To perform a prospective cohort study with \[(18)F\]fluoroethoxybenzovesamicol (FEOBV) brain PET at baseline and 2-year follow-up in PD subjects at risk of conversion to non-episodic and episodic (falls and FoG) PIGD motor features and cognitive changes at the same time points.
Postural instability and gait difficulty (PIGD) motor and cognitive changer features are common in Parkinson disease (PD), and a significant cause of treatment-refractory disability. Accumulating evidence implicates cholinergic systems dysfunctions as significant contributors to gait and balance and cognitive impairment. During the initial funding period, the investigators established the vesicular acetylcholine transporter (VAChT) ligand FEOBV, which uniquely assesses cholinergic terminal density in high density regions such as the striatum. Recent cross-sectional findings suggest that people with Parkinson's (PwP) participants with isolated falls and those with freezing of gait (FoG) status share common cholinergic deficits in the thalamus (lateral geniculate nucleus (LGN)) and striatum (caudate) with more extensive striatal, limbic, and prefrontal VAChT reductions in PwP with FoG. These data suggest that SChI deficits are a common denominator in the etiology of falls and FoG. These results emphasize the need to understand PIGD, falls, and FoG as products of cholinergic projection dysfunctions within the framework of failing Attentional-Motor Integration (AMI) combined with failures of additional multisensory and cognitive integration. There is novel preliminary data that cholinergic deficits of the medial geniculate nucleus (MGN) and the entorhinal cortex (ERC) are robustly associated with non-episodic PIGD deficits. These results imply a significant role of impaired sensorimotor integration underlying non-episodic PIGD motor features in PwP. There is also have novel data that cholinergic changes in the cingulo-opercular task control network (COTC) are a robust correlate of cognitive changes in PwP. The overarching goal of this project is to investigate the evolution of cholinergic deficits within multisensory, cognitive and motor integration brain regions and development of PIGD features and cognitive deficits in PwP. This study will perform a prospective cohort study with FEOBV brain PET at baseline and 2-year follow-up.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
125
Participants will receive an injection of 8 mCi \[18F\]FEOBV PET tracer and undergo a CT of the head.
Participants will receive an injection of 15 mCi \[11C\]DTBZ PET tracer and undergo a CT of the head.
University of Michigan - Michigan Medicine
Ann Arbor, Michigan, United States
Interval change on the Unified Parkinson's disease rating scale (UPDRS) motor rating scale over a 2-yr period
Interval change baseline vs 2-yr follow-up on the UPDRS motor score. UPDRS motor section is scored from 0-132, with higher scores indicating more severe motor symptoms.
Time frame: At Baseline and at 2-year follow up
Cholinergic brain PET FEOBV PET distribution volume ratio (DVR) interval change over a 2-yr period
Interval change baseline vs 2-yr follow in cholinergic brain FEOBV PET DVR
Time frame: At Baseline and at 2-year follow up
Cognitive 2-yr interval change on the Montreal Cognitive Assessment (MoCa) cognitive scale
Interval change baseline vs 2-yr follow-up on the Montreal Cognitive Assessment (MoCa) cognitive scale. The MoCa is scored out of 30, with higher scores indicating better cognition.
Time frame: At Baseline and at 2-year follow up
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