Insulin is differentially related to cognitive decline and atrophy in Alzheimer's disease and aging

Biochim Biophys Acta. 2012 Mar;1822(3):333-9. doi: 10.1016/j.bbadis.2011.06.011. Epub 2011 Jul 1.


We assessed the relationship of insulin resistance with cognitive decline and brain atrophy over two years in early Alzheimer's disease (AD, n=48) and nondemented controls (n=61). Intravenous glucose tolerance tests were conducted at baseline to determine insulin area-under-the-curve (AUC). A standard battery of cognitive tasks and MRI were conducted at baseline and 2-year follow-up. In nondemented controls, higher baseline insulin AUC was associated with 2-year decline in global cognitive performance (beta=-0.36, p=0.005). In early AD, however, higher insulin AUC was associated with less decline in global cognitive performance (beta=0.26, p=0.06), slower global brain atrophy (beta=0.40, p=0.01) and less regional atrophy in the bilateral hippocampi and cingulate cortices. While insulin resistance is associated with cognitive decline in nondemented aging, higher peripheral insulin may have AD-specific benefits or insulin signaling may be affected by systemic physiologic changes associated with AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / metabolism*
  • Aging / pathology
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Area Under Curve
  • Atrophy / metabolism*
  • Atrophy / pathology
  • Cognition Disorders / metabolism*
  • Cognition Disorders / pathology
  • Cohort Studies
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glucose Tolerance Test / methods
  • Gyrus Cinguli / metabolism
  • Gyrus Cinguli / pathology
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Insulin / metabolism*
  • Insulin Resistance
  • Magnetic Resonance Imaging / methods
  • Male
  • Neuroimaging / methods


  • Insulin

Grant support