Background:The differential diagnosis of Parkinson’s disease(PD)and multiple system atrophy(MSA)remains a challenge,especially in the early stage.Here,we assessed the value of transcranial sonography(TCS)to discrimin...Background:The differential diagnosis of Parkinson’s disease(PD)and multiple system atrophy(MSA)remains a challenge,especially in the early stage.Here,we assessed the value of transcranial sonography(TCS)to discriminate non-tremor dominant(non-TD)PD from MSA with predominant parkinsonism(MSA-P).Methods:Eighty-six MSA-P patients and 147 age and gender-matched non-TD PD patients who had appropriate temporal acoustic bone windows were included in this study.All the patients were followed up for at least 2 years to confirm the initial diagnosis.Patients with at least one substantia nigra(SN)echogenic size≥18 mm^(2) were classified as hyperechogenic,those with at least one SN echogenic size≥25 mm^(2) was defined as markedly hyperechogenic.Results:The frequency of SN hyperechogenicity in non-TD PD patients was significantly higher than that in MSA-P patients(74.1%vs.38.4%,p<0.001).SN hyperechogenicity discriminated non-TD PD from MSA-P with sensitivity of 74.1%,specificity of 61.6%,and positive predictive value of 76.8%.If marked SN hyperechogenicity was used as the cutoff value(≥25 mm^(2)),the sensitivity decreased to 46.3%,but the specificity and positive predictive value increased to 80.2 and 80.0%.Additionally,in those patients with SN hyperechogenicity,positive correlation between SN hyperechogenicity area and disease duration was found in non-TD PD rather than in MSA-P patients.In this context,among early-stage patients with disease duration≤3 years,the sensitivity,specificity and positive predictive value of SN hyperechogenicity further declined to 69.8%,52.2%,and 66.7%,respectively.Conclusions:TCS could help discriminate non-TD PD from MSA-P in a certain extent,but the limitation was also obvious with relatively low specificity,especially in the early stage.展开更多
Objectives:Both hyposmia and substania nigra(SN)hyperechogenicity on trascranial sonography(TCS)were risk markers for idiopathic Parkinson’s disease(PD),which was beneficial to the differential diagnosis of the disea...Objectives:Both hyposmia and substania nigra(SN)hyperechogenicity on trascranial sonography(TCS)were risk markers for idiopathic Parkinson’s disease(PD),which was beneficial to the differential diagnosis of the disease.However,each of their single diagnostic value is often limited.The purpose of present study was to explore whether the combination of olfactory test and TCS of SN could enhance the differential diagnostic power in Chinese patients with PD.Methods:Thirty-seven patients with PD and twenty-six patients with essential tremor(ET)were evaluated on 16-item odor identification test from extended version of sniffin’sticks and TCS of SN.The frequency of hyposmia and SN hyperechogenicity in each group was compared.The sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)of the two clinical biomarkers were analyzed.Results:The frequency of hyposmia in patients with PD was significantly higher than in patients with ET(62.2%VS.3.8%,P=0.000).The frequency of SN hyperechogenicity in patients with PD was significantly higher than in ET subjects(48.6%VS.15.4%,P=0.006).The combination of hyposmia and SN hyperechogenicity(if either one or both present)discriminated patients with PD from ET with a sensitivity of 78.4%and 29.7%,specificity of 80.8%and 100%,PPV of 85.3%and 100%,and NPV of 72.4%and 50.0%,respectively.Conclusions:Our preliminary data suggested that the combination of hyposmia and SN hyperechogenicity could improve the diagnostic potential for discriminating Chinese patients with PD from ET.展开更多
