Siming Jiang

Reduced plasma serotonin and 5-hydroxyindoleacetic acid levels in Parkinson's disease are associated with nonmotor symptoms

BACKGROUND Accumulating evidence suggests that serotonergic system may be implicated in the pathophysiology of Parkinsons disease (PD), and particularly in nonmotor symptoms such as depression, fatigue, sleep disorders, sensory and autonomic dysfunction. This study aimed to evaluate plasma levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in PD patients, and investigate their associations with nonmotor symptoms. METHODS Eighty-two PD patients and sixty-four controls underwent a series of clinical assessments, including Hamilton Depression Scale, Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Visual Analog Scale for Pain, and Scale for Outcomes in PD for Autonomic Symptoms. Plasma 5-HT and 5-HIAA levels were measured by HPLC-ECD. RESULTS PD patients exhibited worse performance on nonmotor symptom scales (all P-values <0.001) and presented lower plasma levels of 5-HT (P < 0.001) and 5-HIAA (P < 0.001) than control individuals. Within the PD group, decreased concentrations of plasma 5-HT and 5-HIAA were correlated with more severe depression (r = -0.447, P < 0.001; r = -0.407, P < 0.001, respectively) and pain (r = -0.485, P < 0.001; r = -0.416, P < 0.001, respectively). After performing multiple linear regression, plasma 5-HT (P = 0.01) and 5-HIAA (P = 0.006) remained significantly associated with depression. CONCLUSIONS Our results suggest that serotonergic dysfunction might exist in PD, and specifically correlated with depression and pain in PD. Plasma levels of 5-HT and 5-HIAA may be considered as peripheral markers for depression in PD.

Abnormal Resting-State Neural Activity and Connectivity of Fatigue in Parkinson's Disease

Fatigue is a common burdensome problem in patients with Parkinsons disease (PD), but its pathophysiological mechanisms are poorly understood. This study aimed at investigating the neural substrates of fatigue in patients with PD.

Regional homogeneity alterations differentiate between tremor dominant and postural instability gait difficulty subtypes of Parkinson’s disease

Parkinson’s disease (PD) can be classified into the tremor dominant (TD) subtype and the postural instability gait difficulty (PIGD) subtype, which present with different clinical courses and prognoses. However, the symptom-specific intrinsic neural mechanisms underlying the subtypes of PD still remain elusive. In the current study, we utilized resting-state fMRI (rs-fMRI) combined with the regional homogeneity (ReHo) method to investigate the modulations of neural activity in 13 patients with predominantly PIGD (p-PIGD) and 15 patients with predominantly TD (p-TD) in the resting state. Compared with healthy controls, the p-PIGD and the p-TD groups both displayed ReHo changes in the default mode network (DMN). By contrast, the p-TD group exhibited more ReHo alterations in the cerebellum involved in the cerebello-thalamo-cortical (CTC) loops, whilst the p-PIGD group in extensive cortical and sub-cortical areas, including the frontal, parietal, occipital, temporal, limbic lobes, basal ganglia and thalamus, which are involved in the striatal-thalamo-cortical (STC) loops. Direct comparison between the two groups showed significant ReHo alterations in the primary visual cortex. Our findings underscore the differential involvement of the STC and CTC circuits underlying the two subtypes of PD. Moreover, relatively widespread neural activity abnormality, especially in the motor-related regions as well as the visual network, is apparently a characteristic feature of PIGD symptoms. This study could shed light on the underlying pathophysiology and clinical heterogeneity of PD presentation.

Reduced plasma taurine level in Parkinson's disease: association with motor severity and levodopa treatment.

Purpose: This study aimed to evaluate the level of taurine in plasma, and its association with the severity of motor and non-motor symptoms (NMS) and chronic levodopa treatment in Parkinsons disease (PD). Patients and methods: Plasma taurine level was measured in treated PD (tPD), untreated PD (ntPD) and control groups. Motor symptoms and NMS were assessed using the Unified Parkinsons Disease Rating Scale, the short form of the McGill Pain Questionnaire, the Hamilton Depression Scale, the Scale for Outcomes in Parkinsons disease for Autonomic Symptoms and the Pittsburgh Sleep Quality Index. Longtime exposure to levodopa was indicated by its approximate cumulative dosage. Results: The plasma taurine levels of PD patients were decreased when compared with controls and negatively associated with motor severity but not NMS. Moreover, tPD patients exhibited lower levels of plasma taurine than ntPD patients. Interestingly, plasma taurine levels negatively correlated with cumulative levodopa dosage in tPD. After controlling for potential confounders, the association between taurine and levodopa remained significant. Conclusion: Our study supports that taurine may play important roles in the pathophysiology of PD and the disturbances caused by chronic levodopa administration.

The Neural Basis of Postural Instability Gait Disorder Subtype of Parkinson's Disease: A PET and fMRI Study

The aim of this study is to further uncover the neural basis of postural instability gait disorder (PIGD) subtype of Parkinsons disease.

