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Background: Olfactory function is closely related to mood and the endocrine system. However, the role of olfactory function in bipolar disorder combined with metabolic syndrome remains unclear. The purpose of this study was to explore the associations among olfactory function, tumor necrosis factor alpha (TNF-α), and metabolic syndrome and its components in patients with bipolar disorder., Methods: Ninety-six bipolar disorder patients were divided into two groups with and without metabolic syndrome. We also included 46 healthy controls. Olfactory function was assessed using the Sniffin' Sticks test. Blood samples were collected to measure metabolic indicators and serum TNF-α levels., Results: Significant differences in olfactory function were found among the three groups. Compared with the healthy controls, the bipolar disorder without metabolic syndrome group showed poorer olfactory identification ability (P < 0.001) and the bipolar disorder with metabolic syndrome group showed impaired olfactory sensitivity (P = 0.003) and olfactory identification (P < 0.001). Moreover, the bipolar disorder with metabolic syndrome group had poorer olfactory identification ability than the bipolar disorder without metabolic syndrome group (P = 0.015). Both bipolar disorder groups showed lower TNF-α levels than healthy controls. However, there was no significant difference between the two patient groups. Correlation analysis showed that, in the bipolar disorder with metabolic syndrome group, olfactory identification was negatively correlated with systolic blood pressure (r = - 0.424, P = 0.031), and serum TNF-α level was negatively correlated with body mass index (BMI; r = - 0.398, P = 0.049), triglyceride (r = - 0.503, P = 0.010), total cholesterol (r = - 0.491, P = 0.013), low-density lipoprotein-cholesterol (r = - 0.491, P = 0.013), and high-density lipoprotein-cholesterol (r = - 0.454, P = 0.023)., Conclusions: The olfactory identification ability of patients with bipolar disorder is worse than that of healthy controls, and the occurrence of metabolic syndrome will further aggravate the olfactory identification impairment of those patients. Furthermore, there may be a stronger link between serum TNF-α level and multiple metabolic indicators in bipolar disorder patients with metabolic syndrome than in bipolar disorder patients without metabolic syndrome., (© 2024. The Author(s).)

Objectives: Self-reported olfactory dysfunction is an assessment component criterion for chronic rhinosinusitis (CRS) disease control of the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS). No studies have objectively explored olfactory function across different psychophysical olfactory domains among patients with uncontrolled CRS. We aimed to investigate the patterns of olfactory impairment in patients with uncontrolled CRS with Sniffin' Sticks test., Methods: A total of 79 patients with CRS were prospectively recruited and assessed for disease control based on the EPOS criteria. Sniffin' Sticks test scores, olfactory cleft computed tomography (CT) scores, olfactory cleft endoscopy scale (OCES), questionnaire of olfactory disorders-negative statements (QOD-NS), and sinonasal outcome test-22 (SNOT-22) were obtained. Multiple logistic regression was applied to explore risk factors of uncontrolled CRS., Results: Twenty-six percent of patients with CRS presented with uncontrolled status. The odor threshold (OT) (p = 0.005), odor identification (OI) (p = 0.041), and thresholds-discrimination-identification (TDI) (p = 0.029) scores were significantly lower in patients with uncontrolled CRS when compared with patients with controlled CRS. Furthermore, patients with uncontrolled CRS presented with a significantly increased percentage of anosmia (p = 0.014), olfactory cleft CT score (p = 0.038), OCES (p = 0.016), QOD-NS(p = 0.008), and SNOT-22 (p < 0.001) scores than patients with controlled CRS. After adjusting for patient demographics, as for the subdomain of olfaction, only the OT score was an independent risk factor for uncontrolled CRS (odds ratio = 0.604; p = 0.030). The OT scores less than 5.950 were the best predictor of uncontrolled CRS., Conclusion: Patients with uncontrolled CRS demonstrated distinct patterns of olfactory impairment, and a reduced olfactory threshold was highly associated with uncontrolled CRS., Level of Evidence: 3 Laryngoscope, 134:2341-2348, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Olfactory dysfunction occurs frequently in Parkinson's disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice., Methods: MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP + ). Next, prok2R overexpression (prok2R + ) and knockdown (prok2R - ) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP + were evaluated in prok2R overexpression (prok2R + ) HEK293T cell lines., Results: Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R + and prok2R - HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R + HEK293T cells were resistant to MPP + -induced apoptosis., Conclusions: This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients., (© 2024. The Author(s).)

Methylmercury (MeHg) is a well-known environmental neurotoxicant that causes severe brain disorders such as Minamata disease. Although some patients with Minamata disease develop olfactory dysfunction, the underlying pathomechanism is largely unknown. We examined the effects of MeHg on the olfactory system using a model of MeHg poisoning in which mice were administered 30 ppm MeHg in drinking water for 8 weeks. Mice exposed to MeHg displayed significant mercury accumulation in the olfactory pathway, including the nasal mucosa, olfactory bulb, and olfactory cortex. The olfactory epithelium was partially atrophied, and olfactory sensory neurons were diminished. The olfactory bulb exhibited an increase in apoptotic cells, hypertrophic astrocytes, and amoeboid microglia, mainly in the granular cell layer. Neuronal cell death was observed in the olfactory cortex, particularly in the ventral tenia tecta. Neuronal cell death was also remarkable in higher-order areas such as the orbitofrontal cortex. Correlation analysis showed that neuronal loss in the olfactory cortex was strongly correlated with the plasma mercury concentration. Our results indicate that MeHg is an olfactory toxicant that damages the central regions involved in odor perception. The model described herein is useful for analyzing the mechanisms and treatments of olfactory dysfunction in MeHg-intoxicated patients., (© 2024. The Author(s).)

Recent literature indicates that post-COVID-19 patients suffer from a plethora of complications, including chemosensory dysfunction. However, little attention has been given to understand the interactions between chemosensory, trigeminal, and salivary dysfunctions in these patients. The aims of this study were (1) to investigate the prevalence and combinations of chemosensory, trigeminal, and salivary dysfunctions, (2) to identify the odorants/tastants that are compromised, and (3) to explore possible associations between the four dysfunctions in post-COVID-19 patients. One hundred post-COVID-19 patients and 76 healthy controls (pre-COVID-19) were included in this cross-sectional, case-controlled study. Participants' smell, taste, trigeminal, and salivary functions were assessed. The patients had a significantly higher prevalence of parosmia (80.0%), hyposmia (42.0%), anosmia (53.0%), dysgeusia (34.0%), complete ageusia (3.0%), specific ageusia (27.0%), dysesthesia (11.0%) and dry mouth (18.0%) compared to controls (0.0% for all parameters, except 27.6% for hyposmia). Complete loss of bitter taste was the most prevalent specific ageusia (66.7%) and coffee was the most common distorted smell (56.4%). Seven different combinations of dysfunction were observed in the patients, the most common being a combination of olfactory and gustatory dysfunction (48.0%). These findings indicate that post-COVID-19 patients experience a range of chemosensory, trigeminal, and salivary disturbances, occurring in various combinations., (© 2024. The Author(s).)

The partial or complete loss of the sense of smell, which affects about 20% of the population, impairs the quality of life in many ways. Dysosmia and anosmia are mainly caused by aging, trauma, infections, or even neurodegenerative disease. Recently, the olfactory area-a site containing the olfactory receptor cells responsible for odor perception-was shown to harbor a complex microbiome that reflects the state of olfactory function. This initially observed correlation between microbiome composition and olfactory performance needed to be confirmed using a larger study cohort and additional analyses. A total of 120 participants (middle-aged, no neurodegenerative disease) were enrolled in the study to further analyze the microbial role in human olfactory function. Olfactory performance was assessed using the Sniffin' Stick battery, and participants were grouped accordingly (normosmia: n = 93, dysosmia: n = 27). The olfactory microbiome was analyzed by 16S rRNA gene amplicon sequencing and supplemented by metatranscriptomics in a subset (Nose 2.0). Propidium monoazide (PMA) treatment was performed to distinguish between intact and non-intact microbiome components. The gastrointestinal microbiome of these participants was also characterized by amplicon sequencing and metabolomics and then correlated with food intake. Our results confirm that normosmics and dysosmics indeed possess a distinguishable olfactory microbiome. Alpha diversity (i.e., richness) was significantly increased in dysosmics, reflected by an increase in the number of specific taxa (e.g., Rickettsia , Spiroplasma , and Brachybacterium ). Lower olfactory performance was associated with microbial signatures from the oral cavity and periodontitis ( Fusobacterium , Porphyromonas , and Selenomonas ). However, PMA treatment revealed a higher accumulation of dead microbial material in dysosmic subjects. The gastrointestinal microbiome partially overlapped with the nasal microbiome but did not show substantial variation with respect to olfactory performance, although the diet of dysosmic individuals was shifted toward a higher meat intake. Dysosmia is associated with a higher burden of dead microbial material in the olfactory area, indicating an impaired clearance mechanism. As the microbial community of dysosmics (hyposmics and anosmics) appears to be influenced by the oral microbiome, further studies should investigate the microbial oral-nasal interplay in individuals with partial or complete olfactory loss.IMPORTANCEThe loss of the sense of smell is an incisive event that is becoming increasingly common in today's world due to infections such as COVID-19. Although this loss usually recovers a few weeks after infection, in some cases, it becomes permanent-why is yet to be answered. Since this condition often represents a psychological burden in the long term, there is a need for therapeutic approaches. However, treatment options are limited or even not existing. Understanding the role of the microbiome in the impairment of olfaction may enable the prediction of olfactory disorders and/or could serve as a possible target for therapeutic interventions., Competing Interests: The authors declare no conflict of interest.

