Structural Brain Correlates of Sleep Microstructure in Spinocerebellar Ataxia Type 2 and its role on clinical phenotype

Background: The influence of brain atrophy on sleep microstructure impairments in Spinocerebellar Ataxias (SCAs) has not been extensively explored limiting the use of these sleep traits as surrogate biomarkers of neurodegeneration and clinical phenotype. Objective: To explore the relationship between sleep microstructure and the brain atrophy in SCA2 and its role on the clinical phenotype Methods: . Fourteen SCA2 mutation carriers (7 pre-manifest and 7 manifest subjects) underwent polysomnographic, structural MRI and clinical assessments. Particularly, markers of REM and non-REM sleep microstructure, measures of cerebellar and brainstem atrophy, and clinical scores were analyzed through correlation and mediation analyses. Results: . The sleep spindle activity was directly correlated with the cerebellar volume and the anteroposterior diameter of the pons. Sleep spindles significantly mediated the effect of the cerebellar atrophy on verbal memory test performance. In REM sleep, Phasic EMG activity and REM sleep without atonia were both directly associated with pontine atrophy but showed no causal mediation effect between the atrophy measures and disease severity markers. Conclusions: . Our study provides evidence about the association of the pontocerebellar atrophy with sleep microstructure in SCA2 offering insights into the cerebellar involvement in cognition via the control of the sleep spindles activity. Therefore, our findings may help to understand the disease pathogenesis and to better characterize sleep microstructure parameters as useful disease biomarkers. Clinical trial registration number (TRN): No applicable