Visual hallucinations and memory impairment in Parkinson's Disease: The role of hippocampal networks

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PROJECT SUMMARY Parkinson's disease (PD) is diagnosed based on its characteristic motor symptoms of bradykinesia, rigidity, and tremor. Increasingly, neuropsychiatric symptoms are identified as part of the neurodegenerative process of PD. Cognitive impairment and psychosis increase as PD advances and are associated with increased caregiver burden, impaired daily functioning and nursing home placement, dementia, and greater mortality. Specifically, memory impairment and hallucinations occur in a subset of PD patients and are associated with an increased risk for dementia and functional impairment. It is well established that the hippocampus is critically important for memory function and hippocampal dysfunction has been shown to significantly contribute to memory impairment in numerous human and animal studies. Similarly, it is now recognized that the hippocampus plays an important role in the etiology of hallucinations across various psychotic disorders. However, the role of hippocampal networks in the parallel clinical course of memory impairment and hallucinations in PD remains unclear. The goal of this project is to assess whether hippocampal network dysfunction provides a shared mechanism for memory impairment and hallucinations in PD and determine whether increased activity in specific hippocampal subregions predicts greater cognitive and functional decline longitudinally. The current project aims to achieve these goals using detailed neuropsychological assessment and high- resolution functional magnetic resonance imaging (fMRI) methods in PD patients with episodic memory impairment, PD patients with hallucinations, PD patients without episodic memory impairment or hallucinations, and healthy controls. A targeted fMRI activation task will be employed designed to tax hippocampal subregion specific functioning. High-resolution resting-state fMRI will be used to assess connectivity changes between hippocampal and cortical networks. Clinical and cognitive assessments will be repeated at a two-year follow up to assess longitudinal change and predictive value of these fMRI markers in the progression of cognitive and functional decline in PD. Together the proposed studies will provide insight into the role of the hippocampal network in memory impairment and hallucinations in PD. The results will determine whether dysfunction in hippocampal subregions is a marker of episodic memory impairment and hallucinations in PD patients and a predictor of increased risk for future decline in this subset of patients. Finally, if successful, this work would additionally provide a target for the development of new therapeutic interventions for memory impairment and hallucinations in PD.