Hippocampal resting-state connectivity is associated with posterior-cortical cognitive impairment in Parkinson's disease

Brain Behav. 2024 Mar;14(3):e3454. doi: 10.1002/brb3.3454.


Aim: Frontal and posterior-cortical cognitive subtypes in Parkinson's disease (PD) present with executive/attention and memory/visuospatial deficits, respectively. As the posterior-cortical subtype is predicted to progress rapidly toward dementia, the present study aimed to explore biological markers of this group using resting-state functional magnetic resonance imaging (rs-fMRI).

Methods: K-means cluster analysis delineated subtypes (cognitively intact, frontal, posterior-cortical, and globally impaired) among 85 people with PD. A subset of PD participants (N = 42) and 20 healthy controls (HCs) underwent rs-fMRI. Connectivity of bilateral hippocampi with regions of interest was compared between posterior-cortical, cognitively intact, and HC participants using seed-based analysis, controlling for age. Exploratory correlations were performed between areas of interest from the group analysis and a series of cognitive tests.

Results: The posterior-cortical subtype (N = 19) showed weaker connectivity between the left hippocampus and right anterior temporal fusiform cortex compared to the cognitively intact (N = 11) group, p-false discovery rate (FDR) = .01, and weaker connectivity between bilateral hippocampi and most fusiform regions compared to HCs (N = 20). No differences were found between HCs and cognitively intact PD. Exploratory analyses revealed strongest associations between connectivity of the right anterior temporal fusiform cortex and left hippocampus with category fluency (p-FDR = .01).

Conclusion: Results suggest that weakened connectivity between the hippocampus and fusiform region is a unique characteristic of posterior-cortical cognitive deficits in PD. Further exploration of hippocampal and fusiform functional integrity as a marker of cognitive decline in PD is warranted.

Keywords: Parkinson's disease; cognitive impairment; hippocampus; resting-state FMRI.

MeSH terms

  • Cognition Disorders* / complications
  • Cognitive Dysfunction* / complications
  • Cognitive Dysfunction* / etiology
  • Hippocampus / diagnostic imaging
  • Humans
  • Magnetic Resonance Imaging / methods
  • Parkinson Disease* / complications
  • Parkinson Disease* / diagnostic imaging