Altered Impulsivity Across Drug‐Naïve Parkinsonism, Isolated Rapid Eye Movement Sleep Behavior Disorder, and Their High‐Risk Relatives.

Objective: To determine multidimensional impulsivity levels across different early stages of α‐synucleinopathy. Methods: This cross‐sectional study investigated motor and decisional impulsivity levels using a panel of computerized tasks among drug‐naïve parkinsonism patients, isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) patients and their first‐degree relatives (iRBD‐FDRs), and control participants. Trait impulsivity and impulse control behaviors were assessed by self‐reported questionnaires. Results: A total of 27 drug‐naïve parkinsonism patients, 157 iRBD patients, 66 iRBD‐FDRs, and 82 control participants were recruited. Parkinsonism and iRBD patients had fewer numbers of extracted beads in beads task 1 and 2 (both p < 0.001), and a higher rate of irrational choice in task 1 (p = 0.046) before making decisions, and fewer numbers of pumps of unexploded blue balloons in the balloon analog risk task (p = 0.004) than control participants, indicating a higher level of reflection impulsivity and a lower level of risk taking, respectively. iRBD patients had more no‐go errors in the go/no‐go task than control participants (padjusted = 0.036), suggesting a higher level of motor impulsivity. iRBD‐FDRs with dream‐enactment behaviors had fewer numbers of extracted beads (p = 0.047) in beads task 2 than FDRs without dream‐enactment behaviors, suggesting a possible higher level of reflection impulsivity. Interpretation: A complex construct of altered impulsivity with decreased risk taking, but increased reflection and motor impulsivity, has already occurred at the prodromal and early stages of α‐synucleinopathy, which have implications for underlying pathophysiology and clinical management of α‐synucleinopathy, especially for impulse control behaviors upon dopaminergic drug treatment. ANN NEUROL 2024;95:544–557 [ABSTRACT FROM AUTHOR]