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Parkinson's disease (PD) is typically a sporadic late-onset disorder, which has made it difficult to model in mice. Several transgenic mouse models bearing mutations in SNCA , which encodes alpha-Synuclein (α-Syn), have been made, but these lines do not express SNCA in a physiologically accurate spatiotemporal pattern, which limits the ability of the mice to recapitulate the features of human PD. Here, we generated knock-in mice bearing the G51D SNCA mutation. After establishing that their motor symptoms begin at 9 mo of age, we then sought earlier pathologies. We assessed the phosphorylation at Serine 129 of α-Syn in different tissues and detected phospho-α-Syn in the olfactory bulb and enteric nervous system at 3 mo of age. Olfactory deficit and impaired gut transit followed at 6 mo, preceding motor symptoms. The Snca G51D mice thus parallel the progression of human PD and will enable us to study PD pathogenesis and test future therapies., Competing Interests: Competing interests statement:H.Y.Z. cofounded Cajal Neuroscience, is a Director of Regeneron Pharmaceuticals board, and is on the scientific advisory board of Cajal Neuroscience and the Column Group.

COVID-19 pandemic brought chemosensory impairment to the forefront of medicine, revealing gaps in the knowledge of pathophysiological mechanisms, true prevalence and preventive/therapeutic alternatives. This is a sub-study of the ORCHESTRA cohort focusing on post-COVID-19 chemosensory symptoms. Risk factors for neurosensorial cluster of post-COVID-19 syndrome (NSc-PCS) were assessed through multivariable analysis. Psychophysical validated tests were applied on a sub-population of 50 patients. Qualitative chemosensory symptoms as well as nasal and oral chemesthesis were evaluated through anamnestic interview and the quality of life through the SF-36 questionnaire. Chemosensory symptoms evolution and olfactory training's outcome were assessed through phone-call interviews. Out of 1187 patients (female, N = 630), 550 (47%) presented NSc-PCS, with a lower risk for older age and monoclonal antibodies treatment, and a higher risk in females (p < 0.001). Out of the 50 patients evaluated with psychophysical tests, 66% showed smell reduction with a qualitative alteration in 50% of hyposmic and 35% of normosmic patients. Hypogeusia was present in 14 (28%) of the patients assessed, with 56% showing a qualitative alteration; 53% of normogeusic patients presented qualitative disorders. NSc-PCS has a complex, fluctuating, multifaceted presentation. Quantifying and characterizing COVID-19-related chemosensory impairment is key to understand underlying mechanisms and to develop preventive and therapeutic treatment., (© 2024. The Author(s).)

Background: Hyposmia in Parkinson's disease (PD) had been studied before but had not been detailed by its temporal progression. This study observed how each olfactory subtype evolved in terms of motor symptoms, cardiac sympathetic innervation, and cognition., Methods: Two hundred and three early PD patients were classified as normosmia, hyposmia-converter (hypo-converter), and hyposmia. Their presynaptic monoamine availability at the time of diagnosis was assessed by positron emission tomography imaging using 18 F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and compared across the subtypes. Motor symptoms were evaluated in all patients, cardiac denervation was examined in 183 patients, and cognition in 195 patients were assessed using a neuropsychological battery. The domains were re-assessed 2-4 times, and the longitudinal data were analyzed to discern the natural course of each subtype., Results: Twenty-nine (14.3%) patients belonged to the normosmia group, 34 (16.7%) to the hypo-converter group, and the rest to the hyposmia (69.0%) group. 85.7% of the total population became hyposmic during an average 3 years of follow-up. The baseline motor symptoms, cardiac denervation, and cognition were comparable across the olfactory subtypes. Across the subtypes, a decline in the presynaptic monoamine densities of the caudate, especially the ventral-anterior subdivisions, correlated inversely with olfaction dysfunction. Over time, motor and cardiac denervation burdens worsened regardless of olfactory subtypes, but hypo-converters experienced faster cognitive deterioration than the other two groups., Conclusions: The results suggest that the olfactory subtypes have differential significance along the disease course, which might reflect the involvement of different neuro-biochemical circuitries., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Olfactory functioning involves multiple cognitive processes and the coordinated actions of various neural systems. Any disruption at any stage of this process may result in olfactory dysfunction, which is consequently widely used to predict the onset and progression of diseases, such as Alzheimer's Disease (AD). Although the underlying mechanisms have not yet been fully unraveled, apparent changes were observed in olfactory brain areas form patients who suffer from AD by means of medical imaging and electroencephalography (EEG). Olfactory dysfunction holds significant promise in detecting AD during the preclinical stage preceding mild cognitive impairment (MCI). Owing to the strong specificity, olfactory tests are prevalently applied for screening in community cohorts. And combining olfactory tests with other biomarkers may further establish an optimal model for AD prediction in studies of specific olfactory dysfunctions and improve the sensitivity and specificity of early AD diagnosis., Competing Interests: Declaration of Competing Interest None conflicts of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study aimed to evaluate recovery patterns of olfactory dysfunction among recovered COVID-19 patients, both subjective and objective, and correlate this recovery to the severity of the disease., Methods: The study recruited 200 patients and assigned them to two equal groups, one of them was a control group. The olfactory function of the study group was assessed via subjective and objective methods at baseline and then monthly for three months, with changes in smell function reported at each visit. These patients underwent chemosensory testing using the Sniffin' Sticks test and completed the validated Arabic version of the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS)., Results: Olfactory dysfunction occurred on the first day of COVID-19 symptoms in 37% of participants. Subjective reports suggested smell recovery in 55% after 3 months, but Sniffin' Sticks showed only 1% with normal function, indicating persistent deficits in others. This study revealed smell recovery for 93% of participants (median 14 days), with most (58%) recovering within 2 weeks. No significant links were found between demographics, COVID-smell loss timing, and recovery speed., Conclusion: Three months after COVID-19, many patients perceive smell recovery, but objective tests reveal shockingly high rates of persistent dysfunction. Further follow-up with objective tests is vital to assess the true burden and potential long-term effects of smell loss., (© 2024. The Author(s).)

Background: Diagnosing parosmia is a challenge. The present study aimed to explore the distinctions between hyposmic patients with and without parosmia utilizing electroencephalography-derived olfactory event-related potentials (ERP)., Methods: Forty-four patients with hyposmia were enrolled and divided into a group with parosmia (n = 23, mean age ± standard deviation = 48 ± 14 years, seven men) and a group without parosmia (n = 21, age = 52 ± 12 years, seven men) based on the clinical interview. Additionally, 21 healthy controls (mean age = 45 ± 14 years, six men) were included. Various measurements were obtained, including the Sniffin' Stick test, threshold tests for the odorants furfural mercaptan and 2,6-nonadienal, a modified Sniffin' Stick parosmia test, and well-being ratings. Chemosensory ERPs were recorded separately for each nostril using high-precision, computer-controlled air-dilution olfactometry., Results: Patients with parosmia had a decreased olfactory function similar to that observed in patients with hyposmia, although the odor sensitivity of patients with severe parosmia remained relatively unaffected. Patients with parosmia reported a decrease in well-being compared to controls. The severity of parosmia was positively correlated with odor sensitivity. Furthermore, patients with severe parosmia exhibited faster responses to unpleasant odors than patients without parosmia., Conclusion: Overall, the present findings support the idea that parosmia predominantly occurs during olfactory recovery, significantly disturbing patients and warranting the development of effective treatments. Notably, the relatively faster responses of hyposmic patients with severe parosmia suggest that the generation of distorted olfactory responses may involve early stages of the processing of olfactory information., (© 2024 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Objectives: A large number of patients with olfactory impairment are affected by parosmia or phantosmia. This study aimed to examine the demographic and clinical characteristics of parosmia., Methods: We performed a retrospective data analysis of patients consulting at our Smell and Taste Outpatient Clinic. A total of 297 patients were included (203 women, mean age 44.4 ± 13.7 years). Olfactory function was quantified using the "Sniffin' Sticks" composite TDI (odor threshold, determination, and identification) score. The presence of qualitative olfactory impairment was assessed trough medical history and a parosmia questionnaire., Results: Most of the patients showed olfactory impairment after an infection with SARS-CoV‑2 (84%) and were diagnosed with parosmia (49%). Patients with parosmia (PAR) (n = 201) were significantly younger compared to the group without parosmia (noPAR; n = 92) (PAR 43.2 ± 13 years vs. noPAR 47 ± 15.1 years, p = 0.03) and had a slightly shorter duration of disease, without reaching statistical significance (PAR 10.3 ± 4.9 months, noPAR 13.6 ± 37.6 months, p = 0.23). They also had higher TDI scores (PAR 24.3 ± 7 points, noPAR 21.4 ± 8.2 points, p = 0.003)., Conclusions: Patients affected by parosmia were younger and had a better olfactory function compared to patients without parosmia., (© 2024. The Author(s).)

