Bi Zhao

The impact of non-motor symptoms on the Health-Related Quality of Life of Parkinson's disease patients from Southwest China.

BACKGROUND The impact of non-motor symptoms (NMS) on the Health-Related Quality of Life (HRQoL) of patients with Parkinsons disease (PD) in the Chinese population are largely unknown. OBJECTIVES To study the impact of NMS on the HRQoL in Chinese PD patients. METHODS A total of 693 PD patients from Southwest China were included in the study. NMS of patients were evaluated by non-motor symptoms scale (NMSS) and Parkinsons disease questionnaire-39 item version (PDQ-39) was used to evaluate the HRQoL of PD. RESULTS The mean total score of NMSS was 37.2 ± 33.0 and the most prevalent NMS domain was sleep/fatigue (79.8%). There was a significant strong positive correlation between total NMSS score (rs = 0.71, P < 0.01), sleep/fatigue domain (rs = 0.60, P < 0.01) and PDQ-39 SI. Mood/apathy (rs = 0.55, P < 0.01), attention/memory (rs = 0.42, P < 0.01), gastrointestinal (rs = 0.44, P < 0.01) and Miscellany domains (rs = 0.46, P < 0.01) moderately correlated with PDQ-39 SI. A strong correlation was found between PDQ-39 SI (rs = 0.71, P < 0.01), emotional well-being (rs = 0.62, P < 0.01), cognitions (rs = 0.62, P < 0.01), and the total score of NMSS. Moderate correlation was found between mobility (rs = 0.45, P < 0.01), activities of daily living (rs = 0.43, P < 0.01), stigma (rs = 0.42, P < 0.01), communication (rs = 0.47, P < 0.01), bodily discomfort (rs = 0.46, P < 0.01) and the total score of NMSS. Female, H-Y stage, UPDRS-III and NMSS total score were the potential determinants of worse HRQoL of PD patients. CONCLUSIONS NMS have close association with various aspects of the HRQoL. Severe NMS may be related to dramatic decline of the HRQoL of PD patients.

Mutation scanning of the COQ2 gene in ethnic Chinese patients with multiple-system atrophy

Multiple-system atrophy (MSA) is a fatal neurodegenerative disorder with unknown etiology. It is widely considered to be a nongenetic disorder, but accumulating evidence suggests that several genes are linked to MSA. Recently, functionally impaired variants in the coenzyme Q2 4-hydroxybenzoate polyprenyltransferase (COQ2) gene have been reported to increase the risk of MSA in familial and sporadic Japanese patients. In this study, we investigated the mutation spectrum of COQ2 and analyzed the association between the common variant Val393Ala in exon 7 of COQ2 and MSA in a Chinese population. This study included 312 sporadic MSA patients from the Department of Neurology, West China Hospital of Sichuan University. All 7 exons of COQ2 in all the patients and exon 7 in 598 healthy controls (HCs) were directly sequenced. Novel candidate mutations and variations were confirmed by direct sequencing in 300 HCs. Two novel nonsynonymous variants, including p.R173H and p.N386I, and a reported missense variant, p.L162F, were found in 4 patients (p.R173H in 2 patients). However, the Val393Ala variant was not detected in the above 4 patients. Thirteen MSA patients (4.17%) and 18 controls (3.01%) had the heterozygous variant (Val393Ala/NM) of COQ2. No significant differences existed in the genotype frequency and minor allele frequency of Val393Ala between patients and controls or between MSA characterized predominantly by cerebellar ataxia and by pakinsonism groups. The mutation frequency of COQ2 is 1.28% in a Chinese MSA population. The common variant Val393Ala in COQ2 does not appear to be associated with MSA in ethnic Chinese.

Causes and places of death of patients with amyotrophic lateral sclerosis in south-west China.

