Environmental Risk Factors of Parkinson’s Disease: A Scoping Review

Introduction@#Risk factors for Parkinson’s disease (PD) fall into three broad categories, namely environmental, genetic, and lifestyle factors. Identifying environmental factors that increase the risk of PD would allow these exposure to be reduced and the disease prevented while facilitating experimental investigation of mechanisms and intervention options. Thus, the aim of this review is to summarise the current evidence on the role of environmental factors in the development of PD. @*Methods@#All original articles published between 2018 and 2022 and written in English were searched from three databases, i.e., PubMed, Scopus Web of Science (WoS), using combination of primary keyword (PD and its MeSH and synonyms), and two secondary keywords; (“environment*”) and risk (factor*). @*Result@#After a thorough screening process, nineteen articles were included in this scoping review. The environmental risk factors examined in the included studies fell into five categories: a) pesticide exposure, b) heavy metals and organic solvent exposure, c) drug abuse and d) air pollution and e) source of water.@*Conclusions@#In summary, PD is a complex neurological disorder for which there are several environmental risk factors involved. Identifying and reducing exposure to these environmental factors could have a significant impact on the future occurrence of the disease.

The Discovery of Putative Small Molecules via Ligand-based Pharmacophore Modelling Targeting Human Tau Protein for an Effective Treatment of Parkinson’s Disease

@#Introduction: The human tau protein is a key protein involved in various neurodegenerative disease (NDs) including Parkinson’s disease (PD). The protein has high tendency to aggregate into oligomers, subsequently generating insoluble mass in the brain. Symptoms of PD include tremor, bradykinesia, rigidity, and postural instability. Currently drugs for PD treatment are only symptom-targeted while effective therapeutic treatment remains a challenge. The objective of this study is to identify novel promising anti-PD drugs using computational techniques. Method: ligand-based (LB) receptor modelling was conducted using LigandScout, validated and subjected to Glide XP docking, virtual screening, ADMET, and molecular dynamics predictions. Results: The adopted LB modelling generated pharmacophoric features of 5 hydrogen bond donors, 1 aromatic rings, and 7 hydrogen bond acceptors. The validation result indicated GH score of 0.73 and EF of 36.30 as validation protocols, probing it to be an ideal model. Using 3D query of the modelling a total of 192 compounds were retrieved from interbioscreen database containing 70,436 natural compounds. Interestingly, ligands 1, 2, 3, 4 and 5 orderly indicated higher binding affinities to the receptor with Glide XP docking of -7.451, -7.368, -7.101, -6.878, and -6.789 compared to a clinical drug Anle138b with -4.552 kcal/mol respectively. Furthermore, molecular dynamics and pkCSM pharmacokinetics demonstrated ligands 1, 2, & 4 having better stability and low toxicity profiles compared to the reference. Conclusion: In summary, the study pave way for discovery of small molecules that could be recommended as adjuvant /single candidate as ant-PD candidates upon further translational study.

Botulinum neurotoxin a for hand tremors in Parkinson’s disease: A meta-analytic study

Background@#Resting tremor is a prominent cardinal motor symptom of Parkinson’s disease (PD). In some cases, the tremor may be refractory to dopaminergic and anticholinergic treatment. Multiple studies were previously done to evaluate the effectiveness of Botulinum Neurotoxin A (BoNT/A) with essential tremors and dystonia, but data regarding its use on tremors of PD is still lacking. @*Objective@#This meta-analytic study aims to determine the effectiveness of BoNT/A in treating tremors of patients with PD. @*Data Sources@#Data Sources: Researches were searched at PubMed, ScienceDirect and EBSCO Host. @*Review Methods@#Articles on the effect of BoNT/A on PD hand tremors were searched. Studies and data pertaining to non-PD tremors like essential tremors excluded in the analysis due to difference in pathophysiology. Standardized mean difference was used as the effect measure and was computed with Review Manager version 5.4 software. @*Results@#Three open label studies were used for final analysis in this study. Studies included are those pertaining to tremors due to PD. Pooled estimates showed a significant change in decreasing tremor score after BoNT/A injection. @*Conclusion@#Botulinum Toxin A injections can be used to manage PD tremors effectively.

