Relationship between sleep and progression of Parkinson’s disease – A Mendelian randomization study

Abstract

AbstractBackgroundSleep disturbances are common in Parkinson’s disease (PD) and growing evidence suggests a bidirectional relationship between sleep disruption and neurodegeneration.ObjectivesTo study the causal relationship between sleep and rate of PD progression using two-sample Mendelian randomisation (MR).MethodsGenetic variants linked to sleep duration and insomnia were analysed within a GWAS combining 12 longitudinal cohorts of patients with PD(n=4093 patients) examining motor and cognitive progression.ResultsGenetic liability to insomnia was associated with greater cognitive decline measured by MMSE. Consistent trends across MR estimates suggested a protective effect of increased sleep duration, and detrimental effect of insomnia on motor decline measured using UPDRS-III. Sensitivity analyses reinforced these relationships. The strength of causality among these associations was limited by heterogeneity and balanced pleiotropy.ConclusionSleep related variables may alter the trajectory of cognitive and motor progression in PD and warrants further study.