Associations among Cognitive Functions, Plasma DNA, and Diffusion tensor image along the perivascular space (DTI-ALPS) in Patients with Parkinson's Disease

Abstract

Background Parkinson’s disease (PD) is a common neurodegenerative disease associated with accumulation of misfolding proteins and increased neuroinflammation. 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 lower ALPS-index was correlated with higher plasma nuclear DNA, mitochondrial DNA levels, and lower 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 support the notion that PD patients may exhibit increased oxidative stress associated with glymphatic system microstructural alterations.

Reproducibility of diffusion tensor image analysis along the perivascular space (DTI-ALPS) for evaluating interstitial fluid diffusivity and glymphatic function: CHanges in Alps index on Multiple conditiON acquIsition eXperiment (CHAMONIX) study

“…The DTI-ALPS method is used for evaluating the glymphatic system's function or the interstitial fluid dynamics, and this method has been adopted in several studies evaluating the alteration of the glymphatic system or interstitial fluid dynamics in various pathologies [21][22][23][24][25][26][27][28]. One of the report showed that results of ALPS method were significantly related to glymphatic clearance function calculated on MRI by intrathecal administration of GBCA [28].…”

“…The DTI-ALPS method provides ALPS index, which is a ratio of the diffusivity in the direction of the perivascular space and the diffusivity in the direction perpendicular to both major fiber tract and perivascular space, based on a special spatial relationship in the fiber tracts and the perivascular space in the axial imaging plane at the corona radiata [19,20]. Recently, the DTI-ALPS method has been adopted in several studies evaluating the alteration of the glymphatic system or interstitial fluid dynamics in various pathologies [21][22][23][24][25][26][27][28]. These reports indicated that the ALPS-index is a useful biomarker to evaluate the interstitial fluid dynamics or glymphatic function.…”

Glymphatic function from diffusion-tensor MRI to predict conversion from mild cognitive impairment to dementia in Parkinson’s disease

“…Besides, enlarged perivascular space (EPVS) is reported to be caused by metabolic waste obstruction, serving as an additional index for assessing glymphatic function [10]. Using the DTI-ALPS method, previous researchers have identified the role of glymphatic dysfunction in PD at different stages [11][12][13][14][15][16][17][18][19], as well as patients with isolated eye movement behavior disorder (RBD) [18,20]. They have also reported correlations between DTI-ALPS and cognitive function [11], as well as motor performance [11,21,22].…”