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The earliest neuropathological changes of Alzheimer’s disease, the beta-amyloid plaques, usually appear first in olfactory parts of the brain including the olfactory bulb, anterior olfactory nucleus, and entorhinal cortex. I totally lost my ability to smell several years before I developed any measurable cognitive impairment. Almost all people with Alzheimer’s have at least some impairment of olfaction, but most are not aware of it unless tested, probably because it comes on so gradually.
Recently, I spoke to a group of medical students about Alzheimer’s disease. I have been giving these talks three or four times a year for the last five years now. I know a lot about Alzheimer’s disease because I am a retired neurologist, and I have treated many patients with dementia, including Alzheimer’s disease. I also know a lot because now I have mild Alzheimer’s dementia. As we’ll see in Chapter 3, Alzheimer’s dementia is the late stage of Alzheimer’s disease when cognitive impairment interferes with activities of daily living. The pathological changes in the brain caused by Alzheimer’s disease begin to appear up to 20 years before the onset of cognitive impairment.
The loss of smell seen in Alzheimer’s disease is insidious in onset and slowly progressive. It does not go away. As in my case, it can begin 10 years or more before the onset of cognitive impairment. Many if not most people with Alzheimer’s disease don’t even notice the loss because it progresses so slowly. I don’t think I would have paid any attention to it had it not been for the illusory odors I experienced, the scent of baking bread mixed with perfume.
To analyse variations in the n-butanol threshold and odour identification scores of the Connecticut Chemosensory Clinical Research Centre test in various grades of olfactory dysfunction and in different nasal conditions leading to olfactory loss.
Method
Retrospective observational study.
Results
All grades of olfactory dysfunction were predominantly noted among males. In chronic rhinosinusitis, anosmia or severe hyposmia was seen in 87.5 per cent of patients without polyps in comparison with 68 per cent of patients with polyps. In addition, 90 per cent of patients with atrophic rhinitis and post-traumatic loss had anosmia, but only 30.7 per cent of patients with allergic rhinitis had anosmia. Pepper was the most affected smell for all the nasal diseases except atrophic rhinitis, in which asafoetida and baby powder smells were affected more.
Conclusion
In most inflammatory sinonasal conditions, odour identification is relatively preserved even when the threshold is maximally affected. In patients with comparable olfactory dysfunction based on the Connecticut Chemosensory Clinical Research Centre test score, a relatively preserved suprathreshold odour identification score may predict better prognosis.
This study aimed to evaluate the recovery of olfactory function at six months in individuals infected with the coronavirus disease 2019 omicron variant, using psychophysical tests.
Methods
A prospective case–control study that included severe acute respiratory syndrome coronavirus-2 patients infected in February and March 2022 was conducted. Patients underwent the Sniffin’ Sticks test within 10 days of infection and again after at least 6 months. The olfactory scores were compared with those of a control group.
Results
In all, 102 patients and 120 controls were enrolled in the study. At baseline, 26 patients (25.5 per cent) self-reported smell loss. The median threshold, discrimination and identification score was 33.6 (interquartile range, 12.5) for the cases and 36.5 (interquartile range, 4.38) for the controls (p < 0.001). Based on the threshold, discrimination and identification scores, 12 controls and 34 patients reported olfactory dysfunction (p < 0.001). Eighty cases underwent re-evaluation at six months; the median threshold, discrimination and identification score was 37.1 (interquartile range, 4.75) with no significant differences compared with the controls.
Conclusion
Six months after infection, the prevalence of olfactory dysfunction in patients did not differ significantly from the control population.
Olfactory impairment may be present among patients with coronavirus disease 2019 self-perceived as asymptomatic. This study aimed to assess olfactory function among these individuals.
Methods
A cross-sectional study involving patients with coronavirus disease 2019 self-perceived as asymptomatic was conducted. Assessments included the subjective Malaysian Smell and Taste Questionnaire and the culturally adapted Malaysian version of the objective Sniffin’ Sticks Identification smell test.
Results
In 81 participants (mean age of 31.59 ± 12.04 years), with mean time from diagnosis to smell test of 7.47 ± 3.79 days, subjective assessment showed that 80.2 per cent were asymptomatic (questionnaire score of 6) and 19 per cent had mild symptoms (questionnaire score of 7 and 8). The mean objective smell test score was 10.89 ± 2.11. The prevalence of olfactory impairment was 76.6 per cent among patients with coronavirus disease 2019 self-perceived as asymptomatic. There was no association between the questionnaire and the smell test scores (p = 0.25). There was a correlation between the smell test score and the duration from diagnosis to smell test (p = 0.04).
