Olfactory dysfunction is common in Parkinson's disease (PD) and often predates the diagnosis by years, reflecting early deposition of Lewy pathology, the histo- logic hallmark of PD, in the olfactory bulb. Clinical...Olfactory dysfunction is common in Parkinson's disease (PD) and often predates the diagnosis by years, reflecting early deposition of Lewy pathology, the histo- logic hallmark of PD, in the olfactory bulb. Clinical tests are available that allow for the rapid characterization of olfactory dysfunction, including tests of odor identification, discrimination, detection, and recognition thresholds, memory, and tests assessing the build-up of odor intensity across increasing suprathreshold stimulus concentrations. The high prevalence of olfactory impairment, along with the ease and low cost of assessment, has fostered great interest in olfaction as a potential biomarker for PD. Hyposmia may help differentiate PD from other causes of parkinsonism, and may also aid in the identification of "pre-motor" PD due to the early pathologic involvement of olfactory pathways. Olfactory function is also correlated with other non-motor features of PD and may serve as a predictor of cognitive decline. In this article, we summarize the existing literature on olfaction in PD, focusing on the potential for olfaction as a biomarker for early or differential diagnosis and prognosis.展开更多
Rapid eye movement sleep behavior disorder (RBD) is one of the most common non-motor symptoms of parkinsonism, and it may serve as a prodromal marker of neurodegenerative disease. The mechanism underlying RBD is unc...Rapid eye movement sleep behavior disorder (RBD) is one of the most common non-motor symptoms of parkinsonism, and it may serve as a prodromal marker of neurodegenerative disease. The mechanism underlying RBD is unclear. Several prospective studies have reported that specific non-motor symptoms predict a conversion risk of developing a neurodegenerative disease, including olfactory dysfunction, abnormal color vision, autonomic dysfunction, excessive daytime sleepiness, depression, and cognitive impairment. Parkinson's disease (PD) with RBD exhibits clinical heterogeneity with respect to motor and non-motor symptoms compared with PD without RBD. In this review, we describe the main clinical and pathogenic features of RBD, focusing on its association with other non-motor symptoms of parkinsonism.展开更多
Background: Both Parkinson's disease (PD) and multiple system atrophy (MSA) have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism (...Background: Both Parkinson's disease (PD) and multiple system atrophy (MSA) have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism (MSA-P) resembles PD in the manifestation of prominent parkinsonism, Whether the amount of rapid eye movement (REM) sleep without atonia could be a potential marker for differentiating MSA-P from PD has not been thoroughly investigated. This study aimed to examine whether sleep parameters could provide a method for differentiating MSA-P from PD. Methods: This study comprised 24 MSA-P patients and 30 PD patients, and they were of similar age, gender, and REM sleep behavior disorder (RBD) prevalence. All patients underwent clinical evaluation and one night of video-polysomnography recording. The tonic and phasic chin electromyogram (EMG) activity was manually quantified during REM sleep of each patient. We divided both groups in terms of whether they had RBD to make subgroup analysis. Results: No significant difference between MSA-P group and PD group had been tbund in clinical characteristics and sleep architecture. However, MSA-P patients had higher apnea-hypopnea index (AHI; 1.15 [0.00, 8.73]/h vs. 0.00 [0.00, 0.55]/h, P = 0.024) and higher tonic chin EMG density (34.02 [ 18.48, 57.18]% vs. 8.40 [3.11, 13.061%, P 〈 0.001 ) as compared to PD patients. Subgroup analysis found that tonic EMG density in MSA + RBD subgroup was higher than that in PD + RBD subgroup (55.04 [26.81,69.62]% vs. 11.40 [8.51,20.411%, P 〈 0.001 ). Furthermore, no evidence of any difference in tonic EMG density emerged between PD + RBD and MSA - RBD subgroups (P 〉 0.05). Both disease duration (P = 0.056) and AHI (P = 0.051) showed no significant differences during subgroup analysis although there was a trend toward longer disease duration in PD + RBD subgroup and higher AHI in MSA - RBD subgroup. Stepwise multiple linear regression analysis identified the presence of M展开更多
Recent researches have found that 7 Tesla SWI can detect the alteration of substantia nigra hyperintensity in Parkinson's disease(PD),multiple system atrophy(MSA),and progressive supranuclear palsy(PSP).The aim of...Recent researches have found that 7 Tesla SWI can detect the alteration of substantia nigra hyperintensity in Parkinson's disease(PD),multiple system atrophy(MSA),and progressive supranuclear palsy(PSP).The aim of this study was to investigate whether 3 Tesla SWI(3T SWI)can visualize anatomical alterations occurring in a hyperintense structure of the substantia nigra in PD and vascular parkinsonism(VP),and whether the evaluation of abnormal signal can be used as a factor in the differential diagnosis of PD and VP.Using 3 Tesla MRI,we evaluated 38 healthy subjects,33 patients with PD and 34 patients with VP.Two blinded readers independently assessed the images.We found that the dorsolateral nigral hyperintensity was absent in 31 of 33 patients with PD and 15 of 34 patients with VP.The dorsolateral nigral hyperintensity was present in 19 of 34 patients with VP and 35 of 38 healthy controls.Group comparisons of absence of dorsolateral nigral hyperintensity revealed significant differences between the patients with PD and those with VP(P<0.001).The sensitivity of SWI for PD was 93.9%and the specificity was 92.1%.Visual assessment of dorsolateral nigral hyperintensity on high-field SWI scans may serve as a new simple diagnostic imaging marker for PD.And our study results indicate that 3T SWI can be used as a tool to identify PD and VP.展开更多
