Fixel based analysis of white matter alterations in Mild cognitive impairment and Alzheimer’s disease

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is the leading cause of dementia, and is associated with altered white matter (WM) microstructures in the brain (Clerx et al., 2012; Jack Jr et al., 2013). Diffusion weighted imaging (DWI) is a non‐invasive method of examining white matter alterations in AD and Mild cognitive Impairment (MCI). DWI based Fixel‐based analysis (FBA) is a novel method that enables the investigation of fibre specific WM alterations at the microscopic level. In this study, we investigated fibre tract‐specific changes in the whole‐brain WM, in individuals with MCI and AD using DWI based FBA.MethodN = 102 participants (>70 years) from the University of California Davis Alzheimer’s Disease Research Center were included in this study, including 34 individuals with AD, 34 with MCI, and 34 control subjects. DWI data were obtained on a 3T Siemens TimTrio scanner (resolution = 2mm, 60 directions, at b = 1000s/mm2) and pre‐processed using MRtrix3 (Tournier et al., 2019). Single‐Shell 3‐tissue CSD (SS3T‐CSD) was performed to obtain Fibre Orientation Distributions (FODs) related to WM as well as for gray matter and cerebrospinal fluid compartments in all voxels, using MRtrix3Tissue. A study‐specific unbiased FOD template was generated and used for FBA processing. Whole‐brain FBA maps, including fibre density (FD), fibre cross‐section (FC), and combination of fibre density and cross‐section (FDC), were generated. Statistical analyses were performed using connectivity based fixel enhancement at each fixel using general linear model (Raffelt et al., 2015)(Figure1).ResultThe whole‐brain FBA showed significant reduction in FD in individuals with AD compared to MCI, in regions including splenium of corpus callosum, fornix, and the left uncinate fasciculus (Figure2). Furthermore, AD individuals showed significant reduction in FD in the left uncinate fasciculus compared to controls. We observed subtle reduction in FD and FDC metrics (although not statistically significant after FWE corrections) in regions including corpus callosum, forceps majors, and uncinate fasciculus in AD(Figure3). We did not observe significant difference in FC between groups.ConclusionFBA‐derived measures demonstrated sensitivity in detecting microstructural white matter alterations in AD. These findings highlight the utility of FBA as a promising tool for providing valuable insights into pathophysiologic changes in AD.