Background: Olfactory dysfunction associated with SARS-CoV-2 infection in children has not been verified by a validated olfactory test. We aimed to determine whether these complaints are objectifiable (test-based hyposmia), how often they occur during acute SARS-CoV-2 infection compared to other upper respiratory tract infections (URTI), as well as in children recovered from COVID-19 compared to children with long COVID., Methods: Olfactory testing (U-sniff test; hyposmia<8 points) and survey-based symptom assessments were performed in 434 children (5-17 years; 04/2021-06/2022). 186 symptom-free children served as controls. Of the children with symptoms of acute respiratory tract infection, SARS-CoV-2 PCR test results were positive in 45 and negative in 107 children (URTI group). Additionally, 96 children were recruited at least 4 weeks (17.6±15.2 weeks) after COVID-19, of whom 66 had recovered and 30 had developed long COVID., Results: Compared to controls (2.7%), hyposmia frequency was increased in all other groups (11-17%, p<0.05), but no between-group differences were observed. Only 3/41 children with hyposmia reported complaints, whereas 13/16 children with complaints were normosmic, with the largest proportion being in the long-COVID group (23%, p<0.05)., Conclusion: Questionnaires are unsuitable for assessing hyposmia frequency in children. Olfactory complaints and hyposmia are not specific for SARS-CoV-2 infection. The number of complaints in the long-COVID group could result from aversive olfactory perception, which is undetectable with the U-sniff test., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objectives: Post-operative delirium (POD) affects up to 50% of cardiac surgery patients, with higher incidence in older adults. There is increasing need for screening tools that identify individuals most vulnerable to POD. Here, we examined the relationship between pre-operative olfaction and both incident POD and POD severity in patients undergoing cardiac surgery. We also examined cross-sectional relationships between baseline olfaction, cognition, and plasma neurofilament light (NfL)., Methods: Individuals undergoing cardiac surgery (n = 189; mean age = 70 years; 75% men) were enrolled in a clinical trial of cerebral autoregulation monitoring. At baseline, odor identification performance (Brief Smell Identification Test), cognitive performance, and plasma concentrations of NfL levels (Simoa™ NF-Light Assay) were measured. Delirium was assessed with the Confusion Assessment Method (CAM) or CAM-ICU, and delirium severity was assessed using the Delirium Rating Scale-Revised-98. The association of baseline olfaction, delirium incidence, and delirium severity was examined in regression models adjusting for age, duration of cardiopulmonary bypass, logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE), and baseline cognition., Results: Olfactory dysfunction was present in 30% of patients, and POD incidence was 44%. Pre-operative olfactory dysfunction was associated with both incident POD (OR = 3.17, p = 0.001) and greater severity of POD after cardiac surgery (OR = 3.94 p < 0.001) in models adjusted for age, duration of bypass, and a surgical risk score. The addition of baseline cognition attenuated the strength of the association, but it remained significant for incident POD (OR = 2.25, p = 0.04) and POD severity (OR 2.10, p = 0.04). Poor baseline olfaction was associated with greater baseline cognitive dysfunction (p < 0.001) and increased baseline plasma NfL concentrations (p = 0.04). Neither age, cognition, nor baseline NFL concentration modified the association of impaired olfaction and delirium outcomes., Conclusions: Olfactory assessment may be a useful pre-surgical screening tool for the identification of patients undergoing cardiac surgery at increased risk of POD. Identifying those at highest risk for severe delirium and poor cognitive outcomes following surgery would allow for earlier intervention and pre-operative rehabilitation strategies, which could ultimately impact the functional disability and morbidity associated with POD., (© 2024 John Wiley & Sons Ltd.)

Objective: Our goal was to see if children with a history of COVID infection had subclinical hyposmia., Methods: Consecutive patients at a pediatric otolaryngology clinic aged 5-17 years were recruited. Demographics including gender, race, use of nasal topical medications (NTM), previous nasal surgery including adenoidectomy (NSA), and previous COVID-19 infection were collected. Each child performed a test of their sense of smell using the Pediatric Smell Wheel (PSW, Sensonics Intl, USA) under the direct supervision and scores were compared., Results: 260 children were included; mean age 10.1 years (95% CI 9.7-10.5), 128 (49.2%) female and 132 (50.8%) male. 65 (25%) used steroid nasal sprays, 100 (38.5%) had undergone adenoidectomy, and 36 (13.8%) had other nasal surgery. 120 (46.2%) had a previous COVID-19 infection. The COVID+ and COVID- groups were the same for age, gender, race, use of NTMs, and previous NSA (p > 0.05). Mean PSW score was 7.8 (95% CI 7.6-8.0), median of 8, ranging from 2 to 11. The mean PSW score was 8.0 for the COVID- group and 7.6 for the COVID+ group (p = 0.005). There was no significant difference in total PSW scores based on gender, race, use of NTMs, previous NSA. Linear regression showed previous COVID infection was significantly negatively associated with total PSW score (Beta -0.636, p = 0.006) with age significantly positively associated (Beta 0.122, p < 0.001)., Conclusion: Children with a history of COVID infection performed slightly worse when identifying odors than children without a COVID history. More study into the rates of pediatric anosmia related to COVID infection is needed., Level of Evidence: 3 Laryngoscope, 134:901-906, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: The purpose was to evaluate the relationship between peripheral eosinophilia, Japan Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score, and olfactory dysfunction in chronic rhinosinusitis (CRS) patients and to explore the accuracy and specific cut points of the JESREC score in predicting olfactory dysfunction., Methods: In this cross-sectional, retrospective study, olfactory function was assessed by the Sniffin' Sticks 12-item test and multivariate logistic regression analyses were carried out. Receiver operating characteristic curves were plotted to derive accuracy and cutoff values for the JESREC scores of the olfactory dysfunction criterion., Results: A total of 354 patients [mean (SD) age, 50.0 (14.9) years; 41.8% women] were included in the final analysis. The prevalence of olfactory dysfunction was 46.3%. Individuals who had olfactory dysfunction were more likely to be male (64.6% vs. 52.6%), have eosinophilic chronic rhinosinusitis (ECRS) (39.0% vs. 7.9%), have a longer course of CRS (2.3 years vs. 1.5 years), have higher JESREC scores (8.5 vs. 4.5), and have higher proportions of nasal polyps (78.7% vs. 18.9%) and peripheral eosinophilia (3.3% vs. 1.4%). In logistic analysis, the percentage of eosinophils (1.25, 1.13-1.37), JESREC score (1.31, 1.22-1.40), bilateral lesion (2.06, 1.25-3.41), nasal polyps (15.83, 9.23-27.16), CT shadow (2.73, 1.69-4.43), and ECRS (6.86, 3.68-12.80) were associated with olfactory dysfunction in CRS patients after controlling for covariates, while peripheral neutrophils were not significant. In addition, the area under the curve was 0.778 and the cutoff value for JESREC score for olfactory dysfunction was defined as 5.5., Conclusions: Peripheral eosinophilia and high JESREC scores were significantly associated with the risk of olfactory dysfunction in CRS patients, and special attention should be paid to patients with a JESREC score ≥6., 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 Zhang, Li, Wang, Wang, Wu, Guo, Li, Zhou, Xue and You.)

