Vestibulopathy, imbalance and gait disturbances in Parkinson disease

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Principal Investigator: Nicolaas Ida Bohnen
Organization: VETERANS HEALTH ADMINISTRATION
Fiscal Year: 2024
Funding agency: Veterans Affairs

The management of dopamine resistant postural instability and gait difficulty (PIGD) features, such as freezing
of gait (FoG), represents perhaps the most important unmet clinical need in Parkinson's disease (PD).
Research into the role of the vestibular system in the etiology of FoG has largely been neglected. Age-
associated vestibular impairment (presbyvestibulopathy, PVP) is present in about half of older community-
dwelling older persons and is a significant contributor to imbalance and falls. PVP is also common in PD, an
age-related neurodegenerative disorder. We have novel preliminary data showing that PVP may be an
important factor contributing to FoG. Confirmation of a mechanistic link between vestibular dysfunction and
FoG has high clinical translational impact and may augur novel vestibular rehabilitation interventions, such as
in-home portable thermoneuromodulation (TNM) to treat PD Veterans with otherwise treatment-refractory FoG.
Plan: Our main aim will be a cross-sectional study in 64 Veterans with PD to investigate the relationship
between PVP and FoG. Our exploratory aim will be a mechanistic feasibility trial of portable TNM in PD
Veterans with FoG and PVP.
Methods: We will perform detailed clinical, including dedicated motor and vestibular testing. PE2I dopamine
transporter (DAT) PET will be used to assess the integrity of dopaminergic nigrostriatal innervation.
Hypothesis 1: The prevalence of FoG is higher in Veterans with PD who also have evidence of PVP
compared to those without PVP independent of nigrostriatal dopaminergic losses.
Exploratory hypothesis: Active TNM stimulation will result in improved FoG severity ratings compared to
sham stimulation in PD Veterans with FoG and PVP.

Terms: <65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><Abnormal gait><Activities of Daily Living><Activities of everyday life><Acute><Address><Affect><Aged 65 and Over><Area><Behavior><Bilateral><Brain><Brain Nervous System><Brain Pathology><Causality><Chronic><Clinical><Clinical assessments><Communities><Cross Sectional Analysis><Cross-Sectional Analyses><Cross-Sectional Studies><Cross-Sectional Survey><DAT dopamine transporter><Data><Dedications><Degenerative Neurologic Disorders><Denervation><Disabling><Disease Frequency Surveys><Dopamine><Drugs><Eligibility><Eligibility Determination><Emergent Technologies><Emerging Technologies><Encephalon><Equilibrium><Etiology><Feasibility Studies><Freezing><Frequencies><Gait><Gait abnormality><Gait disorder><Gait disturbances><Gait dysfunction><Gait impairment><Goals><Home><Hydroxytyramine><Intervention><Intervention Strategies><Knowledge><Link><Long-Term Effects><Longterm Effects><Medical Rehabilitation><Medication><Methods><Motor><Movement><Nature><Nervous System Degenerative Diseases><Neural Degenerative Diseases><Neural degenerative Disorders><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic Degenerative Conditions><Older Population><PET><PET Scan><PET imaging><PETSCAN><PETT><Paralysis Agitans><Parkinson><Parkinson Disease><Participant><Pathologic><Persons><Pharmaceutical Preparations><Phase 2 Clinical Trials><Phase II Clinical Trials><Physical activity><Play><Population><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Prevalence><Primary Parkinsonism><Protocol Screening><QOL><Quality of life><Rad.-PET><Refractory><Rehabilitation><Rehabilitation therapy><Research><Resistance><Rest Tremor><Risk Factors><Role><Severities><Societies><Testing><Vestibular><Vestibular Diseases><Vestibular System Impairment><Vestibular defect><Vestibular disorder><Vestibular dysfunction><Vestibular problems><Vestibular system disorder><Vestibulopathy><Veterans><Walking impairment><above age 65><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age associated><age associated neurodegeneration><age associated neurodegenerative disease><age associated neurodegenerative disorder><age correlated><age dependent><age dependent neurodegeneration><age dependent neurodegenerative condition><age dependent neurodegenerative disease><age dependent neurodegenerative disorder><age linked><age of 65 years onward><age related><age related neurodegeneration><age specific><age-driven neurodegenerative disorders><age-related neurodegenerative disease><age-related neurodegenerative disorder><aged 65 and greater><aged 65+><aged ≥65><aging associated neurodegeneration><aging associated neurodegenerative disease><aging related neurodegeneration><aging related neurodegenerative disease><aging related neurodegenerative disorder><balance><balance function><body movement><caloric stimulation><causation><clinical applicability><clinical application><clinical practice><clinical translation><clinically translatable><daily living function><daily living functionality><deconditioning><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><disease causation><dopamine transporter><drug/agent><fall risk><falls><fear of falling><feasibility trial><functional ability><functional capacity><homes><human old age (65+)><improved><improved motor function><innervation><interventional strategy><motor function improvement><neglect><nerve supply><neurodegenerative illness><novel><old age><older groups><older individuals><older person><over 65 years><phase II protocol><portability><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><posture instability><programs><rehab therapy><rehabilitative><rehabilitative therapy><resistant><response to therapy><response to treatment><sedentary><social role><therapeutic response><therapy responders><therapy response><translational impact><treatment responders><treatment response><treatment responsiveness><vestibular deficit><vestibular impairment><vestibular system><vestibular system dysfunction><≥65 years>