Conclusion
The objective assessment demonstrated that coronavirus disease 2019 patients who perceived themselves as asymptomatic showed olfactory impairment.
In presentations of anosmia or dysosmia, magnetic resonance imaging may be required to screen for intracranial pathology such as olfactory neuroblastomas and other intracranial masses impacting on the olfactory pathway. This study aimed to establish positive magnetic resonance imaging findings of anosmia or dysosmia for scans performed before the coronavirus disease 2019 pandemic.
Methods
The study examined the outcome of patients who presented with isolated olfactory dysfunction and who underwent magnetic resonance imaging between 2015 and 2019.
Results
Of the 131 patients, 41 (31.3 per cent) had normal scan findings, 50 (38.2 per cent) had insignificant paranasal mucosal disease and 6 (4.6 per cent) had mucosal thickening significant enough to require additional intervention. These interventions included repeat nasoendoscopy or commencement of intranasal or oral steroids. No patients had olfactory neuroblastoma.
Conclusion
Only 4.6 per cent of the magnetic resonance imaging scans revealed abnormal findings related to anosmia or dysosmia, and none required ENT surgical intervention. None of the magnetic resonance imaging scans identified an olfactory neuroblastoma or intracranial masses impacting on the olfactory pathway.
This study evaluated the olfactory, sinonasal and mucociliary functions of patients with post-coronavirus disease 2019 long-term persistent olfactory dysfunction.
Method
Three groups of 30 patients each were formed: patients with a history of coronavirus disease 2019 infection with self-reported, persistent, sudden-onset olfactory dysfunction (group 1), patients with a history of coronavirus disease 2019 infection without any self-reported olfactory dysfunction (group 2) and healthy controls with no history of coronavirus disease 2019 infection (group 3). Saccharin time, Sniffin’ Sticks, Turkish Nasal Obstruction Symptom Evaluation and Sino-Nasal Outcome Test 22 scores were compared.
Results
Turkish Nasal Obstruction Symptom Evaluation scores were similar between groups (p = 0.252). Sino-Nasal Outcome Test-22 scores were higher in group 1 than groups 2 and 3 (p < 0.01 and p < 0.001, respectively). Saccharin time was significantly longer in group 1 than groups 2 and 3 (p < 0.05 and p < 0.01, respectively). Group 1 had lower olfactory scores than groups 2 and 3 (p < 0.001 and p < 0.001, respectively).
Conclusion
Mucociliary clearance time was significantly prolonged in patients with post-coronavirus disease 2019 persistent olfactory dysfunction. Coronavirus disease 2019 infection was likely to cause asymptomatic olfactory dysfunction.
Objective: To explore food consumption and subsequent behavioural changes amongst PASC suffers associated with alterations in taste and smell. Design: A qualitative study involving five focus groups. Setting: Birmingham and Leicester, England, United Kingdom. Participants: Forty-seven Post-Acute Sequelae of COVID-19 sufferers. Results: Shifts in taste and odour were very common with disgusting or unpleasant notes being perceived in many foods, including animal products rich in protein. Food consumption patterns varied affecting nutrition status, individuals weight, types of foods consumed, cooking habits, coping mechanisms, anxieties, family and social interactions. Individuals expressed the need to taste something or experience normal tastes and flavour. Low pH foods, highly processed foods which may contain large amounts of refined sugars as well as cold processed food were the preferred items for consumption. Conclusion: Olfactory dysfunction was related to the consumption of nutrients that require moderation and to the quality of life. Intervention at an early stage is necessary in order to help avoid such complications and thus, this work informs medical practitioners and health workers of the variety of food choices that are more acceptable for people suffering from altered tastes and odour perception.
The primary goal of this study was to evaluate the association between olfactory dysfunction or taste impairment and disease severity and radiological findings in coronavirus disease-2019. The secondary goal was to assess the prevalence, severity and course of olfactory dysfunction or taste impairment in patients with coronavirus disease 2019.
Method
This prospective observational cohort study evaluated patients hospitalised with coronavirus disease 2019 between April 1 and 1 May 2020. Olfactory dysfunction and taste impairment were evaluated by two questionnaires. Chest computed tomography findings and coronavirus disease-2019 severity were assessed.
Results
Among 133 patients, 23.3 per cent and 30.8 per cent experienced olfactory dysfunction and taste impairment, respectively, and 17.2 per cent experienced both. The mean age was 56.03 years, and 64.7 per cent were male and 35.3 per cent were female. No statistically significant association was found between olfactory dysfunction (p = 0.706) and taste impairment (p = 0.35) with either disease severity or chest computed tomography grading.
