Cognitive and antipsychotic medication use in monoallelic GBA-Related parkinson disease

Abstract

Mutations in glucosidase, beta, acid (GBA) are associated with cognitive impairment in Parkinson disease (PD) as well as dementia with Lewy bodies. For both of these diseases, dementia and hallucinations are typically treated with cholinesterase inhibitors and antipsychotics. However, in some lysosomal storage disorders certain antipsychotic medications are poorly tolerated. This study examined cholinesterase inhibitor and antipsychotic use in monoallelic GBA-related PD to explore potential pharmacogenetic relationships. Monoallelic GBA mutation carriers with PD (GBA-PD) with at least two clinic visits (n = 34) were matched for age-of-onset and gender to GBA and leucine-rich repeat kinase 2 (LRRK2) mutation negative idiopathic PD subjects (IPD) (n = 60). Information regarding cholinesterase inhibitor and antipsychotic use as well as impaired cognition (UPDRS Mentation >1) and hallucinations (UPDRS Thought Disorder >1) were obtained. GBA-PD more frequently reported hallucinations (HR = 5.0; p = 0.01) and they were more likely to have cognitive impairment but this was not statistically significant (HR 2.2, p = 0.07). Antipsychotic use was not significantly different between GBA-PD and IPD (HR = 1.9; p = 0.28), but GBA-PD were more likely to have sustained cholinesterase inhibitor use (HR = 3.1; p = 0.008), even after adjustment for cognition and hallucinations. Consistent with reports of worse cognition, GBA-PD patients are more likely to use cholinesterase inhibitors compared to IPD. While there was no difference in antipsychotic use between IPD and GBA-PD, persistent use of quetiapine in GBA-PD suggests that it is tolerated and that a significant interaction is unlikely. Further prospective study in larger samples with more extensive cognitive assessment is warranted to better understand pharmacogenetic relationships in GBA-PD.