Background and Hypothesis: Persistent auditory verbal hallucinations (pAVHs) and olfactory identification impairment are common in schizophrenia (SCZ), but the neuroimaging mechanisms underlying both pAVHs and olfactory identification impairment are unclear. This study aimed to investigate whether pAVHs and olfactory identification impairment in SCZ patients are associated with changes in cortical thickness., Study Design: In this study, cortical thickness was investigated in 78 SCZ patients with pAVHs (pAVH group), 58 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) using 3T magnetic resonance imaging. The severity of pAVHs was assessed by the Auditory Hallucination Rating Scale. Olfactory identification deficits were assessed using the Odor Stick Identification Test for Japanese (OSIT-J). In addition, the relationship between the severity of pAVHs and olfactory identification disorder and cortical thickness abnormalities was determined., Study Results: Significant reductions in cortical thickness were observed in the right medial orbital sulcus (olfactory sulcus) and right orbital sulcus (H-shaped sulcus) in the pAVH group compared to both the non-AVH and HC groups (P < .003, Bonferroni correction). Furthermore, the severity of pAVHs was found to be negatively correlated with the reduction in cortical thickness in the olfactory sulcus and H-shaped sulcus. Additionally, a decrease in cortical thickness in the olfactory sulcus showed a positive correlation with the OSIT-J scores (P < .05, false discovery rate correction)., Conclusions: Cortical thickness abnormalities in the olfactory sulcus may be a common neuroimaging mechanism for pAVHs and olfactory identification deficits in SCZ patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Key Points: Patients with traumatic brain injury (TBI) had worse olfactory quality of life (QoL) and Sino-Nasal Outcome Test-22 scores compared to a normal cohort. A worse olfactory QoL correlated with concussion symptom burden. Olfactory dysfunction among TBI patients should be addressed to improve overall outcomes., (© 2024 ARS‐AAOA, LLC.)

Objectives: Olfactory habituation is a transient decrease in olfactory sensitivity caused by prolonged odor exposure, aiding in the discernment of new olfactory stimuli against the background. We explored the impact of subclinical olfactory impairment on odor habituation using age as a proxy., Methods: Before the actual experiment, the individual olfactory threshold for the rose-like odorant phenylethyl alcohol (PEA) was assessed separately for the left and right nostril using the "Sniffin' Sticks" test, and ratings for odor intensity and pleasantness were collected. After applying a nasal clip continuously delivering PEA odor to one nostril for 10 min and 2 h, respectively, threshold, intensity, and pleasantness were reassessed immediately after clip removal., Results: In the group of 80 participants (younger adults-mean age 27.7 ± 4.5 years; older adults-mean age 61.5 ± 4.7 years), olfactory thresholds were already significantly elevated after just 10 min, and this habituation was even more pronounced after 2 h. This effect could be observed bilaterally even though significantly more distinct on the exposed side. Older participants generally exhibited a more pronounced habituation on the exposed side after 2 h compared to the younger participants., Conclusion: The results indicate that older people experience more notable habituation after extended exposure to odors. This is most likely due to the compromised olfactory function in age. Although older and younger subjects scored in the normosmic range when tested with standardized olfactory tests, the stress on the system after exposure to an odor clearly revealed the lower functionality of the aging sense of smell., Level of Evidence: 3 Laryngoscope, 134:3765-3768, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Rationale: Adult neurogenesis in the subventricular zone (SVZ) is essential for maintaining neural homeostasis, and its dysregulation contributes to anosmia and delayed tissue healing in neurological disorders, such as Parkinson's disease (PD). Despite intricate regulatory networks identified in SVZ neurogenesis, the molecular mechanisms dynamically maintaining neural stem/progenitor cells (NSPCs) in response to physiological and pathological stimuli remain incompletely elucidated. Methods: We generated an RNA binding motif protein 24 (Rbm24) knockout model to investigate its impact on adult neurogenesis in the SVZ, employing immunofluorescence, immunoblot, electrophysiology, RNA-sequencing, and in vitro experiments. Further investigations utilized a PD mouse model, along with genetic and pharmacological manipulations, to elucidate Rbm24 involvement in PD pathology. Results: Rbm24, a multifaceted post-transcriptional regulator of cellular homeostasis, exhibited broad expression in the SVZ from development to aging. Deletion of Rbm24 significantly impaired NSPC proliferation in the adult SVZ, ultimately resulting in collapsed neurogenesis in the olfactory bulb. Notably, Rbm24 played a specific role in maintaining Notch1 mRNA stability in adult NSPCs. The Rbm24/Notch1 signaling axis was significantly downregulated in the SVZ of PD mice. Remarkably, overexpression of Rbm24 rescued disruption of adult neurogenesis and olfactory dysfunction in PD mice, and these effects were hindered by DAPT, a potent inhibitor of Notch1. Conclusions: Our findings highlight the critical role of the Rbm24/Notch1 signaling axis in regulating adult SVZ neurogenesis under physiological and pathological circumstances. This provides valuable insights into the dynamic regulation of NSPC homeostasis and offers a potential targeted intervention for PD and related neurological disorders., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: Olfactory dysfunction is an overlooked adverse effect of radiation therapy. This study is designed to find the effect of radiation therapy on olfactory function in head and neck malignancy excluding tumors of nose and nasopharynx and correlate the olfactory changes with the radiotherapy dose., Method: This prospective observational study was done over a 2-year period in 34 participants with head and neck malignancies who underwent radiation therapy (RT). The participants olfaction was evaluated subjectively with Italian Nose Obstruction Symptom Evaluation (I-NOSE) scale and objectively by a modified I-Smell test which included an olfactory identification score and an olfactory threshold score at 5 time points. The beginning of RT ( T 0), at 2 weeks of RT( T 1), end of RT ( T 2), 1 month follow-up ( T 3), and 3-month follow-up ( T 4). The near maximum dose to the nasal cavity ( D 2% ) and mean dose to the nasal cavity ( D mean ) were calculated for all participants and correlated with olfactory function., Results: A total of 34 patients with head neck malignancy were recruited. The median I-NOSE score reached maximum at the end of radiation and decreased to baseline at 3 months follow-up ( P  < .001). The olfactory identification score, olfactory threshold score, and median combined olfactory score showed a significant decrease at the end of radiation therapy compared to Pre-radiation therapy values. There was a significant but incomplete recovery in the 3-month follow-up period ( P  < .001)., Conclusion: There was a significant deterioration in quality of life for olfaction, olfactory identification, and olfactory threshold at the completion of radiotherapy. At 3 months follow-up, though there was no complete recovery of olfaction, it did not have an adverse effect on the quality of life., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Olfactory dysfunction is a non-motor symptom and an important biomarker of Parkinson's disease (PD) because of its high prevalence (> 90%). Whether hyposmia correlates with motor symptoms is unclear. In the present study, we aim to investigate the relationship between olfactory impairment with both motor and non-motor features and disease variables (disease duration, stage, and severity)., Methods: One-hundred fifty-four PD patients were evaluated. Odor identification ability was tested using Italian Olfactory Identification Test (IOIT). A comprehensive spectrum of motor and non-motor features was assessed. Cognitive function was investigated through MMSE. Patients were divided into 3 different clinical phenotypes using UPDRS-III: tremor-dominant type (TDT), akinetic-rigid type (ART), and mixed type (MXT)., Results: Three of the 33 IOIT items were most frequently misidentified: basil (74.3%), coffee (66.9%), and mushroom (59.6%). Hyposmia was found in 93%. Hyposmic patients were older than controls (p = 0.01). Hoehn & Yahr (H&Y) score of 2 or greater was associated with higher probability of being hyposmic (OR = 5.2, p = 0.01). IOIT score did not significantly differ between TDT, ART, and MXT of analyzed PD patients. Performance to IOIT inversely correlated with age (p < 0.01), disease duration (p = 0.01), and H&Y score of 2 or higher (p < 0.01). Clinical features that associated with higher IOIT score were freezing of gait (FOG) (p < 0.001) and camptocormia (p < 0.05)., Conclusions: In our cohort, IOIT scores showed a positive correlation with axial motor signs, but not with non-motor symptoms. IOIT may be a useful tool not only for supporting PD diagnosis but also for providing prognostic information about motor function., (© 2024. Fondazione Società Italiana di Neurologia.)

