Interaction of systemic oxidative stress and mesial temporal network degeneration in Parkinson’s disease with and without cognitive impairment

Abstract

BackgroundTo identify the vulnerable areas associated with systemic oxidative stress and further disruption of these vulnerable areas by measuring the associated morphology and functional network alterations in Parkinson’s disease (PD) patients with and without cognitive impairment.MethodsThis prospective study was approved by the institutional review board of KCGMH, and written informed consent was obtained. Between December 2010 and May 2015, 41 PD patients with different levels of cognitive functions and 29 healthy volunteers underwent peripheral blood sampling to quantify systemic oxidative stress, as well as T1W volumetric and resting state functional MRI (rs-fMRI) scans. Rs-fMRI was used to derive the healthy intrinsic connectivity patterns seeded by the vulnerable areas associated with any of the significant oxidative stress markers. The two groups were compared in terms of the functional connectivity correlation coefficient (fc-CC) and gray matter volume (GMV) of the network seeded by the vulnerable areas.ResultsThe levels of oxidative stress markers, including leukocyte apoptosis and adhesion molecules, were significantly higher in the PD group. Using whole-brain VBM-based correlation analysis, the bilateral mesial temporal lobes (MTLs) were identified as the most vulnerable areas associated with lymphocyte apoptosis (P < 0.005). We found that the MTL network of healthy subjects resembled the PD-associated atrophy pattern. Furthermore, reduced fc-CC and GMV were further associated with the aggravated cognitive impairment.ConclusionThe MTLs are the vulnerable areas associated with peripheral lymphocyte infiltration, and disruptions of the MTL functional network in both architecture and functional connectivity might result in cognitive impairments in Parkinson’s disease.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1317-z) contains supplementary material, which is available to authorized users.

Vascular inflammation is a risk factor associated with brain atrophy and disease severity in Parkinson’s disease: a case-control study

“…Partial correlations among disease severity, specific brain atrophy, and vascular markers The PD signature of regional atrophy in this study was characterized by the predominant involvement of the left parahippocampus, bilateral posterior cingulate gyrus, fusiform, left temporal gyrus, and cerebellum, in addition to being correlated with disease severity, findings which were also supported by our previous studies [64,65]. After controlling for age and sex, volume changes in the left parahippocampus were weakly to moderately correlate with VCAM-1 expression levels.…”

“…The parahippocampus is a key component of the human ventral temporal cortex, which has the function of visual categorization and recognition [66], is part of the salience network that functions in memory retrieval [67], and is part of the default-mode network involved in memory encoding [68]. Our previous study demonstrated that mesial temporal network degeneration interacts with systemic oxidative stress and cognitive impairment in PD patients [65]. In parahippocampal gyrus brain tissue, the accumulation of alpha-synclein is directly related to the level of beta-amyloid and the Braak tangle stage and can predict cognitive status in PD dementia patients [69].…”

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

“…Our previous study indeed demonstrated the elevation of plasma nuclear DNA in PD which can even occur in early-onset PD patients [15]. In addition, higher peripheral apoptotic lymphocytes may be associated with a decreased cognition-associated functional network in PD patients with cognitive deficit [5].…”

“…In PD patients, neuroinflammation interacting with systemic oxidative stress may induce further CNS reactive astrogliosis [5], potentially impairing the glymphatic system. In addition, aging, a primary risk factor of PD, has been found to associate with decreased glymphatic activity and could be attributed to increased reactive gliosis.…”

Simultaneously Improved Pulmonary and Cardiovascular Autonomic Function and Short-Term Functional Outcomes in Patients with Parkinson’s Disease after Respiratory Muscle Training

“…It has been recognized that the autonomic nervous system plays a pivotal role in the regulation of lung ventilation, gas exchange, and airway smooth muscle function [8]. The observation that levodopa has a limited impact on the improvement of pulmonary function may suggest that respiration is not only associated with motor function, which is mediated mainly by a dopaminergic system, but also with other networks [9][10][11][12][13][14].…”