Abstract Understanding the causes and places of death of amyotrophic lateral sclerosis (ALS) patients leads to the development of better treatment modalities. The present study aimed to identify the causes and places of death of ALS patients in south-west China. A total of 139 ALS patients (89 males and 50 females) were regularly followed up in the Department of Neurology, West China Hospital of Sichuan University from 2004 to 2010 until their deaths. Information on the causes and places of death was provided by family members, caregivers, or family physicians. Overall, 91 patients (65.5%) died of respiratory failure, 36 patients (25.9%) died of nutritional causes due to dysphagia, five patients (3.6%) met sudden deaths, three patients (2.2%) died of heart related causes, and four patients (2.9%) died of unknown reasons. Of the 139 patients, 114 (82%) died at home. Consistent with reports in the literature, respiratory failure is the leading cause of death in ALS patients. However, unlike in other studies, the second leading cause is nutrition related. Most patients die at home. The inconsistencies of these results with foreign studies may be attributable to economic and cultural differences. The findings have significant implications on the treatment modalities and palliative care for ALS patients in China.

Large C9orf72 repeat expansions are seen in Chinese patients with sporadic amyotrophic lateral sclerosis

An intronic GGGGCC hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 (C9orf72) gene was considered as the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in Caucasian populations. Using repeat-primed polymerase chain reaction analysis and Southern blotting methods, we assessed the frequency and size of hexanucleotide repeat expansion in a cohort of 918 sporadic ALS (SALS) patients and 632 control individuals of Han Chinese origin. We identified 8 (0.87%) of the SALS patients and none of control individuals as carriers of C9orf72 expansions with 700-3500 repeats. A comprehensive neuropsychological battery was conducted on 4 expansion-positive ALS patients, where 3 patients were found to have cognitive impairment. All expansion-positive patients were genotyped for the previously reported 20 single-nucleotide polymorphism (SNP) risk haplotypes on chromosome 9p21. Among them, 13 SNP risk haplotypes were shared in all expansion carriers, suggesting a common founder from European ancestry. Further meta-analysis demonstrated that the intermediate expansion size with 24-30 repeats, rare in both patients and controls, were significantly associated with the risk for ALS. To our knowledge, this is the first study to identify a proportion of Chinese SALS patients carrying this pathologic expansion of up to ∼3500 repeats and to completely elaborate the 20-SNP risk haplotypes in Chinese expansion-positive patients, providing indispensable evidence for the origin, geographical range, and population prevalence of the C9orf72-associated ALS.

Non-motor symptoms and quality of life in tremor dominant vs postural instability gait disorder Parkinson's disease patients.

To explore the differences in the features and impact on quality of life (QOL) of non‐motor symptoms (NMS) of tremor dominant (TD) and postural instability gait disorder (PIGD) phenotypes early Parkinsons disease (PD), as well as the determinants of poor QOL for TD and PIGD phenotypes.

Genetic Variants of SNCA Are Associated with Susceptibility to Parkinson's Disease but Not Amyotrophic Lateral Sclerosis or Multiple System Atrophy in a Chinese Population.

Background The polymorphisms of α-synuclein (SNCA), rs3775444, rs3822086 and rs11931074 that are strongly associated with Parkinson’s disease (PD) in Caucasian populations, were examined in this study to elucidate the role of polymorphisms in different ethnic backgrounds. The possible associations of these three polymorphisms were also investigated in PD, amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA) in a Chinese population based on the overlapping of clinical manifestations and pathological characteristics of these three neurodegenerative diseases. Methods A total of 1276 PD, 885 sporadic ALS (SALS), 364 MSA patients, and 846 healthy controls (HCs) were included. All subjects were genotyped for the three polymorphisms using Sequenom iPLEX Assay technology. Results Significant differences in the genotype distributions (p = 5.99E-06 and p = 4.98E-06, respectively) and the minor allele frequency (MAF) (p = 2.16E-06 and p = 2.15E-06, respectively) of SNCA rs3822086 (C) and rs11931074 (G) were observed between PD and HCs. However, no differences were found in the genotype distributions and MAF of SNCA rs3775444 (T) between PD and HCs. Haplotype that incorporated the three SNPs further strengthened the association with PD (best haplotype, p = 9.62E-005). No significant differences in the genotype distributions and MAF of the SNPs were found between SALS and HCs, MSA and HCs, and subgroups of PD and SALS. However, the MAF of SNCA rs3775444 (T) was significantly higher in MSA patients with frontal lobe dysfunction than MSA patients without dysfunction (p = 0.0002, OR 2.53, 95%CI: 1.55-4.15). Conclusion Our results suggest that the rs3822086 (C) allele and rs11931074 (G) allele in SNCA decrease the risk for PD, and SNCA rs11931074 may affect frontal lobe dysfunction of MSA in the Chinese population. However, these SNCA polymorphisms are not likely a common cause of SALS or MSA.