Conclusion
Olfactory dysfunction or taste impairment does not have prognostic importance in patients with coronavirus disease 2019.
This study aimed to assess olfactory dysfunction in patients at six months after confirmed coronavirus disease 2019 infection.
Methods
Coronavirus disease 2019 positive patients were assessed six months following diagnosis. Patient data were recoded as part of the adapted International Severe Acute Respiratory and Emerging Infection Consortium Protocol. Olfactory dysfunction was assessed using the University of Pennsylvania Smell Identification Test.
Results
Fifty-six patients were included. At six months after coronavirus disease 2019 diagnosis, 64.3 per cent of patients (n = 36) were normosmic, 28.6 per cent (n = 16) had mild to moderate microsmia and 7 per cent (n = 4) had severe microsmia or anosmia. There was a statistically significant association between older age and olfactory dysfunction. Hospital or intensive care unit admission did not lead to worse olfactory outcomes compared to those managed in the out-patient setting.
Conclusion
At six months after coronavirus disease 2019 diagnosis, approximately two-thirds of patients will be normosmic. This study is the first to describe six-month outcomes for post-coronavirus disease 2019 patients in terms of olfactory dysfunction.
To analyse the correlations between olfactory psychophysical scores and the serum levels of D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio in coronavirus disease 2019 patients.
Methods
Patients underwent psychophysical olfactory assessment with the Connecticut Chemosensory Clinical Research Center test, and determination of blood serum levels of the inflammatory markers D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio within 10 days of the clinical onset of coronavirus disease 2019 and 60 days after.
Results
Seventy-seven patients were included in this study. D-dimer, procalcitonin, ferritin and neutrophil-to-lymphocyte ratio correlated significantly with severe coronavirus disease 2019. No significant correlations were found between baseline and 60-day Connecticut Chemosensory Clinical Research Center test scores and the inflammatory markers assessed.
Conclusion
Olfactory disturbances appear to have little prognostic value in predicting the severity of coronavirus disease 2019 compared to D-dimer, ferritin, procalcitonin and neutrophil-to-lymphocyte ratio. The lack of correlation between the severity and duration of olfactory disturbances and serum levels of inflammatory markers seems to further suggest that the pathogenetic mechanisms underlying the loss of smell in coronavirus disease 2019 patients are related to local rather than systemic inflammatory factors.
The long-term recovery rate for coronavirus disease 2019 related chemosensory disturbances has not yet been clarified.
Methods
Olfactory and gustatory functions were assessed with psychophysical tests in patients in the first seven days from coronavirus disease 2019 onset and one, two, three and six months after the first evaluation.
Results
A total of 300 patients completed the study. The improvement in olfactory function was significant at the two-month follow up. At the end of the observation period, 27 per cent of the patients still experienced a persistent olfactory disturbance, including anosmia in 5 per cent of cases. As for taste, the improvement in the psychophysical scores was significant only between the baseline and the 30-day control. At the 6-month evaluation, 10 per cent of the patients presented with a persistent gustatory disturbance with an incidence of complete ageusia of 1 per cent.
Conclusion
Six months after the onset of coronavirus disease 2019, about 6 per cent of patients still had a severe persistent olfactory or gustatory disturbance.
Severe acute respiratory syndrome coronavirus-2 is a formidable virus, responsible for coronavirus disease 2019 and endowed with marked neurotropism. The damage it causes to the nervous system is manifold. The main neurological manifestation is anosmia. Olfactory damage is often transient, but there are no data reflecting an observational period of several months.
Objective
This study evaluated the trend of anosmia in patients affected by coronavirus disease 2019 in the eight months following diagnosis.
Methods
Fifty-five subjects who presented with symptoms suggestive of coronavirus disease 2019 and who developed anosmia, between the end of February and the beginning of March 2020, were investigated. The patients were interviewed after eight months to determine functional recovery and assess the degree of recovery.
Results
Ninety-one per cent of the population reported olfactory recovery and, of these, 53 per cent had total recovery after eight months. Females and younger age groups seem slightly advantaged in functional recovery. The elderly population appears to have excellent prospects for full functional recovery.
Conclusion
Anosmia represents a frequent neurological manifestation during coronavirus disease 2019. Fortunately, it is transient in most cases, and only a small percentage of patients affected by it report long-term functional deficits.
