White matter microstructure alterations in type 2 diabetes mellitus and its correlation with cerebral small vessel disease and cognitive performance

Abstract

Microstructural abnormalities of white matter fiber tracts are considered as one of the etiology of diabetes-induced neurological disorders. We explored the cerebral white matter microstructure alteration accurately, and to analyze its correlation between cerebral small vessel disease (CSVD) burden and cognitive performance in type 2 diabetes mellitus (T2DM). The clinical-laboratory data, cognitive scores [including mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), California verbal learning test (CVLT), and symbol digit modalities test (SDMT)], CSVD burden scores of the T2DM group (n = 34) and healthy control (HC) group (n = 21) were collected prospectively. Automatic fiber quantification (AFQ) was applied to generate bundle profiles along primary white matter fiber tracts. Diffusion tensor images (DTI) metrics and 100 nodes of white matter fiber tracts between groups were compared. Multiple regression analysis was used to analyze the relationship between DTI metrics and cognitive scores and CSVD burden scores. For fiber-wise and node-wise, DTI metrics in some commissural and association fibers were increased in T2DM. Some white matter fiber tracts DTI metrics were independent predictors of cognitive scores and CSVD burden scores. White matter fiber tracts damage in patients with T2DM may be characterized in specific location, especially commissural and association fibers. Aberrational specific white matter fiber tracts are associated with visuospatial function and CSVD burden.

The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients

“…Patients with T2DM experience varying degrees of decline in executive function, memory, and information-processing abilities ( Sadanand et al, 2016 ; Wang H. et al, 2023 ). These cognitive deficits are closely associated with changes in brain function and structure related to T2DM, such as cerebral perfusion deficits ( Cui et al, 2017 ; Wang et al, 2021 ), brain white matter damage ( Jing et al, 2022 ; Liu et al, 2024 ), and hippocampal volume atrophy ( Hirabayashi et al, 2016 ; Ohara et al, 2020 ; Zhang W. et al, 2021 ).…”

“…Simultaneously, researchers have observed abnormal changes in the macrostructure of white matter, including larger volumes of white matter lesions (WMLs), more white matter hyperintensities, and abnormal white matter network connectivity, in prediabetic ( Jing et al, 2022 ) and diabetic patients ( Sanahuja et al, 2016 ; Xiong et al, 2019 ; Huang et al, 2021 ). Moreover, these changes are associated with cognitive decline ( Jing et al, 2022 ; Liu et al, 2024 ). It is widely believed that white matter injury in patients with DM is related to an increased burden of small vessel disease ( Novak et al, 2006 ; Schneider et al, 2017 ; Georgakis et al, 2021 ).…”

“…Additionally, high glucose concentrations may lead to polarization of microglia/macrophages toward a pro-inflammatory phenotype, severely affecting oligodendrocyte differentiation and white matter repair ( Ma et al, 2018 ). Despite incomplete understanding of the molecular mechanisms, abnormalities in white matter microstructure are still considered an important biomarker and a cause of diabetes-induced neurological disorders ( Jing et al, 2022 ; Liu et al, 2024 ).…”