Changes in olfactory function are considered to be early biomarkers of Parkinson’s disease.Olfactory dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients wit...Changes in olfactory function are considered to be early biomarkers of Parkinson’s disease.Olfactory dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients with early-stage Parkinson’s disease,and can often predate the diagnosis by years.Therefore,olfactory dysfunction should be considered a reliable marker of the disease.However,the mechanisms responsible for olfactory dysfunction are currently unknown.In this article,we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson’s disease.On the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels,we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson’s disease.The findings highlighted in this review suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson’s disease.Therefore,therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson’s disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms,highlighting the potential of identifying effective targets for treating Parkinson’s disease by inhibiting the deterioration of olfactory dysfunction.展开更多
Background:Olfactory dysfunction(OD)is a common symptom of Corona Virus Disease 2019(COVID-19).It is defined as the reduced or distorted ability to smell during sniffing(orthonasal olfaction)and represents one of the ...Background:Olfactory dysfunction(OD)is a common symptom of Corona Virus Disease 2019(COVID-19).It is defined as the reduced or distorted ability to smell during sniffing(orthonasal olfaction)and represents one of the early symptoms in the clinical course of COVID-19 infection.A large online questionnaire-based survey has shown that some post-COVID-19 patients had no improvement 1 month after discharge from the hospital.Objective:To explore the efficacy of acupuncture for OD in COVID-19 infected patients and to determine whether acupuncture could have benefits over sham acupuncture for OD in post-COVID-19 patients.Methods:This is a single-blind,randomized controlled,cross-over trial.We plan to recruit 40 post-COVID-19 patients with smell loss or smell distortions lasting for more than 1 month.Qualified patients will be randomly allocated to the intervention group(real acupuncture)or the control group(sham acupuncture)at a 1:1 ratio.Each patient will receive 8 sessions of treatment over 4 weeks(Cycle 1)and a 2-week follow-up.After the follow-up,the control group will be subjected to real acupuncture for another 4 weeks(Cycle 2),and the real acupuncture group will undergo the 4-week sham acupuncture.The primary outcomes will be the score changes on the questionnaire of olfactory functioning and olfaction-related quality of life at week 6,8,12,and 14 from the baseline.The secondary outcomes will be the changes in the olfactory test score at week 6 and 12 from the baseline measured by using the Traditional Chinese version of the University of Pennsylvania Smell Identification Test(UPSIT-TC).Discussion:The results of this trial will help to determine the effectiveness of acupuncture for OD in post-COVID-19 patients.This may provide a new treatment option for patients.展开更多
The natural aging process brings about some inevitable consequences, such as olfactory dysfunction, which is also frequently linked to numerous neurodegenerative disorders. Many age-related dementia, such as Alzheimer...The natural aging process brings about some inevitable consequences, such as olfactory dysfunction, which is also frequently linked to numerous neurodegenerative disorders. Many age-related dementia, such as Alzheimer's disease, Vascular dementia, Parkinson's disease, and Frontotemporal Dementia often display olfactory dysfunction. Despite the overwhelming evidence of above mentioned facts, the symptomatic relevance and potential clinical and pre-clinical value of olfactory dysfunction remains overlooked by many clinicians and public alike. Olfactory dysfunction has strong practical implications on daily activities and, although not as prominent as in other mammals, olfaction is still an evolutionarily relevant sense involved in human survival(e.g., smelling gas; bad food). In this work, we provide a brief review of current research related to the olfactory dysfunction profiles in different types of dementia. Additionally, we present a compilation of accessible, easy to use olfaction assessment tools; and highlight future directions in terms of improving clinical diagnosis in patient care and research.展开更多
Alzheimer's Disease(AD) is a chronic neurodegenerative disease that usually takes many years from preclinical phase to prodromal phase characterized by mild symptoms before the onset of dementia. Once diagnosed wi...Alzheimer's Disease(AD) is a chronic neurodegenerative disease that usually takes many years from preclinical phase to prodromal phase characterized by mild symptoms before the onset of dementia. Once diagnosed with AD, the brain is already severely damaged and the disease will process quickly to the most severe stages since there is no medications that reverse the neuronal injuries in the brain. Thus, simple, inexpensive, and widely available methods for detecting potential AD patients during their preclinical phases are urgently needed. In such case, olfactory testing may offer a chance for early diagnosis of AD. However, there are limitations in these olfactory tests due to the complexity of the brain areas it extends to and the frequently olfactory fatigue occurred in the behavioral olfactory tests. Great efforts have been done epidemiologically to investigate the correlation between olfactory functions and possibility of developing AD. Different patterns of olfactory dysfunction have been found in AD at early stages and even mild cognitive impairment(MIC), but the cause of the dysfunction remained unclear. Various kinds of AD animal models have been used in the field to clarify the existence of olfactory dysfunctions and thus study the underling mechanism of the dysfunction. In this review we discuss(1) the function of Tau physiologically and pathologically;(2) the genetic background and biological characteristics of the most commonly used Tau transgenic mice;(3) the structural and molecule basis of olfaction;(4) the possible relationship between Tau pathology and olfactory dysfunction. Finally, we suggest that the tau transgenic mouse models may be helpful in studying the possible mechanisms of the dysfunction.展开更多
