Task-induced brain activity patterns in type 2 diabetes: a potential biomarker for cognitive decline.
Patients with type 2 diabetes demonstrate reduced functional connectivity within the resting state default mode network (DMN), which may signal heightened risk for cognitive decline. In other populations at risk for cognitive decline, additional magnetic resonance imaging abnormalities are evident during task performance, including impaired deactivation of the DMN and reduced activation of task-relevant regions. We investigated whether middle-aged type 2 diabetic patients show these brain activity patterns during encoding and recognition tasks. Compared with control participants, we observed both reduced 1) activation of the dorsolateral prefrontal cortex during encoding and 2) deactivation of the DMN during recognition in type 2 diabetic patients, despite normal cognition. During recognition, activation in several task-relevant regions, including the dorsolateral prefrontal cortex and DMN regions, was positively correlated with HbA1c and insulin resistance, suggesting that these important markers of glucose metabolism impact the brain's response to a cognitive challenge. Plasma glucose ≥11 mmol/L was associated with impaired deactivation of the DMN, suggesting that acute hyperglycemia contributes to brain abnormalities. Since elderly type 2 diabetic patients often demonstrate cognitive impairments, it is possible that these task-induced brain activity patterns observed in middle age may signal impending cognitive decline.
Clinical, Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, MA.
Thomas J
TJ
Marder
Clinical, Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, MA Department of Psychology, Brandeis University, Waltham, MA.
Veronica L
VL
Flores
Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA Harvard Medical School, Boston, MA.
Nicolas R
NR
Bolo
Clinical, Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, MA Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Boston, MA Albert Einstein College of Medicine, Yeshiva University, Bronx, NY.
Wouter S
WS
Hoogenboom
Harvard Medical School, Boston, MA Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Donald C
DC
Simonson
Clinical, Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, MA Harvard Medical School, Boston, MA Research Institute, Winthrop-University Hospital, Mineola, NY.
Alan M
AM
Jacobson
Clinical, Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, MA Tulane University School of Medicine, Tulane University, New Orleans, LA.
Sarah E
SE
Foote
Harvard Medical School, Boston, MA Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Boston, MA Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, MA.
Martha E
ME
Shenton
Harvard Medical School, Boston, MA Department of Neurology, Massachusetts General Hospital, Boston, MA Department of Neurology, Brigham and Women's Hospital, Boston, MA Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA.
Reisa A
RA
Sperling
Clinical, Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, MA Harvard Medical School, Boston, MA gail.musen@joslin.harvard.edu.
Gail
G
Musen
D015415:Biomarkers; D001921:Brain / Q000502:physiology; D001931:Brain Mapping; D003072:Cognition Disorders / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests
D015415:Biomarkers