Olfactory dysfunction and its related molecular mechanisms in Parkinson’s disease

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.

Post-COVID-19 persistent olfactory,gustatory,and trigeminal chemosensory disorders:Definitions,mechanisms,and potential treatments

The nose and the oral cavities are the main sites for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry into the body.Smell and taste deficits are the most common acute viral manifestations.Persistent smell disorders are the most common and bothersome complications after SARS-CoV-2 infection,lasting for months to years.The mechanisms and treatment of persistent post-coronavirus disease 2019(COVID-19)smell and taste disorders are still challenges.Information sources for the review are PubMed,Centers for Disease Control and Prevention,Ovid Medline,Embase,Scopus,Web of Science,International Prospective Register of Systematic Reviews,Cumulative Index to Nursing and Allied Health Literature,Elton Bryson Stephens Company,Cochrane Effective Practice and Organization of Care,Cooperation in Science and Technology,International Clinical Trials Registry Platform,World Health Organization,Randomized Controlled Trial Number Registry,and MediFind.This review summarizes the up-to-date information about the prevalence,patterns at onset,and prognoses of post-COVID-19 smell and taste disorders,evidence for the neurotropism of SARS-CoV-2 and the overlap between SARSCoV-1,Middle East respiratory syndrome coronavirus,and SARS-CoV-2 in structure,molecular biology,mode of replication,and host pathogenicity,the suggested cellular and molecular mechanisms for these post-COVID19 chemosensory disorders,and the applied pharmacotherapies and interventions as trials to treat these disorders,and the recommendations for future research to improve understanding of predictors and mechanisms of these disorders.These are crucial for hopeful proper treatment strategies.

Is SARS-CoV-2 (COVID-19) postviral olfactory dysfunction (PVOD) different from other PVOD?

Background:The SARS-CoV-2 virus continues to spread rapidly across the globe af-flicting many with Coronavirus Disease 2019(COVID-19).As the infection rates rise,a growing number of SARS-CoV-2 positive individuals have been reported to complain of olfactory distur-bances at an alarming rate.Postviral olfactory dysfunction(PVOD)is a well-known phenome-non that may explain the olfactory dysfunction reported by SARS-CoV-2 infected individuals.Methods:A scoping literature review was performed to identify studies that investigated the mechanisms of postviral olfactory dysfunction.Studies demonstrating pathophysiological,his-tological,immunochemical,and epidemiological outcomes of PVOD were included.Results:Fourteen studies were included in addition to one international news article.Three studies reported destruction of the olfactory epithelium following intranasal inoculation of various viral strains in mice.Three studies isolated pathogenic,anosmia inciting viruses(Para-influenza virus,Human Coronavirus,Rhinovirus)through nucleic acid amplification.Eleven studies demonstrated female predilection in patients with PVOD and COVID-19 associated ol-factory dysfunction,of which the majority were over 50 years old.Conclusions:PVOD and COVID-19 associated olfactory dysfunction demonstrates considerable similarities in epidemiological trends and disease sequela of other viruses to suggest identical pathophysiological mechanisms.Further studies such as intranasal inoculation and histological biopsies are needed to support our hypothesis.

Discordance between olfactory psychophysical measurements and olfactory event related potentials in five patients with olfactory dysfunction following upper respiratory infection

Background Subjective olfactory tests are easy to perform and popularly applied in the clinic, but using only these, it is difficult to diagnose all disorders of the olfactory system. The olfactory event related potentials technique offers further insight into the olfactory system and is an ideal objective test. This analysis was of subjective and objective data on the olfactory function of twelve patients with loss of smell associated with an upper respiratory infection （URI）. Methods We tested the twelve patients with URI induced olfactory loss by medical history, physical examination of the head and neck, olfactory tests and medical imaging. Olfactory function was assessed by Toyota and Takagi olfactometry including olfactory detection and recognition thresholds and olfactory event-related potentials （OERPs） recorded with OEP-98C Olfactometer. Results An unusual phenomenon was observed in five patients in whom the subjective detection and recognition thresholds were normal, while the expected OERPs were not detectable. Conclusions We suggest that the discordance between olfactory psychophysical measurements and OERPs might be the results of abnormal electrophysiology related with olfactory neuropathy caused by viral URI. In addition, the measurement of OERPs might play a significant role in evaluating olfactory dysfunction.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China:A national multicenter survey of 35,566 individuals

Objective:This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China.Methods:This study was conducted by 45 tertiary Grade-A hospitals in China.Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28,2022,and February 21,2023.The collected information included basic demographics,medical history,smoking and drinking history,vaccination history,changes in olfactory and gustatory functions before and after infection,and other postinfection symptoms,as well as the duration and improvement status of olfactory and gustatory disorders.Results:Complete questionnaires were obtained from 35,566 subjects.The overall incidence of olfactory and taste dysfunction was 67.75%.Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction.Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction.Before infection,the average olfactory and taste VAS scores were 8.41 and 8.51,respectively;after infection,they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey.The median duration of dysosmia and dysgeusia was 15 and 12 days,respectively,with 0.5%of patients having symptoms lasting for more than 28 days.The overall self-reported improvement rate was 59.16%.Recovery was higher in males,never smokers,those who received two or three vaccine doses,and those that had never experienced dental health issues,or chronic accompanying symptoms.Conclusions:The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China.Incidence and prognosis are influenced by several factors,including sex,SARS-CoV-2 vaccination,history of head-facial trauma,nasal and oral health status,smoking and drinking history,and the persistence of accompanying symptoms.