White Matter Microstructural Alteration in Type 2 Diabetes: A Combined UK Biobank Study of Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging

Alotaibi, Abdulmajeed; Podlasek, Anna; AlTokhis, Amjad; Tench, Chris R.; Mohammadi-Nejad, Ali-Reza; Sotiropoulos, Stamatios N.; Constantinescu, Cris S.; Lee, Sieun; Dineen, Rob A.

Abstract

Background: Type 2 diabetes mellitus impacts the brain microstructural environment. Diffusion tensor imaging (DTI) has been widely used to characterize white matter microstructural abnormalities in type 2 diabetes but fails to fully characterise disease effects on complex white matter tracts. Neurite orientation dispersion and density imaging (NODDI) has been proposed as an alternative to DTI with higher specificity to characterize white matter microstructures. Although NODDI has not been widely applied in diabetes, this biophysical model has the potential to investigate microstructural changes in white matter pathology.

Aims and objectives: (1) To investigate brain white matter alterations in people with type 2 diabetes using DTI and NODDI; (2) To assess the association between white matter changes in type 2 diabetes with disease duration and diabetes control as reflected by glycated haemoglobin (HbA1c) levels.

Methods: We examined white matter microstructure in 48 white matter tracts using data from the UK Biobank in 3,338 participants with type 2 diabetes (36% women, mean age 66 years) and 30,329 participants without type 2 diabetes (53% women, mean age 64 years). The participants had undergone 3.0T multiparametric brain imaging, including T1 weighted imaging and diffusion imaging for DTI and NODDI. Region of interest analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), orientation dispersion index (ODI), intracellular volume fraction (ICVF), and isotropic water fraction (IsoVF) were conducted to assess white matter abnormalities. A general linear model was applied to evaluate intergroup white matter differences and their association with the metabolic profile.

Result: Reduced FA and ICVF and increased MD, AD, RD, ODI, and IsoVF values were observed in participants with type 2 diabetes compared to non-type 2 diabetes participants (P<0.05). Reduced FA and ICVF in most white matter tracts were associated with longer disease duration and higher levels of HbA1c (0< r ≤0.2, P<0.05). Increased MD, AD, RD, ODI and IsoVF also correlated with longer disease duration and higher HbA1c (0< r ≤0.2, P<0.05).

Discussion: NODDI detected microstructural changes in brain white matter in participants with type 2 diabetes. The revealed abnormalities are proxies for lower neurite density and loss of fibre orientation coherence, which correlated with longer disease duration and an index of poorly controlled blood sugar. NODDI contributed to DTI in capturing white matter differences in participants with type 2 diabetes, suggesting the feasibility of NODDI in detecting white matter alterations in type 2 diabetes.

Conclusion: Type 2 diabetes can cause white matter microstructural abnormalities that have associations with glucose control. The NODDI diffusion model allows the characterisation of white matter neuroaxonal pathology in type 2 diabetes, giving biophysical information for understanding the impact of type 2 diabetes on brain microstructure.

• Deposit Date: Aug 14, 2023
• Publicly Available Date: Aug 18, 2023
• Keywords: Microstructural imaging, diffusion imaging, type 2 diabetes, white matter, neurite density, orientation dispersion, isotropic volume fraction
• Public URL: https://nottingham-repository.worktribe.com/output/23504999
• Related Public URLs: https://www.medrxiv.org/content/10.1101/2022.07.09.22277453v1
• Additional Information: Article submitted to NeuroImage: Clinical