In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study

Parkinsonism Relat Disord. 2021 Jul:88:68-75. doi: 10.1016/j.parkreldis.2021.05.027. Epub 2021 May 31.

Abstract

Introduction: We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia.

Methods: The study included a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions. Volumetric and microstructural (mean diffusivity, MD) indices of CBF degeneration were automatically extracted using a stereotactic CBF atlas. For comparison, we also assessed multimodal indices of hippocampal degeneration. Associations between imaging measures and cognitive performance were assessed using linear models.

Results: Compared to controls, CBF volume was not significantly reduced in PD patients as a group. However, across PD patients lower CBF volume was significantly associated with lower global cognition (PD-CRStotal: r = 0.37, p < 0.001), and this association remained significant after controlling for several potential confounding variables (p = 0.004). Analysis of individual item scores showed that this association spanned executive and memory domains. No analogue cognition associations were observed for CBF MD. In covariate-controlled models, hippocampal volume was not associated with cognition in PD, but there was a significant association for hippocampal MD (p = 0.02).

Conclusions: Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration. In our multicentric imaging acquisitions, DTI-based diffusion measures in the CBF were inferior to standard volumetric assessments for capturing cognition-relevant changes in non-demented PD.

Keywords: DTI; Diffusion; MRI; Nucleus basalis Meynert; Parkinson's disease; Substantia innominata.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Basal Forebrain / diagnostic imaging
  • Basal Forebrain / pathology*
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / physiopathology*
  • Cohort Studies
  • Diffusion Tensor Imaging
  • Female
  • Hippocampus / diagnostic imaging
  • Hippocampus / pathology*
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Multimodal Imaging
  • Neuroimaging
  • Neuropsychological Tests
  • Parkinson Disease / complications
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / pathology*
  • Parkinson Disease / physiopathology*