Zhenzhen Zheng

Reduced functional connectivity in early-stage drug-naive Parkinson's disease: a resting-state fMRI study

Although cardinal motor symptoms in Parkinsons disease (PD) are attributed to dysfunction of corticostriatal loops, early clinical nonmotor features are more likely to be associated with other pathologic mechanisms. We enrolled 52 early-stage drug-naive PD patients and 52 age- and sex-matched healthy controls and used resting-state functional connectivity magnetic resonance imaging to evaluate alteration of the functional brain network in PD, focusing in particular on the functional connectivity of the striatum subregions. Relative to healthy controls, the PD patient group showed reduced functional connectivity in mesolimbic-striatal and corticostriatal loops. Although the deceased functional connectivity within cortical sensorimotor areas was only evident in the most affected putamen subregion, reduced functional connectivity with mesolimbic regions was prevalent throughout the striatum. No increased functional connectivity was found in this cohort. By studying a cohort of early-stage drug-naive PD patients, we ruled out the potential confounding effect of prolonged antiparkinson medication use on the functional integration of neural networks. We demonstrate decreased functional integration across neural networks involving striatum, mesolimbic cortex, and sensorimotor regions in these patients and postulate that the prevalent disconnection in mesolimbic-striatal loops is associated with some early clinical nonmotor features in PD. This study offers additional insight into the early functional integration of neural networks in PD.

SQSTM1 mutations in Han Chinese populations with sporadic amyotrophic lateral sclerosis

Mutations in the sequestosome 1 gene (SQSTM1) have recently been identified in patients with amyotrophic lateral sclerosis, accounting for 1.11%-4.92% of familial ALS and 2.42%-4.37% of sporadic amyotrophic lateral sclerosis (SALS). The mutation spectrum of SQSTM1 in Chinese patients with SALS remains unknown. Three hundred and six patients with SALS from the Department of Neurology, West China Hospital of Sichuan University were recruited for this study. From the same region, 350 healthy individuals were recruited as a control group. The encoding regions of SQSTM1 were screened by direct sequencing. Three novel nonsynonymous mutations- p. I99L, p. D337E, and p. L341V-were identified in 3 patients with SALS, none of which were found in healthy controls. The male patient carrying mutation p. I99L presented limb symptom at age of 34 and died in 34 months. Two late-onset patients carrying D337E and p. L341V mutations had bulbar and limb onset, respectively. Moreover, a c.1166-14_1166-11delTACT mutation in the intron 7 was found in a living male patient with limb onset at age of 62. None of the patients carrying SQSTM1 mutation showed clinical evidence of concomitant Paget disease of bone or mutation of the valosin-containing protein gene. The mutation frequency of SQSTM1 was 0.98% in Chinese patients with SALS, which was lower than those in other racial populations.

Screening for cognitive impairment in a Chinese ALS population

Abstract Despite growing interest in cognitive impairment of ALS patients, there are only limited studies available that characterize cognitive deficits in the Chinese ALS population through highly sensitive and specific screening tools. The Chinese version of the Addenbrooke’s Cognitive Examination-revised (ACE-R) and mini-mental state examination (MMSE) were applied to evaluate cognitive function in 145 sporadic ALS patients and 50 healthy controls. The mean onset age was 50.72 ± 12.38 years. Results showed that the prevalence of cognitive deficits was 14.48% and 30.34% based on the MMSE and ACE-R, respectively. Patients had a broad range of cognitive impairment domains, including language (26.21%), orientation/attention (24.13%), visuospatial ability (24.13%), memory (23.45%) and verbal fluency (22.76%). Logistic regression indicated that older age of onset, female gender and lower educational levels were potential determinants of cognitive deficits in ALS. Multiple regression analyses showed that the cognitive deficit during the baseline visit was not associated with the progression rate of ALS. In conclusion, cognitive impairment is common in Chinese ALS patients, but does not necessarily worsen the progression of ALS. ACE-R is superior to MMSE in detecting deficits in patients. Cognitive impairment in ALS patients may relate to age of onset, female gender and lower education level.

Serum uric acid levels in patients with Alzheimer's disease: a meta-analysis.

Background Serum uric acid (UA) could exert neuro-protective effects against Alzheimers disease (AD) via its antioxidant capacities. Many studies investigated serum UA levels in AD patients, but to date, results from these observational studies are conflicting. Methods We conducted a meta-analysis to compare serum UA levels between AD patients and healthy controls by the random-effects model. Studies were identified by searching PubMed, ISI Web of Science, EMBASE, and the Cochrane library databases from 1966 through July 2013 using the Medical Subject Headings and keywords without restriction in languages. Only case-control studies were included if they had data on serum UA levels in AD patients and healthy controls. Beggs funnel plot and Eggers regression test were applied to assess the potential publication bias. Sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity. Results A total of 11 studies met the inclusion criteria including 2708 participants were abstracted. Serum UA levels were not significantly different in AD patients compared to healthy controls (standardized mean difference (SMD) = −0.50; 95% confidence interval (CI): −1.23 to 0.22). Little evidence of publication bias was observed. Sensitivity analyses showed that the combined SMD was consistent every time omitting any one study, except only one study which greatly influenced the overall results. Meta-regression showed that year of publication, race, sample size, and mean age were not significant sources of heterogeneity. Conclusion Our meta-analysis of case-control studies suggests that serum UA levels do not differ significantly in AD patients, but there may be a trend toward decreased UA in AD after an appropriate interpretation. More well-designed investigations are needed to demonstrate the potential change of serum UA levels in AD patients.