Background and aim It has been shown that olfactory dysfunction is one of Coronavirus disease-2019 (COVID-19)common and puzzling symptoms that may persist weeks after the infection. This study aimed for the objective assessment of persisting olfactory dysfunction in post-COVID-19 patients. It also investigated the factors associated with the development of such symptoms in the Eastern Province of Saudi Arabia., Methods: A cross-sectional study that was conducted in the Department of Physiology, College of Medicine, Imam Abdulrahman bin Faisal University, Khobar, Saudi Arabia. One hundred and forty-seven participants were included in this study, and sixty of them agreed  to participate in the objective testing using the Connecticut Chemosensory Clinical Research Center (CCCRC) olfaction test., Results: There was a significant correlation between the following factors: (1) Persistence of anosmia/hyposmia and the time of onset of anosmia/hyposmia (P=0.015). (2) Persistence of anosmia/hyposmia and the duration of anosmia/hyposmia (P=0.012). (3) Duration of anosmia/hyposmia and the duration of COVID-19 symptoms (P=0.010). Interestingly, there was a significant association between the subjective participants' claim of anosmia/hyposmia and the score of their objective assessment (P=0.026)., Conclusion: The current study demonstrated that post-COVID-19 participants with delayed onset of anosmia/hyposmia and/or longer duration of either anosmia/hyposmia or COVID-19 symptoms were prone to have persistent olfactory dysfunction. Further studies are necessary to uncover the underlying pathophysiology and management of this olfactory dysfunction in COVID-19 patients.

Background: Eosinophils are associated with olfactory dysfunction in chronic rhinosinusitis (CRS) and eosinophil-derived neurotoxin (EDN) is a sensitive marker of intense eosinophil activation. This study aimed to analyze olfactory cleft mucus and olfactory mucosa EDN levels and their association with olfactory dysfunction in CRS., Methods: We prospectively recruited 150 patients with CRS electing endoscopic sinus surgery and 25 healthy controls. Both superior turbinate biopsy specimens and olfactory cleft mucus were collected to analyze EDN levels. Sniffin' Sticks test scores, olfactory cleft computed tomography (CT) scores, and olfactory cleft endoscopy scale (OCES) were obtained. Multivariable logistic regression analysis was applied to analyze the predictability of EDN levels for olfactory dysfunction in CRS., Results: Chronic rhinosinusitis with olfactory dysfunction presented significantly higher olfactory mucosa (p = 0.016) and olfactory cleft mucus (p < 0.001) EDN levels than CRS without olfactory dysfunction. Mucus EDN levels were positively correlated with blood eosinophils (r = 0.625, p = 0.002), olfactory cleft CT scores (r = 0.738, p < 0.001), and OCES (r = 0.605, p = 0.004) in CRS. Furthermore, mucus EDN levels were significantly negatively correlated with threshold, discrimination, and identification (TDI) (r = -0.688), olfactory threshold (r = -0.606), olfactory discrimination (r = -0.608), and olfactory identification (r = -0.697) scores. After adjusting for patient demographics and comorbidities, mucus EDN levels were significantly associated with olfactory dysfunction in CRS (odds ratio = 2.162; p = 0.027). Mucus EDN levels showed a significantly better performance for predicting olfactory dysfunction than blood eosinophil counts (area under the curve, 0.873 vs. 0.764, p = 0.024)., Conclusion: Olfactory cleft mucus EDN level may be a better biomarker for predicting olfactory dysfunction in CRS than blood eosinophil counts., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Loss of sense of smell is one of the most burdensome symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP) but its relationship to sinus disease on imaging is unclear. Dupilumab improves sense of smell and radiographic severity of sinus disease in patients with CRSwNP. We investigated the relationship of sinus opacification severity and loci to olfactory impairment and dupilumab efficacy in patients with CRSwNP from the SINUS-24/SINUS-52 (NCT02912468/NCT02898454) studies., Methods: Sinus opacification was evaluated using the Lund-Mackay computed tomography (LMK-CT) score and sense of smell using patient-reported loss of smell (LoS) score, University of Pennsylvania Smell Identification Test (UPSIT) score and the 22-item Sino-Nasal Outcome Test (SNOT-22) smell/taste item., Results: At baseline, 95% of patients (688/724) had impaired sense of smell and opacification was extensive across all sinuses. Greater olfactory impairment was associated with greater opacification, especially in the ethmoid, sphenoid and frontal sinuses. At Week 24, reductions in LMK-CT total score and ethmoid and sphenoid sinus scores with dupilumab were weakly correlated with improvements in sense of smell assessed by LoS, UPSIT and SNOT-22 smell/taste item. More dupilumab than placebo patients achieved clinically meaningful improvement in LMK-CT total score at Week 24 and Week 52., Conclusion: Radiographic disease severity on imaging was associated with smell outcomes in this cohort. Opacification of the ethmoid, sphenoid and frontal sinuses was associated with severe smell loss. These data suggest that dupilumab effects on smell may be partly mediated through reduced sinus inflammation.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the start of the pandemic, olfactory dysfunction (OD) has been reported as a common symptom of COVID-19. In some asymptomatic carriers, OD is often the first and even the only symptom. At the same time, persistent OD is also a long-term sequela seen after COVID-19 that can have a serious impact on the quality of life of patients. However, the pathogenesis of post-COVID-19 OD is still unclear, and there is no specific treatment for its patients. The aim of this paper was to review the research on OD caused by SARS-CoV-2 infection and to summarize the mechanism of action, the pathogenesis, and current treatments., (© 2023. The Author(s).)

Background: Unilateral cleft lip nasal deformity (uCLND) is associated with olfactory dysfunction, but the underlying etiology remains poorly understood. Objective: To investigate the etiology of uCLND-associated olfactory dysfunction using clinical, computational, and histologic assessments. Methods: Inclusion criteria: uCLND patients >16 years undergoing septorhinoplasty. Exclusion criteria: prior septoplasty or rhinoplasty, pregnancy, sinusitis. Measured outcomes: patient-reported scores, rhinomanometry, smell identification and threshold tests, computational fluid dynamics (CFD) airflow simulations, and histologic analysis of olfactory epithelium. Results: Five uCLND subjects were included: 18-23 years, three male and two female, four left-sided cleft and one right-sided cleft. All subjects reported moderate to severe nasal obstruction. Smell identification and threshold tests showed varying degrees of hyposmia. Nasal resistance was higher on the cleft side versus noncleft side measured by rhinomanometry (median 3.85 Pa-s/mL, interquartile range [IQR] = 21.96, versus 0.90 Pa-s/mL, IQR = 5.17) and CFD (median 1.04 Pa-s/mL, IQR = 0.94 vs. 0.11 Pa-s/mL, IQR = 0.12). Unilateral olfaction varied widely and was dependent on unilateral percentage olfactory airflow. Biopsies revealed intact olfactory neuroepithelium. Conclusions: uCLND-associated olfactory dysfunction appears to be primarily conductive in etiology and highly susceptible to variations in nasal anatomy. Clinical Trial Registration number: NCT04150783.

