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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.

Original publication

DOI

10.3233/jad-140186

Type

Journal article

Journal

Journal of Alzheimer's disease : JAD

Publication Date

01/2014

Volume

42

Pages

137 - 142

Addresses

Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.

Keywords

Humans, Dementia, Alzheimer Disease, Receptor, IGF Type 1, Apolipoproteins E, Incidence, Prevalence, Logistic Models, Proportional Hazards Models, Risk, Longitudinal Studies, Follow-Up Studies, Prospective Studies, Aged, Aged, 80 and over, Female, Male