[P3–326]: FIXEL‐BASED ANALYSIS OF FIBRE TRACT DEGENERATION IN MILD COGNITIVE IMPAIRMENT AND ALZHEIMER's DISEASE (2017)

Alzheimer's disease (AD) is increasingly considered a large-scale network disconnection syndrome, which is presumably associated with substantial disruption to white matter (WM) connectivity. Previous studies have investigated microstructural changes to WM with voxel-based analysis of diffusion-weighted metrics; however, such voxel-averaged studies cannot provide fibre-specific information as they fail to account for the multiple fibre orientations that are present within most WM voxels. Here, we perform fixel-based analysis (FBA; whereby “fixel” refers to a specific fibre population within a voxel) in AD and in mild cognitive impairment (MCI). Diffusion MRI data was acquired from AD patients (n=49), MCI patients (n=33) and healthy elderly control subjects (n=95), as part of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing (see Table 1). A comprehensive metric encapsulating both microscopic changes in fibre density and macroscopic changes in fibre-bundle cross-section (FDC) was obtained for each white matter fixel, and compared across groups using FBA, both at the whole-brain level, and subsequently across specific fibre tracts-of-interest. We further investigated whether changes in FDC were related to amyloid accumulation in MCI patients, by subdividing this group and comparing Aβ+ (n=20) and Aβ- (n=13) MCI participants. Whole-brain FBA exhibited significant FDC decreases in AD patients compared to controls, across various fibre tracts (uncinate, inferior fronto-occipital (IFOF), left arcuate fasciculi, splenium and genu) (see figure 1). When statistical analyses were limited to these fibre tracts-of-interest, MCI patients exhibited significant FDC reductions in the bilateral posterior cingulum and right uncinate fasciculus (see figure 2). When MCI patients were subdivided by Aβ status, only the Aβ- MCI group exhibited significant FDC decrease, and only in the left posterior cingulum. These results suggest substantial reductions in structural connectivity of various WM pathways arise in AD, and exhibit the value of FBA in identifying changes within specific fibre pathways, even in crossing fibre regions. Furthermore, while disruptions to the posterior cingulum and uncinate are likely associated with early cognitive impairment, they do not appear to be associated with high Aβ accumulation. Further longitudinal studies are necessary to determine any relationship between specific changes in white matter connectivity and progression in AD. Significant FDC decreases in AD compared to healthy control subjects. Significant reductions in FDC (FWE-corrected p-value < 0.05) upon whole-brain FBA are shown from coronal, axial and sagittal views. Fixels are coloured by percentage decrease in the AD group compared to healthy controls (HC) as per the scale bar. Significant tracts from tract-of-interest analysis. Left panel: mean FDC (diamonds) and 95% confidence intervals (bars) for each tract-of-interest displayed for AD and MCI groups, displayed as percentage difference from healthy control subjects. Significant tracts (p<0.05) are displayed above dotted line in colour (bilateral posterior cingulum and right uncinate fasciculus), while non-significant findings shown in grey. The corticospinal tract (CST) is displayed at the bottom for comparison. Right panel: tracts-of-interest displayed and colour-coded to match left panel.