Age and gender are the important factors for brain metabolic declines in both normal aging and neurodegeneration,and the confounding effects may influence early and differential diagnosis of neurodegenerative diseases...Age and gender are the important factors for brain metabolic declines in both normal aging and neurodegeneration,and the confounding effects may influence early and differential diagnosis of neurodegenerative diseases based on the[^(18)F]fluorodeoxyglucose positron emission tomography([^(18)F]FDG PET).We aimed to explore the potential of the adjustment of age-and gender-related confounding factors on[^(18)F]FDG PET images in differentiation of Parkinson’s disease(PD),multiple system atrophy(MSA)and progressive supra-nuclear palsy(PSP).Eight hundred and seventy-seven clinically definitely diagnosed Parkinsonian patients from a benchmark Huashan Parkinsonian PET imaging database were included.An age-and gender-adjusted Z(AGAZ)score was established based on the gender-specific longitudinal metabolic changes on healthy subjects.AGAZ scores and standardized uptake value ratio(SUVR)values were quantified at regional-level and support vector machine-based error-correcting output codes method was applied for classification.Additional references of the classifications based on metabolic pattern scores were included.The feature-based AGAZ score showed the best performance in classification(accuracy for PD,MSA,PSP:93.1%,96.3%,94.8%).In both genders,the AGAZ score con-sistently achieved the best efficiency,and the improvements compared to the conventional SUVR value for PD,MSA,and PSP mainly laid in specificity(Male:5.7%;Female:11.1%),sensitivity(Male:7.2%;Female:7.3%),and sensitivity(Male:7.3%;Female:17.2%).Female patients benefited more from the adjustment on[^(18)F]FDG PET in MSA and PSP groups(absolute net reclassification index,p<0.001).Collectively,the adjustment of age-and gender-related confounding factors may improve the differential diagnosis of Parkinsonism.Particularly,the diagnosis of female Parkinsonian population has the best improvement from this correction.展开更多
Neurological and psychiatric complications continue to be a public health concern in long coronavirus disease 2019(COVID-19).This varies from olfactory dysfunctions such as parosmia to cognitive and emotional challeng...Neurological and psychiatric complications continue to be a public health concern in long coronavirus disease 2019(COVID-19).This varies from olfactory dysfunctions such as parosmia to cognitive and emotional challenges.Historically,the surge of neurological disorders followed the viral pandemics,for example,the emergence of Encephalitis Lethargica after the outbreak of Spanish Influenza.During and after COVID-19 infection,the problems associated with the sense of smell and the reports of affected olfactory and limbic brain areas are leading to a growing concern about the similarity with the symptoms and the pattern of degeneration observed at the onset of Parkinson's disease and Alzheimer's disease.These reports reveal the essentiality of long-term studies of olfactory and cognitive functions in the post-COVID era and the experiments using animal models to dissect the neural basis of these complications.In this manuscript,we summarize the research reporting the potential correlation between neurological disorders and viral pandemic outbreaks with a historical perspective.Further,we discuss the studies providing evidence of neurodegeneration due to severe acute respiratory syndrome coronavirus 2 infection by focusing on viral Parkinsonism.展开更多
Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism....Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.展开更多
文摘Olfactory dysfunction is common in Parkinson's disease (PD) and often predates the diagnosis by years, reflecting early deposition of Lewy pathology, the histo- logic hallmark of PD, in the olfactory bulb. Clinical tests are available that allow for the rapid characterization of olfactory dysfunction, including tests of odor identification, discrimination, detection, and recognition thresholds, memory, and tests assessing the build-up of odor intensity across increasing suprathreshold stimulus concentrations. The high prevalence of olfactory impairment, along with the ease and low cost of assessment, has fostered great interest in olfaction as a potential biomarker for PD. Hyposmia may help differentiate PD from other causes of parkinsonism, and may also aid in the identification of "pre-motor" PD due to the early pathologic involvement of olfactory pathways. Olfactory function is also correlated with other non-motor features of PD and may serve as a predictor of cognitive decline. In this article, we summarize the existing literature on olfaction in PD, focusing on the potential for olfaction as a biomarker for early or differential diagnosis and prognosis.