Objective: The aim of this study was to quantify the impact of COVID-19 on olfactory and gustatory function in US adults., Methods: From the 2021 Adult National Health Interview Survey, demographic and survey-specific module data concerning COVID-19 diagnoses, testing and disease severity, and data quantifying disturbances and eventual recovery of smell and taste were extracted. Sample weights were applied to obtain nationally representative statistics. The overall rate of COVID-19 infection was determined, and those diagnosed with COVID-19 were analyzed with respect to disease severity, smell and taste disturbance, and respective recoveries., Results: In 2021, 35.8 million or 14% of the adult population (95% CI 13.5-14.7%; mean age, 43.9 years; 53.8% female) had been diagnosed with COVID-19. Among those, 60.5% (58.6-62.5%) and 58.2% (56.2-60.1%) reported accompanying losses  in smell or taste, respectively; there was a significant association between overall COVID-19 symptom severity and smell (p < 0.001) and taste disturbance (p < 0.001). Following infection, 72.2% (69.9-74.3%), 24.1% (22.2-26.2%), and 3.7% (3.0-4.6%) of the patients experienced complete, partial, and no smell recovery, respectively. Recovery rates for gustatory function paralleled olfaction, with 76.8% (74.6-78.9%), 20.6% (18.7-22.7%), and 2.6 (1.9-3.4%) reporting complete, partial, and no recovery of taste, respectively. When sensory disturbance was present, severity of overall symptomatology was negatively associated with smell and taste recovery (p < 0.001 for each)., Conclusion: The majority of adults infected with COVID-19 in 2021 experienced olfactory or gustatory dysfunction with a non-negligible population reporting incomplete or no near-term sensory recovery. Our results are useful for providers counseling patients and suggest that interventions lessening overall COVID-19 symptom burden may prevent prolonged sensory dysfunction., Level of Evidence: 4 Laryngoscope, 133:2357-2361, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To investigate if intranasal insulin could be a treatment option for those suffering from recalcitrant olfactory dysfunction due to COVID-19., Study Design: Prospective interventional cohort with a single group., Setting: Sixteen volunteers with anosmia, severe hyposmia, or moderate hyposmia for more than 60 days as sequelae of severe acute respiratory syndrome coronavirus 2 infections were selected for the study. All volunteers reported that standard therapies, such as corticosteroids, have failed to improve their olfactory function., Methods: Olfactory function was assessed by the Chemosensory Clinical Research Center test of olfaction (COT) before and after the intervention. Changes in qualitative, quantitative, and global COT scores were investigated. The insulin therapy session consisted of placing into each olfactory cleft 2 pieces of gelatin sponge soaked with neutral protamine Hagedorn (NPH) insulin, 40 IU on each side. The procedure was repeated twice a week for 1 month. Glycaemic blood level was measured before and after each session., Results: The qualitative COT score rose 1.53 points, p = .0001, 95% confidence interval (CI) (-2.12 to -0.94). The quantitative COT score increased by 2.00 points, p = .0002, 95% CI (-3.59 to -1.41). Global COT score had an improvement of 2.01 points, p = .00003, 95% CI (-2.7 to -1.3). Glycaemic blood level dropped on average 10.4 mg/dL, p < .00003, 95% CI (8.1-12.8)., Conclusion: Our results suggest that the administration of NPH insulin into the olfactory cleft yields a rapid improvement in the sense of smell of patients suffering from persistent post-COVID-19 olfactory dysfunction. Moreover, the procedure seems to be safe and tolerable., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: The existing literature suggests that impaired olfaction may be an early marker for cognitive decline. Tracking the earliest stages of the progression to dementia is paramount, and yet the importance of olfactory ability throughout cognitive states and death remains unclear., Methods: Drawing data from the Rush Memory and Aging Project (N = 1 501; 74% female), olfactory ability was assessed using the Brief Smell Identification Test (range = 0-16), while cognitive states (unimpaired, mild cognitive impairment [MCI], and dementia) were determined using a 3-step neuropsychological diagnostic protocol at up to 15 annual occasions. Multistate survival models simultaneously estimated the association of olfactory ability on transitions through cognitive states and death, while multinomial regression models estimated cognitively unimpaired and total life expectancies., Results: Higher olfactory scores were associated with a reduced risk of transitioning from unimpaired cognition to MCI (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.82-0.88) and from MCI to dementia (HR = 0.89, 95% CI = 0.86-0.93), indicating that 1-unit increase in olfactory scores was associated with an approximate 14% and 11% reduction in risk, respectively. Additionally, higher olfactory scores were associated with a greater likelihood of transitioning backward from MCI to unimpaired cognition (HR = 1.07, 95% CI = 1.02-1.12). Furthermore, higher baseline olfactory scores were associated with more years of longevity without cognitive impairment. However, olfaction was not associated with the transition to death when accounting for transitions through cognitive states., Conclusions: Findings suggest that higher olfactory identification scores are associated with a decreased risk of transitioning to impaired cognitive states and that associations between olfaction and mortality may occur primarily through the pathway of neurodegeneration., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Previous research has identified an association between olfactory impairment (reduced odor sensitivity/ identification/ discrimination) and cognitive impairment in older adults. The present study focused on the relationship between olfactory memory performance and cognitive/affective functioning., Method: Recognition performance for olfactory and visual stimuli (control condition) was tested through a matching task in older adults ( n = 44; M age  = 76 years) and younger adults ( n = 56; M age  = 24 years). Additionally, negative affect (anxiety, depression) and cognitive functioning were assessed via validated questionnaires and a neuropsychological test battery., Results: The older participants performed worse than the younger adults in the olfactory memory task. In older adults, difficulties in remembering odors were associated with reduced odor identification and executive functioning (reduced cognitive flexibility). Affective well-being was not related to olfactory memory performance., Implication: Olfactory memory impairment in older adulthood might be a marker for cognitive decline in areas related to executive functions.

Background: COVID-19 has been frequently demonstrated to be associated with anosmia. Calcium cations are a mainstay in the transmission of odor. One of their documented effects is feedback inhibition. Thus, it has been advocated that reducing the free intranasal calcium cations using topical chelators such as pentasodium diethylenetriamine pentaacetate (DTPA) could lead to restoration of the olfactory function in patients with post-COVID-19 anosmia., Methodology: This is a randomized controlled trial that investigated the effect of DTPA on post-COVID-19 anosmia. A total of 66 adult patients who had confirmed COVID-19 with associated anosmia that continued beyond three months of being negative for SARS-CoV-2 infection. The included patients were randomly allocated to the control group that received 0.9 % sodium chloride-containing nasal spray or the interventional group that received 2 % DTPA-containing nasal spray at a 1:1 ratio. Before treatment and 30 days post-treatment, the patients' olfactory function was evaluated using Sniffin' Sticks, and quantitative estimation of the calcium cations in the nasal mucus was done using a carbon paste ion-selective electrode test., Results: Patients in the DTPA-treated group significantly improved compared to the control group in recovery from functional anosmia to hyposmia. Additionally, they showed a significant post-treatment reduction in the calcium concentration compared to the control group., Conclusion: This study confirmed the efficacy of DTPA in treating post-COVID-19 anosmia., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To investigate the prevalence and the evolution of olfactory disorders (OD) related to coronavirus disease 2019 (COVID-19) in patients infected during the first and the second European waves., Methods: From March 2020 to October 2020, COVID-19 patients with OD were recruited and followed over the 12-month post-infection. The following data were collected: demographic, treatments, vaccination status, and olfactory function. Olfaction was assessed with the Olfactory Disorder Questionnaire (ODQ), and threshold, discrimination, and identification (TDI) test. Outcomes were compared between patients of the first wave (group 1: wild/D614G virus) and the second wave (group 2: B.1.1.7. Alpha variant) at 1-, 3- and 12-month post-infection., Results: Sixty patients completed the evaluations accounting for 33 and 27 patients in group 1 and 2, respectively. The 1-month TDI score (23.7 ± 5.3) was significantly lower in group 2 compared to group 1 (29.8 ± 8.7; p = 0.017). Proportion of normosmic patients at 1-month post-infection was significantly higher in group 1 compared to group 2 (p = 0.009). TDI scores only significantly increased from 1- to 3-month post-infection in anosmic and hyposmic patients. Focusing on There was a negative association between the 1-month ODQ and the 1-month TDI (r s  = - 0.493; p = 0.012). ODQ was a significant predictor of TDI scores at 3- and 12-month post-infection. The 12-month prevalence of parosmia was 60.6% in group 1 and 42.4% in group 2, respectively. There was no significant influence of oral corticosteroid treatment, adherence to an olfactory training and vaccination status on the olfactory outcomes., Conclusions: Patients of the second wave (Alpha B.1.1.7. variant) reported significant higher proportion of psychophysical test abnormalities at 1-month post-infection than patients infected during the first wave (D614G virus)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aging contributes to the deterioration of the olfactory system in humans. Several studies indicate that the olfactory identification test alone may function as a screening test for olfactory dysfunction and they are more feasible to apply in clinical practice. Olfactory identification may be a predictor for cognitive impairment. Multiple studies have considered the use of odor identification as a measure to identify the conversion from normality to mild cognitive impairment or dementia. The objectives were (i) to elucidate the associations between cognitive status and olfactory identification performance in aging; (ii) understand the predictive value of olfactory capacity in identifying subjects with cognitive impairment risk; and (iii) to study how cognitive status and olfactory identification relate with other variables of wellness in aging, such as functional capabilities and clinical measures. For this purpose, a group of 149 participants (77.15 ± 7.29 years; 73 women of 76.7 ± 8 years and 76 men of 77.6 ± 6.52 years) were recruited and were subjected to a sociodemographic questionnaire, a psychological screening tool of general cognitive status, an olfactory identification evaluation, and clinical measures. The participants were divided into groups based on their cutoff scores of previous scientific reports about the Spanish version of Montreal Cognitive Assessment. Our results indicate an age-associated decline in olfactory identification ability and intensity of odor perception. The predictive ability of olfactory identification scores for the risk of mild and severe impairment is around 80%. Olfactory identification decreases with cognitive function. Performance in odor identification is associated with impairment of episodic memory and executive functions. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia., (© 2023. The Author(s).)

