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.

Fig. 1. Search flow diagram followed the PRISMA statement.

The systemic searches were separately performed on GM (a) and WM studies (b).

Fig. 2. Significant GM abnormalities between T2DM-CD and HCs.

Patients with T2DM-CD showed significant and consistent decreased GM (Blue) in right superior frontal gyrus, medial orbital (PFCventmed.R, BA 11) (a), left superior temporal gyrus (STG.L, BA 48) (b), and right calcarine fissure/surrounding cortex (CAL.R, BA 17) (c) compared to HCs (P < 0.005). No increased GM was found in T2DM-CD compared to HCs (P = 0.005).

Fig. 3. Significant WM abnormalities between T2DM-CD and HCs.

Patients with T2DM-CD showed the significant and consistent decreased FA (Blue) in right inferior network, inferior fronto-occipital fasciculus (IFOF.R) (a), right inferior network, inferior longitudinal fasciculus (ILF.R) (b), and undefined area of cerebellum (32, −60, −42) (c) (P < 0.005). No increased FA was found in T2DM-CD compared to HCs (P = 0.005).

Fig. 4. The relationship between MoCA score, BMI, and decreased GM in patients with T2DM-CD.

According to the meta-regression, the MoCA score was positively related with the decreased GM in PFCventmed.R (a, c) (r = 0.4290, P < 0.0005), while the BMI was positively related with the decreased GM in STG.L (b, d) (r = 0.3768, P < 0.0005).

Fig. 5. The relationship between BMI, age and decreased FA in patients with T2DM-CD.

According to the meta-regression, both the BMI (a, c) (r = 0.3479, P < 0.0005) and age of patients (b, d) (r = 0.7681, P < 0.0005) were positively related with the decreased FA in IFOF.R.