基金supported by the National Natural Science Foundation of China (91649114)the Jiangsu Provincial Special Program of Medical Science, China (BL2014042)+3 种基金a Jiangsu Provincial Medical Key Discipline Projectthe Suzhou Clinical Research Center of Neurological Disease (Szzx201503)Jiangsu Province Ordinary University Professional Degree Graduate Practice Innovation, China (SJZZ16-0242)the Priority Academic Program Development of Jiangsu Higher Education Institutions, China
文摘Rapid eye movement sleep behavior disorder (RBD) is one of the most common non-motor symptoms of parkinsonism, and it may serve as a prodromal marker of neurodegenerative disease. The mechanism underlying RBD is unclear. Several prospective studies have reported that specific non-motor symptoms predict a conversion risk of developing a neurodegenerative disease, including olfactory dysfunction, abnormal color vision, autonomic dysfunction, excessive daytime sleepiness, depression, and cognitive impairment. Parkinson's disease (PD) with RBD exhibits clinical heterogeneity with respect to motor and non-motor symptoms compared with PD without RBD. In this review, we describe the main clinical and pathogenic features of RBD, focusing on its association with other non-motor symptoms of parkinsonism.
文摘Background: Both Parkinson's disease (PD) and multiple system atrophy (MSA) have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism (MSA-P) resembles PD in the manifestation of prominent parkinsonism, Whether the amount of rapid eye movement (REM) sleep without atonia could be a potential marker for differentiating MSA-P from PD has not been thoroughly investigated. This study aimed to examine whether sleep parameters could provide a method for differentiating MSA-P from PD. Methods: This study comprised 24 MSA-P patients and 30 PD patients, and they were of similar age, gender, and REM sleep behavior disorder (RBD) prevalence. All patients underwent clinical evaluation and one night of video-polysomnography recording. The tonic and phasic chin electromyogram (EMG) activity was manually quantified during REM sleep of each patient. We divided both groups in terms of whether they had RBD to make subgroup analysis. Results: No significant difference between MSA-P group and PD group had been tbund in clinical characteristics and sleep architecture. However, MSA-P patients had higher apnea-hypopnea index (AHI; 1.15 [0.00, 8.73]/h vs. 0.00 [0.00, 0.55]/h, P = 0.024) and higher tonic chin EMG density (34.02 [ 18.48, 57.18]% vs. 8.40 [3.11, 13.061%, P 〈 0.001 ) as compared to PD patients. Subgroup analysis found that tonic EMG density in MSA + RBD subgroup was higher than that in PD + RBD subgroup (55.04 [26.81,69.62]% vs. 11.40 [8.51,20.411%, P 〈 0.001 ). Furthermore, no evidence of any difference in tonic EMG density emerged between PD + RBD and MSA - RBD subgroups (P 〉 0.05). Both disease duration (P = 0.056) and AHI (P = 0.051) showed no significant differences during subgroup analysis although there was a trend toward longer disease duration in PD + RBD subgroup and higher AHI in MSA - RBD subgroup. Stepwise multiple linear regression analysis identified the presence of M
文摘Recent researches have found that 7 Tesla SWI can detect the alteration of substantia nigra hyperintensity in Parkinson's disease(PD),multiple system atrophy(MSA),and progressive supranuclear palsy(PSP).The aim of this study was to investigate whether 3 Tesla SWI(3T SWI)can visualize anatomical alterations occurring in a hyperintense structure of the substantia nigra in PD and vascular parkinsonism(VP),and whether the evaluation of abnormal signal can be used as a factor in the differential diagnosis of PD and VP.Using 3 Tesla MRI,we evaluated 38 healthy subjects,33 patients with PD and 34 patients with VP.Two blinded readers independently assessed the images.We found that the dorsolateral nigral hyperintensity was absent in 31 of 33 patients with PD and 15 of 34 patients with VP.The dorsolateral nigral hyperintensity was present in 19 of 34 patients with VP and 35 of 38 healthy controls.Group comparisons of absence of dorsolateral nigral hyperintensity revealed significant differences between the patients with PD and those with VP(P<0.001).The sensitivity of SWI for PD was 93.9%and the specificity was 92.1%.Visual assessment of dorsolateral nigral hyperintensity on high-field SWI scans may serve as a new simple diagnostic imaging marker for PD.And our study results indicate that 3T SWI can be used as a tool to identify PD and VP.