BACKGROUND General paresis of the insane (GPI) is characterized by cognitive impairment, neuropsychiatric symptoms, and brain structural abnormalities, mimicking many neuropsychiatric diseases. Olfactory dysfunction has been linked to cognitive decline and neuropsychiatric symptoms in numerous neuropsychiatric diseases. Nevertheless, it remains unclear whether patients with GPI experience olfactory dysfunction and whether olfactory dysfunction is associated with their clinical manifestations. MATERIAL AND METHODS Forty patients with GPI and 37 healthy controls (HCs) underwent the "Sniffin Sticks" test battery, Mini-Mental State Examination, and Neuropsychiatric Inventory to measure olfactory function, cognitive function, and neuropsychiatric symptoms, respectively. Brain structural abnormalities were evaluated using visual assessment scales including the medial temporal lobe atrophy (MTA) visual rating scale and Fazekas scale. RESULTS Compared with HCs, patients with GPI exhibited significant olfactory dysfunction, as indicated by deficits in the odor threshold (OT) (P=0.001), odor discrimination (OD) (P<0.001), and odor identification (OI) (P<0.001). In patients with GPI, the OI was positively correlated with cognitive function (r=0.57, P<0.001), but no significant correlation was found between olfactory function and neuropsychiatric symptoms, blood, or cerebrospinal fluid biomarkers (rapid plasma reagin circle card test and Treponema pallidum particle agglutination test), or brain structural abnormalities (MTA and Fazekas scale scores). Mediation analysis indicated that the impaired OI in patients with GPI was mediated by cognitive impairment and impaired OT respectively. CONCLUSIONS Patients with GPI exhibited overall olfactory dysfunction. OI is correlated with cognitive function and the impaired OI is mediated by cognitive impairment in patients with GPI. Thus, OI may serve as a marker for reflecting cognitive function in patients with GPI.

Approximately 30-60% of people suffer from olfactory dysfunction (OD) such as hyposmia or anosmia after being diagnosed with COVID-19; 15-20% of these cases last beyond resolution of the acute phase. Previous studies have shown that olfactory training can be beneficial for patients affected by OD caused by viral infections of the upper respiratory tract. The aim of the study is to evaluate whether a multisensory olfactory training involving simultaneously tasting and seeing congruent stimuli is more effective than the classical olfactory training. We recruited 68 participants with persistent OD for two months or more after COVID-19 infection; they were divided into three groups. One group received olfactory training which involved smelling four odorants (strawberry, cheese, coffee, lemon; classical olfactory training). The other group received the same olfactory stimuli but presented retronasally (i.e., as droplets on their tongue); while simultaneous and congruent gustatory (i.e., sweet, salty, bitter, sour) and visual (corresponding images) stimuli were presented (multisensory olfactory training). The third group received odorless propylene glycol in four bottles (control group). Training was carried out twice daily for 12 weeks. We assessed olfactory function and olfactory specific quality of life before and after the intervention. Both intervention groups showed a similar significant improvement of olfactory function, although there was no difference in the assessment of quality of life. Both multisensory and classical training can be beneficial for OD following a viral infection; however, only the classical olfactory training paradigm leads to an improvement that was significantly stronger than the control group.

Introduction: Alterations in taste and smell are among the most distressing symptoms experienced by haemodialysis patients. There is limited research on the relationship between these two symptoms and malnutrition in haemodialysis patients. This study aimed to investigate alterations in taste and smell in hemodialysis patients and their relationship with malnutrition., Methods: This cross-sectional study was carried out with 149 hemodialysis patients at the dialysis centers of three state hospitals. The Taste and Smell Dysfunction Questionnaire was used to assess the changes in patients' taste and smell, and the Prognostic Nutritional Index (PNI), as well as the Controlling Nutritional Status (CONUT) tool, were utilized to evaluate their nutritional status., Findings: A substantial percentage (45.6%) of patients reported an altered sense of smell, and 40.2% reported an altered sense of taste. The aspect of taste that was most abnormal was bitterness (46.7%); 53.0% of the patients were at moderate risk of malnutrition by PNI score, and 14.8% were categorized as malnourished by CONUT score. Malnutrition was related to dialysis vintage: a 1-year increase in vintage was associated with an increased risk of malnutrition (OR: 1.17, 95% CI 1.02-1.32, p < 0.001). Altered taste was associated with malnutrition: one-unit increase in the standard deviation of the taste subdimension score was associated with a relative risk of malnutrition (OR: 6.89, 95% CI 1.67-28.39, p < 0.001). A one-unit increase in the standard deviation of the smell subdimension was associated with relative risk of malnutrition (OR: 1.35, 95% CI 1.10-1.64, p < 0.001)., Discussion: Malnutrition was found in a significantpercentage of hemodialysis patients. Altered taste and smell and the durationof dialysis treatment were significantly associated with malnutrition scores It isrecommended that healthcare professionals regularly assess alterations in tasteand smell in hemodialysis patients, as these alterations may be associated withmalnutrition, and manage these alterations accordingly., (© 2024 International Society for Hemodialysis.)

