The main objectives of this protocol are as follows:

1. To assess the sensitivity and specificity of ANAM-PD in detecting cognitive status in patients with Parkinson disease (PD) and healthy controls (HC).
2. To validate the specific individual domains of the ANAM-PD cognitive battery by comparisons to available standardized cognitive evaluation scales administered to the patients with Parkinson disease with and healthy control subjects.
3. To evaluate the reliability of the ANAM-PD battery of tests by comparing repeated administrations of the ANAM-PD battery on a sub-set of subjects with Parkinson disease and healthy controls.
4. To characterize cholinergic neurotransmission through imaging the vesicular acetylcholine transporter binding with 123Iodobenzovesamicol (IBVM) and SPECT in PD patients and healthy controls.

General Design and Methods The overall goal of this proposal is to validate ANAM-PD as an assessment tool for cognitive status in PD. We propose a comprehensive strategy to evaluate the sensitivity and specificity of ANAM-PD in detecting cognitive changes in patients with a diagnosis of PD (n=50) and healthy controls (n=25). The specific testing domains of the ANAM-PD battery will be validated against standardized neuropsychological testing, described in detail below. The reliability of the ANAM-PD battery will be evaluated through a test-retest procedure in a subset of 50 subjects (25 PD and 25 HC). This strategy will enable us to evaluate the individual domains of the ANAM-PD computerized cognitive test and establish a battery as a standard test to efficiently measure cognitive changes in PD. We also propose to explore functional neuroimaging of the cholinergic system using [123I] IBVM and SPECT, a marker of vesicular acetylcholine transporter and a measure of the integrity of the cholinergic neuronal system. Identifying and validating ANAM-PD as an efficient tool for assessing cognitive changes in PD and exploring the cholinergic transporter system in PD through functional neuroimaging could predict sub-sets of PD patients 'at risk' for developing dementia and help elucidate the neurochemistry related to cognitive decline in PD

Inclusion and Exclusion Criteria

PD subjects

Inclusion criteria:

• The participant is 30 years or older.
• Written informed consent is obtained.
• Participants have a clinical diagnosis of Parkinson's disease based on Brain Bank Criteria.
• Mini-mental status examination (MMSE) score ≥24 or significant cognitive dysfunction based clinical mental status exam.
• Geriatric Depression Scales (GDS) ≤ 10.
• For females, non-child bearing potential a negative urine or serum pregnancy test on day of 123-I IBVM injection.

Exclusion criteria:

• The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness
• The subject has any disorder that may interfere with drug absorption distribution, metabolism, or excretion (including gastrointestinal surgery).
• Pregnancy

Healthy Control Subjects

Inclusion criteria:

• The participant is 50 years or older.
• Written informed consent is obtained.
• Negative history of neurological or psychiatric illness based on evaluation by a research physician.
• Mini-Mental Status Exam score ≥28.
• For females, non-child bearing potential a negative urine or serum pregnancy test on day of 123-I IBVM injection.

Exclusion criteria:

• The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness.
• The subject has any disorder that may interfere with drug absorption distribution, metabolism, or excretion (including gastrointestinal surgery).
• The subject has received an investigational drug within 60 days before the screening visit.