Objective: We aimed to delineate the dual syndrome subtypes of PD-MCI using a data-driven approach and explore hippocampal functional connectivity of the posterior-cortical syndrome.

Background: The concept of mild cognitive impairment (MCI) has been adopted to identify patients at risk of Parkinson’s disease dementia (PDD). However, the dual syndrome hypothesis proposes frontal vs. posterior-cortical subtypes of PD-MCI that present with distinct cognitive impairments. Evidence has suggested the posterior-cortical subtype may progress more rapidly toward PDD, which may be linked to compromised hippocampal integrity. Using machine learning algorithms to derive cognitive subtypes of PD-MCI, we explored differences in hippocampal functional connectivity between the posterior-cortical and cognitively intact subtypes.

Method: To delineate subtypes, a k-means cluster analysis was performed on 10 frontal- and posterior-based cognitive variables derived from PD patients without dementia. Resting-state functional magnetic resonance imaging (rs-fMRI) data was available for a subset of patients. Seed-based functional connectivity analysis was performed comparing connectivity of bilateral hippocampus and other regions of interest between the posterior-cortical and cognitively intact groups.

Results: Cognitively intact, frontal impaired, posterior-cortical impaired, and globally impaired clusters were revealed. The posterior-cortical (N = 17) subtype showed significantly decreased activation at rest between the right hippocampus and right anterior temporal fusiform gyrus compared to the cognitively intact (N = 10) group (p = .013, FDR-corrected). The posterior-cortical group also performed significantly worse on a measure of semantic memory than the cognitively intact group (p = .004).

Conclusion: Given that the fusiform gyrus is implicated in semantic memory, and semantic memory is an established predictor of PDD, the connection between the hippocampus and fusiform gyrus may reflect a biomarker of PDD. These results encourage further exploration of the fusiform gyrus and its dysfunction as a critical marker of rapid cognitive decline in PD.

Abstract presented at the Australian Society of Medical Research Student Symposium [11/11/2020].

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MDS Abstracts - https://www.mdsabstracts.org/abstract/altered-functional-connectivity-of-the-hippocampus-in-posterior-cortical-subtype-of-cognitive-impairment-in-parkinsons-disease/