Cerebellar grey matter volume is associated with semantic fluency performance in amyotrophic lateral sclerosis patients

The cerebellum has been shown to contribute to different cognitive functions such as verbal fluency and different aspects of executive functioning, which are also commonly impaired in amyotrophic lateral sclerosis (ALS) patients. Whereas cerebellar involvement has been indicated in ALS patients in general, its relative contribution to the patients' specific cognitive deficits remains unclear. In the current analyses, the demographic, clinical, neuropsychological and imaging data of 120 ALS patients and 88 healthy controls were analysed. Grey matter volume (GMV) and white matter (WM) fractional anisotropy were extracted for a comprehensive list of cerebral and cerebellar regions and bootstrapped elastic net regularized regression analyses were employed to identify regional structural metrics that were related to various cognitive scores. We further examined the stability of predictor variables selection and the regression coefficient distributions across the bootstrap samples. Both regional GMV and WM integrity are featured as informative predictors for patients' cognitive scores. The GMV of cerebellar lobules V and VIIIa were related to semantic fluency, but cerebellar regions did not reliably contribute to other cognitive outcomes. The GMV of pallidum was positively correlated with fluency outcomes and working memory, whereas hippocampus volume was positively related to fluency and episodic memory outcomes. Unsurprisingly, educational achievement emerged as the most general and reliable predictor of cognitive performance. Based on the current findings, cerebellar GMV seems to be specifically associated with semantic fluency performance in ALS patients but not any of the other cognitive measures. Further cognitive functions were associated with both cerebral grey matter (GM) and WM metrics. Future investigations could examine the possible involvement of the cerebellum in the affective and social-emotional dysfunction present in a subset of ALS patients.