Analysis of influencing factors of fatigue in Parkinson’s disease / 中风与神经疾病杂志

@#To analyze the influencing factors and clinical significance of fatigue in patients with Parkinson’s disease（PD）. Methods 155 patients with PD were selected from the Department of Neurology of the Second Affiliated Hospital of Baotou Medical College from January 2019 to December 2020.According to the fatigue severity scale（FSS），59 patients in the PD non fatigue group（FSS>4 points） and 96 patients in the PD fatigue group（FSS≤4 points）. Unified Parkinson’s disease rating scale Part III（MDS-UPDRS Ⅲ）、Hoehn-Yahr（H-Y）、Hamilton Depression Scale（HAMA）17，Hamilton Anxiety Scale（HAMD）14,Parkinson’s disease Sleep Scale（PDSS） Chinese version，simple mental state scale and so on. The physical fatigue and mental fatigue of PD patients were scored by fatigue Scale-14（fs-14）. The total scores of tremor items and postural abnormalities gait disorders were calculated according to the items of MDS UPDRS Ⅱ～Ⅲ. Results Compared with the non fatigue group，the mds-updrs Ⅲ，H-Y score，HAMA，HAMD and course of disease in the fatigue group were increased，and the PDSS was decreased（P<0.05）. Mds-updrs Ⅲ score（OR=1.105，P=0.011） and depression（OR=1.160，P=0.028） were independent risk factors for fatigue. Mental fatigue was positively and strongly correlated with HAMD（rs=0.792）；physical fatigue was positively and strongly correlated with mds-updrs Ⅲ（rs=0.645），total score of postural abnormalities gait disorders（rs=0.659），HAMA（rs=0.654） and H-Y score（rs=0.674），which was positively and strongly correlated with PDSS（rs=-0.674） negative strong correlation. Conclusion The incidence rate of fatigue in PD patients is high，and is associated with motor symptoms，sleep disorders，anxiety and depression.

Correlation between serum BDNF，Val66Met gene polymorphism and clinical symptoms in early Parkinson’s disease / 中风与神经疾病杂志

@#To investigate the correlation between serum Brain-derived neurotrophic factor （BDNF），Val66Met gene polymorphism and clinical symptoms in patients with newly diagnosed Parkinson’s disease （PD）. Methods A total of 62 early PD patients and 46 healthy controls were collected from Ningbo First Hospital. General demographics，Hamilton Anxiety Scale （HAMA），Hamilton Depression Scale （HAMD），Orthostatic Hypotension （OH） or not，serum BDNF levels，Val66Met genotype were examined in all subjects，duration of disease，Hoehn-Yahr （HY） Rating Scale，Unified Parkinson’s Disease Rating Scale motor scores （UPDRS-Ⅲ），symptom classification （tremor type，rigid type or mixed type） were also assessed in patients. Results PD patients had significantly higher HAMA，HAMD scores，incidence of OH and lower BDNF levels than controls，there was no significant difference in the distribution of Val66Met gene polymorphism between the two groups. Multiple linear regression revealed that BDNF levels were negatively associated with HAMA （P=0.014） and HAMD （P=0.013） scores in PD patients，however，no significant correlation were found between Val66Met polymorphism and clinical symptoms. Conclusion Evident non-motor symptoms can occur in early PD patients，serum BNDF levels were correlated with the degree of anxiety and depression in patients，and Val66Met gene polymorphism may not play an important role in the course of disease.

The characteristics and gender differences of non-motor symptoms in early diagnosed Parkinson’s disease / 中风与神经疾病杂志

