Cortical Atrophy, White Matter Lesions, and Bulb Configuration in Patients with Idiopathic Olfactory Loss and Other Causes of Olfactory Loss

<b><i>Introduction:</i></b> While magnetic resonance imaging (MRI) is not included in the current guidelines for diagnosing olfactory disorders in the most recent position paper on olfactory dysfunction, both 1.5T and 3T MRI are commonly used in the diagnostic workup of many patients with olfactory loss. Often, MRI is used to rule out intracranial tumours, but other useful information may be obtained from MRI scans in these patients. The potential of MRI in olfactory loss depends on sufficient knowledge of structural changes in different aetiologies of olfactory loss. We present common clinical MRI findings in olfactory loss and evaluate the usefulness of structural integrity scores in differentiating between aetiologies. <b><i>Methods:</i></b> In this study, we investigated if white matter hyperintensities (WMHs, measured by Fazekas score), global cortical atrophy (GCA), and medial temporal lobe atrophy (MTA) are more common in patients with idiopathic olfactory loss than in patients with acquired olfactory loss due to other aetiologies. Furthermore, we compared olfactory bulb (OB) configurations in different olfactory loss aetiologies. <b><i>Results:</i></b> In 88 patients with olfactory loss, WMHs, GCA, and MTA were not more significant findings on MRI in idiopathic olfactory loss (<i>n</i> = 51) compared with other causes of acquired olfactory loss (Fazekas score <i>p</i> = 0.2977; GCA score <i>p</i> = 0.6748; MTA score <i>p</i> = 0.7851). Bulb configurations differed in patients suffering from post-traumatic olfactory loss and may aid in identifying the underlying aetiology in patients where trauma is among the suspected causes of olfactory loss. <b><i>Conclusion:</i></b> We recommend that structural MRI with an OB sequence is included in the diagnostic evaluation of olfactory loss with suspected congenital and post-traumatic aetiology and should be considered in idiopathic olfactory loss with suspected central aetiology (e.g., tumour).

The Effect of Olfactory Training on Olfaction, Cognition, and Brain Function in Patients with Mild Cognitive Impairment

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 magnetic resonance imaging were performed before and after training. Results: The results suggested that OT exhibited no significant effect on olfaction and cognitive function. However, 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.

Olfactory evaluation in hospitalised and self-isolated patients with COVID-19: a single-centre experience on 55 cases

BackgroundSmell loss is a common symptom of COVID-19 infection. Majority of the studies that evaluated olfactory impairment in COVID-19 used questionnaires (subjective smell evaluations) and did not compare the results with objective or semiobjective measures of smell. We performed smell testing in hospitalised and self-isolated patients with COVID-19 and control participants.MethodsFifty-five COVID-19 and 44 control participants underwent smell testing, using Burghart Sniffin’ Sticks ‘Screening 12 Test’. Participants also rated their smelling capability on the numerical scale. Differences between groups and correlation between smell loss and time from acute onset of symptoms were tested, as well as correlation between results of smell test and subjective assessment of smell.ResultsHospitalised patients with COVID-19 correctly determined 6.5/12 odorants compared with 10/12 in the self-isolated and 11/12 in the control group (p<0.001). Hyposmia or anosmia were present in 87.5% of hospitalised and 29.0% of self-isolated patients (p<0.001). The correlation between subjective self-assessment and results of smell testing was non-significant in both groups of patients with COVID-19, while there was a moderate positive correlation (p=0.001, Spearman’s correlation coefficient=0.499) in control participants.ConclusionContrary to some previous reports suggesting that the presence of olfactory loss may predict milder course of disease, our study found that a vast majority of hospitalised patients with COVID-19 had prominent olfactory impairment. The absence of correlation between self-rated and objective smell evaluation in patients with COVID-19 indicates that subjective smell assessment is unreliable.