Substance use disorder (SUD) exacerbates the impact of Long-COVID, particularly increasing the risk of taste and olfactory disorders. Analyzing retrospective cohort data from TriNetX and over 33 million records (Jan 2020-Dec 2022), this study focused on 1,512,358 participants, revealing that SUD significantly heightens the likelihood of experiencing taste disturbances and anosmia in Long-COVID sufferers. Results indicated that individuals with SUD face a higher incidence of sensory impairments compared to controls, with older adults and women being particularly vulnerable. Smokers with SUD were found to have an increased risk of olfactory and taste dysfunctions. The findings underscore the importance of early screening, diagnosis, and interventions for Long-COVID patients with a history of SUD, suggesting a need for clinicians to monitor for depression and anxiety linked to sensory dysfunction for comprehensive care., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: This study aimed to determine the characteristics of patients with qualitative olfactory dysfunction (qualOD) and whether individuals with parosmia exhibit increased olfactory sensitivity to previously reported odorous triggers of parosmia., Methods: This study included individuals aged ≥18 years, divided into quantitative OD only, parosmia, and phantosmia groups. Data collected included: clinical-demographic data, "Sniffin' Sticks" scores, questionnaires (depression scale, importance of olfaction), and information about parosmia and phantosmia. A proportion of patients underwent trigger odor threshold testing for 2-Furfurylthiol [FFT] found in coffee and 2,6-nonadienal [Nonadienal] found in cucumber., Results: Those with parosmia were typically younger women, with shorter OD duration due to post-viral OD (PVOD), hyposmic/normosmic, and experienced parosmia more severely. Parosmia was 3.5 times more likely in PVOD. Those with phantosmia were older, with longer OD duration due to idiopathic OD, hyposmic/anosmic, and experienced phantosmia less severely. There were no significant differences between FFT and Nonadienal threshold scores in patients with parosmia, phantosmia, or only quantitative OD, but all groups had significantly increased olfactory sensitivity for trigger odors compared to phenyl ethyl alcohol (PEA)., Conclusion: Parosmia and phantosmia patients have distinct characteristics. This may provide clinicians with a better understanding of possible olfactory outcomes in these patients. The higher olfactory sensitivity of all groups to trigger odors compared to PEA raises interesting points about parosmia triggers and odors in the context of warning for danger, in relation to the pathophysiology of parosmia that may be worth exploring in future studies., Level of Evidence: 3 Laryngoscope, 134:3277-3285, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Borderline personality disorder (BPD) is a serious disorder with a lifetime prevalence of 2.7-5.9% and is thought to correlate with altered neuroplasticity. The aim of the present study is to investigate possible associations of BPD (-severity) and alterations in neurological soft signs (NSS) and olfactory function., Methods: For the monocentric observational study, 39 female subjects with a BPD diagnosis and 19 female healthy control subjects were recruited. The groups were matched by age. Olfactory functions were examined using Sniffin' Sticks. NSS were assessed by a standardized test with 50 items., Results: BPD subjects have higher NSS scores in group comparison. By contrast, there are no alterations in the total score of olfactory function, while the BPD subjects scored higher in smell identification. Within the BPD group, the total NSS score was discovered to have a negative correlation with olfactory function. BPD subjects taking antipsychotics show more NSS than those without. We found no significant influence of posttraumatic stress disorder on the NSS or olfactory function. The BPD-severity correlates with NSS., Limitations: Due to the cross-sectional design, we did not have a follow up examination. The sample size was small, and all patients had psychiatric comorbidities. Additionally, we did not perform MRI to connect our findings with possible structural abnormalities., Conclusions: Our study confirmed altered NSS in BPD patients, whereas no impairment in the olfactory function was found. Further research is required to establish NSS and smell tests as clinical screening tools in BPD patients and to uncover the disorder's impact on neuroplasticity., Competing Interests: Declaration of competing interest RS took part in an educational event sponsored by Livanova. HF received speaker‘s honararia and served as advisor for Recordati Pharma GmbH and Janssen-Cilag Gmbh. AN received lecture fees from Novartis and Merck. HBM took part in educational events sponsored by Livanova and Rovi. SBe, SH, SDG, LS, FMM, CW, SBl declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Olfactory dysfunction is a common non-motor symptom of Parkinson's disease(PD) and may hold valuable insights into the disease's underlying pathophysiology. This study aimed to investigate cortical morphometry alterations in PD patients with severe hyposmia(PD-SH) and mild hyposmia(PD-MH) using surface-based morphometry(SBM) methods. Participants included 36 PD-SH patients, 38 PD-MH patients, and 40 healthy controls(HCs). SBM analysis revealed distinct patterns of cortical alterations in PD-SH and PD-MH patients. PD-MH patients exhibited reduced cortical thickness in the right supramarginal gyrus, while PD-SH patients showed widespread cortical thinning in regions including the bilateral pericalcarine cortex, bilateral lingual gyrus, left inferior parietal cortex, left lateral occipital cortex, right pars triangularis, right cuneus, and right superior parietal cortex. Moreover, PD-SH patients displayed reduced cortical thickness in the right precuneus compared to PD-MH patients. Fractal dimension analysis indicated increased cortical complexity in PD-MH patients' right superior temporal cortex and right supramarginal gyrus, as well as decreased complexity in the bilateral postcentral cortex, left superior parietal cortex, and right precentral cortex. Similarly, cortical gyrification index and cortical sulcal depth exhibited heterogeneous patterns of changes in PD-SH and PD-MH patients compared to HCs. These findings underscore the multifaceted nature of olfactory impairment in PD, with distinct patterns of cortical morphometry alterations associated with different degrees of hyposmia. The observed discrepancies in brain regions showing alterations reflect the complexity of PD's pathophysiology. These insights contribute to a deeper understanding of olfactory dysfunction in PD and provide potential avenues for early diagnosis and targeted interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Olfactory dysfunction, influenced by factors such as aging and environmental stress, is linked to various neurological disorders. The olfactory bulb's connections to brain areas like the hypothalamus, piriform cortex, entorhinal cortex, and limbic system make olfactory dysfunction a contributor to a range of neuropathological conditions. Recent research has underscored that olfactory deficits are prevalent in individuals with both metabolic syndrome and dementia. These systemic metabolic alterations correlate with olfactory impairments, potentially affecting brain regions associated with the olfactory bulb. In cases of metabolic syndrome, phenomena such as insulin resistance and disrupted glucose metabolism may result in compromised olfactory function, leading to multiple neurological issues. This review synthesizes key findings on the interplay between metabolic-induced olfactory dysfunction and neuropathology. It emphasizes the critical role of olfactory assessment in diagnosing and managing neurological diseases related to metabolic syndrome., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Despite its high prevalence, the determinants of smelling impairment in COVID-19 remain not fully understood. In this work, we aimed to examine the association between olfactory bulb volume and the clinical trajectory of COVID-19-related smelling impairment in a large-scale magnetic resonance imaging (MRI) analysis. Data of non-vaccinated COVID-19 convalescents recruited within the framework of the prospective Hamburg City Health Study COVID Program between March and December 2020 were analyzed. At baseline, 233 participants underwent MRI and neuropsychological testing as well as a structured questionnaire for olfactory function. Between March and April 2022, olfactory function was assessed at follow-up including quantitative olfactometric testing with Sniffin' Sticks. This study included 233 individuals recovered from mainly mild to moderate SARS-CoV-2 infections. Longitudinal assessment demonstrated a declining prevalence of self-reported olfactory dysfunction from 67.1% at acute infection, 21.0% at baseline examination and 17.5% at follow-up. Participants with post-acute self-reported olfactory dysfunction had a significantly lower olfactory bulb volume at baseline than normally smelling individuals. Olfactory bulb volume at baseline predicted olfactometric scores at follow-up. Performance in neuropsychological testing was not significantly associated with the olfactory bulb volume. Our work demonstrates an association of long-term self-reported smelling dysfunction and olfactory bulb integrity in a sample of individuals recovered from mainly mild to moderate COVID-19. Collectively, our results highlight olfactory bulb volume as a surrogate marker that may inform diagnosis and guide rehabilitation strategies in COVID-19., (© 2024. The Author(s).)

