title: Insulin-like growth factor-I receptor stimulating activity is associated with dementia.
abstract: BACKGROUND
  Insulin-like growth factor-I (IGF-I) is a pleiotropic hormone. Several studies have related IGF-I levels to dementia, but evidence remains inconclusive. IGF-I receptor stimulating activity is a more direct measure of biologically available IGF-I than total IGF-I levels.
  
  
  OBJECTIVE
  To investigate whether IGF-I receptor stimulating activity is associated with prevalent and incident dementia.
  
  
  METHODS
  IGF-I receptor stimulating activity was measured using an IGF-I kinase receptor activation assay in 1,014 persons from the Rotterdam Study. Dementia was assessed at baseline (1997-1999) and continuously during follow-up until September 2011. Associations of IGF-I receptor stimulating activity with prevalent dementia were investigated using logistic regression and with incident dementia using Cox proportional hazards models. All models were adjusted for age and gender, and additionally for hypertension, glucose, waist circumference, APOE-ε4 carrier status, total cholesterol, and HDL-cholesterol.
  
  
  RESULTS
  Thirty participants had prevalent dementia and during 8,589 person-years of follow-up, 135 persons developed incident dementia. A higher level of IGF-I receptor stimulating activity was associated with a higher prevalence of dementia (fully adjusted odds ratio 1.47; 95% CI 1.10-1.97) and with a higher risk of incident dementia (fully adjusted hazard ratio 1.15; 95% CI 1.00-1.33). Similar associations were found for Alzheimer's disease and in persons without diabetes mellitus.
  
  
  CONCLUSIONS
  Higher levels of IGF-I receptor stimulating activity are associated with a higher prevalence and with a higher incidence of dementia. These results suggest that IGF-I increases in response to neuropathological changes in dementia and could reflect a state of IGF-I resistance in dementia.
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Renée F A G
authors.initials: RF
authors.lastname: de Bruijn
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Joseph A M J L
authors.initials: JA
authors.lastname: Janssen
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Brugts
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Koudstaal
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D003704:Dementia / Q000097:blood* / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D015995:Prevalence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017526:Receptor, IGF Type 1 / Q000097:blood*; D012306:Risk
chemical_list: D001057:Apolipoproteins E; D017526:Receptor, IGF Type 1
keywords: Alzheimer's disease; dementia; epidemiology; insulin-like growth factor-I