Insulin-like growth factor-I and insulin-like growth factor binding protein-3 in Alzheimer's disease

J Clin Endocrinol Metab. 2012 Dec;97(12):4673-81. doi: 10.1210/jc.2012-2063. Epub 2012 Sep 26.

Abstract

Context: Few large studies have been conducted to assess the relationship between circulating IGF and late-life cognition.

Objective: The aim of the study was to assess the relationship between IGF-I and IGF binding protein-3 (IGFBP-3) serum levels and cognitive impairment, including Alzheimer's disease (AD).

Methods: In this multicentric cross-sectional study, 694 elderly subjects (218 men, 476 women; 78.6 ± 6.7 yr old) were included; 481 had memory complaints and were diagnosed, after comprehensive cognitive assessment, with AD (n = 224) or mild cognitive impairment (MCI) (n = 257). The control group was comprised of 213 subjects without memory complaint and with normal cognition (recruited among patients' caregivers). IGF-I and IGFBP-3 serum levels were determined by ELISA.

Results: IGF-I and IGFBP-3 serum levels were significantly associated with cognitive status in men (IGF-I, 137 ± 69 ng/ml for AD vs. 178 ± 88 ng/ml for MCI and 172 ± 91 ng/ml for controls, P = 0.01; IGFBP-3, 3675 ± 1542 ng/ml for AD vs. 4143 ± 1828 ng/ml for MCI and 4488 ± 1893 ng/ml for controls, P = 0.04). In women, IGFBP-3 was significantly associated with cognitive status (3781 ± 1351 ng/ml for AD vs. 4190 ± 1408 ng/ml for MCI and 4390 ± 1552 ng/ml for controls; P < 0.001), but no significant differences between groups for IGF-I occurred. After adjustment for confounding variables (age, educational level, body mass index, diabetes, apolipoprotein E ε4 status), logistic regression indicated that IGF-I [odds ratio (95% confidence interval) = 0.48 (0.26-0.88)] and IGFBP-3 [odds ratio (95% confidence interval) = 0.71 (0.52-0.97)] serum levels were independently associated with AD in men, but not in women.

Conclusions: We report a significant association between low IGF-I and IGFBP-3 serum levels and AD in men, but not in women.

Trial registration: ClinicalTrials.gov NCT00647478.

Publication types

  • Controlled Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / etiology
  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology
  • Apolipoproteins E / genetics
  • Cognition / physiology
  • Cross-Sectional Studies
  • Female
  • Genotype
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Memory / physiology
  • Neuropsychological Tests

Substances

  • Apolipoproteins E
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I

Associated data

  • ClinicalTrials.gov/NCT00647478