Impaired Macromolecular Protein Pools in Fronto-Striato-Thalamic Circuits in Type 2 Diabetes Revealed by Magnetization Transfer Imaging
ABSTRACT Previous research has shown that type 2 diabetes mellitus (T2DM) is associated with white matter microstructural changes, cognitive impairment, and decreased resting-state functional connectivity and spontaneous brain activity. This study used magnetization transfer (MT) imaging to examine, for the first time, the integrity of macromolecular protein pools in fronto-striato-thalamic circuits and its clinical and cognitive correlates in patients with T2DM. T2DM patients without mood disorders (n=20, age=65.05±11.95 years) and healthy controls (n=26, age=62.92±12.71 years) were recruited. Nodes of fronto-striato-thalamic circuits, including the head of the caudate nucleus (hCaud), putamen, globus pallidus, thalamus, and four cortical regions: rostral and dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex were examined. Compared with healthy controls, patients with T2DM had significantly lower magnetization transfer ratio (MTR) in bilateral anterior cingulate and hCaud. Reduced MTRs in the above regions showed correlations with T2DM-related clinical measures, including hemoglobin A1c level and vascular risk factors, and neuropsychological task performance in the domains of Learning & Memory, Executive Function, and Attention & Information Processing. The impaired biophysical integrity of brain macromolecular protein pools and their local micro-environments in T2DM patients may provide insights into the neurological pathophysiology underlying diabetes-associated clinical and cognitive deficits.
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ABSTRACT: Magnetization transfer (MT) is a neuroimaging technique that is frequently used to characterize the biophysical abnormalities in both gray and white matter regions of the brain. In our study, we used MT to examine the integrity of key nodes in frontal-subcortical circuits in four subject groups: patients diagnosed with type 2 diabetes with and without major depression (MDD), a healthy control group, and a group diagnosed with MDD without diabetes. In the MDD group, MT studies demonstrated lower magnetization transfer ratios (MTR), a marker of abnormalities in the macromolecular protein pool, in the thalami when compared with the control groups. The group with diabetes and MDD showed lower MTR in the globus pallidus when compared with the group with MDD. Biophysical measures, in subcortical nuclei, correlated inversely with measures of glycemic control, cerebrovascular burden and depression scores. These findings have broad implications for the underlying neuronal circuitry and neurobiology of mood disorders.Molecular Psychiatry advance online publication, 14 July 2015; doi:10.1038/mp.2015.89.Molecular Psychiatry 07/2015; DOI:10.1038/mp.2015.89