The olfactory epithelium (OE) is directly exposed to environmental agents entering the nasal cavity, leaving OSNs prone to injury and degeneration. The causes of olfactory dysfunction are diverse and include head trauma, neurodegenerative diseases, and aging, but the main causes are chronic rhinosinusitis (CRS) and viral infections. In CRS and viral infections, reduced airflow due to local inflammation, inflammatory cytokine production, release of degranulated proteins from eosinophils, and cell injury lead to decreased olfactory function. It is well known that injury-induced loss of mature OSNs in the adult OE causes massive regeneration of new OSNs within a few months through the proliferation and differentiation of progenitor basal cells that are subsequently incorporated into olfactory neural circuits. Although normal olfactory function returns after injury in most cases, prolonged olfactory impairment and lack of improvement in olfactory function in some cases poses a major clinical problem. Persistent inflammation or severe injury in the OE results in morphological changes in the OE and respiratory epithelium and decreases the number of mature OSNs, resulting in irreversible loss of olfactory function. In this review, we discuss the histological structure and distribution of the human OE, and the pathogenesis of olfactory dysfunction associated with CRS and viral infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kikuta, Nagayama and Hasegawa-Ishii.)

A preserved sense of smell and taste allows us to understand many environmental "messages" and results in meaningfully improvements to quality of life. With the COVID-19 pandemic, it became clear how important these senses are for social and nutritional status and catapulted this niche chemosensory research area towards widespread interest. In the current exploratory work, we assessed two groups of post-COVID-19 patients who reported having had (Group 1) or not (Group 2) a smell/taste impairment at the disease onset. The aim was to compare them using validated smell and taste tests as well as with brain magnetic resonance imaging volumetric analysis. Normative data were used for smell scores comparison and a pool of healthy subjects, recruited before the pandemic, served as controls for taste scores. The majority of patients in both groups showed an olfactory impairment, which was more severe in Group 1 (median UPSIT scores: 24.5 Group 1 vs 31.0 Group 2, p = 0.008), particularly among women (p = 0.014). No significant differences emerged comparing taste scores between Group 1 and Group 2, but dysgeusia was only present in Group 1 patients. However, for taste scores, a significant difference was found between Group 1 and controls (p = 0.005). No MRI anatomical abnormalities emerged in any patients while brain volumetric analysis suggested a significant difference among groups for the right caudate nucleus (p = 0.028), although this was not retained following Benjamini-Hochberg correction. This exploratory study could add new information in COVID-19 chemosensory long-lasting impairment and address future investigations on the post-COVID-19 patients' research., (© 2024. The Author(s).)

Background and Purpose: Olfaction is an early marker of neurodegenerative disease. Standard olfactory function is essential due to the importance of olfaction in human life. The psychophysical evaluation assesses the olfactory function commonly. It is patient-reported, and results rely on the patient's answers and collaboration. However, methodological difficulties attributed to the psychophysical evaluation of olfactory-related cerebral areas led to limited assessment of olfactory function in the human brain., Materials and Methods: The current study utilized clustering approaches to assess olfactory function in fMRI data and used brain activity to parcellate the brain with homogeneous properties. Deep neural network architecture based on ResNet convolutional neural networks (CNN) and Long Short-Term Model (LSTM) designed to classify healthy with olfactory disorders subjects., Results: The fMRI result obtained by k-means unsupervised machine learning model was within the expected outcome and similar to those found with the conn toolbox in detecting active areas. There was no significant difference between the means of subjects and every subject. Proposing a CRNN deep learning model to classify fMRI data in two different healthy and with olfactory disorders groups leads to an accuracy score of 97 %., Conclusions: The K-means unsupervised algorithm can detect the active regions in the brain and analyze olfactory function. Classification results prove the CNN-LSTM architecture using ResNet provides the best accuracy score in olfactory fMRI data. It is the first attempt conducted on olfactory fMRI data in detail until now., Competing Interests: Declaration of Competing Interest The authors declare that they have no known conflicts of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Olfactory dysfunction together with neurological and cognitive symptoms are common after COVID-19. We aimed to study whether performance on olfactory and neuropsychological tests following infection predict post-COVID condition (PCC), persisting symptoms, and reduced health-related quality of life., Methods: Both hospitalized (N = 10) and non-hospitalized individuals (N = 56) were enrolled in this prospective cohort study. Participants were evaluated 1-3 months after infection with an olfactory threshold test and neuropsychological tests, which was used as predictors of PCC. A questionnaire outlining persisting symptoms and the validated instrument EuroQol five-dimension five-level for health-related quality of life assessment were used as outcome data 1 year after infection (N = 59). Principal component analysis was used to identify relevant predictors for PCC at 1 year., Results: Objectively assessed olfactory dysfunction at 1-3 months post infection, but not subjective olfactory symptoms, predicted post-COVID condition with reduced health-related quality of life (PCC+) at 1 year. The PCC+ group scored more often below the cut off for mild cognitive impairment on the Montreal Cognitive Assessment (61.5% vs. 21.7%) and higher on the Multidimensional Fatigue Inventory-20, compared to the group without PCC+., Conclusion: Our results indicate that objectively assessed, olfactory dysfunction is a predictor for PCC+. These findings underscore the importance of objective olfactory testing. We propose that olfactory screening in the early post-acute phase of COVID-19 infection might identify individuals that are at higher risk of developing long-term health sequalae., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Background: Olfactory perceptions elicited by odors originating from within the body (retronasal olfaction) play a crucial role in well-being and are often disrupted in various medical conditions. However, the assessment of retronasal olfaction in research and the clinical practice is impeded by the lack of commercially available tests and limited standardization of existing testing materials., New Method: The novel ThreeT retronasal odor identification test employs 20 flavored tablets that deliver a standardized amount of odorous stimuli. The items represent common food- and non-food-related odors., Results: The ThreeT test effectively distinguishes patients with olfactory dysfunction from healthy controls, achieving a specificity of 86% and sensitivity of 73%. Its scores remain stable for up to 3 months (r=.79)., Comparison With Existing Method: ThreeT test exhibits a strong correlation with "Tasteless powders" measure of retronasal olfaction (r=.78) and classifies people into healthy and patient groups with similar accuracy. Test-retest stability of ThreeT is slightly higher than the stability of "Tasteless powders" (r=.79 vs r=.74)., Conclusions: ThreeT is suitable for integration into scientific research and clinical practice to monitor retronasal odor identification abilities., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thomas Hummel reports financial support was provided by Volkswagen Foundation. Thomas Hummel reports a relationship with: Veronique Debroise Blanchard-Dignac is the CEO of Sentosphère, Paris, France, which provided the tablets for this study If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is a prevalent neurodegenerative disorder that affects 7-10 million individuals worldwide. A common early symptom of PD is olfactory dysfunction (OD), and more than 90% of PD patients suffer from OD. Recent studies have highlighted a high incidence of OD in patients with SARS-CoV-2 infection. This review investigates the potential convergence of OD in PD and COVID-19, particularly focusing on the mechanisms by which neuroinflammation contributes to OD and neurological events. Starting from our fundamental understanding of the olfactory bulb, we summarize the clinical features of OD and pathological features of the olfactory bulb from clinical cases and autopsy reports in PD patients. We then examine SARS-CoV-2-induced olfactory bulb neuropathology and OD and emphasize the SARS-CoV-2-induced neuroinflammatory cascades potentially leading to PD manifestations. By activating microglia and astrocytes, as well as facilitating the aggregation of α-synuclein, SARS-CoV-2 could contribute to the onset or exacerbation of PD. We also discuss the possible contributions of NF-κB, the NLRP3 inflammasome, and the JAK/STAT, p38 MAPK, TLR4, IL-6/JAK2/STAT3 and cGAS-STING signaling pathways. Although olfactory dysfunction in patients with COVID-19 may be reversible, it is challenging to restore OD in patients with PD. With the emergence of new SARS-CoV-2 variants and the recurrence of infections, we call for continued attention to the intersection between PD and SARS-CoV-2 infection, especially from the perspective of OD., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The prevalence of smell dysfunction, along with its risk factors, has been evaluated in previous literature; however, little has been established regarding its relation to other factors such as disease severity, history of coronavirus disease-2019 (COVID-19) vaccinations, and medical treatment for COVID-19 infection. These factors may impact the overall recovery of olfaction in COVID-19 patients., Objective: This study investigated the prevalence of early olfactory recovery from COVID-19 infection and its associated factors., Methods: This study was a prospective cohort study on 348 COVID-19 patients with a new onset of anosmia or hyposmia. Smell sensation scores on the olfactory self-assessment test were collected at baseline and every week until 6 weeks of follow-up. The primary outcome was the prevalence of early olfactory recovery. The secondary outcomes were analyzing factors associated with early olfactory recovery and the median time to complete recovery of smell loss., Results: The prevalence of early olfactory recovery was 63.1% (95% CI: 0.58-0.68), and significant associated factors in multivariate analysis included patients without allergic rhinitis (OR 2.22, 95% CI: 1.12-4.40, P  = 0.023) and no alteration of taste perception (OR 1.62, 95% CI: 1.02-2.57, P  = 0.042). The median time to complete recovery from smell loss was 2 weeks., Conclusion: The present study found that the prevalence of early olfactory recovery within 2 weeks was 63.1%. The median time to olfactory recovery was also 2 weeks. Patients without allergic rhinitis and taste alteration had a significantly better chance of early recovery of olfactory function., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Different olfactory tests have been performed by otorhinolaryngologists in different parts of the world. For example, the University of Pennsylvania Smell Identification Test (UPSIT) has been used in the U.S., whereas the Sniffin' Sticks Test has been used in Europe, and similarly, T&T olfactometry is used in Japan. Although audiometers with electronic oscillators have long been used in hearing tests, electronic odor generators are not typically used in olfaction tests. We attempted an olfactory test using the AROMASTIC® (SONY, Tokyo, Japan), an electronically controlled device that can diffuse five different odors., Methods: Forty participants who had visited an outpatient olfactory clinic were included in this study. The participants were instructed to answer whether they could smell the five different odors during the AROMASTIC® screening test (AS-test), and the number of odors smelled was summed and scored (AS-score). The patients also underwent T&T olfactometry concurrently., Results: The AS-scores and T&T olfactometry detection and recognition thresholds showed significant correlations, confirming that the AS-test is a valid olfactory test., Conclusion: Electronic odor diffusers may be useful for olfaction tests., Competing Interests: Declaration of Competing Interest The authors received no financial support for the research, authorship, or publication of this article. The first author received an honorarium from SONY-OLYMPUS MEDICAL for his expertise on olfaction testing. The second author has no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

