Wenbiao Xian

Cognitive impairment is common in Parkinson’s disease without dementia in the early and middle stages in a Han Chinese cohort

BACKGROUND Cognitive impairments have been reported to be common in Parkinsons disease (PD) without dementia, which occur not only in the late stages of PD, but also in the early and middle stages. Until now, no reports on the profile of cognitive impairment in Chinese non-demented PD population have been published yet. Different ethnic groups should be assessed to improve evaluation of cognitive impairment in clinical practice. The aims of this study are to estimate the frequencies and profile of cognitive impairments and to explore the risk factors of cognitive impairments in Han Chinese non-demented PD patients at early and middle stages. METHODS Eighty non-demented PD patients in early and middle stages and 86 healthy controls were invited to participate in this study. Neuropsychological batteries testing executive function, visuospatial function, memory and attention were evaluated. Cognitive impairments were defined as impaired performance in at least one cognitive domain. RESULTS Neuropsychological batteries detected 30 cases with executive dysfunction, 27 cases with memory impairment, eight cases with visuospatial dysfunction and seven cases with attention impairment. As many as 48 cases (60%) of PD patients presented cognitive impairment. Logistic regression analysis indicated that education level and Hoehn & Yahr stage were associated with cognitive impairment in PD. CONCLUSIONS Cognitive impairment is common in the early and middle stages of PD without dementia; executive function is the most common domain impaired in a Chinese PD population. Cognitive impairment might be predicted by lower education level and higher Hoehn and Yahr stage.

LRRK2 G2385R and LRRK2 R1628P increase risk of Parkinson's disease in a Han Chinese population from Southern Mainland China

PD group 446 409 36 1 446 399 47 0 Case control group 403 387 16 0 403 382 21 0 OR (95% CI) 2.134 (1.166–3.909) 2.148 (1.26–3.66) P values 0.012 0.004 Parkinson’s disease (PD) is one of the commonest neurodegenerative diseases characterized by resting tremor, rigidity, bradykinesia, and postural instability. Mutations in the leucine-rich repeat kinase 2 (LRRK2) have been reported as the most frequent cause of familial autosomal dominant PD [1]. However, there are variations in the prevalence of LRRK2 substitutions among different populations. For example, LRRK2 G2019S are most frequently identified in the United States, Europe, the Middle East, and North Africa, while LRRK2 G2385R and R1628P mutations are the most common genetic alterations in Asia. Recently, LRRK2 A419V, a new risk variant for PD, has been reported to increase the risk of PDwith an odd’s ratio over 7 [2]. However, subsequent studies revealed a remarkable difference in the frequencyof LRRK2A419Vamong differentHan Chinese populations. LRRK2 A419V was found at a high frequency (3.0%) among Han Chinese from West China (P 1⁄4 0.003; OR 1⁄4 4.14) [3] but very low frequency (w0.4%) among those from Southern China, Singapore and Taiwan [4], suggesting that some LRRK2 variants may be specific to a subset of Chinese Han population. Indeed, as the result of the immigration and assimilation of various regional ethnicities and tribes over the last thousand years, the Han Chinese population now has considerable genetic diversity. It has been reported that there is a north–south division in genetic variation within China. Althoughp.G2385R and p.R1628Phave been investigated in different Chinese Han populations, there is little information about the frequency of those two LRRK2 variants in Southern China. Therefore, we examined the frequency of p.G2385R and p.R1628P in a Han Chinese population from Guangdong which is a Chinese province in the far south, to investigate the potential genetic heterogeneity for these two variants among different Han Chinese populations. The present study included 446 ethnic Han Chinese subjects diagnosed with idiopathic PD according to the criteria of the United Kingdom PD Brain Bank [5] and 403 ageand gender-matched controls. PD patients were recruited from the Department of Neurology, the First Affiliated Hospital, Sun Yat-sen University, China. All subjects gave written informed consent and the study was approved by the Ethics Committee of Sun Yat-sen University. Genomic DNA was extracted from peripheral white blood cells using standard phenol–chloroform procedures. The primers for

LRRK2 R1398H polymorphism is associated with decreased risk of Parkinson's disease in a Han Chinese population.

Parkinson’s Disease is a neurodegenerative disorder caused by multiple genetic and environmental factors. Mutations in leucinerich repeat kinase 2 (LRRK2) are the most common genetic causes for Parkinson’s disease (PD) [1]. Several LRRK2 variants including G2385R, R1628P and S1647T have been reported to increase the risk of PD among Chinese. Recently, two novel LRRK2 variants, R1398H and N551K, were detected in low frequency in PD patients in a Chinese multicenter study [2], indicating that these two variants might be protective. As N551K was in LD with R1398H, the protective effect may be driven primarily by R1398H [2]. However, the significance of the association was limited in each individual cohort. Furthermore, conflict results have been reported by Paisán-Ruiz in two European case-control cohort studies indicating no association of five coding SNPs including R1398H and N551K [3]. To address this question, we conducted a large sample case-control study of R1398H variant involving 882 subjects from southern mainland China.

