Biomarkers and Lifestyle (AIBL) study of ageing. 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 Ab+ (n¼20) and Ab-(n¼13) MCI participants. Results: 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 Ab status, only the Ab-MCI group exhibited significant FDC decrease, and only in the left posterior cingulum. Conclusions: 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 Ab accumulation. Further longitudinal studies are necessary to determine any relationship between specific changes in white matter connectivity and progression in AD.
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