Olfactory dysfunction(OD)has been described in patients with antineutrophil cytoplasmic antibody-associated vasculitides(AAV),but the underlying mechanisms are not completely understood.The causes of altered smell fun...Olfactory dysfunction(OD)has been described in patients with antineutrophil cytoplasmic antibody-associated vasculitides(AAV),but the underlying mechanisms are not completely understood.The causes of altered smell function can generally be divided into conductive,sensorineural or others.To date no specific treatment is available for AAV-related OD and the efficacy of currently available options has not been explored.The aim of this review is to provide an overview of the causes that may lead to OD in patients with AAV.Current available treatments for OD and possible options in patients with AAV presenting with smell impairment are also mentioned.展开更多
Objectives:Prior research on olfactory dysfunction in chronic rhinosinusitis(CRS)has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role.The pu...Objectives:Prior research on olfactory dysfunction in chronic rhinosinusitis(CRS)has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role.The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens,comparing normosmic and dysosmic CRS patients without polyps(CRSsNP).Methods:Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery.Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic(n=7)andnormosmic(n=4)patients.Results:Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes.Using stringent criteria for multiple comparisons,one upregulated gene(lmmediate Early Response3[IER3])had an false discovery rate(FDR)correction adjusted P value considered statistically significant(P<0.001,fold change 2.69).Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients(P<0.05,FDR correction)including IL-4 and IL-13 signaling,IL-10 signaling,and rhodopsin-like receptors.Conclusions:RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction.This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP.This study also prompts questions regarding the role of IL-10,rhodopsin-like receptors,and IER3 in the pathogenesis of olfactory dysfunction.展开更多
基金supported by the National Natural Science Foundation of China,No.82104421the China Postdoctoral Science Foundation,No.2022M721726+1 种基金the Innovation and Entrepreneurship Training Program for College Students of Jiangsu Province,No.202210304155Ythe Research Startup Fund Program of Nantong University,No.135421623023(all to XZ).
文摘Changes in olfactory function are considered to be early biomarkers of Parkinson’s disease.Olfactory dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients with early-stage Parkinson’s disease,and can often predate the diagnosis by years.Therefore,olfactory dysfunction should be considered a reliable marker of the disease.However,the mechanisms responsible for olfactory dysfunction are currently unknown.In this article,we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson’s disease.On the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels,we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson’s disease.The findings highlighted in this review suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson’s disease.Therefore,therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson’s disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms,highlighting the potential of identifying effective targets for treating Parkinson’s disease by inhibiting the deterioration of olfactory dysfunction.
基金jointly-supported by Hong Kong Baptist University(SCM-2020-001)Haven of Hope-The Chinese University of Hong Kong Chinese Medicine Clinic cum Training and Research Centre(Sai Kung District)Tseung Kwan O Hospital of Hospital Authority,Hong Kong,China,on expenses and equipment.
文摘Background:Olfactory dysfunction(OD)is a common symptom of Corona Virus Disease 2019(COVID-19).It is defined as the reduced or distorted ability to smell during sniffing(orthonasal olfaction)and represents one of the early symptoms in the clinical course of COVID-19 infection.A large online questionnaire-based survey has shown that some post-COVID-19 patients had no improvement 1 month after discharge from the hospital.Objective:To explore the efficacy of acupuncture for OD in COVID-19 infected patients and to determine whether acupuncture could have benefits over sham acupuncture for OD in post-COVID-19 patients.Methods:This is a single-blind,randomized controlled,cross-over trial.We plan to recruit 40 post-COVID-19 patients with smell loss or smell distortions lasting for more than 1 month.Qualified patients will be randomly allocated to the intervention group(real acupuncture)or the control group(sham acupuncture)at a 1:1 ratio.Each patient will receive 8 sessions of treatment over 4 weeks(Cycle 1)and a 2-week follow-up.After the follow-up,the control group will be subjected to real acupuncture for another 4 weeks(Cycle 2),and the real acupuncture group will undergo the 4-week sham acupuncture.The primary outcomes will be the score changes on the questionnaire of olfactory functioning and olfaction-related quality of life at week 6,8,12,and 14 from the baseline.The secondary outcomes will be the changes in the olfactory test score at week 6 and 12 from the baseline measured by using the Traditional Chinese version of the University of Pennsylvania Smell Identification Test(UPSIT-TC).Discussion:The results of this trial will help to determine the effectiveness of acupuncture for OD in post-COVID-19 patients.This may provide a new treatment option for patients.