Background:Tai Chi has been shown to improve motor symptoms in Parkinson’s disease(PD),but its long-term effects and the related mechanisms remain to be elucidated.In this study,we investigated the effects of long-te...Background:Tai Chi has been shown to improve motor symptoms in Parkinson’s disease(PD),but its long-term effects and the related mechanisms remain to be elucidated.In this study,we investigated the effects of long-term Tai Chi training on motor symptoms in PD and the underlying mechanisms.Methods:Ninety-five early-stage PD patients were enrolled and randomly divided into Tai Chi(n=32),brisk walk-ing(n=31)and no-exercise(n=32)groups.At baseline,6 months and 12 months during one-year intervention,all participants underwent motor symptom evaluation by Berg balance scale(BBS),Unified PD rating-scale(UPDRS),Timed Up and Go test(TUG)and 3D gait analysis,functional magnetic resonance imaging(fMRI),plasma cytokine and metabolomics analysis,and blood Huntingtin interaction protein 2(HIP2)mRNA level analysis.Longitudinal self-changes were calculated using repeated measures ANOVA.GEE(generalized estimating equations)was used to assess factors associated with the longitudinal data of rating scales.Switch rates were used for fMRI analysis.False discovery rate correction was used for multiple correction.Results:Participants in the Tai Chi group had better performance in BBS,UPDRS,TUG and step width.Besides,Tai Chi was advantageous over brisk walking in improving BBS and step width.The improved BBS was correlated with enhanced visual network function and downregulation of interleukin-1β.The improvements in UPDRS were asso-ciated with enhanced default mode network function,decreased L-malic acid and 3-phosphoglyceric acid,and increased adenosine and HIP2 mRNA levels.In addition,arginine biosynthesis,urea cycle,tricarboxylic acid cycle and beta oxidation of very-long-chain fatty acids were also improved by Tai Chi training.Conclusions:Long-term Tai Chi training improves motor function,especially gait and balance,in PD.The underlying mechanisms may include enhanced brain network function,reduced inflammation,improved amino acid metabolism,energy metabolism and neurotransmitter metabolism,and decreased vulnerability to dopaminergic degeneration.Trial registration This study has been registered at Chinese Clinical Trial Registry(Registration number:ChiCTR2000036036;Registration date:August 22,2020).展开更多
Curcumin,a natural polyphenol obtained from turmeric,has been implicated to be neuroprotective in a variety of neurodegenerative disorders although the mechanism remains poorly understood.The results of our recent exp...Curcumin,a natural polyphenol obtained from turmeric,has been implicated to be neuroprotective in a variety of neurodegenerative disorders although the mechanism remains poorly understood.The results of our recent experiments indicated that curcumin could protect dopaminergic neurons from apoptosis in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)mouse model of Parkinson’s disease(PD).The death of dopaminergic neurons and the loss of dopaminergic axon in the striatum were significantly suppressed by curcumin in MPTP mouse model.Further studies showed that curcumin inhibited JNKs hyperphosphorylation induced by MPTP treatment.JNKs phosphorylation can cause translocation of Bax to mitochondria and the release of cytochrome c which both ultimately contribute to mitochondria-mediated apoptosis.These pro-apoptosis effect can be diminished by curcumin.Our experiments demonstrated that curcumin can prevent nigrostriatal degeneration by inhibiting the dysfunction of mitochondrial through suppressing hyperphosphorylation of JNKs induced by MPTP.Our results suggested that JNKs/mitochondria pathway may be a novel target in the treatment of PD patients.展开更多
Correction to:Translational Neurodegeneration(2023)12:5 https://doi.org/10.1186/s40035-023-00337-1 Following publication of this article[1],three errors were identified about the reference.Correction 1:136.Crocker TF,...Correction to:Translational Neurodegeneration(2023)12:5 https://doi.org/10.1186/s40035-023-00337-1 Following publication of this article[1],three errors were identified about the reference.Correction 1:136.Crocker TF,Brown L,Lam N,Wray F,Knapp P,Forster A.Information provision for stroke survi-vors and their carers.Cochrane Database Syst Rev.2021;11:CD001919.136.Menni C,Valdes AM,Polidori L,Antonelli M,Penamakuri S,Nogal A,et al.Symptom prevalence,duration,and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance:a prospective observational study from the ZOE COVID study.Lancet.2022;399:1618-24.展开更多