Olfactory recovery following infection with COVID-19: A systematic review

Olfactory loss has been identified as one of the common symptoms related to COVID-19 infection. Although olfactory loss is recognized, our understanding of both the extent of loss and time to olfactory recovery following infection is less well known. Similarly, knowledge of potential impactful patient factors and therapies that influence olfactory recovery is desirable but is not overtly clear in the literature. Our systematic review sought to fill this knowledge gap. We included studies that: involved either an observational or an interventional design that reported data on patients with olfactory dysfunction due to Reverse Transcription Polymerase Chain Reaction (RT-PCR) diagnosed COVID-19 infection; and reported data regarding olfactory recovery measured by an objective olfactory test, Likert scale and/or visual analog scale (VAS). The study methods were determined a priori and registered in PROSPERO (Registration Number CRD42020204354). An information specialist searched Medline, Embase, LitCovid and the Cochrane Register of Controlled Trials up to March 2021, and two reviewers were involved in all aspects of study selection and data collection. After screening 2788 citations, a total of 44 studies of assorted observational designs were included. Patients had undergone objective COVID-19 testing, and most were adult patients with mild to moderate COVID-19. Olfactory recovery was found to occur as early as 7 days, with most patients recovering olfaction within 30 days. Few studies included prolonged follow-up to 6 months or longer duration. Poor olfaction at initial presentation was associated with poor recovery rates. Only a small number of studies assessed olfactory retraining and steroid therapy. Additional trials are underway.

Olfactory Signatures in the Food Finding Test in Mice With Normal and Alzheimer’s Disease-Pathological Aging With Special Concerns on the Effects of Social Isolation

The temporal course and the severity of the involution of sensory systems through aging can be critical since they ensure the ability to perceive and recognize the world. In older people, sensory impairments significantly increase their risk of biological, psychological, and social impoverishment. Besides this, olfactory loss is considered an early biomarker in Alzheimer’s disease (AD) neurodegenerative process. Here we studied olfactory ethograms in middle-aged male and female gold-standard C57BL/6 mice and 3xTg-AD mice, a genetic model of AD that presents cognitive dysfunction and a conspicuous neuropsychiatric-like phenotype. A paradigm involving 1-day food deprivation was used to investigate the ethological patterns shown in the olfactory inspection of a new cage and the sniffing, finding, and eating of hidden food pellets. The sniffing–find–eat temporal patterns were independent of the loss of weight and unveiled (fast) olfactory signatures in Alzheimer’s disease, differing from those (slow progressive) in normal aging. Male 3xTg-AD mice exhibited an early signature than female mice, opposite to animals with normal aging. The sequence of actions was correlated in male and female 3xTg-AD mice in contrast to control mice. Social isolation, naturally occurring in male 3xTg-AD due to the death of cage mates, emphasized their olfactory patterns and disrupted the behavioral correlates. The paradigm provided distinct contextual, sex, and genotype olfactory ethogram signatures useful to investigate olfactory function in normal and AD-pathological aging. Isolation had an impact on enhancing the changes in the olfactory signature here described, for the first time, in the 3xTg-AD model of Alzheimer’s disease.

Alterations of Erythrocytic Phosphorylated Alpha-Synuclein in Different Subtypes and Stages of Parkinson's Disease

Serine 129-phosphorylated alpha-synuclein (pS-α-syn) is a major form of α-syn relevant to the pathogenesis of Parkinson's disease (PD), which has been recently detected in red blood cells (RBCs). However, alterations of RBC-derived pS-α-syn (pS-α-syn-RBC) in different subtypes and stages of PD remains to be investigated. In the present study, by using enzyme-linked immunosorbent assay (ELISA) to measure pS-α-syn-RBC, we demonstrated significantly higher levels of pS-α-syn-RBC in PD patients than in healthy controls. pS-α-syn-RBC separated the patients well from the controls, with a sensitivity of 93.39% (95% CI: 90.17–95.81%), a specificity of 93.11% (95% CI: 89.85–95.58%), and an area under the curve (AUC) of 0.96. Considering motor subtypes, the levels of pS-α-syn-RBC were significantly higher in late-onset than young-onset PD (p = 0.013) and in those with postural instability and gait difficulty than with tremor-dominant (TD) phenotype (p = 0.029). In addition, the levels of pS-α-syn-RBC were also different in non-motor subtypes, which were significantly lower in patients with cognitive impairment (p = 0.012) and olfactory loss (p = 0.004) than in those without such symptoms. Moreover, the levels of pS-α-syn-RBC in PD patients were positively correlated with disease duration and Hoehn &amp; Yahr stages (H&amp;Y) (p for trend =0.02 and &lt;0.001) as well as UPDRS III (R2 = 0.031, p = 0.0042) and MoCA scores (R2 = 0.048, p = 0.0004). The results obtained suggest that pS-α-syn-RBC can be used as a potential biomarker for not only separating PD patients from healthy controls but also predicting the subtypes and stages of PD.