Decreased Resting-State Interhemispheric Functional Connectivity in Parkinson's Disease.

Background. Abnormalities in white matter integrity and specific functional network alterations have been increasingly reported in patients with Parkinsons disease (PD). However, little is known about the inter-hemispheric interaction in PD. Methods. Fifty-one drug naive patients with PD and 51 age- and gender-matched healthy subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. We compared the inter-hemispheric resting-state functional connectivity between patients with PD and healthy controls, using the voxel-mirrored homotopic connectivity (VMHC) approach. Then, we correlated the results from VMHC and clinical features in PD patients. Results. Relative to healthy subject, patients exhibited significantly lower VMHC in putamen and cortical regions associated with sensory processing and motor control (involving sensorimotor and supramarginal cortex), which have been verified to play a critical role in PD. In addition, there were inverse relationships between the UPDRS motor scores and VMHC in the sensorimotor, and between the illness duration and VMHC in the supramarginal gyrus in PD patients. Conclusions. Our results suggest that the functional coordination between homotopic brain regions is impaired in PD patients, extending previous notions about the disconnection of corticostriatal circuit by providing new evidence supporting a disturbance in inter-hemispheric connections in PD.

Determinants of the quality of life in Parkinson's disease: Results of a cohort study from Southwest China

BACKGROUND The determinants of the quality of life (QoL) of patients with Parkinsons disease (PD) in Chinese population remain largely unknown. METHODS A total of 649 PD patients from Southwest China participated in this cross-sectional study. Non-motor Symptoms Scale (NMSS) was used to evaluate the non-motor symptoms (NMS), whereas PD Quality of Life Questionnaire (PDQ-39) was used to assess the QoL of the PD patients. Multiple stepwise regression analysis was conducted to identify the determinants of the QoL. RESULTS NMS, H-Y stage, female, disease duration, UPDRS III score, single/divorced/widowed, and motor complications accounted for 66.3% of the variables in the multiple regression analysis and were the negative determinants of the QoL. Among these variables, NMS and H-Y stage accounted for 46.7% and 14.5%, respectively. NMS were closely associated with each domain of PDQ-39. Female sex especially predicted poor emotional well-being and bodily discomfort, whereas single/divorced/widowed especially predicted poor stigma and social support of PD patients. Comorbidity, motor complications and rural living predicted poor mobility, activities of daily living and emotional well-being, respectively. CONCLUSION Both demographic and disease-specific factors influence the QoL in PD patients. NMS are the strongest independent negative determinant of the overall QoL and closely associated with each domain of PDQ-39. The treatment of NMS may help to improve the QoL of PD patients.

VPS35 Asp620Asn and EIF4G1 Arg1205His mutations are rare in Parkinson disease from Southwest China

The Asp620Asn mutation in the vacuolar protein sorting protein 35 (VPS35) gene and the Arg1205His mutation in the eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) gene were identified in autosomal dominant late-onset familial and sporadic Parkinson disease (PD) patients in a Caucasian population. However, the frequencies of these 2 mutations among Chinese PD patients are unknown. We examined these mutations in a large cohort consisting of 609 PD patients and 600 healthy control subjects from Southwest China. Our results suggest that the Asp620Asn mutation in VPS35 and the Arg1205His mutation in EIF4G1 do not play a role in PD in the Southwest China population. The novel Arg1205Cys mutation in EIF4G1 detected in the current study should be further studied among other Asian patients.

An association analysis of the rs1572931 polymorphism of the RAB7L1 gene in Parkinson's disease, amyotrophic lateral sclerosis and multiple system atrophy in China

Recently, the rs1572931 single‐nucleotide polymorphism (SNP) of the putative promoter of the member RAS oncogene family‐like 1 (RAB7L1) gene was reported to be associated with reduced risk for Parkinsons disease (PD) in the Ashkenazi Jewish population. Ethnic‐specific effects are an important consideration in genome‐wide association studies. Considering that the clinical manifestations and pathological characteristics overlap between PD, amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA), the possible associations between the rs1572931 SNP and these three diseases were studied in the Chinese population.