The impact of coronavirus disease 2019(COVID-19)pandemic on patients with neurodegenerative diseases and the specific neurological manifestations of COVID-19 have aroused great interest.However,there are still many is...The impact of coronavirus disease 2019(COVID-19)pandemic on patients with neurodegenerative diseases and the specific neurological manifestations of COVID-19 have aroused great interest.However,there are still many issues of concern to be clarified.Therefore,we review the current literature on the complex relationship between COVID-19 and neurodegenerative diseases with an emphasis on Parkinson’s disease(PD)and Alzheimer’s disease(AD).We summarize the impact of COVID-19 infection on symptom severity,disease progression,and mortality rate of PD and AD,and discuss whether COVID-19 infection could trigger PD and AD.In addition,the susceptibility to and the prognosis of COVID-19 in PD patients and AD patients are also included.In order to achieve better management of PD and AD patients,modifications of care strategies,specific drug therapies,and vaccines during the pandemic are also listed.At last,mechanisms underlying the link of COVID-19 with PD and AD are reviewed.展开更多
Background Little is known about the impact of the COVID-19 pandemic on patients with Parkinson’s disease(PD)at different stages of the pandemic.This study aims to assess the lives and disease status of PD patients d...Background Little is known about the impact of the COVID-19 pandemic on patients with Parkinson’s disease(PD)at different stages of the pandemic.This study aims to assess the lives and disease status of PD patients during the zero-COVID policy period and after ending the zero-COVID policy.Methods This multicenter cross-sectional study included two online surveys among PD patients in China,from May 30 to June 30 in 2022 and from January 1 to February 28 in 2023,respectively.The survey questionnaires contained four sections:(1)status of COVID-19 infection;(2)impact on motor and non-motor symptoms;(3)impact on daily and social lives;and(4)impact on PD disease management.Results A total of 1764 PD patients participated in the first online survey,with 200 patients having lockdown experience and 3 being COVID-19-positive(0.17%).In addition,537 patients participated in the second online survey,with 467 patients having COVID-19 infection(86.96%).(1)During zero-COVID,all of the COVID-19-positive patients had mild symptoms of COVID-19 and no death was reported.After zero-COVID,83.51%of the COVID-19-positive patients had mild symptoms.The overall death rate and inpatient mortality rate of COVID-19-positive PD patients were 3.21%and 30.00%,respectively.(2)During zero-COVID,49.43%of PD patients reported worsening of PD-related symptoms(lockdown vs.unlockdown,60.50%vs.48.02%,P=0.0009).After zero-COVID,54.93%of PD patients reported worsening of PD-related symptoms(COVID-19 positive vs.COVID-19 negative,59.31%vs.25.71%,P<0.0001).(3)During zero-COVID,62.36%of patients felt worried,and‘limited outdoor activities’(55.39%)was the top reason for mental health problems.After zero-COVID,59.03%of patients felt worried,with‘poor health’(58.10%)being the top reason.The PD patients tended to change their daily activities from offline to online,and their economic and caregiver burdens increased both during and after zero-COVID.(4)Most PD patients would like to choose online rehabilitation during(69.56%)and after zero-COVID(69.27%).The demand for online medication purchasing also increased during(47.00%)and after zero-COVID(26.63%).Conclusions The COVID-19 pandemic aggravated the motor and non-motor symptoms of PD patients either during or after the zero-COVID policy period.The PD patients also experienced prominent mental health problems,changes in daily activities,and increases in economic and caregiver burdens.The COVID-19 pandemic has changed ways of PD management with increasing demands for online medication purchasing and rehabilitation.展开更多
基金This study was supported by Natural Science Fund of China(No.81430022,81371407,81771374)Innovation Program of Shanghai Municipal Education Commission(2017–01–07-00-01-E00046)Natural Science Foundation of Science and Technology of Shanghai(No.15ZR1426700).
