Amnestic mild cognitive impairment in Parkinson's disease: White matter structural changes and mechanisms.

Zhihao Li,Xianghong Meng,Wei Tao,Haobo Zhang,Yuejia Luo,Fuyong Chen,Tao Wu,Qing Guan

doi:10.1371/journal.pone.0226175

Abstract

Mild cognitive impairment (MCI) is a heterogeneous cognitive disorder that is often comorbid with Parkinson’s diseases (PD). The amnestic subtype of PD-MCI (PD-aMCI) has a higher risk to develop dementia. However, there is a lack of studies on the white matter (WM) structural changes of PD-aMCI. We characterized the WM structural changes of PD-aMCI (n = 17) with cognitively normal PD (PD-CN, n = 19) and normal controls (n = 20), using voxel-based and tract-based spatial statistics (TBSS) analyses on fractional anisotropy (FA) axial diffusivity (AD), and radial diffusivity (RD). By excluding and then including the motor performance as a covariate in the comparison analysis between PD-aMCI and PD-CN, we attempted to discern the influences of two neuropathological mechanisms on the WM structural changes of PD-aMCI. The correlation analyses between memory and voxel-based WM measures in all PD patients were also performed (n = 36). The results showed that PD-aMCI had smaller FA values than PD-CN in the diffuse WM areas, and PD-CN had higher AD and RD values than normal controls in the right caudate. Most FA difference between PD-aMCI and PD-CN could be weakened by the motor adjustment. The FA differences between PD-aMCI and PD-CN were largely spatially overlapped with the memory-correlated FA values. Our findings demonstrated that the WM structural differences between PD-aMCI and PD-CN were mainly memory-related, and the influence of motor adjustment might indicate a common mechanism underlying both motor and memory impairment in PD-aMCI, possibly reflecting a predominant influence of dopaminergic neuropathology.

Highlights

Parkinson’s disease (PD) is often comorbid with mild cognitive impairment (MCI), a heterogeneous cognitive disorder characterized as mild deficits in various cognitive functions, with the prevalence varying between 25% and over 80% at different stages of PD [1]
Given that a lower fractional anisotropy (FA) value indicates decreased fiber integrity induced by demyelination [14, 35, 36], our findings possibly suggested that PD-aMCI might have an extensive fiber integrity disruption, relative to PD-CN
Our study showed that the adjustment of UPDRS-III could weaken the originally significant FA differences between PD-aMCI and PD-CN and FA correlates of memory to non-significant

Summary

Introduction

Parkinson’s disease (PD) is often comorbid with mild cognitive impairment (MCI), a heterogeneous cognitive disorder characterized as mild deficits in various cognitive functions, with the prevalence varying between 25% and over 80% at different stages of PD [1]. According to the impaired cognitive functions, MCI can be classified into different subtypes with disparate neuroanatomical abnormalities [2, 3]. Several studies have investigated the neuroanatomical changes of PD-MCI [6,7,8]; few studies focused on any specific subtypes of PD-MCI [9]. Without specifying the subtypes of PD-MCI, several studies investigated the WM structural changes in PD-MCI, and the findings were inconsistent, possibly owing to the heterogeneous nature of PD-MCI [10,11,12,13]. Compared to cognitively normal PD patients, Agosta and colleagues found that PD-MCI showed a diffuse pattern of WM abnormalities [10], while two studies showed a localized WM decrease pattern for PD-MCI in the frontal, temporal and anterior cingulate WM bundles [11, 13]. There was a report of no significant WM structural difference between PD-MCI and cognitively normal PD patients [12]

Methods

Results

Discussion

Conclusion