Abstract
The study aimed to investigate the aberration of brain spontaneous activity and synchronization in type 2 diabetes mellitus (T2DM) patients homozygous for the apolipoprotein E (APOE)-ε3 allele. In the APOE-ε3 homozygotes, 37 T2DM patients and 37 well-matched healthy controls (HC) were included to acquire blood sample measurements, neuropsychological tests, and brain functional MRI data. The amplitude of low-frequency fluctuations (ALFF) analysis was conducted to identify the brain areas with abnormal spontaneous activity. Then, the identified brain areas were taken as seeds to compute their functional connectivity (FC) with other brain regions. The two-sample t-test or the Mann–Whitney U test were applied to reveal significant differences in acquired measurements between the two groups. The potential correlations among the three types of measurements were explored using partial correlation analysis in the T2DM group. The T2DM group had elevated glycemic levels and scored lower on the cognitive assessment but higher on the anxiety and depression tests (p < 0.05). The T2DM group exhibited higher ALFF in the left middle occipital gyrus, and the left middle occipital gyrus had lower FC with the left caudate nucleus and the left inferior parietal gyrus (p < 0.05). No significant correlations were observed. T2DM patients homozygous for the APOE-ε3 allele exhibited aberrant brain spontaneous activity and synchronization in brain regions associated with vision-related information processing, executive function, and negative emotions. The findings may update our understanding of the mechanisms of brain dysfunction in T2DM patients in a neuroimaging perspective.
Highlights
Diabetes is an established risk factor for brain dysfunction, especially cognitive impairment, which ranges from subtle cognitive changes to dementia (Biessels and Despa, 2018)
According to the two-sample t-test, significantly elevated levels of HbA1c, fasting plasma glucose and triglyceride and reduced levels of free triiodothyronine (FT3), free thyroxine (FT4) and high-density lipoprotein (HDL) cholesterol were observed in the type 2 diabetes mellitus (T2DM) group compared to the healthy controls (HC) group (p < 0.05)
There were no significant differences between the T2DM group and the HC group in terms of age, sex, education years, body mass index (BMI), systolic and diastolic blood pressure and other blood chemistry parameters (p > 0.05; Table 1)
Summary
Diabetes is an established risk factor for brain dysfunction, especially cognitive impairment, which ranges from subtle cognitive changes to dementia (Biessels and Despa, 2018). Aberrant Brain Activities in T2DM account for the majority of the population with diabetes (Koekkoek et al, 2015), the elucidation of the underlying neurological mechanisms of T2DM-related brain dysfunction may be a crucial part of mitigating the economic burden of diabetes. Even more importantly, it may enable early diagnosis and treatment to enhance the quality of life of patients. Experimental investigations into the domain of T2DM-related brain dysfunction have increased to characterize the aberrant brain activity of patients, from the regional oscillations to the layout of the network (Xia et al, 2017; Liu et al, 2019; Xu et al, 2019). We focus on apolipoprotein E (APOE) variations in the present study
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