Depression and anxiety in amyotrophic lateral sclerosis: Correlations between the distress of patients and caregivers

Introduction: Depression and anxiety are common in amyotrophic lateral sclerosis (ALS) patients and caregivers. Methods: In this study we investigated 93 ALS patients and their 93 caregivers. Depression and anxiety were quantified by the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, respectively. Results: Very strong correlations between depression and anxiety were found among patients and their caregivers. The severity of depression and anxiety of patients correlated moderately with that of their caregivers. No correlations were found between the severity of depression and anxiety and ALS Functional Rating Scale–Revised (ALSFRS‐R) score or for disease duration among patients and caregivers. However, severity of depression and anxiety in caregivers correlated with their age. Conclusions: Depression and anxiety in ALS patients and their caregivers were associated closely with each other but not with physical disability or disease duration in our Chinese population. Muscle Nerve 51: 353–357, 2015

Evidence for peripheral immune activation in amyotrophic lateral sclerosis

There is evidence of the activity of immune system in the spinal cords of patients with amyotrophic lateral sclerosis (ALS), however; few studies to date have explored the status of peripheral immune response in ALS patients. Blood samples from 284 ALS patients and 217 aged-match controls were evaluated, and parameters of T cell subset, humoral immunity, and complement system activation were observed. CD4+ T lymphocytes and circulating immune complexes (CICs) were significantly decreased, and component C3 was significantly increased in ALS patients compared with normal controls. Patients with severe or moderate impairment had a higher CD4+ T cell percentage and a lower IgG levels when compared to those with mild impairment. There was an inverse correlation between CD4 T cell percentage and both revised ALS Functional Rating Scale (ALSFRS-R) score and disease duration, but the correlation was positive between IgG level and both ALSFRS-R score and disease duration among ALS patients. These correlations were gender-specific. This investigation demonstrated the existence of peripheral immune abnormalities in ALS patients.

PRRT2 mutation screening in patients with paroxysmal kinesigenic dyskinesia from Southwest China.

Proline‐rich transmembrane protein 2 (PRRT2) has recently been identified as a causative gene of paroxysmal kinesigenic dyskinesia (PKD). However, the frequencies of its mutations and their correlation with the clinical features of PKD remain largely unknown.

The predictors of survival in Chinese amyotrophic lateral sclerosis patients.

Abstract Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease, so it is important to explore the survival factors for ALS. Our aim was to evaluate the predictors of survival in Chinese ALS patients. A total of 1049 sporadic ALS patients were enrolled. Kaplan-Meier curves were used to compare survival time. Cox proportional hazards function and the hazard ratio were used to identify adjusted prognostic predictors. Results showed that the mean age of onset was 52.6 ± 12.0 years. During follow-up, 155 patients (14.8%) were lost and 378 patients were deceased. Median survival was 33 months for the deceased patients. In the adjusted Cox proportional hazard model, age of onset, diagnosis delay, rate of disease progression, and non-invasive positive pressure ventilation (NIPPV) treatment had an effect on survival in ALS. In conclusion, our study provides information on survival factors for Chinese ALS patients. Although the onset age of Chinese ALS patients is earlier than that of Caucasian patients, survival factors, including the age of onset, diagnostic delay, rate of disease progression, and NIPPV treatment, are similar.

The serum lipid profiles of amyotrophic lateral sclerosis patients: A study from south-west China and a meta-analysis

Associations between the fasting levels of serum lipid and amyotrophic lateral sclerosis (ALS) in Chinese populations remain largely unknown. Our objective was to analyse data from a cohort of ALS patients to determine these associations. Four hundred and thirteen ALS patients and 400 age- and gender-matched healthy controls were included. Fasting serum lipid concentration of all subjects, including total cholesterol, low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C) and triglyceride (TG), were measured at the time of first visit. The revised ALS Functional Rating Scale (ALSFRS-R) was used to assess the severity of ALS. Systems Analysis by Review Manager 5 was used to evaluate differences in dyslipidaemia between ALS patients and controls. Results showed that ALS patients with higher triglyceride levels had longer survival time compared to patients with lower triglyceride levels (p < 0.05). We found a median prolonged life expectancy of 5.8 months for patients with serum triglyceride levels above the median of 127.5 mg/dl. Cox regression analysis indicated that disease duration and age were positively correlated with death, and triglyceride was positively correlated with survival. A meta-analysis indicated that there were no significant differences in mean total cholesterol, TG, LDL or the LDL/HDL ratio between patients and controls. In conclusion, high serum TG might be a protective factor for the survival of patients with ALS.

Clinical features of amyotrophic lateral sclerosis in south-west China

Our objective was to profile clinical features of amyotrophic lateral sclerosis (ALS); we performed a large sample, cross-sectional study based on a hospital registry of ALS in south-west China. Patients were coded in our tertiary referral centre from May 2006 to September 2014. Demographic data and disease-related parameters were collected. A total of 1131 patients were included. Mean age of onset was 54.3 ± 11.6 years and the highest proportion of onset age (30.6%) was between 51 and 60 years. Male:female ratio was 1.45:1. Nearly 30% of the patients were young onset, and 20.3% of the patients were bulbar onset; only 35% received riluzole treatment. The young-onset patients had a higher educational level with a higher proportion performing manual labour and living in rural areas, and a lower proportion with bulbar onset than those who were older at onset. The bulbar-onset patients were older at age of onset, with a lower proportion of males than spinal-onset patients. In conclusion, Chinese ALS patients may be younger at age of onset than Caucasian patients. Environmental and geographical factors are related to the occurrence of ALS. The large treatment gap indicated a pressing need for medical and financial support for Chinese ALS patients.