Cerebrospinal fluid ceramides and cognition as a function of striatal asymmetry in early Parkinson's disease

Abstract A growing interest in studying the impact of brain asymmetry on physiological markers and cognition in people with Parkinson's disease (PwPD) recently emerged. The aim of this study was to test the impact of striatal denervation asymmetry on brain markers such as ceramides accumulation (ng/ml), as well as its impact on cognitive performances in early PwPD. We analysed data from 329 PwPD patients at the beginning of the disease (mean 6.9 months after diagnosis) (72 left-asymmetric, 83 right-asymmetric and 174 symmetric PwPD) and 167 healthy controls. Asymmetry was based on the difference in putamen denervation greater than 20%. Patients with genetic mutations were excluded. We performed generalized linear mixed models introducing the amount of cerebrospinal fluid ceramides (ng/ml) and cognitive functions as discriminating factors. Finally, Spearman correlations were used to highlight the relationship between cognition and cerebrospinal fluid ceramides on the whole pathological group and within each sub-group, as a function of striatal denervation asymmetry. First, a reduced concentration of ceramide (C18:0 CER) in the symmetrical group compared to the asymmetrical group and the control group was observed. More specifically left denervation predominant PwPD had significantly more ceramides (C22:0 CER) than the right and controls. Second, poorer cognitive performance for the symmetric group compared to the asymmetric and control groups was reported. Overall, positive correlations between cognition and ceramides (C18:0, C22:0 CER) was observed. Conversely, glucosylceramide correlation (C22:0 GlcCer) showed a negative link with cognition. This study shows that asymmetry of striatal degeneration in early Parkinson's disease is accompanied by metabolic variations related to cognitive processes.