title: 37 Years of Body Mass Index and Dementia: Effect Modification by the APOE Genotype: Observations from the Prospective Population Study of Women in Gothenburg, Sweden.
abstract: BACKGROUND
  Overweight and obesity in mid- and late-life may increase risk for dementia, whereas a decline in body weight or body mass index (BMI) and underweight in years preceding a clinical dementia diagnosis are also associated with dementia. Little is known about the modifying effect of the APOE genotype, a major susceptibility gene for Alzheimer's disease (AD), on the BMI-dementia adult life course trajectory.
  
  
  OBJECTIVE
  We evaluated the exposure, BMI, in relationship to the outcome, clinical dementia, over 37 years, considering the effect modification of the APOE ɛ4 allele.
  
  
  METHODS
  The Prospective Population Study of Women (PPSW) in Sweden is a systematic sample of 1462 women born 1908, 1914, 1918, 1922, and 1930 and aged 38-60 years at baseline. Examinations occurred in 1968, 1974, 1980, 1992, 2000, and 2005; 559 women had information on dementia, BMI, and APOE ɛ4 allele status, in addition to covariates. Statistical analyses were conducted using mixed effects regression models.
  
  
  RESULTS
  Trajectories of BMI over 37 years differed by APOE ɛ4 allele status. While women gained BMI similarly from mid-life to age 70 years, women with at least one APOE ɛ4 allele experienced BMI decline more quickly after age 70 years compared to women without an APOE ɛ4 allele. However, upon stratifying the sample by dementia occurrence, it appeared that dementia drove the overall BMI-trajectory. There was a main effect of age, interactions of age by APOE ɛ4 allele status, and age by presence versus absence of dementia.
  
  
  CONCLUSIONS
  Women with similar average BMI at mid-life exhibited different BMI trajectories in relation to dementia occurrence. In addition, the pattern of BMI decline in late-life differed on the basis of APOE ɛ4 allele possession. Thus, these data suggest roles for both dementia- and APOE-associated changes in BMI during the adult life course.
authors.affiliation: Department of Neurochemistry and Psychiatry, Neuropsychiatric Epidemiology Unit, at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Bäckman
authors.affiliation: Department of Neurochemistry and Psychiatry, Neuropsychiatric Epidemiology Unit, at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Joas
authors.affiliation: Department of Neurochemistry and Psychiatry, Neuropsychiatric Epidemiology Unit, at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Margda
authors.initials: M
authors.lastname: Waern
authors.affiliation: Department of Neurochemistry and Psychiatry, Neuropsychiatric Epidemiology Unit, at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Svante
authors.initials: S
authors.lastname: Östling
authors.affiliation: Department of Neurochemistry and Psychiatry, Neuropsychiatric Epidemiology Unit, at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Neurochemistry and Psychiatry, Neuropsychiatric Epidemiology Unit, at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Neurochemistry and Psychiatry, Neuropsychiatric Epidemiology Unit, at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Skoog
authors.affiliation: Department of Neurochemistry and Psychiatry, Neuropsychiatric Epidemiology Unit, at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Neurology, State University of New York-Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Gustafson
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D003704:Dementia / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
chemical_list: D053327:Apolipoprotein E4
keywords: APOE; Alzheimer’s disease; body mass index change; dementia; prospective; risk factor