Brain Atrophy in Type 2 Diabetes

Regional distribution and influence on cognition

  1. Velandai Srikanth, PHD1,2,4
  1. 1Stroke and Ageing Research Group, Department of Medicine, Southern Clinical School, Monash University, Melbourne, Australia
  2. 2Neurosciences, Monash Medical Centre, Southern Health, Melbourne, Australia
  3. 3Developmental Imaging, Murdoch Children’s Research Institute, Melbourne, Australia
  4. 4Menzies Research Institute Tasmania, Hobart, Tasmania, Australia
  5. 5Department of Pharmacology and Molecular Medicine Research Group, School of Medicine, University of Western Sydney, Campbelltown, Australia
  6. 6Critical Care and Neurosciences, Murdoch Children’s Research Institute, Melbourne, Australia
  7. 7School of Psychology, University of Birmingham, Edgbaston, U.K.
  8. 8Department of Medicine, Southern Clinical School, Monash University, Melbourne, Australia
  9. 9Baker-IDI Heart and Diabetes Institute, Monash University, Melbourne, Australia
  10. 10Mater Medical Research Institute, Brisbane, Australia
  11. 11Royal Hobart Hospital, Hobart, Tasmania, Australia
  1. Corresponding author: Velandai Srikanth, velandai.srikanth{at}
  1. C.M., L.B., and V.S. contributed equally to the statistical analysis.


OBJECTIVE Type 2 diabetes (T2DM) is associated with brain atrophy and cerebrovascular disease. We aimed to define the regional distribution of brain atrophy in T2DM and to examine whether atrophy or cerebrovascular lesions are feasible links between T2DM and cognitive function.

RESEARCH DESIGN AND METHODS This cross-sectional study used magnetic resonance imaging (MRI) scans and cognitive tests in 350 participants with T2DM and 363 participants without T2DM. With voxel-based morphometry, we studied the regional distribution of atrophy in T2DM. We measured cerebrovascular lesions (infarcts, microbleeds, and white matter hyperintensity [WMH] volume) and atrophy (gray matter, white matter, and hippocampal volumes) while blinded to T2DM status. With use of multivariable regression, we examined for mediation or effect modification of the association between T2DM and cognitive measures by MRI measures.

RESULTS T2DM was associated with more cerebral infarcts and lower total gray, white, and hippocampal volumes (all P < 0.05) but not with microbleeds or WMH. T2DM-related gray matter loss was distributed mainly in medial temporal, anterior cingulate, and medial frontal lobes, and white matter loss was distributed in frontal and temporal regions. T2DM was associated with poorer visuospatial construction, planning, visual memory, and speed (P ≤ 0.05) independent of age, sex, education, and vascular risk factors. The strength of these associations was attenuated by almost one-half when adjusted for hippocampal and total gray volumes but was unchanged by adjustment for cerebrovascular lesions or white matter volume.

CONCLUSIONS Cortical atrophy in T2DM resembles patterns seen in preclinical Alzheimer disease. Neurodegeneration rather than cerebrovascular lesions may play a key role in T2DM-related cognitive impairment.


  • Received January 17, 2013.
  • Accepted May 19, 2013.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.

| Table of Contents

This Article

  1. Diabetes Care vol. 36 no. 12 4036-4042
  1. Supplementary Data
  2. Slide Set
  3. All Versions of this Article:
    1. dc13-0143v1
    2. 36/12/4036 most recent