文摘Background:The differential diagnosis of Parkinson’s disease(PD)and multiple system atrophy(MSA)remains a challenge,especially in the early stage.Here,we assessed the value of transcranial sonography(TCS)to discriminate non-tremor dominant(non-TD)PD from MSA with predominant parkinsonism(MSA-P).Methods:Eighty-six MSA-P patients and 147 age and gender-matched non-TD PD patients who had appropriate temporal acoustic bone windows were included in this study.All the patients were followed up for at least 2 years to confirm the initial diagnosis.Patients with at least one substantia nigra(SN)echogenic size≥18 mm^(2) were classified as hyperechogenic,those with at least one SN echogenic size≥25 mm^(2) was defined as markedly hyperechogenic.Results:The frequency of SN hyperechogenicity in non-TD PD patients was significantly higher than that in MSA-P patients(74.1%vs.38.4%,p<0.001).SN hyperechogenicity discriminated non-TD PD from MSA-P with sensitivity of 74.1%,specificity of 61.6%,and positive predictive value of 76.8%.If marked SN hyperechogenicity was used as the cutoff value(≥25 mm^(2)),the sensitivity decreased to 46.3%,but the specificity and positive predictive value increased to 80.2 and 80.0%.Additionally,in those patients with SN hyperechogenicity,positive correlation between SN hyperechogenicity area and disease duration was found in non-TD PD rather than in MSA-P patients.In this context,among early-stage patients with disease duration≤3 years,the sensitivity,specificity and positive predictive value of SN hyperechogenicity further declined to 69.8%,52.2%,and 66.7%,respectively.Conclusions:TCS could help discriminate non-TD PD from MSA-P in a certain extent,but the limitation was also obvious with relatively low specificity,especially in the early stage.
基金This study was supported by grants from the National Program of Basic Research(2011CB504104)of ChinaNational“Twelfth Five-Year”Plan for Science&Technology Support(2012BAI10B03)+1 种基金Shanghai Key Project of Basic Science Research(10411954500)Program for Outstanding Medical Academic Leader(LJ 06003)。
文摘Objectives:Both hyposmia and substania nigra(SN)hyperechogenicity on trascranial sonography(TCS)were risk markers for idiopathic Parkinson’s disease(PD),which was beneficial to the differential diagnosis of the disease.However,each of their single diagnostic value is often limited.The purpose of present study was to explore whether the combination of olfactory test and TCS of SN could enhance the differential diagnostic power in Chinese patients with PD.Methods:Thirty-seven patients with PD and twenty-six patients with essential tremor(ET)were evaluated on 16-item odor identification test from extended version of sniffin’sticks and TCS of SN.The frequency of hyposmia and SN hyperechogenicity in each group was compared.The sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)of the two clinical biomarkers were analyzed.Results:The frequency of hyposmia in patients with PD was significantly higher than in patients with ET(62.2%VS.3.8%,P=0.000).The frequency of SN hyperechogenicity in patients with PD was significantly higher than in ET subjects(48.6%VS.15.4%,P=0.006).The combination of hyposmia and SN hyperechogenicity(if either one or both present)discriminated patients with PD from ET with a sensitivity of 78.4%and 29.7%,specificity of 80.8%and 100%,PPV of 85.3%and 100%,and NPV of 72.4%and 50.0%,respectively.Conclusions:Our preliminary data suggested that the combination of hyposmia and SN hyperechogenicity could improve the diagnostic potential for discriminating Chinese patients with PD from ET.
基金the National Natural Science Foundation of China(81430022,91332107,81371407,81801267,31771174,82151303)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)Shanghai Municipal Education Commission(2017NKX001).