@#To explore the characteristics and gender differences of non-motor symptoms（NMS） in De Novo Parkinson’s diseases （PD）. Methods 203 newly diagnosed PD patients （102 males，101 females） and 255 healthy controls （110 males，145 females） were selected. The clinical data were collected and evaluated by mini-mental State Examination （MMSE），Montreal Cognitive Assessment （MoCA），Hamilton Depression Scale （HAMD），Hamilton Anxiety Scale （HAMA），Parkinson’s disease Sleep Scale （PDSS），Unified PD Rating Scale Part III （UPDRS-III） and Hoehn Yahr （H-Y） stage. Non-motor questionnaire screening scale （NMSQ） was used to assess their non-motor symptoms，and compared the characteristics of NMS in different genders. Multivariate linear regression was used to analyze the influencing factors of NMDQ score in PD patients. Results 98.5% of PD patients had at least one NMS，among which forgetfulness （ 67.5%），depression （49.8%） were the most common. The total score and nine domains of NMS in PD group were significantly higher than those in healthy controls （all P<0.05）. The rates of interest decline，depression，anxiety and excessive sweating in female in PD group were significantly higher than those in male，while the rate of dysphagia was significantly lower （all P<0.05）. The rates of hallucination and sweating increase in female in healthy controls were significantly higher than those inmale，the rate of memory decline was significantly lower （all P<0.05）. The total scores of NMS in male and female patients with PD were affected by HAMD and PDSS （all P<0.05），while male patients were more likely to be affected by the disease duration （β= 0.181，P=0.032）. Conclusion The incidence of non motor symptoms in newly diagnosed PD patients is significantly higher than that in healthy controls and different in gender.

Correlation between serum bone protein and disease severity and cognitive impairment in patients with Parkinson’s disease / 中风与神经疾病杂志

@#Objective　To investigate the relationship between serum Osteopontin (OPN),Osteoprotegerin (OPG) and Osteocalcin (OCN) in patients with Parkinson’s disease (PD) and the severity of the disease and cognitive impairment Relationship.Methods　Fifty-two PD patients (PD group) were included,and H-Y staging,UPDRSⅢ,and MoCA score were performed.According to the MoCA score,PD was divided into a cognitively normal group of 20 cases and a cognitively impaired group of 32 cases.In the same period,36 healthy subjects (control group) were included,and the serum OPN,OPG and OCN levels in each group were detected for statistical analysis.Results　The serum OPN and OCN levels in the PD group were higher than those in the control group (P<0.05),and OPG was lower than the control group (P<0.05);serum OPN was higher in PD cognitive impairment group than in normal PD cognitive group (P<0.05);Results from spearman correlation analysis showed that serum OPN and OCN of PD patients were positively correlated with H-Y staging and UPDRSⅢ score (P<0.05).OPN was negatively correlated with MoCA score,attention,calculation ability and abstract thinking (P<0.05),and serum OCN level was positively correlated with delayed recall (P<0.05);Logistic regression analysis suggests that OPN is a risk factor for PD cognitive impairment.Conclusion　Serum OPN,OPG and OCN are related to the pathogenesis of PD.Serum OPN and OCN can further evaluate the condition of PD patients and are related to cognitive impairment.

The effects mutant DJ-1 and sumoylation of DJ-1 protein on DJ-1 mitochondrial localization / 中风与神经疾病杂志

@#Objective To investigate the effects of DJ-1 A39S mutation in Parkinson’s disease（PD）and SUMO modification of DJ-1 on DJ-1 mitochondrial localization. Methods Five COS-7 cell lines that can stably express wild type，A39S mutant，K130R mutant，A39S K130R double mutant DJ-1 protein and SUMO-1 protein were constructed. The transfection results were detected by Western blot，double enzyme digestion and PCR sequencing. The expression and subcellular localization of DJ-1 protein were observed by Western blotting，confocal microscope and immunofluorescence.Results Immunofluorescence showed that DJ-1 protein was mainly distributed in the cytoplasm and also in the nucleus.Some wild-type and K130R DJ-1 proteins were distributed in mitochondria，most of A39S and A39S-K130R mutant DJ-1 proteins were transferred to mitochondria，and SUMO-1 was mainly distributed in the nucleus and around the nucleus.Immunofluorescence co localization showed that four DJ-1 proteins were colocalize with SUMO-1 protein. Conclusion The pathogenic mutation A39S of DJ-1 transferred DJ-1 protein from cytoplasm to mitochondria；DJ-1 and SUMO-1 have colocalization，and they may interact.mitochondrial localization.Methods Five COS-7 cell lines that can stably express wild type，A39S mutant，K130R mutant，A39S K130R double mutant DJ-1 protein and SUMO-1 protein were constructed. The transfection results were detected by Western blot，double enzyme digestion and PCR sequencing.The expression and subcellular localization of DJ-1 protein were observed by Western blotting，confocal microscope and immunofluorescence.Results Immunofluorescence showed that DJ-1 protein was mainly distributed in the cytoplasm and also in the nucleus.Some wild type and K130R DJ-1 proteins were distributed in mitochondria，most of A39S and A39S-K130R mutant DJ-1 proteins were transferred to mitochondria，and SUMO-1 was mainly distributed in the nucleus and around the nucleus.Immunofluorescence colocalization showed that four DJ-1 proteins were colocalize with SUMO-1 protein.Conclusion The pathogenic mutation A39S of DJ-1 transferred DJ-1 protein from cytoplasm to mitochondria；DJ-1 and SUMO-1 have colocalization，and they may interact.

