Male sex accelerates cognitive decline in GBA1 Parkinson’s Disease
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We evaluated 128 GBA and 432 nonGBA Parkinson’s disease (PD) subjects. Baseline clinical features and dopaminergic activity were assessed, together with 7-year clinical follow-up. Survival analyses assessed the independent and interactive effects of male sex and GBA1 mutations on cognitive impairment. At baseline, GBA-PD males showed greater motor impairment, sleep disorders and memory deficits, GBA-PD females showed greater dopaminergic denervation. In longitudinal assessment, GBA-PD males showed greater MoCA rate of change per year and greater risk of cognitive impairment than GBA-PD females and nonGBA-PD, also when excluding subjects with LRRK2 mutations. In GBA-PD males, both late age at onset and “severe/mild” GBA variants were associated with increased risk of cognitive impairment. Male sex and GBA1 carrier status have an additive value in increasing the risk of cognitive decline in PD. The effect of sex on GBA1-related pathology warrants further examination to address future trials design and patients’ selection.
