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Constipation is one of the most frequent non-motor symptoms of Parkinson disease (PD) and it may be ignored by PD patients, leading to this problem not to be reported in time. The relationships between constipation and demographic variables, motor symptoms and other non-motor symptoms of PD are still unknown. PD patients were evaluated by diagnostic criteria of functional constipation in Rome III and divided into PD with constipation (PD-C) and PD with no constipation (PD-NC) groups. PD patients were assessed by rating scales of motor symptoms and other non-motor symptoms, activity of daily living and quality of life. The frequency of constipation in PD patients was 61.4%, and 24.5% of PD patients had constipation before the onset of motor symptoms. PD-C group had older age and age of onset, longer disease duration, more advanced disease stage, and more severe motor symptoms and non-motor symptoms, including worse cognition and emotion, poorer sleep quality, severer autonomic symptoms, fatigue and apathy. Binary Logistic regression analysis showed that the age, H-Y stage, depression, anxiety and autonomic dysfunction increased the risk of constipation in PD patients. Constipation exerted serious impact on the activity of daily living and quality of life in PD patients.

Relationships among clinical characteristics, iron metabolism and neurotransmitters in Parkinson disease (PD) patients with restless legs syndrome (RLS) remains unclear. We divided 218 patients into PD with and with no RLS (PD-RLS and PD-NRLS) groups by RLS-rating scale (RLS-RS) score. Motor and non-motor symptoms were rated by related scales. Iron and related proteins, and neurotransmitters in cerebrospinal fluid (CSF) and serum were measured. PD-RLS frequency was 40.37%. PD-RLS group had longer duration, higher stage and scores of motor symptoms, depression, anxiety, sleep disorders, fatigue and apathy, and increased transferrin and decreased iron, ferritin, dopamine (DA) and 5-hydroxytryptamine (5-HT) in CSF. In CSF of PD-RLS group, RLS-RS score was positively correlated with transferrin level and negatively correlated with iron and ferritin levels; RLS-RS score was negatively correlated with DA and 5-HT levels; transferrin level was negatively correlated with DA and 5-HT levels, and ferritin level was positively correlated with DA level. In serum, PD-RLS group had decreased iron and transferrin levels, which were negatively correlated with RLS-RS score. PD-RLS was common and severer in motor and some non-motor symptoms. Iron deficiency induced by its metabolism dysfunctions in peripheral and central systems might cause PD-RLS through decreasing brain DA and 5-HT.

To investigate the clinical characteristics, iron metabolism and neuroinflammation in Parkinson's disease (PD) patients with excessive daytime sleepiness (EDS). We studied 379 patients with PD and 30 age-matched controls. All subjects were evaluated by Epworth sleepiness scale (ESS) and a series of rating scales and were divided into PD-EDS and PD-NEDS groups according to ESS score. The concentrations of iron and iron-related proteins and inflammatory cytokines in both cerebrospinal fluid (CSF) and serum were examined. 1. The occurrence rate of EDS in total PD patients was 16.09%. 2. PD-EDS group had significantly severer disease stages, more severe motor and non-motor features of the disease. 3. In CSF, the concentrations of iron and IL-1β in the PD-EDS group were significantly higher and ferritin concentration was prominently lower when compared with the PD-NEDS group and the control group; ESS score was significantly associated with high concentrations of iron and IL-1β and low concentration of ferritin in the PD group. Iron concentration was positively correlated with IL-1β concentration in the PD-EDS group. 4. In serum, no changes were observed in iron and iron-related proteins and inflammatory cytokines among the three groups. EDS was a common symptom in PD patients. PD patients with EDS had more severe motor and some non-motor symptoms. Overloaded iron-relevant inflammation in the brain might be an underlying mechanism of PD-EDS.

