Abstract
IntroductionThe 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. MethodsDiffusion-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. ResultsVoxel-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. ConclusionsThe 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.
Highlights
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 tremordominant subtype (TD-PD)
One of the most common classifications is based on the prominent motor symptoms, which differentiate between the tremor-dominant (TD-PD) and the postural instability and gait disorders (PIGD-PD) subtype [4]
As on one hand, the nucleus basalis of Meynert (NBM) cholinergic neurons are responsible for maintaining the attentional function, and on the other hand, the atten tional state contributes to gait impairment in PD [18,19], we predict that the significant association between the NBM-associated white matter tract (NBM-WM) tract integrity on postural instability and gait difficulty (PIGD) severity is, at least, partially mediated by subjects’ attentional state
Summary
Parkinson’s disease (PD) is a progressive neurodegenerative disease with a heterogeneous clinical and neuropathological manifestation [1,2,3]. Levodopa and deep brain stimulation provide limited ef fects on the balance and gait symptoms in PIGD-PD This suggests that the underlying pathophysiology at least involves non-dopaminergic systems [7,8,9]. We compared the microstructural integrity of the white matter tracts that are associated with the cortically-projecting cholin ergic structure in the basal forebrain, the nucleus basalis of Meynert (NBM), between TD-PD and PIGD-PD subtypes, using DTI-MRI. This technique allows in vivo measurement of water molecule diffusion which is restricted along coherently oriented axonal fibers in normal white matter, highly anisotropic. As on one hand, the NBM cholinergic neurons are responsible for maintaining the attentional function, and on the other hand, the atten tional state contributes to gait impairment in PD [18,19], we predict that the significant association between the NBM-WM tract integrity on PIGD severity is, at least, partially mediated by subjects’ attentional state
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