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  • Karlsson, Ida K.Karolinska Institutet,Jönköping University,HHJ, Institutet för gerontologi,HHJ. ARN-J (Aging Research Network - Jönköping),Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden ; Aging Research Network – Jönköping (ARN-J), School of Health and Welfare, Jönköping University, Sweden (author)

Adiposity and the risk of dementia : mediating effects from inflammation and lipid levels

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-10-03
  • Springer Nature Switzerland AG.2022
  • electronicrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:his-21976
  • https://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-21976URI
  • https://doi.org/10.1007/s10654-022-00918-wDOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-58661URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:150872530URI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • CC BY 4.0Published: 03 October 2022© 2022, The Author(s)© 2022 Springer Nature Switzerland AG. Part of Springer Nature.Ida K. Karlsson ida.karlsson@ki.seThis work was supported by the Strategic Research Program in Epidemiology at Karolinska Institutet; the Swedish Research Council for Health, Working Life and Welfare (2018-01201); the Swedish Research Council (2016-03081); and the National Institutes of Health (R01 AG060470).Open access funding provided by Karolinska Institute. We acknowledge the Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the Grant No. 2017-00641. The STR substudies were supported by the National Institutes of Health (Grants R01 AG10175, R01 AG08724, R01 AG08861, R01 AG028555, and U01 DK066134), the MacArthur Foundation Research Network on Successful Aging, the Axel and Margaret Ax:son Johnsons Foundation, the Swedish Research Council, the Swedish Foundation for Health Care Sciences and Allergy Research, and the Swedish Council for Working Life and Social Research (2013-2292).
  • While midlife adiposity is a risk factor for dementia, adiposity in late-life appears to be associated with lower risk. What drives the associations is poorly understood, especially the inverse association in late-life. Using results from genome-wide association studies, we identified inflammation and lipid metabolism as biological pathways involved in both adiposity and dementia. To test if these factors mediate the effect of midlife and/or late-life adiposity on dementia, we then used cohort data from the Swedish Twin Registry, with measures of adiposity and potential mediators taken in midlife (age 40–64, n = 5999) or late-life (age 65–90, n = 7257). Associations between body-mass index (BMI), waist-hip ratio (WHR), C-reactive protein (CRP), lipid levels, and dementia were tested in survival and mediation analyses. Age was used as the underlying time scale, and sex and education included as covariates in all models. Fasting status was included as a covariate in models of lipids. One standard deviation (SD) higher WHR in midlife was associated with 25% (95% CI 2–52%) higher dementia risk, with slight attenuation when adjusting for BMI. No evidence of mediation through CRP or lipid levels was present. After age 65, one SD higher BMI, but not WHR, was associated with 8% (95% CI 1–14%) lower dementia risk. The association was partly mediated by higher CRP, and suppressed when high-density lipoprotein levels were low. In conclusion, the negative effects of midlife adiposity on dementia risk were driven directly by factors associated with body fat distribution, with no evidence of mediation through inflammation or lipid levels. There was an inverse association between late-life adiposity and dementia risk, especially where the body’s inflammatory response and lipid homeostasis is intact. 

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  • Zhan, YiqiangKarolinska Institutet (author)
  • Wang, YunzhangDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (author)
  • Li, XiaDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (author)
  • Jylhävä, JuuliaDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (author)
  • Hägg, SaraKarolinska Institutet (author)
  • Dahl Aslan, Anna K.,1975-Högskolan i Skövde,Institutionen för hälsovetenskaper,Forskningsmiljön hälsa, hållbarhet och digitalisering,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; School of Health Sciences, University of Skövde, Skövde, Sweden,Välbefinnande vid långvariga hälsoproblem (WeLHP), Wellbeing in Long-term Health Problems(Swepub:hj)daan (author)
  • Gatz, MargaretDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden ; Center for Economic and Social Research, University of Southern California, Los Angeles, United States (author)
  • Pedersen, Nancy L.Karolinska Institutet (author)
  • Reynolds, Chandra A.Department of Psychology, University of California, Riverside, United States (author)
  • Jönköping UniversityHHJ, Institutet för gerontologi (creator_code:org_t)

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  • In:European Journal of Epidemiology: Springer Nature Switzerland AG.37:12, s. 1261-12710393-29901573-7284

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