A comparative study of rapid eye movement sleep behavior disorders on Parkinson’s disease and multiple system atrophy Parkinsonism type / 中风与神经疾病杂志

@#Objective To compare the differences in incidence of rapid eye movement sleep behavior disorder（RBD）on Parkinson’s disease（PD） and multiple system atrophy parkinsonism type（MSAP），and to investigate the correlation factors of the RBD screening questionnaire （RBDSQ） scores.Methods Thirty-four PD patients and 30 MSAP patients without dementia within 5 years of onset were included. Baseline data were collected in detail，and UPDRS Ⅲ score，HY staging score and RBDSQ score were performed between the two groups to compare the difference in the incidence of RBD between the two groups，as well as the correlation factors of RBDSQ score.Results The incidence of RBD in prodrome MSA （40.0%） was significantly higher than that in prodrome PD （2.9%，χ2=11.330，P=0.001）.The incidence of RBD in the clinical stage of MSAP（63.3%）was significantly higher than that in the clinical stage of PD（29.4%，χ2=7.401，P=0.007）.The RBDSQ score of MSAP patients was significantly higher than that of PD patients （6.6±3.9 vs.4.7±3.4，Z=-2.084，P=0.037）.There was no clear correlation between RBDSQ scores in PD group or MSAP group and disease course，UPDRS Ⅲ score，MMSE score and disease progression rate. Conclusion Compared with PD group，the incidence of RBD in prodrome and clinical MSAP group was significantly higher than that in PD group. In MSAP patients and PD patients with normal cognitive function，there was no clear correlation between RBDSQ score and UPDRS Ⅲ score and MMSE score.

Factors of surgical selection in the evaluation cohort of deep brain stimulation in Parkinson’s disease / 中风与神经疾病杂志

@#Abstract Objective To investigate the related factors of surgical treatment and the reasons for non-operation in the evaluation cohort of deep brain stimulation.Methods A total of 406 patients who undergo DBS preoperative evaluation were selected from two clinical centers. According to whether the patients were operated or not，the patients were divided into operation group（n=302）and non-operation group（n=104）.Demographic characteristics，clinical characteristics and scale evaluation results of the two groups were compared.The correlation information between baseline characteristics and surgery was analyzed，and the reasons for non-operation were summarized.Results Compared with baseline data，none operation group had higher age of onset，longer course of disease，bilateral onset，poorer cognitive status，poorer balance function，higher Hoehn Yahr stage，worse QOL，and worse balance function.Diagnostic problems were the main reasons of non-operation （44.2%），followed by poor levodopa response （15.4%），the operation intention （9.6%） and the operation expectation of patients （6.7%）.Conclusion By comparing the baseline clinical characteristics of patients who underwent surgery and those who did not，it was found that the side of onset，age of onset，disease duration，cognitive status，balance function，QOL，motor symptoms and motor complications may be considered in surgical decision-making. Diagnostic problems were the main reasons for non-operation （44.2%）.

Clinical and polysomnography findings in patients with Parkinson’s disease with restless leg syndrome / 中风与神经疾病杂志

@#Objective　To evaluate the differences of clinical and sleep characteristics and related factors between patients with Parkinson’s disease (PD) with restless leg syndrome (RLS) and idiopathic restless leg syndrome (iRLS).Methods　One hundred and twenty-five patients with PD and 137 patients with iRLS from 2015 to 2020 were collected.PD patients were divided into PD with RLS group (PD-RLS) and PD without RLS group (PD-NRLS).The general condition,clinical features,subjective and objective sleep examination of the three groups were compared and analyzed.Results　The prevalence of comorbid RLS in PD patients was 27.2%.The score of UPDRS-Ⅲ score in patients with PD-RLS was higher than that in PD-NRLS.The objective sleep quality of patients with PD-RLS was worse than that of patients with iRLS.Age and comorbid PD were the risk factors of poor sleep quality in patients with RLS.IRLS-RS and HAMD scores are risk factors for poor subjective sleep quality in patients with RLS.Conclusion　Objective sleep disorders are more likely to occur in patients with PD-RLS than in patients with iRLS.While subjective sleep disorders in patients with iRLS are more severe.Which may be related to the clinical heterogeneity of RLS complicated with PD.

