Abnormal changes of brain function and structure in patients with T2DM-related cognitive impairment: a neuroimaging meta-analysis and an independent validation

Abstract

Type 2 diabetes mellitus (T2DM) seriously threatens human health and the quality of life, cognitive impairment is considered as a common complication of T2DM. Neuroimaging meta-analysis found brain functional and structural abnormality in patients with T2DM. Therefore, the purpose of the meta-analysis was to identify brain regions of patients with T2DM-related cognitive impairment (T2DM-CI) where functional and structural indicators changed together or could not synchronize. A literature screening of neuroimaging studies on cognitive impairment in T2DM was conducted from 1 January 2007 to 26 May 2023 in PubMed, Web of Science, Cochrane Library, and Medline databases. The functional indicators we studied were amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and degree centrality (DC), while the structural indicator was gray matter (GM), which included gray matter volume (GMV) and cerebral cortical thickness. Studies reporting ALFF, ReHo, DC and GM abnormalities between T2DM-CI and healthy controls (HCs) were selected and their significant peak coordinates (x, y, z) and effect size (t-value) were extracted to perform a meta-analysis using anisotropic effect size sign differential mapping (AES-SDM) 5.15 software. Moreover, the brain regions with significant differences obtained from meta-analysis were saved as masks and then validated in our data. Total 19 studies and 20 datasets were involved in this study. Compared to HCs, combining ALFF, ReHo, and DC measurements, the brain activity of the left anterior cingulate/paracingulate gyri (ACC.L, BA24) in T2DM-CI patients increased significantly, while the brain activity of the left lingual gyrus (LING.L, BA18) in T2DM-CI patients decreased significantly. The GM indicator of the right superior temporal gyrus (STG.R, BA42) and left inferior occipital gyrus (IOG.L, BA19) in T2DM-CI patients decreased significantly. Meta-regression analysis showed the negative relationship between the brain activity reduction in LING.L and the percentage of female patients, as well as the negative relationship between GM reduction in IOG.L and T2DM duration. Furthermore, we validated a decrease in brain activity in the LING.L of T2DM-CI patients in our independent dataset. The decrease of brain activity in LING.L and the decrease of GM in IOG.L were closely related to visual impairment in T2DM-CI patients. These abnormal brain regions may be the main targets for future research, early intervention can delay the further development of cognitive impairment in T2DM patients and improve their quality of life, which also provided early biomarkers for clarifying the mechanism of cognitive impairment in T2DM.