Postural and gait symptoms in de novo Parkinson's disease patients correlate with cholinergic white matter pathology

Parkinsonism Relat Disord. 2021 Dec:93:43-49. doi: 10.1016/j.parkreldis.2021.11.010. Epub 2021 Nov 12.

Abstract

Introduction: The postural instability gait difficulty motor subtype of patients with Parkinson's disease (PIGD-PD) has been associated with more severe cognitive pathology and a higher risk on dementia compared to the tremor-dominant subtype (TD-PD). Here, we investigated whether the microstructural integrity of the cholinergic projections from the nucleus basalis of Meynert (NBM) was different between these clinical subtypes.

Methods: Diffusion-weighted imaging data of 98 newly-diagnosed unmedicated PD patients (44 TD-PD and 54 PIGD-PD subjects) and 10 healthy controls, were analysed using diffusion tensor imaging, focusing on the white matter tracts associated with cholinergic projections from the NBM (NBM-WM) as the tract-of-interest. Quantitative tract-based and voxel-based analyses were performed using FA and MD as the estimates of white matter integrity.

Results: Voxel-based analyses indicated significantly lower FA in the frontal part of the medial and lateral NBM-WM tract of both hemispheres of PIGD-PD compared to TD-PD. Relative to healthy control, several clusters with significantly lower FA were observed in the frontolateral NBM-WM tract of both disease groups. Furthermore, significant correlations between the severity of the axial and gait impairment and NBM-WM FA and MD were found, which were partially mediated by NBM-WM state on subjects' attentional performance.

Conclusions: The PIGD-PD subtype shows a loss of microstructural integrity of the NBM-WM tract, which suggests that a loss of cholinergic projections in this PD subtype already presents in de novo PD patients.

Keywords: DTI; Motor subtype; Nucleus basalis of meynert; Parkinson's disease.

MeSH terms

  • Aged
  • Attention
  • Basal Nucleus of Meynert / pathology
  • Case-Control Studies
  • Cholinergic Neurons / pathology
  • Diffusion Magnetic Resonance Imaging
  • Diffusion Tensor Imaging
  • Female
  • Gait Disorders, Neurologic / etiology
  • Gait Disorders, Neurologic / pathology*
  • Gait Disorders, Neurologic / psychology
  • Gait*
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / complications
  • Parkinson Disease / pathology*
  • Parkinson Disease / psychology
  • Postural Balance*
  • Posture
  • Sensation Disorders / etiology
  • Sensation Disorders / pathology*
  • Sensation Disorders / psychology
  • White Matter / pathology