Purpose: To report biomarkers present in the olfactory mucosa in chronic rhinosinusitis with nasal polyps (CRSwNP) in comparison with nasal polyps and to nasal mucosal tissues from control patients. To evaluate the kinetics of smell over 6 months in patients who underwent Reboot surgery., Methods: Cohort study from May 2021 to May 2022. We collected samples of olfactory mucosa and nasal polyps from 16 CRSwNP patients and inferior turbinate samples from 20 control subjects. The study was not randomized for surgical and/or medical treatment. Samples were analyzed by Luminex and Unicap 100 to measure biomarkers of inflammation (IL1-β, IL4, IL5, IL6, IL17, CCL3, CCL4, G-CSF, SE-IgE, total IgE and ECP). 12 of the CRSwNP patients underwent Extended Sniffin'tests at timepoints 1-4 days pre-surgery, and 1, 3 and 6 months after Reboot surgery., Results: Type-2 markers were significantly elevated in OM and polyp tissue in CRSwNP (n = 16) vs. controls (n = 20), P < 0.05. TDI scores improved already 1 month (P < 0.05) after surgery and remained stable for 6 months. Type-2 inflammation in nasal polyps was associated with decreased sense of smell and taste before surgery, but improved after surgery (P = 0.048). Type-3 inflammation was present in the olfactory mucosa and was associated with a better sense of smell before surgery, but a smaller improvement of smell afterward., Conclusions: Type-2 inflammation is present in the olfactory mucosa in CRSwNP patients and is associated with smell loss. Reboot surgery, aiming to completely remove inflamed sinus mucosa, significantly improves the smell in this group of patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate safety, feasibility, and effectiveness of platelet-rich plasma (PRP) injection into the olfactory clefts of COVID-19 patients with persistent olfactory dysfunction (OD)., Methods: From March 2022 to July 2022, COVID-19 patients with persistent OD were consecutively recruited to benefit from PRP injection into the olfactory clefts. Patient pain, annoyance, time of procedure, and adverse events were evaluated. Olfactory function was evaluated at baseline and 2-month post-injection with the olfactory disorder questionnaire (ODQ) and threshold, discrimination, and identification (TDI) test., Results: Eighty-seven patients with anosmia (N = 30), hyposmia (N = 40), or parosmia (N = 17) with a mean OD duration of 15.7 months completed the evaluations. The PRP injection was successfully performed in all patients with a mean procedure time of 18.4 ± 3.4 min. The adverse events included transient epistaxis (N = 31), parosmia related to xylocaine spray (N = 10), and vasovagal episode (N = 2). The injection procedure was evaluated as somewhat or moderately painful by 41 (47%) and 22 (25%) patients, respectively. Thirty-seven patients were assessed after 2 months post-injection. The mean ODQ and TDI scores significantly improved from baseline to 2-month post-injection (p < 0.01). The olfactory improvement occurred after a mean of 3.6 ± 1.9 weeks., Conclusion: The injection of PRP into the olfactory clefts is safe and associated with adequate patient-reported outcomes. The findings of this preliminary study suggest possible efficacy on subjective and psychophysical evaluations, but future randomized controlled studies are needed to determine the superiority of PRP injection over placebo., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The taste buds in the human tongue contain specialized cells that generate taste signals when they are stimulated. These signals are then transmitted to the central nervous system, allowing the human body to distinguish nutritious substances from toxic or harmful ones. This process is critical to the survival of humans and other mammals. A number of studies have shown that dysgeusia, or taste disorder, is a common complication of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which can severely affect patients' nutritional intake and quality of life. Based on the physiological process of taste perception, the direct causes of dysgeusia include dysfunction of taste receptors and damage to the taste nervous system, while indirect causes include genetic factors, aging-related changes, bacterial and viral infections, and cancer treatments such as radiotherapy and chemotherapy. The pathogenic factors of dysgeusia are complicated, further research is needed to fully understand the underlying mechanisms, and some of the reported findings and conclusions still need further validation. All these form a great challenge for clinical diagnosis of the cause and targeted treatment of dysgeusia. Herein, we reviewed published research on the physiological process of taste perception, the potential mechanisms of taste disorders related to SARS-CoV-2 infection, and strategies for prevention and treatment, providing theoretical support for establishing and improving the comprehensive management of COVID-19 complicated by taste disorders., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Background and Objectives: Olfactory function declines with aging, and olfactory deficits are one of the earliest features of neurodegenerative diseases, such as Parkinson disease and Alzheimer disease. Previous studies have shown that olfaction is associated with brain volumes and cognitive function, but data are exclusively cross-sectional. We aimed to examine longitudinal associations of olfaction with changes in brain volumes and neuropsychological function., Methods: In the Baltimore Longitudinal Study of Aging, we chose the first assessment of olfaction to examine the associations with retrospective and prospective changes in neuropsychological performance and brain volumes in participants aged 50 years or older using linear mixed-effects models, adjusted for demographic variables and cardiovascular disease. Olfaction was measured as odor identification scores through the 16-item Sniffin' Sticks., Results: We analyzed data from 567 (58% women, 42% men, 27% Black, 66% White, and 7% others) participants who had data on odor identification scores and brain volumetric MRI (n = 420 with retrospective repeats over a mean of 3.7 years, n = 280 with prospective repeats over a mean of 1.2 years). We also analyzed data from 754 participants (56% women, 44% men, 29% Black, 65% White, and 6% others) with neuropsychological assessments (n = 630 with retrospective repeats over a mean of 6.6 years, n = 280 with prospective repeats over a mean of 1.5 years). After adjustment, higher odor identification scores were associated with prior and subsequent slower brain atrophy in the entorhinal cortex (β ± SE = 0.0093 ± 0.0031, p = 0.0028 and β ± SE = 0.0176 ± 0.0073, p = 0.0169, respectively), hippocampus (β ± SE = 0.0070 ± 0.0030, p = 0.0192 and β ± SE = 0.0173 ± 0.0066, p = 0.0089, respectively), and additional frontal and temporal areas (all p < 0.05). Higher odor identification scores were also associated with prior slower decline in memory, attention, processing speed, and manual dexterity and subsequent slower decline in attention (all p < 0.05). Some associations were attenuated after exclusion of data points at and after symptom onset of cognitive impairment or dementia., Discussion: In older adults, olfaction is related to brain atrophy of specific brain regions and neuropsychological changes in specific domains over time. The observed associations are driven, in part, by those who developed cognitive impairment or dementia. Future longitudinal studies with longer follow-ups are needed to understand whether olfactory decline precedes cognitive decline and whether it is mediated through regionally specific brain atrophy., (© 2022 American Academy of Neurology.)

Objectives: Olfactory dysfunction is reproducibly reported in psychotic disorders, particularly in association with negative symptoms. The superior frontal gyrus (SFG) has been frequently studied in patients with psychotic disorders, in particular with their associations with negative symptoms. The relationship between olfactory functions and brain structure has been studied in healthy controls (HCs). Nevertheless, the studies with patients with psychotic disorders are limited. Here we report the olfactory-brain relationship in a first episode psychosis (FEP) cohort through both hypothesis-driven (centred on the SFG) and data-driven approaches., Methods: Using data from 88 HCs and 76 FEP patients, we evaluated the correlation between olfactory functions and structural/resting-state functional magnetic resonance imaging (MRI) data., Results: We found a significant correlation between the left SFG volume and odour discrimination in FEP patients, but not in HCs. We also observed a significant correlation between rs-fMRI connectivity involving the left SFG and odour discrimination in FEP patients, but not in HCs. The data-driven approach didn't observe any significant correlations, possibly due to insufficient statistical power., Conclusion: The left SFG may be a promising brain region in the context of olfactory dysfunction and negative symptoms in FEP.

