Hippocampal, basal ganglia and olfactory connectivity contribute to cognitive impairments in Parkinson's disease

Eur J Neurosci. 2023 Feb;57(3):511-526. doi: 10.1111/ejn.15899. Epub 2023 Jan 6.


Cognitive impairment is increasingly recognized as a characteristic feature of Parkinson's disease (PD), yet relatively little is known about its underlying neurobiology. Previous investigations suggest that dementia in PD is associated with subcortical atrophy, but similar studies in PD with mild cognitive impairment have been mixed. Variability in cognitive phenotypes and diversity of PD symptoms suggest that a common neuropathological origin results in a multitude of impacts within the brain. These direct and indirect impacts of disease pathology can be investigated using network analysis. Functional connectivity, for instance, may be more sensitive than atrophy to decline in specific cognitive domains in the PD population. Fifty-eight participants with PD underwent a neuropsychological test battery and scanning with structural and resting state functional MRI in a comprehensive whole-brain association analysis. To investigate atrophy as a potential marker of impairment, structural gray matter atrophy was associated with cognitive scores in each cognitive domain using voxel-based morphometry. To investigate connectivity, large-scale networks were correlated with voxel time series and associated with cognitive scores using distance covariance. Structural atrophy was not associated with any cognitive domain, with the exception of visuospatial measures in primary sensory and motor cortices. In contrast, functional connectivity was associated with attention, executive function, language, learning and memory, visuospatial, and global cognition in the bilateral hippocampus, left putamen, olfactory cortex, and bilateral anterior temporal poles. These preliminary results suggest that cognitive domain-specific networks in PD are distinct from each other and could provide a network signature for different cognitive phenotypes.

Keywords: ICA; distance covariance; fMRI; independent components analysis; resting state.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atrophy / complications
  • Atrophy / pathology
  • Basal Ganglia
  • Cognitive Dysfunction* / diagnostic imaging
  • Cognitive Dysfunction* / etiology
  • Hippocampus
  • Humans
  • Magnetic Resonance Imaging / methods
  • Neuropsychological Tests
  • Parkinson Disease* / complications
  • Parkinson Disease* / diagnostic imaging
  • Parkinson Disease* / pathology