Associations among Cognitive Functions, Plasma DNA, and Diffusion Tensor Image along the Perivascular Space (DTI-ALPS) in Patients with Parkinson's Disease.

Hsiu-Ling Chen,Toshiaki Taoka,Chiun-Chieh Yu,Pei-Chin Chen,Nai-Wen Tsai,Yun-Ru Lai,Kun-Hsien Chou,Cheng-Hsien Lu,Wei-Che Lin,Ana Lloret

doi:10.1155/2021/4034509

Abstract

Background Parkinson's disease (PD) is a common neurodegenerative disease associated with accumulation of misfolding proteins and increased neuroinflammation, which may further impair the glymphatic system. The purpose of this study was to utilize diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate glymphatic system activity and its relationship with systemic oxidative stress status in PD patients. Methods Magnetic resonance imaging and neuropsychological tests were conducted on 25 PD patients with normal cognition (PDN), 25 PD patients with mild cognitive impairment (PD-MCI), 38 PD patients with dementia (PDD), and 47 normal controls (NC). Oxidative stress status was assessed by plasma DNA level. Differences in ALPS-index among the subgroups were assessed and further correlated with cognitive functions and plasma DNA levels. Results The PD-MCI and PDD groups showed significantly lower ALPS-index compared to normal controls. The ALPS-index was inversely correlated with plasma nuclear DNA, mitochondrial DNA levels, and cognitive scores. Conclusions Lower diffusivity along the perivascular space, represented by lower ALPS-index, indicates impairment of the glymphatic system in PD patients. The correlation between elevated plasma nuclear DNA levels and lower ALPS-index supports the notion that PD patients may exhibit increased oxidative stress associated with glymphatic system microstructural alterations.

Highlights

Parkinson’s disease (PD) is a common neurodegenerative disease presenting motor and nonmotor symptoms
Using analysis of variance (ANOVA) analysis, it was determined that age data (p = 0:034) differed significantly among the groups, and the PDD group was significantly older than the control group in the post hoc analysis
There were no significant differences in sex, disease duration, and disease severity (UPDRS, modified HY stage, SE-ADL) between the normal controls (NC) group and the overall PD group

Summary

Introduction

Parkinson’s disease (PD) is a common neurodegenerative disease presenting motor and nonmotor symptoms. The glymphatic system is a recently discovered waste drainage system in the brain which involves movement of cerebrospinal fluid (CSF) along the perivascular space to promote elimination of soluble proteins, including misfolding proteins [4]. In this system, CSF is exchanged with interstitial fluid (ISF), facilitated by the aquaporin-4 (AQP4) water channels in the astroglial endfeet/endfeet of astrocytes. The correlation between elevated plasma nuclear DNA levels and lower ALPS-index supports the notion that PD patients may exhibit increased oxidative stress associated with glymphatic system microstructural alterations

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