文摘The natural aging process brings about some inevitable consequences, such as olfactory dysfunction, which is also frequently linked to numerous neurodegenerative disorders. Many age-related dementia, such as Alzheimer's disease, Vascular dementia, Parkinson's disease, and Frontotemporal Dementia often display olfactory dysfunction. Despite the overwhelming evidence of above mentioned facts, the symptomatic relevance and potential clinical and pre-clinical value of olfactory dysfunction remains overlooked by many clinicians and public alike. Olfactory dysfunction has strong practical implications on daily activities and, although not as prominent as in other mammals, olfaction is still an evolutionarily relevant sense involved in human survival(e.g., smelling gas; bad food). In this work, we provide a brief review of current research related to the olfactory dysfunction profiles in different types of dementia. Additionally, we present a compilation of accessible, easy to use olfaction assessment tools; and highlight future directions in terms of improving clinical diagnosis in patient care and research.
文摘Alzheimer's Disease(AD) is a chronic neurodegenerative disease that usually takes many years from preclinical phase to prodromal phase characterized by mild symptoms before the onset of dementia. Once diagnosed with AD, the brain is already severely damaged and the disease will process quickly to the most severe stages since there is no medications that reverse the neuronal injuries in the brain. Thus, simple, inexpensive, and widely available methods for detecting potential AD patients during their preclinical phases are urgently needed. In such case, olfactory testing may offer a chance for early diagnosis of AD. However, there are limitations in these olfactory tests due to the complexity of the brain areas it extends to and the frequently olfactory fatigue occurred in the behavioral olfactory tests. Great efforts have been done epidemiologically to investigate the correlation between olfactory functions and possibility of developing AD. Different patterns of olfactory dysfunction have been found in AD at early stages and even mild cognitive impairment(MIC), but the cause of the dysfunction remained unclear. Various kinds of AD animal models have been used in the field to clarify the existence of olfactory dysfunctions and thus study the underling mechanism of the dysfunction. In this review we discuss(1) the function of Tau physiologically and pathologically;(2) the genetic background and biological characteristics of the most commonly used Tau transgenic mice;(3) the structural and molecule basis of olfaction;(4) the possible relationship between Tau pathology and olfactory dysfunction. Finally, we suggest that the tau transgenic mouse models may be helpful in studying the possible mechanisms of the dysfunction.
文摘Olfactory dysfunction(OD)has been described in patients with antineutrophil cytoplasmic antibody-associated vasculitides(AAV),but the underlying mechanisms are not completely understood.The causes of altered smell function can generally be divided into conductive,sensorineural or others.To date no specific treatment is available for AAV-related OD and the efficacy of currently available options has not been explored.The aim of this review is to provide an overview of the causes that may lead to OD in patients with AAV.Current available treatments for OD and possible options in patients with AAV presenting with smell impairment are also mentioned.
基金National Institute of General Medical Sciences,Grant/Award Number:NIGMS GM103499MUSC's Office of the Vice President for Research。
文摘Objectives:Prior research on olfactory dysfunction in chronic rhinosinusitis(CRS)has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role.The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens,comparing normosmic and dysosmic CRS patients without polyps(CRSsNP).Methods:Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery.Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic(n=7)andnormosmic(n=4)patients.Results:Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes.Using stringent criteria for multiple comparisons,one upregulated gene(lmmediate Early Response3[IER3])had an false discovery rate(FDR)correction adjusted P value considered statistically significant(P<0.001,fold change 2.69).Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients(P<0.05,FDR correction)including IL-4 and IL-13 signaling,IL-10 signaling,and rhodopsin-like receptors.Conclusions:RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction.This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP.This study also prompts questions regarding the role of IL-10,rhodopsin-like receptors,and IER3 in the pathogenesis of olfactory dysfunction.