Background: This study examined the association between memory function and reduced olfactory and gustatory function among independent community-dwelling older adults., Methods: This cross-sectional study included 127 older adults (65.4% women). We assessed their memory, odor, and taste identification skills. Open essence (OE) test and taste strips (TS) were used to identify hyposmia (OE test ≤6) and hypogeusia (TS test ≤8), respectively., Results: Participants with severe hyposmia had significantly poorer memory functions compared to participants without severe hyposmia. After adjusting for covariates, multivariate logistic regression models revealed a significant association between immediate recognition performance and a decreased likelihood of severe hyposmia (odds ratio=0.65; 95% confidence interval 0.47-0.90). We observed no significant association between taste function and memory., Conclusion: Memory function may be associated with olfactory impairment in older adults.

Olfactory dysfunctions decrease daily quality of life (QOL) in part by reducing the pleasure of eating. Olfaction plays an essential role in flavor sensation and palatability. The decreased QOL due to olfactory dysfunction is speculated to result from abnormal neural activities in the olfactory and limbic areas of the brain, as well as peripheral odorant receptor dysfunctions. However, the specific underlying neurobiological mechanisms remain unclear. As the olfactory tubercle (OT) is one of the brain's regions with high expression of endogenous opioids, we hypothesize that the mechanism underlying the decrease in QOL due to olfactory dysfunction involves the reduction of neural activity in the OT and subsequent endogenous opioid release in specialized subregions. In this review, we provide an overview and recent updates on the OT, the endogenous opioid system, and the pleasure systems in the brain and then discuss our hypothesis. To facilitate the effective treatment of olfactory dysfunctions and decreased QOL, elucidation of the neurobiological mechanisms underlying the pleasure of eating through flavor sensation is crucial., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Murata, Maegawa, Imoto, Fujieda and Fukazawa.)

After contracting COVID-19, a substantial number of individuals develop a Post-COVID-Condition, marked by neurologic symptoms such as cognitive deficits, olfactory dysfunction, and fatigue. Despite this, biomarkers and pathophysiological understandings of this condition remain limited. Employing magnetic resonance imaging, we conduct a comparative analysis of cerebral microstructure among patients with Post-COVID-Condition, healthy controls, and individuals that contracted COVID-19 without long-term symptoms. We reveal widespread alterations in cerebral microstructure, attributed to a shift in volume from neuronal compartments to free fluid, associated with the severity of the initial infection. Correlating these alterations with cognition, olfaction, and fatigue unveils distinct affected networks, which are in close anatomical-functional relationship with the respective symptoms., (© 2024. The Author(s).)

Introduction: Olfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying neurobiology for this relationship remains unclear but may involve distinct patterns of neurodegeneration. This study aimed to examine longitudinal cortical atrophy and thinning in early-stage PD with severe olfactory deficit (anosmia) without and with concurrent probable RBD., Methods: Longitudinal MRI data over four years of 134 de novo PD and 49 healthy controls (HC) from the Parkinson Progression Marker Initiative (PPMI) cohort were analyzed using a linear mixed-effects model. Patients were categorized into those with anosmia by the University of Pennsylvania Smell Identification Test (UPSIT) score ≤ 18 (AO+) and those without (UPSIT score > 18, AO-). The AO+ group was further subdivided into AO+ with probable RBD (AO+RBD+) and without (AO+RBD-) for subanalysis., Results: Compared to subjects without baseline anosmia, the AO+ group exhibited greater longitudinal declines in both volume and thickness in the bilateral parahippocampal gyri and right transverse temporal gyrus. Patients with concurrent anosmia and RBD showed more extensive longitudinal declines in cortical volume and thickness, involving additional brain regions including the bilateral precuneus, left inferior temporal gyrus, right paracentral gyrus, and right precentral gyrus., Conclusions: The atrophy/thinning patterns in early-stage PD with severe olfactory dysfunction include regions that are critical for cognitive function and could provide a structural basis for previously reported associations between severe olfactory deficit and cognitive decline in PD. Concurrent RBD might enhance the dynamics of cortical changes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Age-related declines in olfaction contribute to low quality of life and appear to occur with declines in cognitive function, including diminished episodic memory. We tested the hypothesis that low gray matter volume within cortical regions that support olfaction and episodic memory can explain age-related differences in olfactory and episodic memory functions., Methods: T1-weighted images, Sniffin' Sticks olfactory measures, and the NIH Toolbox-Cognition Battery were administered to 131 middle-aged to older adults (50-86 years; 66% female). Correlation was used to examine the associations between these measures. A network-based image processing approach was then used to examine the degree to which spatial patterns of gray matter variance were related to the olfactory and cognitive measures. Structural equation modeling was used to characterize the relative specificity of olfactory, cognitive, gray matter, and aging associations., Results: Olfactory threshold, discrimination, and identification exhibited small to medium effect size associations with episodic memory performance (rs = 0.27-0.42, ps < 0.002). Gray matter volume within medial temporal and orbitofrontal cortex was also related to olfactory (discrimination and identification) and episodic memory function (rs = 0.21-0.36, ps < 0.019). Age and episodic memory explained the same variance in olfaction that was explained by the medial temporal and orbitofrontal pattern of gray matter volume., Conclusions: The results of this cross-sectional study suggest that identifying mechanisms contributing to differences in medial temporal and orbitofrontal cortex will advance our understanding of co-morbid olfactory and cognitive declines., (© 2023 ARS‐AAOA, LLC.)

