The overarching goal of this prospective cohort study is to test the hypotheses that greater severity of hyposmia is associated with increased risk of cognitive decline in PD and that worsening hyposmia parallels progressive cholinergic limbic denervation. To achieve the goals of this project, patients with PD without dementia or at-risk of dementia or with dementia will undergo longitudinal olfactory, cognitive and clinical testing for 2-4 years. AChE [11C]PMP or VAchT (vesicular acetylcholine transporter) [F18]-FEOBV PET will be performed both at study entry and at 2-years (± 6 months) follow-up. Brain MRI scans will also be performed at study entry and at 2-years (± 6 months) follow-up. Brain Beta-amyloid PET will be performed at study entry or at 2 years (± 6 months). Annual olfactory testing will be performed to better understand dynamic changes underlying the clinical and PET outcome measures.

Smell functions will be assessed using a test battery of odor identification, odor memory, and odor discrimination tests.

Inclusion Criteria:

• Diagnosed with Parkinson disease
• Hoehn & Yahr stage 2 and higher, and/or duration of motor disease 5 years or longer
• 50 and older

Exclusion Criteria:

• other disorders which may resemble PD
• subjects with definite dementia
• subjects with unstable or severe medical disorders
• subjects receiving neuroleptic, anticholinergic, or cholinesterase inhibitor drugs
• subjects in whom MRI imaging is contraindicated
• subjects who have received ionizing radiation that would, together with the current project exposures, exceed exposure limits permissible to research volunteers
• pregnant

Movement Disorders Clinic, Hospital, Primary Care, Community