文摘Background:Tai Chi has been shown to improve motor symptoms in Parkinson’s disease(PD),but its long-term effects and the related mechanisms remain to be elucidated.In this study,we investigated the effects of long-term Tai Chi training on motor symptoms in PD and the underlying mechanisms.Methods:Ninety-five early-stage PD patients were enrolled and randomly divided into Tai Chi(n=32),brisk walk-ing(n=31)and no-exercise(n=32)groups.At baseline,6 months and 12 months during one-year intervention,all participants underwent motor symptom evaluation by Berg balance scale(BBS),Unified PD rating-scale(UPDRS),Timed Up and Go test(TUG)and 3D gait analysis,functional magnetic resonance imaging(fMRI),plasma cytokine and metabolomics analysis,and blood Huntingtin interaction protein 2(HIP2)mRNA level analysis.Longitudinal self-changes were calculated using repeated measures ANOVA.GEE(generalized estimating equations)was used to assess factors associated with the longitudinal data of rating scales.Switch rates were used for fMRI analysis.False discovery rate correction was used for multiple correction.Results:Participants in the Tai Chi group had better performance in BBS,UPDRS,TUG and step width.Besides,Tai Chi was advantageous over brisk walking in improving BBS and step width.The improved BBS was correlated with enhanced visual network function and downregulation of interleukin-1β.The improvements in UPDRS were asso-ciated with enhanced default mode network function,decreased L-malic acid and 3-phosphoglyceric acid,and increased adenosine and HIP2 mRNA levels.In addition,arginine biosynthesis,urea cycle,tricarboxylic acid cycle and beta oxidation of very-long-chain fatty acids were also improved by Tai Chi training.Conclusions:Long-term Tai Chi training improves motor function,especially gait and balance,in PD.The underlying mechanisms may include enhanced brain network function,reduced inflammation,improved amino acid metabolism,energy metabolism and neurotransmitter metabolism,and decreased vulnerability to dopaminergic degeneration.Trial registration This study has been registered at Chinese Clinical Trial Registry(Registration number:ChiCTR2000036036;Registration date:August 22,2020).
基金This work was supported by grants from the National Program of Basic Research(2010CB945200,2011CB504104)of ChinaNational Natural Science Fund(34900454,30900454,30971031)+4 种基金Key Discipline Program of Shanghai Municipality(S30202)Shanghai Key Project of Basic Science Research(10411954500)Program for Outstanding Medical Academic Leader(LJ 06003)Research Fund for the Doctoral Program of Higher Education of China(20090073120090)Special funding for original sci-tech research supported by Shanghai Municipal Education Commission(09YZ87).
文摘Curcumin,a natural polyphenol obtained from turmeric,has been implicated to be neuroprotective in a variety of neurodegenerative disorders although the mechanism remains poorly understood.The results of our recent experiments indicated that curcumin could protect dopaminergic neurons from apoptosis in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)mouse model of Parkinson’s disease(PD).The death of dopaminergic neurons and the loss of dopaminergic axon in the striatum were significantly suppressed by curcumin in MPTP mouse model.Further studies showed that curcumin inhibited JNKs hyperphosphorylation induced by MPTP treatment.JNKs phosphorylation can cause translocation of Bax to mitochondria and the release of cytochrome c which both ultimately contribute to mitochondria-mediated apoptosis.These pro-apoptosis effect can be diminished by curcumin.Our experiments demonstrated that curcumin can prevent nigrostriatal degeneration by inhibiting the dysfunction of mitochondrial through suppressing hyperphosphorylation of JNKs induced by MPTP.Our results suggested that JNKs/mitochondria pathway may be a novel target in the treatment of PD patients.
文摘Correction to:Translational Neurodegeneration(2023)12:5 https://doi.org/10.1186/s40035-023-00337-1 Following publication of this article[1],three errors were identified about the reference.Correction 1:136.Crocker TF,Brown L,Lam N,Wray F,Knapp P,Forster A.Information provision for stroke survi-vors and their carers.Cochrane Database Syst Rev.2021;11:CD001919.136.Menni C,Valdes AM,Polidori L,Antonelli M,Penamakuri S,Nogal A,et al.Symptom prevalence,duration,and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance:a prospective observational study from the ZOE COVID study.Lancet.2022;399:1618-24.
