Meynert nucleus-related cortical thinning in Parkinson's disease with mild cognitive impairment

Abstract

Background: Cognitive impairment in Parkinson's disease (PD) involves the cholinergic system and cholinergic neurons, especially the nucleus basalis of Meynert (NBM/Ch4) located in the basal forebrain (BF). We analyzed associations between NBM/Ch4 volume and cortical thickness to determine whether the NBM/Ch4-innervated neocortex shows parallel atrophy with the NBM/Ch4 as disease progresses in PD patients with cognitive impairment (PD-MCI).

Methods: We enrolled 35 PD-MCI patients, 48 PD patients with normal cognition (PD-NC), and 33 age- and education-matched healthy controls (HCs), with all participants undergoing neuropsychological assessment and structural magnetic resonance imaging (MRI). Correlation analyses between NBM/Ch4 volume and cortical thickness and correlation coefficient comparisons were conducted within and across groups.

Results: In the PD-MCI group, NBM/Ch4 volume was positively correlated with cortical thickness in the bilateral posterior cingulate, parietal, and frontal and left insular regions. Based on correlation coefficient comparisons, the atrophy of NBM/Ch4 was more correlated with the cortical thickness of right posterior cingulate and precuneus, anterior cingulate and medial orbitofrontal lobe in PD-MCI versus HC, and the right medial orbitofrontal lobe and anterior cingulate in PD-NC versus HC. Further partial correlations between cortical thickness and NBM/Ch4 volume were significant in the right medial orbitofrontal (PD-NC: r=0.3, P=0.045; PD-MCI: r=0.51, P=0.003) and anterior cingulate (PD-NC: r=0.41, P=0.006; PD-MCI: r=0.43, P=0.013) in the PD groups and in the right precuneus (r=0.37, P=0.04) and posterior cingulate (r=0.46, P=0.008) in the PD-MCI group.

Conclusions: The stronger correlation between NBM/Ch4 and cortical thinning in PD-MCI patients suggests that NBM/Ch4 volume loss may play an important role in PD cognitive impairment.

Keywords: Parkinson’s disease (PD); cholinergic system; cognitive impairment; cortical thickness; nucleus basalis of Meynert.

Figure 1

The regions with significant positive correlation between the volume of the NBM/Ch4 and cortical thickness in PD-MCI patients (correcting for sex, age and duration of disease). (A,B) Lateral aspect; (B,E) medial aspect; (C,F) inferior aspect. The red-orange areas highlight areas of significant positive correlation. The color bar shows the logarithmic scale of P values (-log10).

Figure 2

The regions with significantly stronger correlations between the volume of the NBM/Ch4 and cortical thickness in the comparison of the PD-MCI versus HC groups (left) and the PD-NC versus HC groups (right). (A,D) Medial aspect; (B,E) lateral aspect; (C,E) inferior aspect. The red-orange areas highlight areas of significance. The color bar shows the logarithmic scale of P values (-log10).