Smell deficits and neurobiological changes in the olfactory bulb (OB) and olfactory epithelium (OE) have been observed in schizophrenia and related disorders. The OE is the most peripheral olfactory system located outside the cranium, and is connected with the brain via direct neuronal projections to the OB. Nevertheless, it is unknown whether and how a disturbance of the OE affects the OB in schizophrenia and related disorders. Addressing this gap would be the first step in studying the impact of OE pathology in the disease pathophysiology in the brain. In this cross-species study, we observed that chronic, local OE inflammation with a set of upregulated genes in an inducible olfactory inflammation (IOI) mouse model led to a volume reduction, layer structure changes, and alterations of neuron functionality in the OB. Furthermore, IOI model also displayed behavioral deficits relevant to negative symptoms (avolition) in parallel to smell deficits. In first episode psychosis (FEP) patients, we observed a significant alteration in immune/inflammation-related molecular signatures in olfactory neuronal cells (ONCs) enriched from biopsied OE and a significant reduction in the OB volume, compared with those of healthy controls (HC). The increased expression of immune/inflammation-related molecules in ONCs was significantly correlated to the OB volume reduction in FEP patients, but no correlation was found in HCs. Moreover, the increased expression of human orthologues of the IOI genes in ONCs was significantly correlated with the OB volume reduction in FEP, but not in HCs. Together, our study implies a potential mechanism of the OE-OB pathology in patients with psychotic disorders (schizophrenia and related disorders). We hope that this mechanism may have a cross-disease implication, including COVID-19-elicited mental conditions that include smell deficits., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Chronic rhinosinusitis (CRS) is a highly prevalent disease and up to 83% of CRS patients suffer from olfactory dysfunction (OD). Because OD is specifically seen in those CRS patients that present with a type 2 eosinophilic inflammation, it is believed that type 2 inflammatory mediators at the level of the olfactory epithelium are involved in the development of this olfactory loss. However, due to the difficulties in obtaining tissue from the olfactory epithelium, little is known about the true mechanisms of inflammatory OD. Thanks to the COVID-19 pandemic, interest in olfaction has been growing rapidly and several studies have been focusing on disease mechanisms of OD in inflammatory conditions. In this paper, we summarize the most recent data exploring the pathophysiological mechanisms underlying OD in CRS. We also review what is known about the potential capacity of olfactory recovery of the currently available treatments in those patients.

Only a few studies have investigated olfactory function in patients with obstructive sleep apnea syndrome (OSAS) using psychophysical testing, and there is a scarcity of data regarding taste evaluation in the existing literature. The primary objectives of this study were to assess both smell and taste in patients with OSAS and to explore the correlation between the severity of symptoms and sensory perception. A total of 85 OSAS patients and a control group comprising 81 subjects were enrolled. Initial assessments included anamnesis, nasal endoscopy, and the completion of questionnaires (Epworth Sleepiness Scale, Visual Analogue Scale, Questionnaire of Olfactory Disorders, and the importance of olfaction questionnaire). The diagnosis of OSAS was confirmed by polysomnography, while nasal airflow was evaluated using rhinomanometry. Olfaction was assessed using the Sniffin' Sticks test, and the Threshold-Discrimination-Identification (TDI) score was calculated. Taste evaluation was conducted in a subgroup of participants (42 patients, 38 controls) using taste strips. The mean TDI score was 31 ± 5.6 for OSAS patients and 35 ± 4.6 for controls, indicating a significant difference (P < 0.001). Similarly, the taste score was 7 ± 3.0 for OSAS patients and 12.6 ± 3.2 for controls (P < 0.001). No correlations were observed between TDI and Apnea Hypopnea Index (AHI) (r = -0.12; P = 0.28), as well as between the taste score and AHI (r = -0.31; P = 0.22). However, a weak but significant correlation between TDI score and Epworth Sleepiness Scale was detected (r = -0.05; P = 0.002). The study revealed a significant decrease in sensory perception among patients with OSAS, though open questions persist about the pathophysiology., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Olfactory dysfunction (OD) is not uncommon following viral infection. Herein, we explore the interplay of host genetics with viral correlates in coronavirus disease 2019 (COVID-19)- and long COVID-related OD, and its diagnosis and treatment that remain challenging. Two genes associated with olfaction, UGT2A1 and UGT2A2, appear to be involved in COVID-19-related anosmia, a hallmark symptom of acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly in the early stages of the pandemic. SARS-CoV-2 infects olfactory support cells, sustentacular and Bowman gland cells, that surround olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) where the initial step of odor detection takes place. Anosmia primarily arises from the infection of support cells of the OE, followed by the deciliation and disruption of OE integrity, typically without OSN infection. Through the projected axons of OSNs, the virus could theoretically reach the olfactory bulb and brain, but current evidence points against this route. Intriguingly, SARS-CoV-2 infection of support cells leads to profound alterations in the nuclear architecture of OSNs, leading to the downregulation of odorant receptor-related genes, e.g., of Adcy3. Viral factors associated with the development of OD include spike protein aminoacidic changes, e.g., D614G, the first substitution that was selected early during SARS-CoV-2 evolution. More recent variants of the Omicron family are less likely to cause OD compared to Delta or Alpha, although OD has been associated with a milder disease course. OD is one of the most prevalent post-acute neurologic symptoms of SARS-CoV-2 infection. The tens of millions of people worldwide who have lingering problems with OD wait eagerly for effective new treatments that will restore their sense of smell which adds value to their quality of life., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Data on the state of sense of smell in patients who had a new coronavirus infection caused by the SARS-CoV-2 virus are currently reduced because of the impairment of the olfactory nerve system. There are practically no results in studies of disorders in the trigeminal nerve system., Objective: Qualitative assessment of olfactory disorders after COVID-19 according to the system of olfactory and trigeminal nerves with a targeted assessment of the functional component of olfactory disorders., Material and Methods: We examined 40 patients aged 19 to 66 who had a coronavirus infection. All patients underwent neurological, otorhinolaryngological examinations, olfactometry, filled out the hospital anxiety and depression scale., Results: Anosmia was diagnosed in 5 (12.5%) patients, hyposmia in 21 (52.5%) patients, and normosmia in 14 (35%) patients. Formed: the 1st group - 14 patients (35%) with normogram according to olfactometry; the 2nd group - 26 patients (65%) with anosmia/hyposmia. In the 1st group, disorders of the anxiety-depressive spectrum were significantly more common. In the 2nd group, a low identification of odors was found, lying in the spectrum of fresh, sharp, unpleasant, irritating, compared with sweet and pleasant or neutral, which indicates a predominant lesion of the trigeminal system., Conclusion: In patients with complaints of impaired sense of smell after undergoing COVID-19, the possible functional nature of anosmia/hyposmia should be taken into account, which requires the referral of such patients to psychotherapeutic specialists, and the possible entry of olfactory disorders into the 'trigeminal' spectrum.

