Neuropsychiatric Features of GBA-Associated Parkinson Disease (P2.024)

OBJECTIVE: To explore neuropsychiatric symptomatology in Parkinson disease (PD) associated with monoallelic glucocerebrosidase mutations. BACKGROUND: Mutations in the glucocerebrosidase gene, GBA1, are associated with Parkinson disease and dementia with Lewy bodies. Depression and anxiety have been reported as prominent features in PD associated with biallelic GBA mutation carriage(i.e., Gaucher disease). There is incomplete knowledge about the burden of these symptoms in monoallelic GBA-PD compared to IPD. DESIGN/METHODS: 14 GBA-PD and 52 GBA-negative, LRRK2-negative IPD participants ascertained from our center completed a battery of motor and non-motor assessments, including Unified Parkinson’s Disease Rating Scale(UPDRS), State Trait Anxiety Inventory(STAI), Beck Depression Inventory(BDI), and Montreal Cognitive Assessment(MoCA). STAI State(STAI-S) and Trait(STAI-T) subscales, MoCA and UPDRS were treated as continuous variables. Continuous and categorical scores were compared between groups. RESULTS: A greater proportion of GBA-PD were women(50% of GBA-PD vs. 26.9% of IPD;p=0.1) but the GBA-PD and IPD groups did not differ in age of onset(55.4+/-9.9 vs. 59.7+/-9.1;p=0.14), disease duration(8.7+/-5.3 years vs. 9.1+/-6.4 years;p=0.95), UPDRS-III(median[IQR]: 14.5[16] vs. 19[17.75];p=0.58) or MoCA(median[IQR]: 25[5] vs. 26[4];p=0.16). Trait-anxiety severity was greater in GBA-PD compared to IPD(42.8±3.2 vs. 37.4±1.5) in models adjusting for UPDRS-III and MoCA(p=0.008). Depression was also more prevalent in GBA-PD compared to IPD(43% vs. 16%;p=0.03), even after adjusting for UPDRS-III and MoCA scores(p=0.014). Of interest, in comparisons of GBA-PD and IPD by gender, GBA-PD men had more prevalent depression(57.1% vs. 13.9%;p=0.01) and higher trait-anxiety scores(median[IQR]:50.0[23] vs. 35.5[17];p=0.05) than IPD men; this difference was not present in women. CONCLUSIONS: GBA-PD has a neuropsychiatric phenotype of increased anxiety and depression, which is present even after adjustment for cognitive and motor impairments. Some of this effect may be mediated by a disproportionate burden of anxiety and depression among GBA-PD men compared to IPD men. Study supported by: NYS-DOH(Empire Clinical Research Investigator Program), Marcled Foundation, Bigglesworth Family Foundation, NIH(5K02NS073836-03) Disclosure: Dr. Swan has nothing to disclose. Dr. Ortega has nothing to disclose. Dr. Barrett has nothing to disclose. Dr. Soto-Valencia has nothing to disclose. Dr. Boschung has nothing to disclose. Dr. Deik Acosta Madiedo has nothing to disclose. Dr. Sarva has nothing to disclose. Dr. Cabassa has nothing to disclose. Dr. Johannes has nothing to disclose. Dr. Raymond has nothing to disclose. Dr. Miravite has nothing to disclose. Dr. Severt has received personal compensation for activities with Teva Neuroscience, Allergan Inc., Merz Pharma, and UCB Pharma. Dr. Severt has received research support from Teva Neuroscience and Merz Pharma. Dr. Sachdev has nothing to disclose. Dr. Shanker has nothing to disclose. Dr. Bressman has received a royalty, liscense fee or contractual rights payment from Athena Diagnostics. Dr. Saunders-Pullman has nothing to disclose.