Purpose: The decrease in smell in the elderly population is frequent and considered a natural process. However, sometimes it can be associated with the decline of cognitive functions, and it is considered a warning for the early stage of neurodegenerative diseases and social impairment., Objective: To assess the prevalence of olfactory dysfunction in previous healthy elderly that attended a tertiary hospital in Brazil as escorts and the clinical alterations associated in this population., Methods: Subjects 60 years or over attending the University Hospital of Campinas were evaluated. Each participant answered a questionnaire, followed by an otorhinolaryngological exam with flexible nasal endoscopy and the Connecticut smell test produced by the Connecticut Chemosensory Clinical Research Center (CCCRC). Elderly people with nasosinusal diseases or with a history of nasal surgery were excluded., Results: Of the total of 103 participants, 16 (15.5%) reported olfactory complaints and 68 (66%) presented impairment in the olfactory test. It was observed that older individuals showed more changes in olfactory function (p = 0.001). Gender, education, lifestyle, comorbidities, medications in use and exposure to pollutants did not influence the impairment olfactory function of this population., Conclusions: There is a significant prevalence of olfactory dysfunction in the elderly population evaluated. Most of these elderlies also present an inability to identify odours, not having awareness of this olfactory impairment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Previous studies assessing olfactory function and cognition have mostly been cross-sectional, and few have investigated the Asian geriatric population., Objective: To examine the relationships of olfaction with global or domain-specific cognitive function in Taiwanese community-dwelling older adults., Methods: This cohort study (2015-2019) is part of the Taiwan Initiative for Geriatric Epidemiological Research. The Taiwanese version of the Montreal Cognitive Assessment (MoCA-T) and a battery of neuropsychological tests were assessed at baseline and at a two-year follow-up. The cross-culture modified Sniffin' Sticks Identification Test (SSIT) was utilized to measure olfactory function. Generalized linear mixed models were used to examine the association of olfaction with cognitive performance over two years., Results: Data were collected from 376 participants (55.1% women), with a mean age of 75.6 years. A one-point decrease in the SSIT score (worsening of olfaction) was associated with worse global cognition (MoCA-T: βˆ= -0.13), memory (βˆ= -0.08 to -0.06), and verbal fluency (βˆ= -0.07). Compared with an SSIT score ≥ 11 (normosmia), an SSIT score < 8 (anosmia) was associated with worse global cognition (MoCA-T: βˆ= -0.99), memory (βˆ= -0.48 to -0.42), executive function (Trail Making Test A: βˆ= -0.36), attention (digit span backward: βˆ= -0.34), and verbal fluency (βˆ= -0.45). After stratified analyses, the associations remained in older adults ≥ 75 years, males, and non-carriers of apolipoprotein E ɛ4 in terms of global cognition, memory, and verbal fluency., Conclusions: Odor identification deficits were associated with poor global or domain-specific cognitive function in a four-year cohort of community-dwelling older adults. Cognitive assessments should be conducted in dementia-free elderly individuals with impaired odor identification.

Objectives: The questionnaire of olfactory disorder-negative statements (QOD-NS) is a valid and reliable instrument for assessing the olfactory-specific quality of life. This study aimed to explore the association between the QOD-NS and objective olfactory metrics (including objective olfactory cleft assessment) and then evaluate the predictive significance of the QOD-NS for olfactory loss in Chinese patients with chronic rhinosinusitis (CRS)., Methods: A total of 70 patients with CRS were enrolled in the study. Olfaction was assessed with Sniffin' Sticks. The olfactory cleft was assessed by the sinus CT scan and nasal endoscopy (the Lund-Mackay olfactory cleft scale, LM-OC and olfactory cleft endoscopy scale, OCES). The QOD-NS and its short version were utilized to assess the patient-reported olfaction. The predictors associated with olfactory loss were analyzed by the logistic regression analysis. The optimal cutoff points of the predictors were determined by the receiver-operating characteristic curves and the Youden index., Results: The TDI score in patients with CRS significantly correlated with the QOD-NS (r = - 0.755, P < 0.001), OCES (r = - 0.520, P < 0.001), LM-OC (r = - 0.615, P < 0.001). After adjusting for patient demographics and comorbidities, QOD-NS was significantly associated with olfactory dysfunction [odds ratio (OR) = 1.243; P = 0.001] and anosmia in patients with CRS (OR = 1.838; P = 0.006). Furthermore, the QOD-NS significantly correlated with the LM-OC (r = 0.610, P < 0.001), and the OCES (r = 0.464, P < 0.001) in patients with CRS. The QOD-NS had the highest predictive value for olfactory dysfunction (optimal cutoff = 10.5; Youden index = 0.635; area under the curve = 0.861) and anosmia (optimal cutoff = 20.5; Youden index = 0.790; area under the curve = 0.928) in patients with CRS., Conclusion: The QOD-NS showed high validity and correlated well with objective olfactory metrics and olfactory cleft assessment in patients with CRS. The QOD-NS was a reliable predictor for olfactory dysfunction and anosmia in patients with CRS, which may aid in the fast screening of olfactory loss in the clinic., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Charcot neuroarthropathy (CN) is a devastating complication of some diseases affecting the peripheral nervous system. Initial subjective and objective presentation of the disease can be variable. Common among all presentations seems to be uncontrolled inflammation yielding dislocations and/or fractures. The exact cause remains the subject of much debate., Methods: Our study retrospectively looks at the function of olfactory function in consecutive patients with CN and compares the findings with a nonaffected population. The University of Pennsylvania Smell Identification Test was used to assess olfaction and document microsomia., Results: Twenty consecutive patients presenting with CN demonstrated significant (P < .0001) microsomia when compared to an unaffected population with diabetes., Conclusions: Microsomia is strongly associated with CN. This finding may be correlated to voltage-gated sodium 1.7 channel impairment and appears to be a candidate precursor for the development of CN.

Background and Objectives: There is clinical and phenotypic heterogeneity in LRRK2 G2019S Parkinson disease (PD), including loss of smell. Olfactory scores have defined subgroups of LRRK2 PD at baseline. We now extend this work longitudinally to better determine features associated with olfactory classes and to gain further insight into this heterogeneity., Methods: Evaluation of 162 patients with LRRK2 PD and 198 patients with idiopathic PD (IPD) from the LRRK2 Ashkenazi Jewish Consortium was performed, with follow-up available for 92 patients with LRRK2 PD and 74 patients with IPD. Olfaction (University of Pennsylvania Smell Identification Test [UPSIT]), motor function (Unified Parkinson Disease Rating Scale), and cognition (Montreal Cognitive Assessment), as well as sleep, nonmotor, and mood, were measured. Gaussian mixture models were applied on the UPSIT percentile score to determine subgroups based on olfactory performance. Linear mixed effects models, using PD duration as the time scale, assessed the relationship between UPSIT subgroup membership and motor/cognitive change., Results: Baseline olfaction was better in LRRK2 PD compared with IPD (mean UPSIT ± SD: 24.2 ± 8.8 vs 18.9 ± 7.6), with higher mean percentile scores (difference: 15.3 ± 11.6) ( p < 0.001) and less frequent hyposmia (55.6% vs 85.4%; p < 0.001). Analysis suggested 3 classes among LRRK2 PD. Age at onset in LRRK2 PD was earlier in the worst olfaction group (group 1), compared with groups 2 and 3 (54.5 ± 11.1 vs 61.7 ± 9.3) ( p = 0.012), and separately in the hyposmic group overall (55.0 ± 11.3 vs 61.7 ± 9.1) ( p < 0.001). Longitudinal motor deterioration in LRRK2 PD was also significantly faster in the worst UPSIT group than the best UPSIT group (group 3 vs group 1: B = 0.31, SE = 0.35 vs B = 0.96, SE = 0.28) (rate difference = -0.65, SE = 0.29) ( p = 0.03). However, olfactory group membership was not significantly associated with cognitive decline., Discussion: In this large LRRK2 cohort with longitudinal analysis, we extend prior work demonstrating subgroups defined by olfaction in LRRK2 G2019S PD and show that the worst olfaction group has earlier age at PD onset and more rapid motor decline. This supports a subgroup of LRRK2 PD that might show more rapid change in a clinical trial of LRRK2 -related agents and highlights the need to integrate careful phenotyping into allocation schema in clinical trials of LRRK2 -related agents., Classification of Evidence: This study provides Class II evidence that worse olfactory scores were associated with an earlier age at symptomatic onset and a faster rate of motor deterioration in patients with LRRK2 PD., (© 2022 American Academy of Neurology.)

