A Diffusion Tensor Imaging Study on White Matter Abnormalities in Patients with Type 2 Diabetes Using Tract-Based Spatial Statistics

Abstract

Background and Purpose To demonstrate that gradual and continuous WM change and the associated cognitive decline in type 2 diabetes mellitus (T2DM) patients can be captured by DTI parameters and the DTI parameters can be used to complement neuropsychological test scores in identifying T2DM patients with and without mild cognitive impairment (MCI). Materials and Methods Forty-two T2DM patients, divided into a group with MCI (DM-MCI; n = 20) and a group with normal cognition (DM-NC; n = 22) based on cognitive assessments, were enrolled together with age-, gender-, and education-matched healthy controls (HC; n = 26). DTI was performed at 3 Tesla, followed by an analysis using tract-based spatial statistics (TBSS) to investigate the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1), and radial diffusivity (λ23) among the groups. A receiver operating characteristic (ROC) analysis was used to assess the performance of using DTI parameters for separating the two T2DM groups. Results The whole-brain TBSS analysis revealed that 7.3% and 24.9% of the WM exhibited decreased FA and increased MD (p < 0.05), respectively, between the DM-MCI and the DM-NC groups, while considerably larger WM regions showed FA (36.6%) and MD (58.8%) changes between the DM-MCI and the HC groups. These changes were caused primarily by an elevated radial diffusivity observed in the DM-MCI patients. Radial diffusivity also exhibited subtle but statistically significant changes between the DM-NC and the HC group. Analyses on individual fiber tracts showed pronounced FA reduction and MD elevation in regions related to cognitive functions. The ROC analysis on the right cingulum (hippocampus) showed that FA produced a larger area under the curve (AUC = 0.832) than MD (0.753) for separating MCI from normal cognition among T2DM patients. When FA was combined with MD, the AUC was further improved to 0.857. Conclusion This study demonstrates that the DTI parameters can show a significant difference between the T2DM patients with and without MCI, suggesting their potential use as an imaging marker for detecting cognitive decline in T2DM patients. More importantly, this study also suggests that the DTI parameters may capture gradual and continuous WM changes that can be associated with early stages of cognitive decline in T2DM patients before they can be diagnosed clinically using the conventional neuropsychological tests.

Insulin resistance in Alzheimer's disease

“…Advanced two-dimensional (2D MRS) methods currently gaining favor are capable of detecting glucose concentrations within specific regions of the brain [179] and may be used some day to study IR in relation to AD. Diffusion MRI has revealed deficits in the microstructural integrity of grey and white matter in AD [180–183] and T2D [184–186] that are associated with impaired cognitive performance. Functional MRI (fMRI) has been used to demonstrate that insulin infusion enhances neuronal activity in the medial temporal lobe [187], that patients with T2D showed connectivity decreases in regions associated with AD [188, 189], and that higher peripheral insulin levels are associated with less cognitive decline and atrophy in AD patients [190].…”

Application of neurite orientation dispersion and density imaging to characterize brain microstructural abnormalities in type‐2 diabetics with mild cognitive impairment

“…Through modeling the microscopic diffusion properties of water molecules, different parameters can be estimated, such as fractional anisotropy (FA) and mean diffusivity (MD). Previous DTI studies have demonstrated widespread white matter integrity alterations in several important regions and their correlations with neuropsychological function . It was hypothesized that the FA reductions and MD elevations may reflect axonal degeneration or myelin breakdown in T2DM brains .…”

“…Previous DTI studies have demonstrated widespread white matter integrity alterations in several important regions and their correlations with neuropsychological function. [12][13][14] It was hypothesized that the FA reductions and MD elevations may reflect axonal degeneration or myelin breakdown in T2DM brains. 13,14 Alternatively, these effects may simply reflect changes in the spatial organization of neurites.…”

“…[12][13][14] It was hypothesized that the FA reductions and MD elevations may reflect axonal degeneration or myelin breakdown in T2DM brains. 13,14 Alternatively, these effects may simply reflect changes in the spatial organization of neurites. 15 However, although it can provide good sensitivity, DTI lacks specificity for individual tissue microstructure features, as they are based on a simplified model of brain tissue microstructure involving a single compartment with anisotropic and apparent Gaussian diffusion of water molecules.…”

Cerebral Pathology and Cognition in Diabetes: The Merits of Multiparametric Neuroimaging

“…Microstructural abnormalities have been published for various brain regions in type 2 diabetes (Yau et al, 2009, 2010; Falvey et al, 2013; Zhang J. et al, 2014, 2016; van Bussel et al, 2016b; Xiong et al, 2016). Reduced FA has been observed in the white matter (Yau et al, 2010; Falvey et al, 2013) mostly concentrated in frontal and temporal regions (Yau et al, 2009), while elevated ADC values were found in a number of brain regions, including the hippocampus (Falvey et al, 2013) and multiple gray matter regions (Yau et al, 2010).…”