Long-term Efficacy of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A 5-year Follow-up Study in China.

Background: Subthalamic nucleus deep brain stimulation (STN DBS) is effective against advanced Parkinsons disease (PD), allowing dramatic improvement of Parkinsonism, in addition to a significant reduction in medication. Here we aimed to investigate the long-term effect of STN DBS in Chinese PD patients, which has not been thoroughly studied in China. Methods: Ten PD patients were assessed before DBS and followed up 1, 3, and 5 years later using Unified Parkinsons Disease Rating Scale Part III (UPDRS III), Parkinsons Disease Questionnatire-39, Parkinsons Disease Sleep Scale-Chinese Version, Mini-mental State Examination, Montreal Cognitive Assessment, Hamilton Anxiety Scale and Hamilton Depression Scale. Stimulation parameters and drug dosages were recorded at each follow-up. Data were analyzed using the ANOVA for repeated measures. Results: In the “off” state (off medication), DBS improved UPDRS III scores by 35.87% in 5 years, compared with preoperative baseline (P < 0.001). In the “on” state (on medication), motor scores at 5 years were similar to the results of preoperative levodopa challenge test. The quality of life is improved by 58.18% (P < 0.001) from baseline to 3 years and gradually declined afterward. Sleep, cognition, and emotion were mostly unchanged. Levodopa equivalent daily dose was reduced from 660.4 ± 210.1 mg at baseline to 310.6 ± 158.4 mg at 5 years (by 52.96%, P < 0.001). The average pulse width, frequency and amplitude at 5 years were 75.0 ± 18.21 &mgr;s, 138.5 ± 19.34 Hz, and 2.68 ± 0.43 V, respectively. Conclusions: STN DBS is an effective intervention for PD, although associated with a slightly diminished efficacy after 5 years. Compared with other studies, patients in our study required lower voltage and medication for satisfactory symptom control.

Confirmation of LRRK2 S1647T variant as a risk factor for Parkinson's disease in southern China.

Background: Leucine‐rich repeat kinase 2 (LRRK2) S1647T has been identified as a risk variant for Parkinson’s disease (PD) in Han Chinese.

Potential protective effects of autophagy activated in MPP+ treated astrocytes

Astrocytes, which have various important functions, have previously been associated with Parkinsons disease (PD), particularly in 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of PD. MPP+ is the toxic metabolite of MPTP and is generated by the enzymatic activity of monoamine oxidase B, which is predominantly located in astrocytes. MPP+ acts as a mitochondrial complex I inhibitor. Autophagy is an evolutionarily conserved self-digestion pathway in eukaryotic cells, which occurs in response to various types of stress, including starvation and oxidative stress. Lithium treatment has previously been shown to induce autophagy in astrocytes by inhibiting the enzyme inositol monophosphatase, which may aid in the treatment of neurodegenerative diseases, including Huntingtons disease, in which the toxic protein is an autophagy substrate. Therefore, using western blotting and MTT assay, the present study aimed to investigate the protective effects of lithium-induced autophagy against astrocyte injury caused by MPP+ treatment, as well as the potential underlying mechanisms. The results of the present study suggested that lithium was able to induce autophagy in astrocytes treated with MPP+, and this likely occurred via activation of the phosphoinositide 3-kinase/AKT pathway.

Cognitive Impairments in LRRK2-Related Parkinson’s Disease: A Study in Chinese Individuals

Background. LRRK2 S1647T has been identified as a polymorphic risk variant for Parkinsons disease (PD) in Chinese individuals. As LRRK2 is the most common genetic cause for PD, it has drawn great interest regarding whether cognitive impairments in PD are related with LRRK2. Purpose. This study aimed to explore the effects of LRRK2 S1647T polymorphism on cognitive function in PD. Method. 90 PD patients were randomly recruited. They underwent a series of clinical evaluations and genetic testing for the LRRK2 S1647T polymorphism. Global intellect and five cognitive domains (language fluency, visuospatial function, attention, memory, and executive function) were compared between S1647T carriers and noncarriers. Results. No differences in motor features were found between two groups, but the executive function evaluation showed that Stroop word colour test time (SWCT-TIME) scores were lower in LRRK2 S1647T carriers than in noncarriers (P = 0.017). However, multiple linear regression analysis indicated that the correlation between S1647T polymorphism and SWCT-TIME scores did not reach significant level (P = 0.051). Conclusion. Our findings suggest that cognitive impairments are not correlated with different LRRK2 S1647T polymorphisms in Chinese PD individuals.

