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A Prospective Study on Circulating Insulin-Like Growth Factor I (IGF-I), IGF-Binding Proteins, and Cognitive Function in the Elderly

Departments of Epidemiology and Biostatistics (S.K., H.A.P.P., M.M.B.B.) and Internal Medicine (S.K., J.A.M.J.L.J., H.A.P.P., S.W.J.L.), Erasmus Medical Center Rotterdam, 3000 DR Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Dr. M. M. B. Breteler, Department of Epidemiology and Biostatistics, Erasmus Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.

The objective of this study was to investigate the longitudinal relation between the insulin-like growth factor I (IGF-I)/IGF-binding protein (IGFBP) system and cognitive function. The study population consisted of a sample of 186 healthy participants from the population-based Rotterdam Study, aged 55–80 yr. At baseline, we determined fasting blood levels of free and total IGF-I, IGFBP-1, and IGFBP-3. The 30-point Mini-Mental State Examination (MMSE) was used to assess cognitive impairment at baseline (MMSE score of <26; 6% of the sample) and cognitive decline after, on the average, 1.9 yr of follow-up (drop in MMSE score of >1 point/year; 22% of the sample). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression, with adjustment for age, sex, education, body mass index, and fasting insulin levels. Total IGF-I appeared to be inversely related to cognitive impairment, although not significantly. Higher total IGF-I and the total IGF-I/IGFBP-3 ratio were associated with less cognitive decline (OR per SD increase = 0.65; 95% CI = 0.44–0.95 and OR = 0.59; 95% CI = 0.39–0.87, respectively). No relation was observed between free IGF-I and cognitive decline (OR = 0.99; 95% CI = 0.68–1.44). In conclusion, in this prospective study higher serum total IGF-I levels and higher total IGF-I/IGFBP-3 ratios, but not higher free IGF-I levels, were associated with less cognitive decline over the following 2 yr. Circulating total IGF-I levels may reflect an underlying biological process that influences cognitive decline.

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