Our long-term goal is to develop effective rehabilitation to improve balance and gait in patients with Parkinson's disease (PD). To reach this goal, the purpose of this proposal is to develop a valid, objective measure of 'freezing of gait', relate it to abnormal brain connectivity and [determine the feasibility of using these freezing and brain biomarkers for rehabilitation of gait disorders in PD.] Freezing of gait is the intermittent inability to step and is a common cause of falls in patients with PD and other degenerative neurological diseases in the elderly. The [three] aims of this study are: 1) To objectively characterize freezing in PD with body-worn sensors, 2) To explore how these objective measures of freezing are associated with abnormal functional connectivity in the brain using resting state functional imaging (fMRI), and [3) To determine the number of subjects needed for a future randomized, controlled trial of the ABC rehabilitation intervention on FoG.] We hypothesize that valid, instrumented measures of severity of freezing can be developed from portable, wireless inertial sensors practical for clinical trials and clinica practice. We also hypothesize that freezing severity will be related to abnormal functional connectivity of the medial frontal cortex with the basal ganglia and the brainstem locomotor region. [We predict that use of objective gait and brain connectivity biomarkers will be useful to evaluate how rehabilitation intervention reduces freezing and improves gait and balance in patients with PD.] An observational study will relate quantitative measures of coordination of balance and gait during turning and walking to frontal-subcortical functional connectivity from state-of-the art, resting state fMRI in three matched groups of 30 subjects: PD with freezing, PD without freezing, and elderly control subjects. To evaluate freezing of gait, subjects with idiopathic PD will be tested in the OFF levodopa state after withholding their antiparkinson medication for 12 hours. To develop a 'freezing index', all subjects will turn in place and walk through narrow doorways with auditory tones in their left or right ears to indicate change in direction. Wireless, synchronized inertial sensors on the two shanks, low back and sternum will record angular velocity and linear accelerations. Resting-state (task free) fMRI connectivity will be obtained on the same day and analyzed based on synchronization of low frequency activity in a functional network involving the medial frontal cortex, brainstem locomotor region, the striatum and subthalamic nucleus of the basal ganglia, and the cerebellum. [In addition, a pilot, interventional study will randomize 20 of these PD subjects with freezing of gait into either an 8- week ABC rehabilitation program or usual care. A blinded examiner will conduct objective FoG assessment, rsfMRI, and cognitive tests before and after the 8-week period in both groups as pilot data for a clinical trial in the competing renewal of this proposal.] The results of this stdy will identify the best mobility and brain outcome measures for our long- term goal of a rehabilitation intervention study for FoG in Veterans with PD. Clarifying the relationships between gait deficits and frontal lobe deficits will lead to more effective rehabilitation interventions that can improve both mobility and cognitive function not only in Veterans with PD, but also in many elderly Veterans at high risk of falling due to neurological deficits that affect the frontal lobe of the brain.)
Parkinson's disease (PD) imposes a heavy burden on over 3% of US veterans in the VHA health care system. PD is responsible for major mobility disability as well as cognitive disabilit, resulting in worse quality of life than most other chronic diseases. Freezing of gait is a major reason for mobility disability and associated with cognitive disability, leading to falls and mortality in PD and many other degenerative neurological disorders in the elderly. Over 80% of patients with PD develop this intermittent failure to initiate or maintain walking. The results of this study will identify the best mobility and brain outcome measures for our long-term goal of a rehabilitation intervention study for FoG in Veterans with PD. Clarifying the relationships between gait deficits and frontal lobe deficits will lead to more effective rehabilitation interventions that can improve both mobility and cognitive function not only in Veterans with PD, but also in many elderly Veterans at high risk of falling due to neurological deficits that affect the frontal lobe of the brain.
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