Background: Apathy remains a disabling symptom in Parkinson's disease (PD) with limited therapeutic success. Processing of emotions and smell share neuroanatomical and evolutionary pathways., Objectives: To explore the association of apathy with smell dysfunction (SD) in early PD., Methods: We analyzed patients with de-novo PD, with follow-up of at least 5 years from the Parkinson's Progression Markers Initiative. SD and apathy were defined using University of Pennsylvania Smell Identification Test and MDS-UPDRS part 1A. Odds ratios were calculated between apathy and olfaction groups. Kaplan-Meier survival analysis was grouped by presence/ absence of smell dysfunction. The Log Rank test was used to compare time to apathy., Results: We found no association between presence of apathy in patients with and without SD (OR 1.01 [0.49-2.08]). There was no significant difference between PD patients with and without SD in time to apathy (p = 0.72)., Conclusions: SD does not portend greater risk of apathy in PD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Parosmia, distorted smell sensations, is a common consequence of respiratory virus infections. The phenomenon is not well understood in terms of its impact and long-term outcomes. We examined self-reported experiences of parosmia in a population-based sample from the Betula study that was conducted in Umeå in northern Sweden (baseline data collected in 1998-2000). We used a baseline sample of 2168 individuals aged 35-90 years and with no cognitive impairment at baseline. We investigated the prevalence of parosmia experiences and, using regression analyses, its relationship to other olfactory and cognitive variables and quality of life. Benefitting from the longitudinal study design, we also assessed the persistence of parosmia over 5 and 10 years prospectively. Parosmia experiences were prevalent in 4.8% of the population and it often co-occurred with phantosmia ("olfactory hallucinations"), but was not associated with lower self-rated overall quality of life or poor performance on olfactory or cognitive tests. For some individuals, parosmia was retained 5 years (17.0%) or even 10 years later (10.3%). Thus, parosmia experiences are commonly reported in the population, and can be persistent for some individuals, but might be mostly benign in nature. Our work complements research on clinical-level parosmia, which is typically more severe, and recent parosmia reports during the COVID-19 pandemic, where long-term outcomes are still unknown., (© 2022. The Author(s).)

Burning mouth syndrome (BMS) is a rare but serious medical condition with important psychiatric comorbidity and specific psychological correlates. Psychopathology related with BMS represents a real challenge for clinical decision-making. In this case, depression is the leading psychiatric diagnosis associated with patient's BMS somatic pain and is driven by anxiety and a dissociative functioning. Facing a complex psychosomatic symptomatology, we offer new clinical perspectives for the screening of psychological traits of BMS. Moreover, we highlight the need to foster interdisciplinarity to improve differential diagnosis and defining an optimal care path. This case report stimulates a reflection on management challenges for the consultation-liaison psychiatry and shows the importance of a person-centred approach when communicating the diagnosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The purpose of this study is to determine the volumes of primary brain regions associated with smell and taste in Alzheimer's and Parkinson's patients and healthy controls using MR imaging and examine volumetric changes in comparison to smell/taste questionnaire and test results and endocannabinoid (EC) levels. The study included 15 AD patients with mild cognitive dysfunction scored as 18 ≤ MMSE ≤ 23, 15 PD patients with scores of 18 < MoCA < 26 and 18 ≤ MMSE ≤ 23, and 15 healthy controls. A taste and smell questionnaire was given to the participants, and their taste and smell statuses were examined using the Sniffin' Sticks smell identification test and Burghart Taste Strips. EC levels were analyzed in the blood serum samples of the participants using the ELISA method. The volumes of the left olfactory bulb (p = 0.001), left amygdala (p = 0.004), left hippocampus (p = 0.008), and bilateral insula (left p = 0.000, right p = 0.000) were significantly smaller in the Alzheimer's patients than the healthy controls. The volumes of the left olfactory bulb (p = 0.001) and left hippocampus (p = 0.009) were significantly smaller in the Parkinson's patients than the healthy controls. A significant correlation was determined between volume reduction in the left Rolandic operculum cortical region and taste dysfunction. EC levels were significantly higher in both AD (p = 0.000) and PD (p = 0.006) in comparison to the controls. Our results showed that volumetric changes occur in the brain regions associated with smell and taste in Alzheimer's and Parkinson's patients. It was observed that ECs played a role in these volumetric changes and the olfactory and taste dysfunctions of the patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: It is important to implement disease-specific precautions to develop quality of life in migraine. The effect of osmophobia, which is one of the specific symptoms of migraine that might help to differentiate migraine from other headache disorders, on quality of life is unknown. The aim of the present study was to develop a practicable and reliable scale that assesses the effect of osmophobia on quality of life in migraine., Methods: This cross-sectional study was carried out with 163 patients with migraine and 110 healthy individuals for control group. The scale items were constructed based on after literature review, expert opinions, and preliminary trial stage. A semi-structured interview was conducted with the patients by the Neurologist to evaluate the presence of osmophobia retrospectively. Migraine osmophobia-related quality of life assessment (MORA) consisted of 6 items including personal care, eating or cooking, house cleaning, close relationship, social life and traveling., Results: The Cronbach's α coefficient was 0.86; and the Guttman split-half coefficient was 0.83. Receiver operating characteristic analysis showed an area under the curve of 0.943 (95%) confidence interval [CI] = 0.902-0.984), a cutoff score of >9.5, a sensitivity of 91.6%, a specificity of 85.7%. Mean scores of the MORA differed between people with migraine (with and without osmophobia) and healthy controls (<0.001)., Conclusion: MORA is a valid and reliable self-report questionnaire that assesses the effect of osmophobia on quality of life in migraine. This questionnaire appears to be a practicable diagnostic instrument in clinical practice and research., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Hyposmia is a common feature of COVID-19 and Parkinson's disease (PD). As parkinsonism has been reported after COVID-19, a link has been hypothesized between SARS-CoV2 infection and PD. We aimed to evaluate brain metabolic correlates of isolated persistent hyposmia after mild-to-moderate COVID-19 and to compare them with metabolic signature of hyposmia in drug-naïve PD patients., Methods: Forty-four patients who experienced hyposmia after SARS-COV2 infection underwent brain [ 18 F]-FDG PET in the first 6 months after recovery. Olfaction was assessed by means of the 16-item "Sniffin' Sticks" test and patients were classified as with or without persistent hyposmia (COVID-hyposmia and COVID-no-hyposmia respectively). Brain [ 18 F]-FDG PET of post-COVID subgroups were compared in SPM12. COVID-hyposmia patients were also compared with eighty-two drug-naïve PD patients with hyposmia. Multiple regression analysis was used to identify correlations between olfactory test scores and brain metabolism in patients' subgroups., Results: COVID-hyposmia patients (n = 21) exhibited significant hypometabolism in the bilateral gyrus rectus and orbitofrontal cortex with respect to COVID-non-hyposmia (n = 23) (p < 0.002) and in middle and superior temporal gyri, medial/middle frontal gyri, and right insula with respect to PD-hyposmia (p < 0.012). With respect to COVID-hyposmia, PD-hyposmia patients showed hypometabolism in inferior/middle occipital gyri and cuneus bilaterally. Olfactory test scores were directly correlated with metabolism in bilateral rectus and medial frontal gyri and in the right middle temporal and anterior cingulate gyri in COVID-hyposmia patients (p < 0.006) and with bilateral cuneus/precuneus and left lateral occipital cortex in PD-hyposmia patients (p < 0.004)., Conclusion: Metabolic signature of persistent hyposmia after COVID-19 encompasses cortical regions involved in olfactory perception and does not overlap metabolic correlates of hyposmia in PD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Various symptoms have been associated with COVID-19, but little is known about the impacts of COVID-19 on the sensory system, risk factors, and the duration of symptoms. This study assesses olfactory, gustatory, hearing, and vestibular systems after COVID-19., Methods: This cross-sectional, single-center study involved 50 patients one to six months after COVID-19 and reports their patient records and the extent, onset, and duration of olfactory, gustatory, hearing, and balance disorders using questionnaires during and after COVID-19. Sensory symptoms were objectively studied using the following clinical tests after COVID-19 Sniffin' Sticks, taste tests, tone/speech audiometry, and video head impulse test., Results: Post-COVID-19-patients were suffering from olfactory and gustatory impairment for up to six months. According to the Dizziness Handicap Inventory, balance disorders were less noticed: Overall, about 40% of the patients during COVID-19 and nearly all patients recovered within six months. After COVID-19, clinical tests revealed that 75% were suffering from hyposomnia/anosmia, and 20% of all patients reported mild hypogeusia for up to six months. Vestibular disorders and hearing impairment rarely/did not occur. Females were significantly more affected by sensory impairments than males., Conclusions: COVID-19 particularly caused olfactory and gustatory impairment; balance disorders were present too; vestibular and auditory symptoms were negligible.

