Funded Studies
Objective/Rationale:
The project aims to understand the mechanisms underlying cognitive deficits that are associated with visual hallucinations (VH) in Parkinson’s disease (PD). We have previously shown that non-demented PD patients with VH have increased 5HT2A receptors in areas of the inferotemporal cortex that mediated vision. We now plan to investigate whether 5HT2A receptor binding is associated with certain patterns of cognitive change and whether having higher 5HT2A receptors in these brain regions results in a greater risk of dementia.
Project Description:
We will recruit 40 PD subjects; 20 with VH and 20 without. All participants will be matched for age, sex and mediation use. We will assess each person using neuropsychiatric evaluations to measure depression and anxiety and extensive neuropsychological testing will be performed to assess cognitive function. To determine effects due to PD per se, we will also perform cognitive testing on 20 non-PD healthy controls. Each of the PD subjects will then undergo a PET scan using a labeled chemical called setoperone. This will enable us to see the distribution and amount of 5HT2A receptors in the brain. We will then compare the level of binding to the patterns of cognitive impairment.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The results of our study may have implications for treatment of PD patients. Given that PD patients with VH generally show a more rapid decline to dementia, the elucidation of a cognitive phenotype and associated pathological substrate may allow for the earlier identification and treatment of such individuals. For example, in individuals who on examination show the expected cognitive phenotype, early intervention with 5HT2A antagonists (such as low dose quetiapine or clozapine) may prevent the development of VH and possibly the progression of cognitive deterioration. Longer term follow-up studies will be needed to show if the cognitive phenotype and changes in 5HT2A receptors are indeed prodromal markers of VH and subsequent dementia.
Anticipated Outcome:
Our study aims to delineate the cognitive phenotype in association with VH in PD. A novel aspect to our study is an examination of changes in 5HT2A receptor binding as a pathological substrate underlying VH and its associated cognitive phenotype in PD patients.