Combined detrimental effect of male sex and GBA1 variants on cognitive decline in Parkinson's Disease

Background and Objective: Heterozygous variants in the glucocerebrosidase gene (GBA1) are the major genetic risk factor for Parkinson’s Disease (PD). GBA-PD has been associated with worse progression and higher risk of cognitive decline. Here we took advantage of the Parkinson’s Progression Markers Initiative (PPMI) to investigate whether sex could interact with GBA1 carrier status in determining the clinical phenotype, with a special focus on cognitive decline. Methods: We evaluated 118 PD subjects carrying GBA1 variants (GBA-PD) and 450 with wild-type alleles (nonGBA-PD) included in the PPMI…