Imaging a Cholinergic Biomarker of Cognition in Parkinson's Disease

Imaging a Cholinergic Biomarker of Cognition in Parkinson's Disease

This is an imaging study designed to illuminate the function of the cholinergic system and its association with cognitive skills in people with Parkinson's disease. The hypothesis of this study is that there will be an association between cholinergic terminal density, sex hormones, and cognitive functioning. Participants will receive a PET and MRI scan along with a battery of neurocognitive tests at baseline and again at 18 months follow-up. Hormone levels will be measured at baseline.

This is an imaging study designed to illuminate the functioning of the cholinergic system in people with Parkinson's disease. Some people with Parkinson's disease develop trouble with certain aspects of thinking such as memory. Studies have shown an association between a decline in thinking skills and dysfunction of the cholinergic system. This study will use the novel PET tracer [18F]VAT to provide more specific information about how the cholinergic system works by enabling direct measurement of cholinergic terminal density and projections. The hypothesis of this study is that there will be an association between cholinergic terminal density, sex hormones, and cognitive functioning. This is a longitudinal observational study that involves a screening visit and four study visits over the course of 18 months. The visits consist of neurocognitive assessments and imaging (MRI and PET scans) administered at baseline and at 18 months follow-up. Hormone levels will also be measured at baseline. This study is open to people with Parkinson's disease who have either normal cognition or mild cognitive impairment.

Inclusion Criteria:

• Age 50-80
• Diagnosis of Parkinson's disease
• Ability to provide informed consent
• Ability to speak English
• Normal cognition or mild cognitive impairment
• Willingness to go off parkinsonian medication for 12 hours prior to two of the study visits

Exclusion Criteria:

• Contraindication for MRI
• Abnormal clinical brain MRI, specifically with evidence of large-vessel stroke or mass lesion
• History of stereotactic or ablative brain surgery
• Pregnancy
• Recent participation in other research studies involving radiation such that the annual research radiation dose would exceed FDA Limit if participating in this study
• Prior brain injury (eg., TBI)
• Baseline cognitive impairment due to genetic or developmental disorder
• Active illicit drug use or alcohol abuse
• Incapable of staying still for a 2-hour PET or MRI study
• Use of CNS-penetrating medications affecting the cholinergic system, including cholinesterase inhibitors and anticholinergics, up to 60 days prior to study participation