Spatial Patterns of Structural Brain Changes in Type 2 Diabetic Patients and Their Longitudinal Progression With Intensive Control of Blood Glucose

Abstract

OBJECTIVEUnderstanding the effect of diabetes as well as of alternative treatment strategies on cerebral structure is critical for the development of targeted interventions against accelerated neurodegeneration in type 2 diabetes. We investigated whether diabetes characteristics were associated with spatially specific patterns of brain changes and whether those patterns were affected by intensive versus standard glycemic treatment.RESEARCH DESIGN AND METHODSUsing baseline MRIs of 488 participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) study, we applied a new voxel-based analysis methodology to identify spatially specific patterns of gray matter and white matter volume loss related to diabetes duration and HbA1c. The longitudinal analysis used 40-month follow-up data to evaluate differences in progression of volume loss between intensive and standard glycemic treatment arms.RESULTSParticipants with longer diabetes duration had significantly lower gray matter volumes, primarily in certain regions in the frontal and temporal lobes. The longitudinal analysis of treatment effects revealed a heterogeneous pattern of decelerated loss of gray matter volume associated with intensive glycemic treatment. Intensive treatment decelerated volume loss, particularly in regions adjacent to those cross-sectionally associated with diabetes duration. No significant relationship between low versus high baseline HbA1c levels and brain changes was found. Finally, regions in which cognitive change was associated with longitudinal volume loss had only small overlap with regions related to diabetes duration and to treatment effects.CONCLUSIONSApplying advanced quantitative image pattern analysis methods on longitudinal MRI data of a large sample of patients with type 2 diabetes, we demonstrate that there are spatially specific patterns of brain changes that vary by diabetes characteristics and that the progression of gray matter volume loss is slowed by intensive glycemic treatment, particularly in regions adjacent to areas affected by diabetes.

HbA1c levels as a function of emotional regulation and emotional intelligence in patients with type 2 diabetes

“…In T2D individuals, treatment with metformin has been reported to reduce the risk of cognitive decline over time [32]. Neuroimaging studies report corresponding findings suggesting a link between chronic hyperglycemia and brain atrophy [33], reduced brain volume [34], and cognitive function [35] in T2 diabetic subjects.…”

Diabetes and Cognitive Impairment

“…Cross-sectional data from over 3000 patients with T2DM demonstrated an age-adjusted inverse relationship between cognitive function and A1C levels [32]. However, prospectively collected data found that total brain volumes were higher in the intensive treatment group but cognitive outcomes were not significantly different between the two groups [33, 34]. …”

“…There is evidence of MRI abnormalities including a reduction in hippocampal volumes in both animal models [37•] and human subjects [33, 34, 38–40] with IGR. With improvement in glycemic control, there is stabilization of the rate of brain atrophy [33, 34].…”

“…With improvement in glycemic control, there is stabilization of the rate of brain atrophy [33, 34]. Working memory (WM), which is a susceptible cognitive domain of mild cognitive impairment, and AD have been assessed in T2DM.…”

“…In The Memory in Diabetes (ACCORD-MIND) study, there was slowing in the rate of brain atrophy on MRI in patients with T2DM receiving intensive glycemic control compared with those receiving standard therapy. However, this was not accompanied by improved cognitive function [33, 34]. Clearly, glycemic level has little impact on neurological function in T2DM [33, 34, 95].…”