Symptoms of Depression Change With Olfactory Functions

Olfactory loss is associated with symptoms of depression. The present study, conducted on a large cohort of mostly dysosmic patients, aimed to investigate whether improvement in olfactory performance would correspond with a decrease in depression severity and, if so, to what extent. In 171 participants, we assessed olfactory function and severity of depression before and after an average interval of 11 months, with many patients improving in function. Separate analyses were conducted for a) the whole group of patients and b) the group of dysosmic patients in both classic and Bayesian ways. Student t-test demonstrates that the whole sample improved consistently, especially within the group of dysosmic patients in terms of odor identification, and the dysosmic group also improved in terms of odor threshold and olfactory functions in general. Pearson correlation showed that the increase in olfactory functions corresponded with the decrease in depression severity, particularly in dysosmic patients. To conclude, the present study results indicate that symptoms of depression change with olfactory functions in general and odor identification in particular.

Predicting Olfactory Loss In Chronic Rhinosinusitis Using Machine Learning

Objective Compare machine learning (ML) based predictive analytics methods to traditional logistic regression in classification of olfactory dysfunction in chronic rhinosinusitis (CRS-OD), and identify predictors within a large multi-institutional cohort of refractory CRS patients. Methods Adult CRS patients enrolled in a prospective, multi-institutional, observational cohort study were assessed for baseline CRS-OD using a smell identification test (SIT) or brief SIT (bSIT). Four different ML methods were compared to traditional logistic regression for classification of CRS normosmics versus CRS-OD. Results Data were collected for 611 study participants who met inclusion criteria between April 2011 and July 2015. 34% of enrolled patients demonstrated olfactory loss on psychophysical testing. Differences between CRS normosmics and those with smell loss included objective disease measures (CT and endoscopy scores), age, sex, prior surgeries, socioeconomic status, steroid use, polyp presence, asthma, and aspirin sensitivity. Most ML methods performed favorably in terms of predictive ability. Top predictors include factors previously reported in the literature, as well as several socioeconomic factors. Conclusion Olfactory dysfunction is a variable phenomenon in CRS patients. ML methods perform well compared to traditional logistic regression in classification of normosmia versus smell loss in CRS, and are able to include numerous risk factors into prediction models. Several actionable features were identified as risk factors for CRS-OD. These results suggest that ML methods may be useful for current understanding and future study of hyposmia secondary to sinonasal disease, the most common cause of persistent olfactory loss in the general population.

1481 Is Imaging for the Evaluation of Anosmia Really Necessary?

Aim Although it is rare for anosmia to be caused by olfactory lesions, it is commonplace for some form of imaging to be undertaken to investigate olfactory loss in patients. This study aimed to identify the pick-up rate of pathology in patients who had an isolated complaint of anosmia. Method We undertook a retrospective study over a 2-year period between 2018 to 2020 in a teaching hospital. The cases were identified using the hospital radiology database for patients referred for CT or MRI of their head or sinuses due to anosmia. Patients referred with symptoms other than olfactory loss were excluded. Results Out of the 132 scans undertaken in this period, 52 were included with 47 being MRI scans. There were 5 (10%) patients who had intracranial pathology identified and these were all on MRI scans. Only 2 (4%) cases had actual olfactory tract-related abnormalities. This included absent olfactory bulbs and a soft tissue lesion within the region of the olfactory apparatus. Conclusions This study suggests a 4% pick up rate of olfactory tract-related pathology which demonstrates some value when investigating anosmia. However, with the large number of scans that do not alter management and the ever-increasing burden on our health system, large scale studies are needed to develop an evidence-based risk stratification approach.