Gray and white matter abnormality in patients with T2DM-related cognitive dysfunction: a systemic review and meta-analysis

Abstract

Aims/hypothesis Brain structure abnormality in patients with type 2 diabetes mellitus (T2DM)-related cognitive dysfunction (T2DM-CD) has been reported for decades in magnetic resonance imaging (MRI) studies. However, the reliable results were still unclear. This study aimed to make a systemic review and meta-analysis to find the significant and consistent gray matter (GM) and white matter (WM) alterations in patients with T2DM-CD by comparing with the healthy controls (HCs). Methods Published studies were systemically searched from PubMed, MEDLINE, Cochrane Library and Web of Science databases updated to November 14, 2021. Studies reporting abnormal GM or WM between patients with T2DM-CD and HCs were selected, and their significant peak coordinates (x, y, z) and effect sizes (z-score or t-value) were extracted to perform a voxel-based meta-analysis by anisotropic effect size-signed differential mapping (AES-SDM) 5.15 software. Results Total 15 studies and 16 datasets (1550 participants) from 7531 results were involved in this study. Compared to HCs, patients with T2DM-CD showed significant and consistent decreased GM in right superior frontal gyrus, medial orbital (PFCventmed. R, BA 11), left superior temporal gyrus (STG. L, BA 48), and right calcarine fissure / surrounding cortex (CAL. R, BA 17), as well as decreased fractional anisotropy (FA) in right inferior network, inferior fronto-occipital fasciculus (IFOF. R), right inferior network, longitudinal fasciculus (ILF. R), and undefined area (32, −60, −42) of cerebellum. Meta-regression showed the positive relationship between decreased GM in PFCventmed.R and MoCA score, the positive relationship between decreased GM in STG.L and BMI, as well as the positive relationship between the decreased FA in IFOF.R and age or BMI. Conclusions/interpretation T2DM impairs the cognitive function by affecting the specific brain structures. GM atrophy in PFCventmed. R (BA 11), STG. L (BA 48), and CAL. R (BA 17), as well as WM injury in IFOF. R, ILF. R, and undefined area (32, −60, −42) of cerebellum. And those brain regions may be valuable targets for future researches. Age, BMI, and MoCA score have a potential influence on the altered GM or WM in T2DM-CD.

Altered functional connectivity between the default mode network in diabetic retinopathy patients

“…The cognitive impairment in patients with type 2 diabetes is manifested mainly in the impairment of working memory, learning and memory ability, and executive function [44,45]. Similar to our results, previous studies have found a significant decrease in the gray matter of the SFG medial in patients with diabetes with cognitive impairment, and the fractional anisotropy of SFG decreases [46]. However, contrary to our results, a decrease in the functional connectivity in the right SFG and PCC was found in patients with diabetes without cognitive impairment and microangiopathy [26].…”

Multi-organ imaging-derived polygenic indexes for brain and body health

“…There were significant associations between diabetes and PRS of all three modalities (|𝛽| > 0.0105, P < 5.92 × 10 -7 ), especially for the DTI parameters of the superior and inferior longitudinal fasciculus tracts and the inferior fronto-occipital fasciculus tract. These findings were consistent with two recent studies that investigated the effects of type 2 diabetes (T2D) on brain white matter 38,39 .…”

Diabetes, antidiabetic medications and risk of dementia: A systematic umbrella review and meta‐analysis

“…5-6). Of the 100 included reviews, 32 related diabetes to cognitive function in mixed diabetic populations, 2,6,8, seven examined the effect of type 1 diabetes, 3,55-60 19 focused on type 2 diabetes, 5,7,61-77 14 observed brain structure in diabetes, 1,4,[78][79][80][81][82][83][84][85][86][87][88][89] two examined genetic and other biomarkers of dementia 90,91 and 26 focused on cognitive effects of antidiabetic treatment. 14,15,[20][21][22] Of the 27 studies included in the meta-analyses, 15 related metformin use to risk of dementia, [113][114][115][116][117][118][119][120][121][122][123][124][125][126][127] 10 were used in the thiazolidinedione metaanalysis, 113,[122][123][124][125][126][127][128]...…”

“…5‐6). Of the 100 included reviews, 32 related diabetes to cognitive function in mixed diabetic populations, 2,6,8,26–54 seven examined the effect of type 1 diabetes, 3,55–60 19 focused on type 2 diabetes, 5,7,61–77 14 observed brain structure in diabetes, 1,4,78–89 two examined genetic and other biomarkers of dementia 90,91 and 26 focused on cognitive effects of antidiabetic treatment 14,15,20–22,92–112 . Of the 27 studies included in the meta‐analyses, 15 related metformin use to risk of dementia, 113–127 10 were used in the thiazolidinedione meta‐analysis, 113,122–130 four for pioglitazone, 126,129–131 seven for DPP‐4is, 123,125–127,132–134 five for α‐glucosidase inhibitors, 123,126,127,129,135 two for meglitinides, 126,129 seven for insulin, 122,123,125,127,129,136,137 11 for sulphonylureas,…”