Type 2 Diabetes Mellitus May Exacerbate Gray Matter Atrophy in Patients With Early-Onset Mild Cognitive Impairment.

Chang Li,Daihong Liu,Kunlin Xiong,Rui Jiang,Jian Wang,Yuqi Lai,Haitao Li,Yang Li,Zhiwei Zuo,Xuntao Yin

doi:10.3389/fnins.2020.00856

Abstract

BackgroundThe precise physiopathological association between the courses of neurodegeneration and cognitive decline in type 2 diabetes mellitus (T2DM) remains unclear. This study sought to comprehensively investigate the distribution characteristics of gray matter atrophy in middle-aged T2DM patients with newly diagnosed mild cognitive impairment (MCI).MethodsFour groups, including 28 patients with early-onset MCI, 28 patients with T2DM, 28 T2DM patients with early-onset MCI (T2DM-MCI), and 28 age-, sex-, and education-matched healthy controls underwent three-dimensional high-resolution structural magnetic resonance imaging. Cortical and subcortical gray matter volumes were calculated, and a structural covariance method was used to evaluate the morphological relationships within the default mode network (DMN).ResultsOverlapped and unique cortical/subcortical gray matter atrophy was found in patients with MCI, T2DM and T2DM-MCI in our study, and patients with T2DM-MCI showed lower volumes in several areas than patients with MCI or T2DM. Volume loss in subcortical areas (including the thalamus, putamen, and hippocampus), but not in cortical areas, was related to cognitive impairment in patients with MCI and T2DM-MCI. No associations between biochemical measurements and volumetric reductions were found. Furthermore, patients with MCI and those with T2DM-MCI showed disrupted structural connectivity within the DMN.ConclusionThese findings provide further evidence that T2DM may exacerbate atrophy of specific gray matter regions, which may be primarily associated with MCI. Impairments in gray matter volume related to T2DM or MCI are independent of cardiovascular risk factors, and subcortical atrophy may play a more pivotal role in cognitive impairment than cortical alterations in patients with MCI and T2DM-MCI. The enhanced structural connectivity within the DMN in patients with T2DM-MCI may suggest a compensatory mechanism for the chronic neurodegeneration.

Highlights

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by sustained hyperglycemia and insulin resistance correlated with multiple macrovascular and microvascular complications, which are important vascular risk factors for accelerated cognitive impairment and dementia (Allen et al, 2004)
Twenty-eight age, sex, and education-matched healthy controls (HCs) (15 females) who had no history of an alcohol or substance use disorder, vascular risk factors, psychiatric disease, traumatic brain injury, and neurological disease were recruited from the general public through advertisements
Compared with the HC group, the mild cognitive impairment (MCI) group had smaller cortical areas mainly located in the left hemisphere

Summary

Introduction

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by sustained hyperglycemia and insulin resistance correlated with multiple macrovascular and microvascular complications, which are important vascular risk factors for accelerated cognitive impairment and dementia (Allen et al, 2004). Neuroanatomical changes in the gray matter of patients with MCI were predominantly located in medial temporal areas, such as the hippocampus and entorhinal cortex (Pennanen et al, 2004; Zeifman et al, 2015; Gong et al, 2017), and in the frontal, parietal and occipital cortices (Tondelli et al, 2012; Zheng et al, 2014; Lei et al, 2016) Some of these structural alterations in patients with diabetes or MCI appeared to overlap; many of the above-mentioned neuropathological studies of T2DM excluded patients with dementia but did not rule out patients with concomitant MCI (Chen et al, 2012; Moran et al, 2013; Garcia-Casares et al, 2014; Mehta et al, 2014); the inclusion of these subjects in statistical analyses may reflect the results of combining patients with T2DM with normal cognitive function and those with T2DM-MCI. This study sought to comprehensively investigate the distribution characteristics of gray matter atrophy in middle-aged T2DM patients with newly diagnosed mild cognitive impairment (MCI)

Methods

Results

Discussion

Conclusion