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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