Project Grant F32AG104551

GAIT AND BALANCE IN PARKINSON'S DISEASE AND RAPID EYE MOVEMENT SLEEP BEHAVIOR DISORDER - PROJECT SUMMARY/ABSTRACT RAPID EYE MOVEMENT (REM) SLEEP BEHAVIOR DISORDER (RBD) IS A SLEEP DISORDER IN WHICH INDIVIDUALS PHYSICALLY ACT OUT THEIR VIVID DREAMS DURING REM SLEEP. RBD IS RECOGNIZED AS THE STRONGEST PREDICTOR OF PARKINSON'S DISEASE (PD) AND IS PRESENT IN APPROXIMATELY 50% OF INDIVIDUALS WITH PD. HOWEVER, RELATIVELY LITTLE IS KNOWN ABOUT THE EFFECT OF RBD ON PD MOTOR SYMPTOMS. NEUROMELANIN-SENSITIVE IMAGING (NM-MRI) IS A PROMISING TOOL TO ASSESS BRAINSTEM NEURODEGENERATION IN PD. THIS IMAGING APPROACH IS NON-INVASIVE AND CAN DIRECTLY VISUALIZE BRAINSTEM STRUCTURES SUCH AS THE SUBSTANTIA NIGRA AND LOCUS COERULEUS (VIA CATECHOLAMINERGIC NEURONS). BOTH REGIONS ARE THOUGHT TO PLAY A KEY ROLE IN RBD PATHOPHYSIOLOGY AND THE NEURAL MECHANISM UNDERLYING MOBILITY. THE GOALS OF THIS F32 PROPOSAL ARE TO ASSESS THE FUNCTIONAL RELEVANCE AND NEURAL MECHANISMS OF RBD-RELATED DEFICITS IN PD. SPECIFICALLY, WE PROPOSE TO 1) ASSESS THE IMPACTS OF RBD ON GAIT, QUIET STANDING SWAY (STATIC BALANCE) AND REACTIVE STEPPING (REACTIVE BALANCE), IMPROVING KNOWLEDGE OF FALL-RISK IN PEOPLE WITH RBD, AND 2) DETERMINE HOW THE BRAINSTEM STRUCTURES ARE ASSOCIATED WITH I) MOBILITY AND II) RBD SEVERITY. THERE ARE THREE INDEPENDENT AIMS WITHIN THIS PROPOSAL. AIM 1 WILL ASSESS IF THERE ARE GAIT, QUIET STANDING SWAY AND REACTIVE STEPPING DEFICITS IN PD WITH RBD (PD+RBD) COMPARED WITH PD WITHOUT RBD (PD- RBD). AIM 2 WILL ASSESS THE RELATIONSHIP BETWEEN NM-MRI AND GAIT, REACTIVE STEPPING, AND QUIET STANDING SWAY IN PD. AIM 3 WILL ASSESS THE RELATIONSHIP BETWEEN NM-MRI AND RBD SEVERITY IN PD. MY LONG-TERM CAREER GOAL IS TO BECOME AN INDEPENDENT RESEARCHER AND LEADER IN PD AND RBD RESEARCH. THE PROPOSED STUDY BUILDS ON MY PREVIOUS FORCE CONTROL, TASK-BASED FUNCTIONAL MRI AND FREE-WATER DIFFUSION IMAGING RESEARCH IN ISOLATED RBD AND EARLY-STAGE PD BY ADDING NEW SKILLS IN 1) BIOMECHANICS OF GAIT, BALANCE, AND FALLS, 2) NM-MRI, AND 3) CLINICAL EXPERIENCE IN PD WITH AND WITHOUT RBD. I PROPOSE A RIGOROUS TRAINING PROGRAM WITH ADVANCED COURSEWORK IN BIOMECHANICS, BIOSTATISTICS, AND RESPONSIBLE CONDUCT OF RESEARCH, AS WELL AS TRAINING IN NM-MRI, RESEARCH DESIGN AND EXECUTION, CLINICAL TRIALS, LEADERSHIP, AND SCIENTIFIC COMMUNICATION SKILLS. TOGETHER, THE ASSEMBLED MENTORSHIP TEAM WILL HELP ME CONDUCT MENTORED RESEARCH IN 1) BIOMECHANICS OF GAIT AND BALANCE WHICH IS IMPORTANT FOR CHARACTERIZING GAIT AND BALANCE IN THE PD+RBD PHENOTYPE, 2) ADVANCE NEUROIMAGING TECHNIQUES IMPORTANT FOR UNDERSTANDING NEURAL MECHANISMS OF MOBILITY AND RBD SYMPTOMS IN PD, AND 3) CLINICAL EXPERIENCE WITH PATIENTS WITH PD WITH AND WITHOUT RBD WHICH WILL HELP ME DEVELOP A MORE INTEGRATED UNDERSTANDING OF THESE DISEASES, ITS TREATMENTS AND DEVELOP RESEARCH QUESTIONS WITH A STRONGER CLINICAL RELEVANCE.