Cholinergic Nicotinic Receptors and Cognition in PD

Parkinson's disease patients will undergo nicotinic acetylcholine receptor PET imaging with
the radioligand [18F]flubatine and MRI on one day and extensive neuropsychological testing
on another day. The degree of nicotinic receptor expression obtained with PET imaging will
be correlated with the neuropsychology test results.

Positive [18F]flubatine PET findings in this study would establish nicotinic receptors as an
important contributor to cognitive dysfunction in Parkinson's disease and could kindle
pharmaceutical interest in pursuing these agents for Parkinson's disease applications.

We expect that lower nicotinic receptor expression is associated with impaired cognitive
functioning in Parkinson's disease. In a personalized medicine approach the PET radioligand
[18F]flubatine could serve as an important marker to identify those patients who are
expected to benefit most from nicotinic receptor drug treatment.

Inclusion criteria:

- PD subjects (M/F, non-smoking, ≥ 50 years old, Hoehn & Yahr stages 1-4)

- Normal control subjects (N=15, M/F, non-smoking, ≥ 50 years old)

Exclusion Criteria:

- Active smoking, use of other tobacco products, or use of nicotinic drugs such as
nicotine patches or varenicline.

- Subjects with contra-indications to MR imaging, including pacemakers or
claustrophobia.

- Evidence of large vessel stroke or mass lesion on MRI.

- Use of (anti-)cholinergic or neuroleptic drugs.

- Dementia or severe cognitive impairment confirmed by clinical and detailed
neuropsychological assessment precluding safe study participation, performing study
procedures, or unable to follow directions by study personnel.

- Evidence of atypical parkinsonism on neurological exam.

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

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