Yaffe K . Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study. BMJ 2005; 330: 1360. source

      Not checked in the free run.

    • cites [14] Hayden KM, Zandi PP, Lyketsos CG, Khachaturian AS, Bastian LA, Charoonruk G et al. Vascular risk factors for incident Alzheimer disease and vascular dementia: the Cache County study. Alzheimer Dis Assoc Disord 2006; 20: 93–100. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A recent study by the same group found that central obesity in midlife predicted dementia.

    “In a recent study by the same group, midlife central obesity was found to predict dementia 4.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Whitmer RA, Gustafson DR, Barrett-Connor E, Haan MN, Gunderson EP, Yaffe K . Central obesity and increased risk of dementia more than three decades later. Neurology 2008; 71: 1057–1064. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Hayden and colleagues observed increased dementia risk only among women, but noted low power in their male analyses.

    “Hayden et al.14 who used BMI in a sample of people aged 65 years and older to predict incident dementia, found an increased risk only for women, however, the authors reported a problem with low statistical power in the analyses of men.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Hayden KM, Zandi PP, Lyketsos CG, Khachaturian AS, Bastian LA, Charoonruk G et al. Vascular risk factors for incident Alzheimer disease and vascular dementia: the Cache County study. Alzheimer Dis Assoc Disord 2006; 20: 93–100. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Analyses controlled for demographic variables, smoking, and alcohol use.

    “Logistic regression analyses, adjusted for demographic factors, smoking and alcohol habits”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Two studies found that overweight raised Alzheimer's disease risk but not vascular dementia risk in women.

    “Two studies reported that overweight increases the risk of AD and not VaD in women 1, 14.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Gustafson D, Rothenberg E, Blennow K, Steen B, Skoog I . An 18-year follow-up of overweight and risk of Alzheimer disease. Arch Intern Med 2003; 163: 1524–1528. source

      Not checked in the free run.

    • cites [14] Hayden KM, Zandi PP, Lyketsos CG, Khachaturian AS, Bastian LA, Charoonruk G et al. Vascular risk factors for incident Alzheimer disease and vascular dementia: the Cache County study. Alzheimer Dis Assoc Disord 2006; 20: 93–100. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Statistical models that account for the non-independence of twin pairs were used in the analysis.

    “This was, however, dealt with in the statistical analyses by using multilevel models that account for the dependency within pairs.”
    • Also stated in: § Data analyses · plain
      “to account for the hierarchical structure in the data while accounting for the dependency associated with twin pair status”
    Quote in the paperSubstantial claim
23 of 23

  • The authors state this as an assumption.

    The random effect of the intercept across twin pairs is normally distributed with mean zero.

    “The random effect was assumed to take a normal distribution with a mean of zero.”
1 of 1

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Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting p-values for the adjusted vascular dementia result

    Minor

    The abstract and Results section report different p-values for the same adjusted vascular dementia odds ratio: .116 and .162, respectively.

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Authors
Hassing, L. B., Dahl, A. K., Thorvaldsson, V, Berg, S., Gatz, M., Pedersen, N. L., & Johansson, B.
Affiliations
  • University of Gothenburg (SE)
  • Jönköping University (SE)
  • University of Southern California (US)
Corresponding author
Hassing, L B
ORCID
Venue
International Journal of Obesity
Publisher
Springer Science and Business Media LLC
Published
2009-06-09
Volume
33
Issue
8
Pages
893-898
ISSN
  • 0307-0565 (ISSN-L)
  • 1476-5497
DOI
10.1038/ijo.2009.104
PMC
PMC3025291
OpenAlex
W1971559855
Semantic Scholar
148f24651fd855dd68fba99dc9a43aa9bd9b3532
Cited by
197
References
36
Citations by year
2026: 4 · 2025: 14 · 2024: 8 · 2023: 9 · 2022: 11 · 2021: 14 · 2020: 20 · 2019: 13 · 2018: 13 · 2017: 8 · 2016: 11 · 2015: 13 · 2014: 17 · 2013: 13 · 2012: 6
FWCI
5.75
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • International Journal of Obesity (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (R01AG004563, AG-10175, R37AG008861, AG04563, AG 08724, AG 08861, R01AG010175, R01AG008724)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Oncology › Cancer Risks and Factors
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
Keywords
overweight, midlife, dementia risk, Alzheimer's disease, vascular dementia, body mass index, diabetes mellitus, vascular disease, APOE ε4, sex differences, Swedish Twin Registry
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Female, Follow-Up Studies, Humans, Male, Middle Aged, Risk Factors, Sweden, Dementia, Vascular, Body Mass Index, Overweight

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