Background: Chronic rhinosinusitis (CRS) is typically accompanied by impairment of olfaction. Despite of this, until today the efficacy of endonasal sinus surgery (ESS) in terms of olfactory function is still unclear. So far it is known that patients with nasal polyps are most likely to experience post-operative recovery. Within the present study we investigated the sense of smell and other parameters of impairment in CRS before and after ESS in relation to the degree of nasal polyposis, determined with the nasal endoscopic Lildholdt-score., Methods: Patients with different degrees of severity of nasal polyposis were included. Olfactory function was assessed for odor thresholds [T], odor discrimination [D] and odor identification [I] and the changes of these parameters were investigated postoperatively., Results: For 72 patients baseline measures were available and in 47 patients, postoperative changes were described. There was a correlation between olfactory scores and nasal anatomy/polyposis scores (Lildholdt scores, Lund-Mackay CT score), rated nasal health, and nasal quality of life (sinonasal outcome test). Three months after surgery the average TDI-Score improved by 3.1 points with 30% of patients showing significant clinical improvement. Patients with severe polyposis (Lildholdt score of 5 or 6) benefited most in terms of olfaction. Other significant prognostic indicators of a postoperative increase of olfactory scores included younger age, low pre-operative TDI-scores and high CT-scores., Conclusions: This study shows that not only the presence of polyps in CRS, but also the degree of nasal polyposis - measured by a grading system - predicts the results in olfactory test results. Additionally, the degree of recovery of olfaction after ESS seems to be most relevant in patients with high polyp scores.

Purpose: Obstructive sleep apnea (OSA) increases the risk for olfactory dysfunction. However, the relationship between olfactory function and cognition in OSA patients is unclear. The present study aimed to investigate the relationship between cognition and olfactory dysfunction (OD) in patients with OSA., Method: This was a cross-sectional study in which 74 patients with OSA and 22 controls were recruited. All subjects completed polysomnography, Sniffin' Sticks, and -neurocognitive assessments. According to results of Sniffin' Sticks, OSA patients were divided into two groups: OSA with OD (53 cases) and OSA without OD (21 cases). Neurocognitive function was assessed by Montreal Cognitive Assessment (MoCA), Memory and Executive Screening (MES), and Shape Trail Test (STT). Cognition was compared between OSA with and without OD. Correlation between olfactory parameters and respiratory sleep parameters and neurocognitive assessments was analyzed., Results: Compared with OSA without OD, OSA with OD showed significantly decreased neurocognitive scores of MoCA (29-27 vs 27-23, p < 0.01), MES-5R (45-40.1 vs 43-33.5, p < 0.01) and increased consuming time of STT-B (91.66 vs 121.63, p < 0.01). A positive correlation was found between the scores of MoCA and MES-5R and all olfactory parameters. In addition, a negative correlation was present between the time consumed for STT-B and odor thresholds (r = - 0.344, p < 0.01), odor identification (r = - 0.335, p < 0.01), and threshold-discrimination-identification scores (r = - 0.448, p < 0.01)., Conclusion: Olfactory function is associated cognitive function in patients with OSA and may provide a new direction for early treatment interventions in OSA patients at risk for cognitive impairment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Olfactory functional deficits have been reported in psychotic disorders. Olfactory dysfunction has a predictive value for prognosis and disease course. Thus, it is important to know which specific symptoms and cognitive changes are associated with olfactory dysfunction in early-stage psychosis. Deficits in social cognition are a difficult problem in psychosis. Here we conduct a detailed assessment of odor function and face processing and show that odor discrimination capacity is specifically associated with face processing function in patients with first episode psychosis. This finding indicates that the high-throughput olfactory assessment may aid a prediction of the difficult clinical dimension from early-stage psychosis., (Copyright © 2021 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

Abstract: Olfactory disorders may be observed together with cognitive impairment in patients with major depressive disorder (MDD). This study compared olfactory performances between patients with MDD and healthy controls and investigated the relationship between olfactory performance and subjective cognitive impairment in these patients. This study included 52 patients diagnosed with MDD and 46 healthy controls. The participants were evaluated in terms of their olfactory capacities (threshold, discrimination, and identification), subjective cognitive impairment, and depression. Although the olfactory threshold (OT) and olfactory discrimination scores were lower in patients with MDD compared with those in the control group, their olfactory identification scores did not differ significantly. OT was negatively correlated with subjective cognitive impairment and may serve as a determinant for subjective cognitive changes. Consequently, patients with MDD had lower olfactory performances compared with healthy controls. Finally, OT may be a component of subjective cognitive impairment in MDD., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Level of Evidence: 4.

Background: Early-onset obsessive-compulsive disorder (EOCD) is a comparatively severe subtype of obsessive-compulsive disorder (OCD). Olfactory dysfunction is a common symptom of OCD, but all previous studies have focused on late-onset OCD (LOCD)., Methods: The current study compared olfactory identification ability in EOCD patients and age-matched and sex-matched LOCD patients and healthy controls. Thirty patients with EOCD, 30 patients with LOCD and 30 healthy controls were included in the study. Olfactory function was measured using the University of Pennsylvania Smell Identification Test. The Logical Memory and Visual Reproduction components of the Revised Wechsler Memory Scale were used to evaluate verbal and visual memory., Results: There were significant differences in olfactory identification ability between the three groups. EOCD patients were comparable to LOCD patients, while both patients' group showing worse olfactory identification ability than controls. Olfactory identification ability was not significantly correlated with verbal and visual memory or clinical symptoms in the EOCD group or the LOCD group., Conclusions: The results of the present study suggest that olfactory identification ability may be a relatively stable indicator of OCD, independent of age, duration of illness, verbal and visual memory, and severity of clinical symptoms., (© 2021 John Wiley & Sons Australia, Ltd.)

The olfactory dysfunction can signal and act as a potential biomarker of preclinical AD. However, the precise regulatory mechanism of olfactory function on the neural pathogenesis of AD is still unclear. The impairment of neural networks in olfaction system has been shown to be tightly associated with AD. As key brain regions of the olfactory system, the olfactory bulb (OB) and the piriform cortex (PCx) have a profound influence on the olfactory function. Therefore, this review will explore the mechanism of olfactory dysfunction in preclinical AD in the perspective of abnormal neural networks in the OB and PCx and their associated brain regions, especially from two aspects of aberrant oscillations and synaptic plasticity damages, which help better understand the underlying mechanism of olfactory neural network damages related to AD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: The underlying mechanism of the association between olfactory impairment and dementia may be explained by neurodegenerative changes detected on magnetic resonance imaging (MRI). The purpose of this systematic review is to describe neurodegenerative changes on MRI in patients with olfactory impairment and mild cognitive impairment (MCI) or dementia., Study Design: Systematic review., Methods: A literature search encompassing PubMed, Embase, Cochrane Library, Web of Science, Scopus, and Google Scholar for studies with MRI and olfactory testing among participants diagnosed with MCI or dementia was performed. Sample size, study design, cognitive impairment type, olfactory testing, and MRI findings were abstracted. Two investigators independently reviewed all articles., Results: The search yielded 556 nonduplicate abstracts, from which 86 articles were reviewed and 24 were included. Seventeen (71%) of 24 studies reported hippocampal volume findings, with 14 studies reporting a relationship between hippocampal volume and olfactory performance. Two (50%) of four prospective studies reported the potential utility of baseline hippocampal volume as a marker of dementia conversion from MCI. Five (21%) of 24 studies reporting olfactory functional MRI (fMRI) findings highlighted the utility of olfactory fMRI to identify individuals in the early stages of cognitive decline., Conclusion: Current evidence suggests hippocampal volume correlates with olfactory performance in individuals with cognitive impairment, and that olfactory fMRI may improve early detection of AD. However, the predictive utility of these imaging markers is limited in prospective studies. MRI may be a useful modality for selecting patients at high risk of future cognitive decline for enrollment in early treatment trials. Laryngoscope, 132:177-187, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background and Purpose: Recent evidence has suggested that hyposmia in patients with Parkinson's disease (PD) may be due to impaired central processing. Furthermore, the hippocampus has been regarded as a critical structure linking olfactory impairment and cognitive impairment in PD patients. This study aimed to identify significant structural alterations of the hippocampus in PD patients with hyposmia, and to determine whether these structural changes are significantly associated with olfactory impairment severity., Methods: Eighteen idiopathic PD patients with hyposmia and 18 age- and sex-matched PD patients without hyposmia were enrolled. Hippocampal volume and its subfields were measured using FreeSurfer software and compared between hyposmic and normosmic PD patients. We also compared hippocampal substructures' volumes and correlated the hippocampal volumes with hyposmia severity., Results: PD patients with hyposmia had significantly smaller hippocampal volumes. Among the three components of the hippocampus, the hippocampal body showed a markedly lower volume, which correlated significantly with the cross-cultural smell identification test score that represents olfactory function status. Hippocampal subfield analysis showed that substructures (subiculum, molecular layer) that constitute the hippocampal body showed the most significant volume difference., Conclusions: We suggest that atrophy of the bilateral hippocampus implies underlying problems in the central olfaction process in PD patients. In particular, the hippocampus might not only play a critical role in olfaction but could also be important for elucidating possible mechanisms of broad nonmotor symptoms in PD patients., (© 2021 American Society of Neuroimaging.)