Expression of miRNA-153 and miRNA-223 in serum of patients with Parkinson’s disease / 中风与神经疾病杂志

@#ObjectiveTo explore the expression levels of miRNA-153 and miRNA-223 in the serum of patients with Parkinson’s disease（PD）and their clinical value，as well as the correlation between the expression of miRNA-153 and miRNA-223 in the serum of PD patients and Hoehn-Yahr（H-Y）scales. 〖WTHZ〗Methods〖WTBZ〗The relative expression levels of serum miRNA-153 and miRNA-223 in 35 patients with PD（PD group）and 40 healthy people（healthy control group）were quantitatively detected. The H-Y scales of PD patients were evaluated. The results were analyzed. 〖WTHZ〗Results〖WTBZ〗The relative expression levels of serum miRNA-153 in PD group were significantly lower than that in healthy control group（t=5.71；P<0.01）. The relative expression levels of serum miRNA-223 in PD group were also significantly lower than that in healthy control group（t=6.07；P<0.01）. There was a negative correlation between the relative expression levels of serum miRNA-153 and H-Y scales in PD group（r=-0.4504，P<0.01）. 〖WTHZ〗Conclusion〖WTBZ〗Serum miRNA-153 and miRNA-223 may be used as biomarkers for the diagnosis of PD；serum miRNA-153 may become an indicator for evaluating the progress of PD.

Correlation between serum uric acid and homocysteine levels in Parkinson’s disease / 中风与神经疾病杂志

@#Objective　To investigate the correlation between serum uric acid and homocysteine levels in Parkinson’s disease (PD)，as well as the relationship between serum uric acid and homocysteine levels with cognitive impairment,clinical subtypes，different disease stages in PD.Methods　One hundred and fourteen patients with Parkinson’s disease and 123 healthy controls were included.Detailed baseline data were collected and patients with Parkinson’s disease were evaluated and grouped by Hoehn and Yahr、MDS-UPDRS and MMSE scale.Serum uric acid and homocysteine levels were measured and compared in all subjects.Results　The serum uric acid level of PD group was significantly lower than that of the control group［（241.2±60.8）μmol/L vs （271.2±55.7）μmol/L，P＜0.05］.The serum homocysteine level of PD group was significantly higher than that of the control group［（16.11±6.01）μmol/L vs (12.41±2.94) μmol/L，P＜0.05］.In PD group,serum uric acid level of patients with cognitive impairment was significantly lower than that of patients without cognitive impairment ［（22457.94）μmol/L vs （248.560.96）μmol/L，P＜0.05］,and there was no statistically significant difference between clinical subtypes and different disease stages in PD.Conclusion　Compared with the normal control group,serum uric acid level was significantly decreased in PD group,serum homocysteine level was significantly increased in PD group.In PD group,serum uric acid level was significantly lower in patients with cognitive impairment.

Comparison of pain in patients with young-onset and late-onset Parkinson’s disease and analysis of influencing factors / 中风与神经疾病杂志

