0894 Impulsivity across early stages of synucleinopathy: from high-risk relatives, REM sleep behavior disorder to Parkinson’s disease

Abstract Introduction Increased impulsivity is a common neuropsychiatric feature in patients with Parkinson’s disease (PD), especially attributed to the use of dopaminergic medications. Interestingly, emerging evidence suggested that impulsivity had changed in drug-naïve PD patients. However, it remains unclear whether impulsivity has been altered in prodromal stage of PD, namely isolated rapid eye movement sleep behavior disorder (iRBD) and their high-risk relatives. Methods This was a cross-sectional study with four groups of subjects, including early drug-naive PD patients, patients with iRBD and their first-degree relatives (iRBD-FDRs, a high-risk group with potential prodromal RBD features), and controls. A panel of neuropsychological computerized tasks, including go/no-go task, four-choice serial reaction time task (4CSRTT), beads task, balloon analogue risk task (BART) and delay/effort discounting task, would measure various dimensions of motor and decisional impulsivity. Results A total of 331 subjects were recruited, including 27 early drug-naïve PD patients (mean age ± SD: 70.1 ± 5.8 years, 77.8% man), 152 iRBD patients (67.2 ± 6.6 years, 77.6% man), 68 iRBD-FDRs (63.2 ± 6.4 years, 51.5% man), and 84 controls (67.4 ± 8.1years, 61.9% man). Early drug-naïve PD and iRBD patients had fewer numbers of extracted beads in beads task 1 (P< 0.001) and task 2 (P< 0.001) in making decisions and fewer numbers of pumps of unexploded blue balloons in BART (P< 0.001) than controls and iRBD-FDRs, suggesting a higher level of reflection impulsivity and a lower level of risk taking, respectively. In addition, early drug-naïve PD and iRBD patients had more no-go errors in go/no-go task (P=0.023), suggesting a marginally lower level of response inhibition in PD and iRBD groups. Early drug-naïve PD and iRBD patients had more premature responses in 4CSRTT than iRBD-FDRs (P=0.008). The delay and effort discounting indexes were comparable among four groups. Conclusion While risk taking and response inhibition decreased, reflection impulsivity actually increased in iRBD and drug-naïve PD patients. These novel findings indicated that a complex construct of altered impulsivity has already occurred at the earlier stage (at iRBD) of α-synucleinopathy, which will have implications for pathophysiology and clinical management. Support (if any) This study has been supported by the General Research Fund (14116119).