Title : Along tract analysis for cerebellar pathways in AD
Abstract:
Background: The cerebellum's role in cognitive processing and its potential contribution to Alzheimer's disease (AD) pathology has gained increasing research attention. However, microstructural changes within cerebellar white matter pathways across the AD continuum remain insufficiently characterized. This study aimed to investigate along-tract diffusion tensor imaging (DTI) alterations in two major cerebellar pathways the Cortico-Ponto-Cerebellar (CPC) and Cerebello-Thalamo-Cortical (CTC) tracts across cognitively normal (CN) individuals, patients with mild cognitive impairment (MCI), and those with Alzheimer's disease (AD).
Methods: DTI data from 55 participants (AD: n = 19, MCI: n = 18, CN: n = 18) were utelized from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Manual tractography was performed bilaterally for the CPC and CTC tracts using ExploreDTI. Each tract was divided into five segments, and fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were extracted per segment. Group differences and Group × Segment interactions were examined using linear mixed-effects models, with CN as the reference group.
Results: Significant segment-level variation in microstructural indices was observed across all four tracts, reflecting their anatomical heterogeneity. No group differences survived FDR correction. At the uncorrected level, AD patients showed higher FA and MD in the left CTC tract overall, but lower FA and MD at segments 2 and 5 specifically (Group × Segment interactions: p = 0.045, 0.048, 0.044, and 0.002, respectively), suggesting localized rather than uniform microstructural differences. MCI patients exhibited higher FA in the right CTC tract overall (p = 0.048) and lower FA at segment 5 (p = 0.032). In the right CPC tract, AD patients showed focal MD elevation at segment 3 (p = 0.004).
Conclusion: These findings provide preliminary evidence of segment-specific white matter microstructural differences within cerebellar pathways in AD and MCI, most prominently in the left CTC tract. The absence of FDR-corrected significant results likely reflects the modest sample size, and the along-tract approach demonstrated potential for detecting localized changes that global tract-averaged measures would miss. Larger studies are needed to confirm these patterns and evaluate their utility as early biomarkers of neurodegeneration along the cerebellar-cortical axis.