@#Objective　To compare pain in patients with young-onset (YOPD) and late-onset (LOPD) Parkinson’s disease and analyze influencing factors.Methods　Seventy participants who visiting outpatient and inpatient of the neurology department of the Provincial Hospital Affiliated to Anhui Medical University from October 2018 to July 2020 were selected and divided into YOPD and LOPD group according to age and Hoehn-Yahr (H-Y) Scale.General data were collected.The king’s Parkinson’s disease pain scale (KPPS)，part 3 of the Unified Parkinson’s disease rating scale (UPDRS-Ⅲ).The hamilton rating scale for depression (HAMD） were used to assess the item of pain,motor function and prevalence of depression.And further analyses of their effects on pain were made.Results　Compared with LOPD patients,YOPD patients had lower mean age,HAMA score and prevalence of hypertension and constipation,longer mean duration of disease,higher mean HAMD score,MMSE score,KPPS score and incidence of pain (P<0.05).Compared with LOPD patients with pain,YOPD patients with pain had higher prevalence of pain occurring in the waist,lower prevalence of pain occurring in the legs (P<0.05).YOPD patients with pain had higher mean UPDRS-Ⅲ score,HAMD score,HAMA score and dyskinesia stage than those without pain (P<0.05).LOPD patients with pain had higher mean HAMD score,HAMA score and dyskinesia stage than those without pain (P<0.05).Conclusion　Patients with YOPD have a higher incidence of PD pain and more severe pain than those with LOPD.The more severe the emotional disorders and motor symptoms are,the more likely they will suffer from pain.Clinicians should standardize the treatment of pain according to the type and location of pain in PD patients,so as to improve the quality of life of patients.

Effect of pramipexole combined with benzhexol on the efficacy of elderly patients with PD and the influencing factors of anxiety and depression / 中风与神经疾病杂志

@#Objective　To explore and analyze the effect of pramipexole combined with benzhexol on the efficacy of elderly Parkinson’s disease (PD) patients and the influencing factors of anxiety and depression.Methods　85 elderly patients with PD in our hospital were selected and divided into observation group (n=43 cases) and control group (n=42 cases).Patients in the control group were given benzhexol treatment,while patients in the observation group were given benzhexol combined with pramipexole.The general information,anxiety and depression before and after treatment,linical efficacy,quality of life score before and after treatment, adverse reactions,anxiety and depression related factors were observed and recorded.Results　Before treatment,there was no significant difference in SAS score and SDS score between the two groups (P>0.05).After treatment,SAS and SDS scores of the two groups were significantly improved (P<0.05),SAS and SDS scores of the observation group were significantly lower than those of the control group (P<0.05);the total effective rate of the observation group was significantly higher than that of the control group (P<0.05);the quality of life in the observation group was significantly higher than that in the control group after treatment (P<0.05) and the quality of life scores were significantly higher than that before treatment (P<0.05);the incidence of total adverse reactions in the observation group was significantly lower than that in the control group (P<0.05);according to the results of single factor and correlation analysis,multiple linear regression analysis was conducted.The results showed that hardiness,H-Y stage and social support were the influencing factors of depression in patients with Parkinson’s disease.Conclusion　Pramipexole combined with benzhexol can effectively improve the treatment effect of elderly PD patients,reduce the generation of negative emotions such as anxiety and depression,and improve their quality of life.Tenacity,H-Y staging and social support are the influencing factors of depression in patients with Parkinson’s disease,which deserves clinical attention.

Differential expression of circulating miRNAs in Parkinson’s disease patients: Potential early biomarker?

@#Background & Objective: Circulating microRNAs (miRNAs) expressions have been suggested as potential biomarkers for Parkinson’s Disease (PD). Identification of early biomarkers for PD is important and crucial as PD symptoms occur at a late stage. Hence, these biomarkers could be used in molecular diagnosis for early detection. We therefore examined and compared the expression of circulating miRNAs between PD patients and controls. We also compared the miRNAs expression between early-onset PD (EOPD) and late-onset PD (LOPD). Methods: RNA was extracted from the plasma of EOPD (onset age <50 years; n=14), LOPD (onset age < 60 years; n=14) and healthy controls (n=11). The miRNAs expression was determined using the Affymetrix GeneChip microarray. Differential analysis was performed using the R software. Significantly differentiated miRNAs were subsequently analyzed for functional enrichment and biological pathway using the FunRich v1.3 software based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The Omics.net was used to determine the predicted target mRNAs of these miRNAs, and their interactions, based on the five most differentially expressed miRNAs. Results: In total, 273 miRNAs were upregulated in PD patients compared to controls. The most significant miRNAs were hsa-miR-301a-3p, 100-5p, 140-5p, 486-3p, 143-3p (fold change ranging from 11.2 – 32.0). A total of 140 circulating miRNAs were differentially expressed in EOPD compared to LOPD. Five of these miRNAs (one upregulated miRNA (hsa-miR-29b-3p) and four downregulated miRNAs (hsa-miR-297, 4462, 1909-5p and 346) belonged exclusively to the EOPD patients. The predicted gene targets of these miRNAs involved in dopaminergic synapse regulation, crucial to the pathogenesis of PD. Conclusion: Circulating miRNAs differ between PD patients and controls, and between EOPD and LOPD patients. A validation study with a larger and more diverse multi-ethnic population should be conducted to confirm our results.