基金supported in part by grants from the National Natural Science Foundation of China(Grant Nos.81971183,81971187,82171401,82001249)Shanghai Municipal Science and Technology Major Project(Grant No.2018SHZDZX05)+1 种基金Shanghai Sailing Program(Grant No.20YF1440200)Natural Science Foundation of Shanghai(Grant No.20ZR1445400).
文摘The impact of coronavirus disease 2019(COVID-19)pandemic on patients with neurodegenerative diseases and the specific neurological manifestations of COVID-19 have aroused great interest.However,there are still many issues of concern to be clarified.Therefore,we review the current literature on the complex relationship between COVID-19 and neurodegenerative diseases with an emphasis on Parkinson’s disease(PD)and Alzheimer’s disease(AD).We summarize the impact of COVID-19 infection on symptom severity,disease progression,and mortality rate of PD and AD,and discuss whether COVID-19 infection could trigger PD and AD.In addition,the susceptibility to and the prognosis of COVID-19 in PD patients and AD patients are also included.In order to achieve better management of PD and AD patients,modifications of care strategies,specific drug therapies,and vaccines during the pandemic are also listed.At last,mechanisms underlying the link of COVID-19 with PD and AD are reviewed.
基金supported in part by grants from the National Natural Science Foundation of China(82171401,81971187,81971183,82371414)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05).
文摘Background Little is known about the impact of the COVID-19 pandemic on patients with Parkinson’s disease(PD)at different stages of the pandemic.This study aims to assess the lives and disease status of PD patients during the zero-COVID policy period and after ending the zero-COVID policy.Methods This multicenter cross-sectional study included two online surveys among PD patients in China,from May 30 to June 30 in 2022 and from January 1 to February 28 in 2023,respectively.The survey questionnaires contained four sections:(1)status of COVID-19 infection;(2)impact on motor and non-motor symptoms;(3)impact on daily and social lives;and(4)impact on PD disease management.Results A total of 1764 PD patients participated in the first online survey,with 200 patients having lockdown experience and 3 being COVID-19-positive(0.17%).In addition,537 patients participated in the second online survey,with 467 patients having COVID-19 infection(86.96%).(1)During zero-COVID,all of the COVID-19-positive patients had mild symptoms of COVID-19 and no death was reported.After zero-COVID,83.51%of the COVID-19-positive patients had mild symptoms.The overall death rate and inpatient mortality rate of COVID-19-positive PD patients were 3.21%and 30.00%,respectively.(2)During zero-COVID,49.43%of PD patients reported worsening of PD-related symptoms(lockdown vs.unlockdown,60.50%vs.48.02%,P=0.0009).After zero-COVID,54.93%of PD patients reported worsening of PD-related symptoms(COVID-19 positive vs.COVID-19 negative,59.31%vs.25.71%,P<0.0001).(3)During zero-COVID,62.36%of patients felt worried,and‘limited outdoor activities’(55.39%)was the top reason for mental health problems.After zero-COVID,59.03%of patients felt worried,with‘poor health’(58.10%)being the top reason.The PD patients tended to change their daily activities from offline to online,and their economic and caregiver burdens increased both during and after zero-COVID.(4)Most PD patients would like to choose online rehabilitation during(69.56%)and after zero-COVID(69.27%).The demand for online medication purchasing also increased during(47.00%)and after zero-COVID(26.63%).Conclusions The COVID-19 pandemic aggravated the motor and non-motor symptoms of PD patients either during or after the zero-COVID policy period.The PD patients also experienced prominent mental health problems,changes in daily activities,and increases in economic and caregiver burdens.The COVID-19 pandemic has changed ways of PD management with increasing demands for online medication purchasing and rehabilitation.
