Longitudinal cerebellar changes in mild cognitive impairment and Alzheimer’s disease

Background
While, the acceleration in age-related cerebral atrophy has been well documented in Alzheimer’s disease (AD), the cerebellar contributions in AD pathology have considered less likely and have not been as thoroughly investigated as the cerebrum. This study investigated cerebellar volume and longitudinal volume changes using FreeSurfer volumetry and voxel-based morphometry in cognitively normal and impaired groups including mild cognitive impairment (MCI).

Methods
Multiple linear regressions was used for cross-sectional comparison of the cerebellar volume in 818 ADNI1 participants (CN= 229, MCI=398, AD=191) with screening magnetic resonance imaging, and all subjects with 2 or more follow up scans (N=758) were included for longitudinal evaluation of the cerebellar volume changes using linear mixed effects model. Participants were categorized into different diagnostic groups regarding to their diagnosis at the first and last scans and pair-wised comparison analyses applied.

Results
Cross sectional analysis demonstrated that cerebellar volume was significantly different between cognitively normal and AD but there were no differences between normal and MCI and MCI and AD. Similarly atrophy rates were slightly different between stable normal and AD groups, normal and MCI converted to AD groups and also stable MCI and MCI converted to AD groups in longitudinal analysis. Volume changes were not different between normal and stable MCI and stable MCI and AD.

Conclusions
The evidence indicating that cerebellar contributions in AD pathology is relatively small and mostly happen at the late stage of the disease when it is clinically well-developed. Additional work needs to further elucidate the role of biological factors in protecting the cerebellum against the shrinkage.