Vestibulopathy as a Cause of Imbalance in Parkinson
Vestibulopathy as a Cause of Imbalance in Parkinson
Balance problems and falls are common in people with Parkinson's disease but respond poorly
 to dopamine stimulating medications suggesting other causes. The main goal of this study is
 to assess whether imbalance and gait problems in people with Parkinson's disease may be
 related to vestibular (inner ear balance center) changes not related to loss of dopamine in
 the brain.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by resting
 tremor, slowness of movement, rigidity as well as postural instability and gait difficulties
 (PIGD) motor features. Nigrostriatal dopaminergic denervation is a key pathological factor in
 PD. Advancing PD is associated with disabling PIGD motor features, in particular freezing of
 gait (FoG). This is further complicated by fear of falling resulting in pervasive
 sedentariness where avoidance of physical activity leads to deconditioning, thereby
 aggravating a downward functional spiral. The dopaminergic medication-refractory nature of
 PIGD motor features in advancing PD implicates non-dopaminergic brain pathologies.

 The investigators have novel preliminary data showing that non-acute vestibulopathy may be
 another important factor contributing to PIGD motor features in PD. Unlike sporadic
 intermittent vestibular disorders with a more acute onset, chronic bilateral vestibular
 dysfunction of older age. The investigators preliminary data suggest that vestibulopathy may
 be a critical determinant of imbalance and gait problems in PD (scientific premise). However,
 these preliminary observations need to be confirmed in a larger study using more dedicated
 assessment methods (knowledge gap). Closing this gap is important because of the potentially
 high clinical translational impact if preliminary findings can be verified. The investigators
 will also explore whether stimulation of the vestibular system may help to improve PIGD in a
 small exploratory pilot biomechanistic sub-study.
Inclusion Criteria:

 -  PD based on the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic
 Research Criteria (n=64, gross recruitment)

 -  M/F

 -  age 45 years or older

 -  duration of disease > 5 years and/or Hoehn & Yahr stages 1.5-4 able to ambulate
 independently and no evidence of dementia.

 Exclusion Criteria:

 -  History of Meniere disease or recent onset of acute vestibular dysfunction, such as
 otolith disorders (BBPV etc).

 -  Other disorders which may resemble PD, such as progressive supranuclear palsy (PSP),
 vascular dementia, normal pressure hydrocephalus, multiple system atrophy (MSA),
 corticobasal ganglionic degeneration, or toxic causes of parkinsonism. Prototypical
 cases have distinctive clinical profiles, like early and severe dysautonomia (MSA) or
 appendicular apraxia, which may differentiate them from idiopathic PD and PSP. The use
 of the UKPDSBRC clinical diagnostic criteria for PD will mitigate the inclusion of
 subjects with atypical parkinsonism.

 -  Evidence of a stroke or mass lesion on structural brain imaging (MRI).

 -  Participants in whom MRI is contraindicated including, but not limited to, those with
 a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear
 implant.

 -  Severe claustrophobia precluding MR or PET imaging.

 -  Subjects limited by participation in research procedures involving ionizing radiation.

 -  Pregnancy (test within 48 hours of each PET session) or breastfeeding.