Covid-19 perception and self reported impact of pandemic on Parkinson’s disease symptoms of patients with physically independent Parkinson’s disease

@#Objective: The novel coronavirus disease 2019 (Covid-19) pandemic has affected many people with chronic diseases, including Parkinson’s disease (PD). We aimed to investigate the perception of Covid-19 and the self-reported impact of the pandemic on PD symptoms of a group of patients with physically independent PD from Turkey. Methods: We applied a questionnaire to idiopathic PD patients aged ≥65 years, who did not have known dementia, who were physically independent and who had at least one visit in the year before the telephone interview. The study patients were selected from the medical records of two different centers in Kirikkale, Turkey. Two neurologists conducted a semi-structured telephone interview to evaluate the perception of Covid-19 and new or worsening PD symptoms after the home quarantine. Results: In total, 86 patients were included in the study. Although most of the patients (97.7%) knew of Covid-19, knowledge of the Covid-19 symptoms was moderate (54.7%). Most patients reported that they washed their hands often (100%) and wore a mask (98.8%); 76 (88.4%) of them stayed at home. Compliance with other preventive measures was above 80%. In total, 40 (46.5%) patients (28 male, 12 female) reported worsening bradykinesia. Fatigue (24.4%), daytime sleepiness (20.9%), pain (20.9%) and anxiety (15.2%) were the most common new or worsening non-motor symptoms. Conclusions: The Covid-19 knowledge in a group of patients with PD from Turkey can be considered adequate. They have a high compliance with preventive measures. However, reduced non-exercise physical activity due to the pandemic affected both their motor symptoms and non-motor symptoms.

Glucocerebrosidase genetic variants in Malays with early and late-onset Parkinson’s disease

@#Background: Mutations in glucocerebrosidase (GBA) have been associated with the risk of developing Parkinson’s disease (PD) in different ethnic populations. The prevalence of GBA mutations among Malay PD patients is unknown. Thus, the aim of this study was to determine the frequency of GBA mutations among Malay PD patients, focusing on early (EOPD) and late-onset (LOPD) patients. Methods:EOPD (n = 50) and LOPD (n = 50) patients along with 50 ethnically and age-matched control wererecruited. The GBA exons of these patients were sequenced using the Ion Torrent PGMTM System. Results: Five heterozygous mutations exclusive to EOPD patients were identified; c.-203A>G,p.S146L, p.R159Q, p.L483P and p.L483R+c.-145G>A. In LOPD patients, c.543C>T(p.(F181=)), c.28-10C>A and p.R202Q were identified in which this p.R202Q was also present in a control subject. In addition, c.259C>A(p.(R87=)) and c.-145G>A were identified in two control subjects. In summary, we observed GBA mutations in 8% and 6% of Malay PD cases and control subject, respectively. The prevalence of GBA mutations was higher in EOPD (10%) than LOPD (6%). However, these differences were not statistically significant; [PD vs. controls: OR = 1.36, 95%CI 0.35-5.38, p = 0.752] and [EOPD vs. LOPD: OR = 1.74, 95%CI 0.39-7.71, p = 0.715]. Conclusion: We identified five exclusive heterozygous GBA mutations in EOPD patients which might predict the increase susceptibility of Malays to develop PD at young age. These findings could add knowledge into the existing evidences linking genetic alterations in GBA and PD.

