Alzheimer’s disease (AD) is characterised by progressive grey matter neurodegeneration, but there is increasing evidence that pathological changes affect also white matter (WM)¹, in particular pathways between parietal and frontotemporal areas.

In this perspective, this work assessed differences in association fibers among AD patients, patients with mild cognitive impairment (MCI) and healthy participants (HC). Towards this goal, 59 participants (26HC/21MCI/12AD) were scanned with a protocol that included T1-weighted data, MR fingerprinting (MRF)² and multi-shell diffusion MRI (dMRI). MRF were reconstructed and used to estimate T1 and T2 relaxation times, while dMRI were pre-processed, used for reconstructing fiber orientation distributions, segmenting WM tracts of interest³ (fig.1, cingulum(CG), inferior longitudinal fasciculus(ILF), inferior fronto-occipital fasciculus(IFO)) and estimating neurite density (NDI) and orientation dispersion (ODI) indices with the NODDI model. The average metrics (T1,T2,NDI,ODI) were tested for progressive changes using the Jonckhere-Terpstra test⁴ (Bonferroni-corrected). Each tract was then assessed through tractometry, resampling the streamlines to 100 segments, determining their centroid, assigning each segment to the correspondent centroid one, and finally averaging along the centroid. AD-HC and MCI-HC differences were tested separately with two-sample t-tests (family-wise error corrected).

Significantly increasing trends (AD>MCI>HC, p<0.05) were observed for T1 (bilateral CG, right IFO) and T2 (bilateral IFO and ILF). Using tractometry, differences in T1 and NDI were observed only for AD-HC, while T2 showed differences in right ILF and IFO in distinct sections for AD-HC and MCI-HC (fig.2). As T2 has been related to amyloid deposition⁵, these results provide potential directions to explore for disease progression assessment.

Figure 1. WM tracts for a representative HC (orange: cingulum [CG], sand: inferior-fronto occipital [IFO], light blue: inferior longitudinal [ILF]).

Figure 2.  Tractometry analysis of WM tracts for T2, with highlighted significance level (p<0.05, FEW-corrected) along the trajectory for AD-HC (dashed grey line) and for MCI-HC (dotted dark grey line).

References

1. Nasrabady, S.E., Rizvi, B., Goldman, J.E. et al. (2018) White matter changes in Alzheimer’s disease: a focus on myelin and oligodendrocytes. Acta neuropathol commun. 6,22.
2. Cao, X., Ye, H., Liao, C., et al. (2019) Fast 3D brain MR fingerprinting based on multi-axis spiral projection trajectory. Magn Reson Med. 82(1):289-301.
3. Wasserthal, J., Neher, P., Maier-Hein, K.H. (2018) TractSeg – Fast and accurate white matter tract segmentation. NeuroImage. 183:239-253.
4. Bewick, V., Cheek, L., Ball, J. (2004) Statistics review 10: further nonparametric methods. Crit Care. 8(3):196-9.
5. Tang, X., Cai, F., Ding, et al. (2018) Magnetic resonance imaging relaxation time in Alzheimer’s disease. Brain Research Bulletin. 140:176-189.