基金supported by National Natural Science Foundation of China(81671239,81361120393,82171252,81701250,81401135,81971641,91949118,81771372,82021002)the Ministry of Science and Technology of China(2016YFC1306504)+5 种基金Shanghai Municipal Science and Technology Major Project(2017SHZDZX01,2018SHZDZX03)ZJ Lab,Shanghai Aging and Maternal and Child Health Research Special Project(2020YJZX0111)Clinical Research Plan of Shanghai Hospital Development Center(SHDC-2020CR1038B),Science and Technology Innovation 2030 Major Projects(2022ZD0211600)Youth Medical Talents-Medical Imaging Practitioner Program by Shanghai Municipal Health Commission and Shanghai Medical and Health Development Foundation(SHWRS(2020)_087)the Swiss National Science Foundation(188350)Jacques&Gloria Gossweiler Foundation and Siemens Healthineers.
文摘Age and gender are the important factors for brain metabolic declines in both normal aging and neurodegeneration,and the confounding effects may influence early and differential diagnosis of neurodegenerative diseases based on the[^(18)F]fluorodeoxyglucose positron emission tomography([^(18)F]FDG PET).We aimed to explore the potential of the adjustment of age-and gender-related confounding factors on[^(18)F]FDG PET images in differentiation of Parkinson’s disease(PD),multiple system atrophy(MSA)and progressive supra-nuclear palsy(PSP).Eight hundred and seventy-seven clinically definitely diagnosed Parkinsonian patients from a benchmark Huashan Parkinsonian PET imaging database were included.An age-and gender-adjusted Z(AGAZ)score was established based on the gender-specific longitudinal metabolic changes on healthy subjects.AGAZ scores and standardized uptake value ratio(SUVR)values were quantified at regional-level and support vector machine-based error-correcting output codes method was applied for classification.Additional references of the classifications based on metabolic pattern scores were included.The feature-based AGAZ score showed the best performance in classification(accuracy for PD,MSA,PSP:93.1%,96.3%,94.8%).In both genders,the AGAZ score con-sistently achieved the best efficiency,and the improvements compared to the conventional SUVR value for PD,MSA,and PSP mainly laid in specificity(Male:5.7%;Female:11.1%),sensitivity(Male:7.2%;Female:7.3%),and sensitivity(Male:7.3%;Female:17.2%).Female patients benefited more from the adjustment on[^(18)F]FDG PET in MSA and PSP groups(absolute net reclassification index,p<0.001).Collectively,the adjustment of age-and gender-related confounding factors may improve the differential diagnosis of Parkinsonism.Particularly,the diagnosis of female Parkinsonian population has the best improvement from this correction.
基金DBT/Wellcome Trust India Alliance senior,Grant/Award Number:IA/S/22/2/506517Ramalingaswami Fellowship,Department of Biotechnology,Govt.of India,Grant/Award Number:BT/RLF/Re-entry/45/2014Council of Scientific and Industrial Research,India。
文摘Neurological and psychiatric complications continue to be a public health concern in long coronavirus disease 2019(COVID-19).This varies from olfactory dysfunctions such as parosmia to cognitive and emotional challenges.Historically,the surge of neurological disorders followed the viral pandemics,for example,the emergence of Encephalitis Lethargica after the outbreak of Spanish Influenza.During and after COVID-19 infection,the problems associated with the sense of smell and the reports of affected olfactory and limbic brain areas are leading to a growing concern about the similarity with the symptoms and the pattern of degeneration observed at the onset of Parkinson's disease and Alzheimer's disease.These reports reveal the essentiality of long-term studies of olfactory and cognitive functions in the post-COVID era and the experiments using animal models to dissect the neural basis of these complications.In this manuscript,we summarize the research reporting the potential correlation between neurological disorders and viral pandemic outbreaks with a historical perspective.Further,we discuss the studies providing evidence of neurodegeneration due to severe acute respiratory syndrome coronavirus 2 infection by focusing on viral Parkinsonism.
基金supported by the Research Project of the Shanghai Health Commission,No.2020YJZX0111(to CZ)the National Natural Science Foundation of China,Nos.82021002(to CZ),82272039(to CZ),82171252(to FL)+1 种基金a grant from the National Health Commission of People’s Republic of China(PRC),No.Pro20211231084249000238(to JW)Medical Innovation Research Project of Shanghai Science and Technology Commission,No.21Y11903300(to JG).
文摘Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.