Incidence of Depression among Parkinson’s Disease in China：A Meta-Analysis / 中风与神经疾病杂志

@#Objective　To analyze the rate of depression among Chinese Parkinson’s disease patients by Meta-analysis. Methods　CNKI，VIP，Wanfang，PubMed，Web of Science and Embase databases were searched systematically. The studies focus on depression of Parkinson’s disease patients in China from the year of establishment to 2019 were collected. Two researchers independently screened literature，extracted data and applied the standard of Agency for Healthcare Research and Quality to evaluate the quality of literatures. According to the results of heterogeneity test，the data were analyzed by Stata 12.0 software using random effect model. Results　A total of 7842 PD patients，4394 males and 3088 females，were included in 37 studies. The combined value of depression detection rate was 43.0% ［95%CI （0.370，0.490）］. Subgroup analysis showed that the incidence of depression in the study with sample size<150 was 47.7% ［95%CI （0.413，0.542）］，and the incidence of depression in the study with sample size≥ 150 was 34.3% ［95%CI （0.254，0.432）］，respectively. The prevalence rates of depression with assessment tools were different，Hamilton Depression Rating for Depression 43.0%［95%CI（0.359，0.501）］，Center for Epidemiologic Studies Depression Scale 38.1% ［95% CI （0.301，0.461）］，Self-Rating Depression Scale 41.0% ［95%CI （0.163，0.657）］，Beck Depression Inventory 46.0% ［95%CI （0.353，0.567）］. The incidence of depression in female PD patients was 43.0% ［95%CI（0.340，0.519）］，43.2% ［95%CI （0.330，0.533）］ in male. The incidence of depression was 43.2% ［（95%CI （0.330，0.533）］，among patients disease duration ≤ 5 years，44.4% ［（95%CI （0.362，0.501）］ in patients with PD whose disease duration more than 5 years. The incidence of depression was 40.2%［95%CI（0.226，0.538）］in PD patients whose onset age ≥60 years，45.3% ［95%CI（0.335，0.570）］in PD patients whose onset age <60 years. The incidence of depression was 45.4%［95%CI（0.441，0.497）］in patients with UPDRSIII score > 25，39.1%［95%CI（0.261，0.521）］ in those with score ≤ 25.42.1%［95%CI（0.303，0.538）］PD patients with mild depression，22.7%［95%CI（0.160，0.293）］with moderate depression and 7.4%［95%CI（0.049，0.100）］ with severe depression. Conclusion　The incidence of depression is high in PD patients. The emotion of PD patients in every stage need evaluate，diagnose and cure earlier.

The Gender and Clinical Symptoms Difference in Depression of Parkinson’s Disease / 中风与神经疾病杂志

@#Objective　We aimed to analyze the gender differences by evaluating the motor and non-motor symptoms among the patients with parkinson’s disease and the patients with depression of parkinson’s disease，and to explore the possible pathogenesis further and make sex-specific therapeutic strategies. Methods　Two hundred patients with parkinson’s disease from both the outpatients department and the ward were included in this analysis. There were 56 patients whose HAMD scores exceeded 19，which were divided into the depession of parkinson’s disease （dPD） group。There are 144 patients whose HAMD scores under 20，which were divided into the non-depession of parkinson’s disease （ndPD） group. The scores from all the scales were analyzed using statistical software. Results　①The depression incidence of females was significantly higher than that of males in PD patients （P<0.05）. ②Rigidity score and Bradykinesia score in males were significantly higher than that in females in dPD patients （P<0.05）. Tremor score in males was significantly lower than that in females in dPD patients （P<0.05）. ③A significantly higher score in mood/apathy and feel problem/hallucination domains were observed in female PD patients （P<0.05）. ④The HAMA score，HAMD score，NMSQ total score of dPD patients were all significantly higher than that of ndPD patients （P<0.05）. The PDSS score of dPD patients was significantly lower than that of ndPD patients （P<0.05）. The tremor score，rigidity score，postural instability score，bradykinesia score，UPDRS-III score of dPD patients were all significantly higher than that of ndPD patients （P<0.05）. ⑤The HAMD scores correlated with levodopa equivalent doses （Led） （r=-0.31，P=0.01），H-Y stage （r=0.23，P=0.03），PDSS （r=0.36，P=0.01） and rigidity （r=0.27，P=0.04） scores. Conclusion　①There are gender differences bewteen males and females in motor disorders in depression of parkinson’s disease. ②The motor disorders and non-motor disorders were more severe in depression of parkinson’s disease than in non-depression of parkinson’s disease. ③The HAMD score in depression of parkinson’s disease correlated with levodopa equivalent doses，the motor disorders and the non-motor disorders. ④The spectrum of motor and non-motor symptoms showed different gender distribution in PD and dPD patients. Gender-specific therapeutic agents hold particula attention for developing treatments with optimal efficaty in men and women in the future.