The Associations Between Serum Insulin-like Growth Factor-I, Brain White Matter Volumes, and Cognition in Mild Cognitive Impairment and Alzheimer's Disease

J Alzheimers Dis. 2024;99(2):609-622. doi: 10.3233/JAD-231026.

Abstract

Background: Insulin-like growth factor-I (IGF-I) regulates myelin, but little is known whether IGF-I associates with white matter functions in subjective and objective mild cognitive impairment (SCI/MCI) or Alzheimer's disease (AD).

Objective: To explore whether serum IGF-I is associated with magnetic resonance imaging - estimated brain white matter volumes or cognitive functions.

Methods: In a prospective study of SCI/MCI (n = 106) and AD (n = 59), we evaluated the volumes of the total white matter, corpus callosum (CC), and white matter hyperintensities (WMHs) as well as Mini-Mental State Examination (MMSE), Trail Making Test A and B (TMT-A/B), and Stroop tests I-III at baseline, and after 2 years.

Results: IGF-I was comparable in SCI/MCI and AD (113 versus 118 ng/mL, p = 0.44). In SCI/MCI patients, the correlations between higher baseline IGF-I and greater baseline and 2-year volumes of the total white matter and total CC lost statistical significance after adjustment for intracranial volume and other covariates. However, after adjustment for covariates, higher baseline IGF-I correlated with better baseline scores of MMSE and Stroop test II in SCI/MCI and with better baseline results of TMT-B and Stroop test I in AD. IGF-I did not correlate with WMH volumes or changes in any of the variables.

Conclusions: Both in SCI/MCI and AD, higher IGF-I was associated with better attention/executive functions at baseline after adjustment for covariates. Furthermore, the baseline associations between IGF-I and neuropsychological test results in AD may argue against significant IGF-I resistance in the AD brain.

Keywords: Alzheimer’s disease; attention; corpus callosum; executive function; insulin-like growth factor-I; magnetic resonance imaging; mild cognitive impairment; speed; subjective mild cognitive impairment; white matter hyperintensities.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / pathology
  • Brain* / diagnostic imaging
  • Brain* / pathology
  • Cognition / physiology
  • Cognitive Dysfunction* / blood
  • Cognitive Dysfunction* / diagnostic imaging
  • Cognitive Dysfunction* / pathology
  • Female
  • Humans
  • Insulin-Like Growth Factor I* / analysis
  • Insulin-Like Growth Factor I* / metabolism
  • Insulin-Like Peptides
  • Magnetic Resonance Imaging*
  • Male
  • Mental Status and Dementia Tests
  • Middle Aged
  • Neuropsychological Tests* / statistics & numerical data
  • Organ Size
  • Prospective Studies
  • White Matter* / diagnostic imaging
  • White Matter* / pathology