Insulin-Like Growth Factor-1 but Not Insulin Predicts Cognitive Decline in Huntington's Disease

PLoS One. 2016 Sep 14;11(9):e0162890. doi: 10.1371/journal.pone.0162890. eCollection 2016.

Abstract

Background: Huntington's disease (HD) is one of several neurodegenerative disorders that have been associated with metabolic alterations. Changes in Insulin Growth Factor 1 (IGF-1) and/or insulin input to the brain may underlie or contribute to the progress of neurodegenerative processes. Here, we investigated the association over time between changes in plasma levels of IGF-1 and insulin and the cognitive decline in HD patients.

Methods: We conducted a multicentric cohort study in 156 patients with genetically documented HD aged from 22 to 80 years. Among them, 146 patients were assessed at least twice with a follow-up of 3.5 ± 1.8 years. We assessed their cognitive decline using the Unified Huntington's Disease Rating Scale, and their IGF-1 and insulin plasmatic levels, at baseline and once a year during the follow-up. Associations were evaluated using a mixed-effect linear model.

Results: In the cross-sectional analysis at baseline, higher levels of IGF-1 and insulin were associated with lower cognitive scores and thus with a higher degree of cognitive impairment. In the longitudinal analysis, the decrease of all cognitive scores, except the Stroop interference, was associated with the IGF-1 level over time but not of insulin.

Conclusions: IGF-1 levels, unlike insulin, predict the decline of cognitive function in HD.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cognition Disorders / blood*
  • Cognition Disorders / etiology
  • Disease Progression
  • Female
  • Humans
  • Huntington Disease / blood*
  • Huntington Disease / complications
  • Huntington Disease / pathology
  • Insulin / blood*
  • Insulin-Like Growth Factor I / analysis*
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Insulin
  • Insulin-Like Growth Factor I

Grant support

A-C Bachoud-Lévi is the PI of the biomarker program financed first by Gis A02216JS /A04159JS and then Assistance Publique - Hôpitaux de Paris (Département de la Recherche Clinique et du Développement); she had full access to all of the data for this study and takes responsibility for the integrity of the data and the accuracy of data analysis. She is supported by an interface contract from INSERM and is the head of the French National Centre for Huntington’s disease, granted by the Ministry of Health.