Parkinson disease (PD) is identified as tremor-dominant (TD) and postural instability and gait difficulty (PIGD) phenotypes. The relationships between motor phenotypes and cognitive impairment and the underlying mechanisms relating pathological proteins and neurotransmitters in cerebrospinal fluid (CSF) are unknown. We evaluated the motor symptoms and cognitive function by scales, and detected the levels of pathological proteins and neurotransmitters in CSF. TD group and PIGD group had significantly higher levels of total tau, tau phosphorylated at the position of threonine 181(P-tau181t), threonine 231, serine 396, serine 199 and lower β amyloid (Aβ) 1–42 level in CSF than those in control group; PIGD group had significantly higher P-tau181t level and lower Aβ 1–42 level than those in TD group. In PD group, PIGD severity was negatively correlated with MoCA score and Aβ 1–42 level in CSF, and positively correlated with Hoehn-Yahr stage and P-tau181t level in CSF. In PIGD group, PIGD severity was negatively correlated with homovanillic acid (HVA) level in CSF, and HVA level was positively correlated with Aβ 1–42 level in CSF. PIGD was significantly correlated with cognitive impairment, which underlying mechanism might be involved in Aβ 1–42 aggregation in brain and relevant neurochemical disturbance featured by the depletion of HVA in CSF.

To investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD). Total 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed. (1) The frequency of PRBD in PD patients is 31.90%. (2) PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3) In CSF, levels of iron, transferrin, NO and IL-1β in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL-1β in PD group. Iron level is positively correlated with the levels of NO and IL-1β in PD group. (4) In serum, transferrin level is prominently decreased in PRBD group. PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE2 level in PD group. PRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation.

Fatigue is a very common non-motor symptom in Parkinson disease (PD) patients. It included physical fatigue and mental fatigue. The potential mechanisms of mental fatigue involving serotonergic dysfunction and abnormal iron metabolism are still unknown. Therefore, we evaluated the fatigue symptoms, classified PD patients into fatigue group and non-fatigue group, and detected the levels of serotonin, iron and related proteins in CSF and serum. In CSF, 5-HT level is significantly decreased and the levels of iron and transferrin are dramatically increased in fatigue group. In fatigue group, mental fatigue score is negatively correlated with 5-HT level in CSF, and positively correlated with the scores of depression and excessive daytime sleepiness, and disease duration, also, mental fatigue is positively correlated with the levels of iron and transferrin in CSF. Transferrin level is negatively correlated with 5-HT level in CSF. In serum, the levels of 5-HT and transferrin are markedly decreased in fatigue group; mental fatigue score exhibits a negative correlation with 5-HT level. Thus serotonin dysfunction in both central and peripheral systems may be correlated with mental fatigue through abnormal iron metabolism. Depression, excessive daytime sleepiness and disease duration were the risk factors for mental fatigue of PD.

Background Transcranial ultrasound is a useful tool for providing the evidences for the early diagnosis and differential diagnosis of Parkinson disease (PD). However, the relationship between hyper echogenicity in substantia nigra (SN) and clinical symptoms of PD patients remains unknown, and the role of dysfunction of iron metabolism on the pathogenesis of SN hyper echogenicity is unclear. Methods PD patients was detected by transcranial sonography and divided into with no hyper echogenicity (PDSN-) group and with hyper echogenicity (PDSN+) group. Motor symptoms (MS) and non-motor symptoms (NMS) were evaluated, and the levels of iron and related proteins in serum and cerebrospinal fluid (CSF) were detected for PD patients. Data comparison between the two groups and correlation analyses were performed. Results PDSN+ group was significantly older, and had significantly older age of onset, more advanced Hohen-Yahr stage, higher SCOPA-AUT score and lower MoCA score than PDSN- group ( P  < 0.05). Compared with PDSN- group, the levels of transferrin and light-ferritin in serum and iron level in CSF were significantly elevated (P < 0.05), but ferroportin level in CSF was significantly decreased in PDSN+ group ( P  < 0.05). Conclusions PD patients with hyper echogenicity in SN are older, at more advanced disease stage, have severer motor symptoms, and non-motor symptoms of cognitive impairment and autonomic dysfunction. Hyper echogenicity of SN in PD patients is related to dysfunction of iron metabolism, involving increased iron transport from peripheral system to central nervous system, reduction of intracellular iron release and excessive iron deposition in brain.

Objective To investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD). Methods Total 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed. Results (1)The frequency of PRBD in PD patients is 31.90%. (2)PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3)In CSF, levels of iron, transferrin, NO and IL-1[Beta] in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL-1[Beta] in PD group. Iron level is positively correlated with the levels of NO and IL-1[Beta] in PD group. (4)In serum, transferrin level is prominently decreased in PRBD group. PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE2 level in PD group. Conclusions PRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation.