Abstract
Previous studies have shown that type 2 diabetes mellitus (T2DM) can accelerate the rate of cognitive decline in patients. As an organ with high energy consumption, the brain network balances between lower energy consumption and higher information transmission efficiency. However, T2DM may modify the proportion of short- and long-range connections to adapt to the inadequate energy supply and to respond to various cognitive tasks under the energy pressure caused by homeostasis alterations in brain glucose metabolism. On the basis of the above theories, this study determined the abnormal functional connections of the brain in 32 T2DM patients compared with 32 healthy control (HC) subjects using long- and short-range functional connectivity density (FCD) analyses with resting-state fMRI data. The cognitive function level in these patients was also evaluated by neuropsychological tests. Moreover, the characteristics of abnormal FCD and their relationships with cognitive impairment were investigated in T2DM patients. Compared with the HC group, T2DM patients exhibited decreased long-range FCD in the left calcarine and left lingual gyrus and increased short-range FCD in the right angular gyrus and medial part of the left superior frontal gyrus (p < 0.05, Gaussian random-field theory corrected). In T2DM patients, the FCD z scores of the medial part of the left superior frontal gyrus were negatively correlated with the time cost in part B of the Trail Making Test (ρ = -0.422, p = 0.018). In addition, the FCD z scores of the right angular gyrus were negatively correlated with the long-term delayed recall scores of the Auditory Verbal Learning Test (ρ = -0.356, p = 0.049) and the forward scores of the Digital Span Test (ρ = -0.373, p = 0.039). T2DM patients exhibited aberrant long-range and short-range FCD patterns, which may suggest brain network reorganization at the expense of losing the integration of long-range FCD to adapt to the deficiency in energy supply. These changes may be associated with cognitive decline in T2DM patients.
Highlights
Type 2 diabetes mellitus (T2DM) is characterized by disordered glucose metabolism and the number of affected individuals increased rapidly from 415 million in 2015 to 425 million in 2017 according to the 8th edition of Diabetes Atlas published by the International Diabetes Federation
Higher triglyceride and lower high-density lipoprotein (HDL) cholesterol, free triiodothyronine (FT3) and free thyroxine (FT4) levels were observed in type 2 diabetes mellitus (T2DM) patients (p < 0.05, Table 1)
As the disturbance in glucose metabolism may affect the brain energy homeostasis in T2DM, the present study investigated the disruption in the balance between the long- and short-range functional connectivity density (FCD)
Summary
Type 2 diabetes mellitus (T2DM) is characterized by disordered glucose metabolism and the number of affected individuals increased rapidly from 415 million in 2015 to 425 million in 2017 according to the 8th edition of Diabetes Atlas published by the International Diabetes Federation. Type 2 diabetes mellitus is associated with reduced glucose metabolism in the brain, which may result in putative reorganization of long- and short-range functional connections. Brain regions with short-range functional connections are often specialized for modular information processing and operate with lower time- and energy-cost. Long-range functional connections allow integrative information processing across distributed brain systems with higher time- and energycost (Sepulcre et al, 2010). The balance of long- and shortrange functional connections is critical for the efficiency of cortical information communication and energy-cost (Sepulcre et al, 2010). Impaired glucose homeostasis may disrupt the established balance of long- and short-range functional connections for the economical trade-off between cost and efficiency in T2DM patients (Bullmore and Sporns, 2012). As the alterations in glucose metabolism are coupled with alterations in blood-oxygen level-dependent signals, functional magnetic resonance imaging (fMRI) is advantageous in mapping the reorganization of long- and short-range functional connections (Sepulcre et al, 2010; Magistretti and Allaman, 2015)
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