Large-scale functional connectivity predicts cognitive impairment related to type 2 diabetes mellitus

BACKGROUND: Large-scale functional connectivity (LSFC) patterns in the brain have unique intrinsic characteristics. Abnormal LSFC patterns have been found in patients with dementia, as well as in those with mild cognitive impairment (MCI), and these patterns predicted their cognitive performance. It has been reported that patients with type 2 diabetes mellitus (T2DM) may develop MCI that could progress to dementia. We investigated whether we could adopt LSFC patterns as discriminative features to predict the cognitive function of patients with T2DM, using connectome-based predictive modeling (CPM) and a support vector machine. AIM: To investigate the utility of LSFC for predicting cognitive impairment related to T2DM more accurately and reliably. METHODS: Resting-state functional magnetic resonance images were derived from 42 patients with T2DM and 24 healthy controls. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Patients with T2DM were divided into two groups, according to the presence (T2DM-C; n = 16) or absence (T2DM-NC; n = 26) of MCI. Brain regions were marked using Harvard Oxford (HOA-112), automated anatomical labeling (AAL-116), and 264-region functional (Power-264) atlases. LSFC biomarkers for predicting MoCA scores were identified using a new CPM technique. Subsequently, we used a support vector machine based on LSFC patterns for among-group differentiation. The area under the receiver operating characteristic curve determined the appearance of the classification. RESULTS: CPM could predict the MoCA scores in patients with T2DM (Pearson’s correlation coefficient between predicted and actual MoCA scores, r = 0.32, P=0.0066 [HOA-112 atlas]; r = 0.32, P=0.0078 [AAL-116 atlas]; r = 0.42, P=0.0038 [Power-264 atlas]), indicating that LSFC patterns represent cognition-level measures in these patients. Positive (anti-correlated) LSFC networks based on the Power-264 atlas showed the best predictive performance; moreover, we observed new brain regions of interest associated with T2DM-related cognition. The area under the receiver operating characteristic curve values (T2DM-NC group vs. T2DM-C group) were 0.65-0.70, with LSFC matrices based on HOA-112 and Power-264 atlases having the highest value (0.70). Most discriminative and attractive LSFCs were related to the default mode network, limbic system, and basal ganglia. CONCLUSION: LSFC provides neuroimaging-based information that may be useful in detecting MCI early and accurately in patients with T2DM.