The psychophysical Sniffin' Sticks test, which includes an odor identification test, is the gold standard for assessing the sense of smell in clinical and scientific practice. A necessary requirement for the odor identification test is a close familiarity with the odors used by the inhabitants of the region in which it is used. We studied 77 healthy volunteers and 51 patients with olfactory dysfunction and we found that Russians are not familiar with the three smells from the test (licorice, turpentine and anise) and are completely unfamiliar with the one proposed alternative answer (chives). Moreover, four odors demonstrated very low recognition (less than 75%). The test has been adapted for the use In Russia. In the booklet, licorice is replaced by cough syrup, turpentine by paint thinner, and chives by bay leaf. For odors with low recognition (lemon, apple, pineapple), the alternative fruity odors in the booklet were replaced with more contrasting ones. Based on the data obtained, we are going to develop a domestic version of the odor identification test.

Introduction: Parkinson's disease (PD) is characterized by a prodromal phase preceding the onset of classic motor symptoms. The duration and clinical manifestations of prodromal PD vary widely, indicating underlying heterogeneity within this stage. This discrepancy prompts the question of whether specific factors contribute to the divergent rates of progression in prodromal PD., Methods: This study included prodromal PD patients from the Parkinson's progression marker initiative. They were followed up to assess the disease progression. The data collected during the follow-up period were analyzed to identify potential predictors of rapid disease progression in prodromal PD., Results: In this study, 61 individuals with prodromal PD were enrolled. Among them, 43 patients presented with both RBD and hyposmia, 17 had hyposmia alone, and 1 had RBD alone at baseline. 13 (21.3%) prodromal PD participants exhibited rapid disease progression, with two of these cases advancing to non-neurological diseases. Significant differences were observed between the rapid progression group and no rapid progression group in terms of MDS-UPDRS II score and UPSIT score. Longitudinal analysis showed a significant increase in the MDS-UPDRS III score and MDS-UPDRS total score in the rapid progression group. Regression analyses identified the MDS-UPDRS II score and UPSIT score as predictors of rapid disease progression in prodromal PD., Conclusion: Our study findings suggest that the MDS-UPDRS II score and UPSIT score may serve as clinical markers associated with rapid disease progression. Further research and development of precise biomarkers and advanced assessment methods are needed to enhance our understanding of prodromal PD and its progression patterns., (© 2024 S. Karger AG, Basel.)

Alterations in the three chemosensory modalities-smell, taste, and chemesthesis-have been implicated in Coronavirus Disease 2019 (COVID-19), yet emerging data suggest a wide geographic and ethnic variation in the prevalence of these symptoms. Studies on chemosensory disorders in COVID-19 have predominantly focused on Caucasian populations whereas Asians remain understudied. We conducted a nationwide, multicentre cross-sectional study using an online questionnaire on a cohort of RT-PCR-confirmed adult COVID-19 patients in Malaysia between 6 June and 30 November 2020. The aim of our study was to investigate their presenting symptoms and assess their chemosensory function using self-ratings of perceived smell, taste, chemesthesis, and nasal blockage. In this cohort of 498 patients, 41.4% reported smell and/or taste loss when diagnosed with COVID-19, which was the commonest symptom. Blocked nose, loss of appetite, and gastrointestinal disturbances were independent predictors of smell and/or taste loss on multivariate analysis. Self-ratings of chemosensory function revealed a reduction in smell, taste, and chemesthesis across the entire cohort of patients that was more profound among those reporting smell and/or taste loss as their presenting symptom. Perceived nasal obstruction accounted for only a small proportion of changes in smell and taste, but not for chemesthesis, supporting viral disruption of sensorineural mechanisms as the dominant aetiology of chemosensory dysfunction. Our study suggests that chemosensory dysfunction in COVID-19 is more widespread than previously reported among Asians and may be related to the infectivity of viral strains.Study Registration: NMRR-20-934-54803 and NCT04390165., (© 2022. The Author(s).)

Volatile solvents exposure can result in various behavioral impairments that have been partly associated to altered adult hippocampal neurogenesis. Despite recent evidence supporting this association, few studies have been devoted to examine the impact on olfactory functioning and olfactory bulb (OB) neurogenesis, although olfactory system is directly in contact with volatile molecules. Thus, this study was designed to evaluate in adult mice the potential modifications of the olfactory functioning after acute (1 day), subchronic (6 weeks) and chronic (12 weeks) exposure to thinner vapor at both behavioral and cellular levels. Firstly, behavioral evaluations showed that chronic thinner exposure impacts on odor detection ability of treated mice but does not affect mice ability to efficiently discriminate between two different odors. Moreover, chronic thinner exposure produces impairment in the olfactory-mediated associative memory. Secondly, analysis of the effects of thinner exposure in the subventricular zone (SVZ) of the lateral ventricle and in the OB revealed that thinner treatments do not induce apoptosis nor glial activation. Thirdly, immunohistochemical quantification of different markers of adult olfactory neurogenesis showed that inhalant treatments do not change the number of proliferating progenitors in the SVZ and the rostral migratory stream (RMS), as well as the number of newborn cells reaching and integrating in the OB circuitry. Altogether, our data highlight that the impaired olfactory performances in chronically-exposed mice are not associated to an alteration of adult neurogenesis in the SVZ-OB system., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The olfactory system is affected very early in Alzheimer's disease and olfactory loss can already be observed in patients with mild cognitive impairment (MCI), an early stage of AD., Objective: The aim of this randomized, prospective, controlled, blinded study was to evaluate whether olfactory training (OT) may have an effect on olfactory function, cognitive impairment, and brain activation in MCI patients after a 4-month period of frequent short-term exposure to various odors., Methods: A total of 38 MCI outpatients were randomly assigned to OT or a control training condition, which were performed twice a day for 4 months. Olfactory testing, comprehensive neuropsychological assessment, and a passive odor perception task based on magnetic resonance imaging were performed before and after training., Results: The results suggested that OT exhibited no significant effect on olfaction and cognitive function. Additionally, OT exhibited a positive effect on frontal lobe activation (left middle frontal gyrus and orbital-frontal cortex) but exhibited no effect on grey matter volume. Moreover, the change of olfactory scores was positively associated with the change of frontal activation., Conclusion: OT was found to have a limited effect on olfaction and cognition in patients with MCI compared to a non-OT condition but increased their functional response to odors in frontal area.

Objective: To determine which factors (demographic, symptoms, comorbidities, and treatments) are associated with recovery of smell in patients with COVID-19 associated olfactory loss., Study Design: Prospective, longitudinal questionnaires., Setting: National survey., Methods: A longitudinal web-based nationwide survey of adults with COVID-19 associated smell and taste loss was launched April 10, 2020. After completing an initial entry survey, participants received detailed follow-up questionnaires 14 days, and 1, 3 and 6 months later., Results: As of June 25, 2021, 798 participants met study inclusion criteria and completed 6-month questionnaires. Of demographic characteristics only age <40 years was positively associated with smell recovery (p < .003). Of symptoms, difficulty breathing was negatively associated with smell recovery (p < .004), and nasal congestion positively associated with smell recovery (p < .03). Of pre-existing comorbidities only previous head injury (p < .017) was negatively associated with smell recovery. None of the queried medications used to treat COVID were associated with better rates of smell recovery., Conclusions: Age <40 and presence of nasal congestion at time of COVID-19 infection were predictive of improved rates of smell recovery, while difficulty breathing at time of COVID-19 infection, and prior head trauma predicted worsened rates of recovery. Further study will be required to identify potential mechanisms for the other observed associations. Such information can be used by clinicians to counsel patients suffering COVID-19 associated smell loss as to prognosis for recovery., (Copyright © 2021 Elsevier Inc. All rights reserved.)