Risk of Regurgitation and Aspiration in Patients Infused with Different Volumes of Enteral Nutrition

BACKGROUND Patients with stroke suffer from nutrition impairments and often rely on enteral nutrition (EN), which is associated with respiratory complications such as regurgitation and aspiration. OBJECTIVE To evaluate the incidence of regurgitation and aspiration in patients with severe stroke infused with different volumes of EN. METHODS A randomized controlled trial was conducted on 210 patients with severe stroke undergoing EN therapy. Patients were randomly assigned into two groups. Subjects in the treatment group received EN with an initial rate defined according to the total volume and the infusion rate was adjusted based on gastric residual volume (GRV) assessed every 4 hours. Subjects of the control group received EN without monitoring the GRV and reached the target infusion volume within 72 hours. The incidence of reflux and aspiration was recorded. RESULTS The incidences of regurgitation and aspiration were significantly lower in treatment group (6.3% and 7.9%, respectively) than control group (18.8% and 17.5%, respectively). In the treatment group, 1 patient developed regurgitation while 2 developed aspiration when EN was 500 mL. When EN increased to 1000 mL, 2 patients developed regurgitation and 2 developed aspiration, and 5 patients developed regurgitation and 6 had aspiration when EN was 1500 mL. There was no significant difference in the risk of reflux and aspiration when total volume of EN increased from 500 to 1500 mL. CONCLUSIONS During EN therapy for patients with stroke, using feeding pump with a continuous infusion for 20 hours and adjusting infusion rate based on GRV could reduce the incidence of respiratory complications.

Voltage adjustment improves rigidity and tremor in Parkinson's disease patients receiving deep brain stimulation

Deep brain stimulation of the subthalamic nucleus is recognized as the most effective treatment for moderate and advanced Parkinsons disease. Programming of the stimulation parameters is important for maintaining the efficacy of deep brain stimulation. Voltage is considered to be the most effective programming parameter. The present study is a retrospective analysis of six patients with Parkinsons disease (four men and two women, aged 37–65 years), who underwent bilateral deep brain stimulation of the subthalamic nucleus at the First Affiliated Hospital of Sun Yat-sen University, China, and who subsequently adjusted only the stimulation voltage. We evaluated motor symptom severity using the Unified Parkinsons Disease Rating Scale Part III, symptom progression using the Hoehn and Yahr scale, and the levodopa equivalent daily dose, before surgery and 1 and 2 years after surgery. The 2-year follow-up results show that rigidity and tremor improved, and clinical symptoms were reduced, while pulse width was maintained at 60 μs and frequency at 130 Hz. Voltage adjustment alone is particularly suitable for patients who cannot tolerate multiparameter program adjustment. Levodopa equivalent daily dose was markedly reduced 1 and 2 years after surgery compared with baseline. Our results confirm that rigidity, tremor and bradykinesia can be best alleviated by voltage adjustment. The trial was registered at ClinicalTrials.gov (identifier: NCT01934881).

Tremor and clinical fluctuation are related to sleep disorders in Chinese patients with Parkinson's disease

ObjectiveTo study the relationship between sleep disturbances and symptoms in patients with Parkinson’s disease (PD).MethodsThe Parkinson’s Disease Sleep Scale-Chinese Version (PDSS-CV) was used to evaluate the sleep disturbances of PD patients in a cross sectional study. The Unified Parkinson’s Disease Rating Scale (UPDRS) parts II-IV, and the Hoehn & Yahr (H&Y) stage were used to determine the level of motor function in PD and the severity of PD. The Spearman correlation and a multiple regression analysis were used to identify the relationship between sleep disturbances and symptoms of PD. The quantities derived from the UPDRS and the H&Y stage and disease duration were compared between groups of patients either with or without sleep disturbances identified by the PDSS. This study was conducted from December 2011 to March 2012 at the First Affiliated Hospital of Sun Yat-sen University, in Guangzhou.ResultsA total of 136 PD patients were included in this study. The overall total PDSS score in PD patients was 107.58 ± 23.35 points (range: 30–146). There were significant differences in the disease duration, the H&Y stage, and the UPDRS section subscores between groups of patients either with or without sleep disturbances (Kruskal-Wallis Test, p <0.05). There were significant negative correlations between PDSS scores and the UPDRS subscores, the H&Y stage and the disease duration (Spearman correlation, p < 0.05). The multiple regression analysis indicated that sleep disturbances identified by the PDSS were only associated with daily life activity, tremor intensity and clinical fluctuation (R2 = 0.22, F(3,132) = 12.4, p < 0.001). The correlations were also significant when the contribution of the other two factors was excluded using partial correlations.ConclusionsThe level of daily life activity and the occurrences of tremor and clinical fluctuation are likely to be important factors that lead to PD patients’ sleep disturbances. This study may elucidate an important clue for the relationship between sleep disturbances and PD symptoms.