Characterization of the Serotonin 2A Receptor Selective PET Tracer [18F]MH.MZ in Patients With Neurodegenerative Diseases

It is hypothesized that improvement in psychosis symptoms in patients taking pimavanserin will be associated with increased baseline receptor density (Hypothesis 1A), and increased receptor occupancy of 5HT2A receptors following pimavanserin administration (Hypothesis 1B). This will be done by measuring 5HT2A receptor density using the PET radioligand (R)-[18F]MH.MZ within predefined symptom networks for hallucinations, delusions, and sleep. A PET scan will be obtained in PD patients with psychosis at enrollment to measure baseline 5HT2A receptor density and then again after 6 weeks of pimavanserin. The change in binding between baseline and post-drug treatment window will be used to measure 5HT2A receptor occupancy.

It is hypothesize that improvement in psychosis symptoms in patients taking pimavanserin will be associated with increased functional connectivity and cerebral blood flow within predefined symptom networks for hallucinations, delusions, and sleep. This will be tested by obtaining MRI scans assessing resting state functional connectivity and arterial spin labeling in PD patients with psychosis at enrollment (baseline) and then again after 6 weeks of pimavanserin.

It is hypothesized that functional neuroimaging changes in response to pimavanserin will be associated with baseline 5HT2A receptor density and 5HT2A receptor occupancy after pimavanserin administration. To test this hypothesis, the differences in functional neuroimaging measures and PET 5HT2A receptor will be measured in PD psychosis patients off (at baseline) and on Pimavanserin (post-treatment window).

Inclusion criteria

• Patient arm - clinical diagnosis of Parkinson disease, diffuse Lewy body disease, multiple systems atrophy, Huntington's Disease, Frontotemporal Dementia, and other variants
• Healthy arm - age and gender matched to patient arm
• Psychosis (presence of hallucinations or delusions) starting after the diagnosis of Parkinson's disease, occurring at least weekly for 4 weeks, severe enough to warrant treatment.
• Study partner available for study visits

Exclusion criteria

• Prior stroke or other uncontrolled serious neurological or medical illness
• Contra-indication or inability to tolerate MRI scan
• Use of serotonergic medications in the last 6 weeks
• Incapable of providing independent consent.
• Pregnant or breastfeeding women
• psychosis due to a metabolic, toxic, or primary psychiatric disease
• Deemed unable to complete neurocognitive testing
• For PD Participants: current or prior use of pimavanserin
• Use of antipsychotics in the last 2 weeks