Cerebral White Matter Integrity and Resting-State Functional Connectivity in Middle-aged Patients With Type 2 Diabetes

  1. Gail Musen1,6
  1. 1Clinical, Behavioral, and Outcomes Research, Joslin Diabetes Center, Boston, MA
  2. 2Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Boston, MA
  3. 3Faculty of Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
  4. 4Unit for Experimental Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
  5. 5Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA
  6. 6Harvard Medical School, Boston, MA
  7. 7Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Boston, MA
  8. 8Research Institute, Winthrop-University Hospital, Mineola, NY
  9. 9Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, MA
  1. Corresponding author: Gail Musen, gail.musen{at}


Early detection of brain abnormalities at the preclinical stage can be useful for developing preventive interventions to abate cognitive decline. We examined whether middle-aged type 2 diabetic patients show reduced white matter integrity in fiber tracts important for cognition and whether this abnormality is related to preestablished altered resting-state functional connectivity in the default mode network (DMN). Diabetic and nondiabetic participants underwent diffusion tensor imaging, functional magnetic resonance imaging, and cognitive assessment. Multiple diffusion measures were calculated using streamline tractography, and correlations with DMN functional connectivity were determined. Diabetic patients showed lower fractional anisotropy (FA) (a measure of white matter integrity) in the cingulum bundle and uncinate fasciculus. Control subjects showed stronger functional connectivity than patients between the posterior cingulate and both left fusiform and medial frontal gyri. FA of the cingulum bundle was correlated with functional connectivity between the posterior cingulate and medial frontal gyrus for combined groups. Thus, middle-aged patients with type 2 diabetes show white matter abnormalities that correlate with disrupted functional connectivity in the DMN, suggesting that common mechanisms may underlie structural and functional connectivity. Detecting brain abnormalities in middle age enables implementation of therapies to slow progression of neuropathology.

  • Received August 8, 2013.
  • Accepted October 25, 2013.

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  1. Diabetes vol. 63 no. 2 728-738
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