Cholinergic Mechanisms of Attentional-motor Integration and Gait Dysfunction in Parkinson Disease (UDALL)

Prior treatment

• Subjects on neuroleptic, anticholinergic (trihexyphenidyl, benztropine), or cholinesterase inhibitor drugs. Subjects with prior exposure to disallowed medications may be eligible if there has been an interval of \> 2 months off these medications.\*\* Note that patients on pimavanserin will be eligible.
• 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.\*\*
• Subjects limited by previous participation in research procedures involving ionizing radiation.\*\*
• Subjects from the previous U-M Udall Center cohort who have developed a contraindication for neuroimaging procedures (Exclusion criteria #4 - #9) or have started taking cholinergic medications (Exclusion criterion #3) will be eligible to continue their participation in clinical assessments but will not be referred to neuroimaging assessments.

Other illness

• Disorders which may resemble PD, such as dementia with Lewy bodies, vascular dementia, normal pressure hydrocephalus, multiple system atrophy, corticobasal ganglionic degeneration, or toxic causes of parkinsonism. The use of the Movement Disorder Society-revised clinical diagnostic criteria will mitigate the inclusion of PD subjects with atypical parkinsonism.
• Evidence of a large vessel stroke in a clinically relevant area (cerebral cortex, basal ganglia, thalamus) or mass lesion on structural brain imaging (MRI or CT).\*\*
• History of deep brain stimulation surgery.\*\*

Other

• Severe claustrophobia precluding MR or PET imaging.\*\*
• Pregnancy (test within 48 hours of each PET session) or breastfeeding.\*\*
• Suicidality (responses 2 or 3 for question 9 on the Beck Depression Inventory).

• Age ≥21 for normal control subjects (Male/Female) and ≥45 for Parkinson's disease (PD), Progressive supranuclear palsy (PSP), or Alzheimer's disease (AD) participants (Male/Female).
• For normal control subjects, no significant neurological or psychiatric symptoms and normal neuropsychological examination for age.
• PD diagnosis (with or without Mild Cognitive Impairment/dementia) will follow the Movement Disorder Society-revised clinical diagnostic criteria for PD or Parkinson-PSP patients.
• Modified Hoehn and Yahr stages 1-4.
• AD subjects meeting the criteria listed in Guy M. McKhann et al.
• All PD subjects are required to have nigrostriatal dopaminergic denervation as demonstrated by vesicular monoaminergic transporter type-2 (VMAT) \[18F\]9-fluoropropyl-(+)-dihydrotetrabenazine (DTBZ) positron emission tomography (PET) imaging. This may be based on a prior DTBZ PET scan or the DTBZ PET scan performed as part of this study.