Alterations in regional homogeneity of resting-state brain activity in fatigue of Parkinson’s disease

Fatigue is a common complaint in patients with Parkinson’s disease (PD). However, the neural bases of fatigue in PD remain uncertain. In this cross-sectional study, our aim was to study the change of the local brain function in PD patients with fatigue. Among 49 patients with PD, 17 of them had fatigue and the remaining 32 patients without fatigue, and 25 age- and gender-matched healthy controls were enrolled. All subjects were evaluated with Fatigue Severity Scale (FSS) and had a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The fMRI images were analyzed using regional homogeneity (ReHo) to study the change of the local brain function. ReHo analysis controlling for gray matter volume, age, gender, and education showed decreased ReHo in the left anterior cingulate cortex (ACC) and the right superior frontal gyrus (dorsolateral part), and increased ReHo in the left postcentral gyrus and the right inferior frontal gyrus (orbital and triangular part), compared PD-F with PD-NF; In PD patients, the regional activity in the left ACC and the right superior frontal gyrus (dorsolateral part) was negatively correlated with the FSS scores, while that in the left postcentral gyrus, the right inferior frontal gyrus (orbital and triangular part) was positively correlated with the FSS scores. This study demonstrates that brain areas including frontal, postcentral and ACC regions indicative of sensory, motor, and cognitive systems are involved in fatigue in PD patients.

Brain metabolic correlates of fatigue in Parkinson's disease: A PET study

ABSTRACT Purpose: The neural bases of fatigue in Parkinsons disease (PD) remain uncertain. We aimed to assess the brain metabolic correlates of fatigue in patients with PD. Patients and methods: Twenty-seven PD patients without clinically relevant depression (17-item Hamilton Depression Rating Scale (HAMD) score ≥ 14), apathy (Apathy Scale (AS) score ≥ 14) and excessive daytime somnolence (Epworth Sleepiness Scale (ESS) score ≥ 10) were evaluated with Fatigue Severity Scale (FSS). Each patient had an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan. Motor symptoms were measured with the Unified Parkinsons Disease Rating Scale motor part. Levodopa equivalent daily dose for each patient was also calculated. The PET images were analyzed using statistical parametric mapping software. We introduced the age, educational level, HAMD scores, AS scores and ESS scores as covariates. Results: High FSS scores were associated with brain hypermetabolism in areas including the right middle temporal gyrus (Brodmann area (BA) 37) and left middle occipital gyrus (BA 19). Increased FSS scores correlated with hypometabolism in regions such as the right precuneus (BA 23), left inferior frontal gyrus (BA 45) and left superior frontal gyrus (orbital part, BA 11). Conclusion: This study demonstrates that brain areas including frontal, temporal and parietal regions indicative of emotion, motivation and cognitive functions are involved in fatigue in PD patients.

Plasma antioxidant status and motor features in de novo Chinese Parkinson's disease patients

Purpose: This study aimed to explore plasma antioxidant status in de novo Chinese Parkinsons disease (PD) patients and investigate its relationship with specific motor features of PD. Patients and methods: Sixty-four de novo Chinese PD patients and 40 age- and sex-matched healthy controls were recruited. Each motor feature of PD patients was assessed by unified Parkinsons disease rating scale. Plasma antioxidant status, including plasma level of glutathione (GSH) and plasma activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), was detected using enzyme-linked immunosorbent assay. The relationship between the plasma antioxidant status and motor features of PD was evaluated by Spearmans coefficient. Results: Plasma GSH level and plasma activities of GSH-Px, CAT and SOD of PD patients were lower than those of healthy controls. Moreover, the declining activity of plasma CAT was related with the increasing mean postural instability and gait disorder (PIGD) score and growing age. In contrast, the severity of tremor was positively correlated with plasma SOD activity. Conclusion: Our study demonstrates that the plasma antioxidant status is impaired in de novo Chinese PD patients. The complex relationship between the plasma antioxidant status and different motor features indicates that the antioxidant mechanisms underlying tremor and PIGD of PD may be different.

Cerebral metabolic change in Parkinson’s disease patients with anxiety: A FDG-PET study

OBJECT To detect the cerebral metabolic bases of Parkinsons disease (PD) patients with anxiety. METHODS Totally 28 idiopathic PD patients without depression (17-item Hamilton Depression Rating Scale, HAMD score <14) were enrolled in our study. All subjects were classified into PD with anxiety (PD-A) (n=13) and PD without anxiety (PD-NA) (n=15) by cutoff score of 11 according to Hamilton Anxiety Rating Scale (HAMA). Besides, age- and gender- matched healthy controls (HCs) (n=15) were selected. A resting-state F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan was applied to estimate cerebral metabolic activity. All statistical analyses were performed using IBM SPSS Statistics V20.0.0 software, while statistical parametric mapping software (SPM) was used to analyze the FDG-PET images. RESULTS PD-A showed decreased glucose metabolism in the bilateral orbitofrontal cortex (OFC, BA10 and BA11) when compared with PD-NA. Significant decrease of cerebral glucose metabolism in the bilateral OFC, bilateral supplementary motor area (SMA, BA6), bilateral dorsal anterior cingulate cortex (dACC, BA32), right dorsolateral prefrontal cortex (dlPFC, BA9), right ventrolateral prefrontal cortex (vlPFC, BA44), right putamen and left caudatum was detected in PD-A compared with HCs. There was significant reduced glucose metabolism of the bilateral SMA in PD-NA when compared with HCs (uncorrected p<0.005). CONCLUSION The anxiety of PD was associated with the metabolic reductions of PFC and striatal areas. OFC, part of PFC, could be taken as a characteristic feature for anxiety in PD. This metabolic pattern suggested that deficits of prefrontostriatal pathways might affect anxiety mood in PD.