We report the development of a regression model to predict the prevalence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) antibodies on a population level based on self-reported symptoms. We assessed participant-reported symptoms in the past 12 weeks, as well as the presence of SARS-CoV-2 antibodies during a study conducted in April 2020 in Ischgl, Austria. We conducted multivariate binary logistic regression to predict seroprevalence in the sample. Participants (n = 451) were on average 47.4 years old (s.d. 16.8) and 52.5% female. SARS-CoV-2 antibodies were found in n = 197 (43.7%) participants. In the multivariate analysis, three significant predictors were included and the odds ratios (OR) for the most predictive categories were cough (OR 3.34, CI 1.70–6.58), gustatory/olfactory alterations (OR 13.78, CI 5.90–32.17) and limb pain (OR 2.55, CI 1.20–6.50). The area under the receiver operating characteristic curve was 0.773 (95% CI 0.727–0.820). Our regression model may be used to estimate the seroprevalence on a population level and a web application is being developed to facilitate the use of the model.
Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n = 3261) completing the C-19 COVID-19 symptom tracker app allowed classical twin studies of COVID-19 symptoms, including predicted COVID-19, a symptom-based algorithm to predict true infection, derived from app users tested for SARS-CoV-2. We found heritability of 49% (32−64%) for delirium; 34% (20−47%) for diarrhea; 31% (8−52%) for fatigue; 19% (0−38%) for anosmia; 46% (31−60%) for skipped meals and 31% (11−48%) for predicted COVID-19. Heritability estimates were not affected by cohabiting or by social deprivation. The results suggest the importance of host genetics in the risk of clinical manifestations of COVID-19 and provide grounds for planning genome-wide association studies to establish specific genes involved in viral infectivity and the host immune response.
This study aimed to evaluate the association between serum D-dimer, ferritin and vitamin D levels, and dysgeusia symptoms, in patients with coronavirus disease 2019.
Methods
The present study was conducted with the medical records of 300 patients positive for coronavirus disease 2019, hospitalised between 28 March and 15 August 2020. The patients were divided into two groups regarding the presence or absence of dysgeusia symptoms.
Results
Fever and sore throat rates, and the mean D-dimer level, were considerably higher in the dysgeusia group than in the non-dysgeusia group (32.1 vs 21.6 per cent, p = 0.04; 43.6 vs 20.7 per cent, p < 0.001; and 0.54 ± 0.32 vs 0.49 ± 0.51 mg/l FEU, p = 0.008, respectively). The mean age was significantly lower in the dysgeusia group than in the non-dysgeusia group (42.83 ± 12.31 vs 50.51 ± 13.67 years, p < 0.001).
Conclusion
Younger age, fever and shortness of breath could be observed in patients with dysgeusia symptoms. In addition, the D-dimer level was significantly higher in the dysgeusia group.
Olfactory dysfunction represents one of the most frequent symptoms of coronavirus disease 2019, affecting about 70 per cent of patients. However, the pathogenesis of the olfactory dysfunction in coronavirus disease 2019 has not yet been elucidated.
Case report
This report presents the radiological and histopathological findings of a patient who presented with anosmia persisting for more than three months after infection with severe acute respiratory syndrome coronavirus-2.
Conclusion
The biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.
To evaluate the occurrence, clinical course and outcomes of olfactory and gustatory dysfunction in patients with laboratory confirmed coronavirus disease 2019 infection.
Methods
This is a prospective cross-sectional study of patients diagnosed with coronavirus disease 2019 infection by reverse transcription polymerase chain reaction over two months. The epidemiological and clinical outcomes studied were: age, sex, general symptoms, and olfactory and taste dysfunction.
Results
A total of 410 coronavirus disease 2019 infected patients were included in the study, with 262 males (63.9 per cent) and 148 females (36.1 per cent). Ninety-nine patients (24.1 per cent) reported chemosensory dysfunction, of which 85 patients (20.7 per cent) reported both olfactory and taste dysfunction. Olfactory and taste dysfunction were proportionally more common in females. The mean duration of olfactory and taste dysfunction was 4.9 days, with a range of 2–15 days.
Conclusion
Olfactory and taste dysfunction are prevalent symptoms in coronavirus disease 2019 patients. In this study, they were more common in females than males. The occurrence of such dysfunctions is lower in the Indian population than in the European population.
The long-term recovery rate of chemosensitive functions in coronavirus disease 2019 patients has not yet been determined.
Method
A multicentre prospective study on 138 coronavirus disease 2019 patients was conducted. Olfactory and gustatory functions were prospectively evaluated for 60 days.
Results
Within the first 4 days of coronavirus disease 2019, 84.8 per cent of patients had chemosensitive dysfunction that gradually improved over the observation period. The most significant increase in chemosensitive scores occurred in the first 10 days for taste and between 10 and 20 days for smell. At the end of the observation period (60 days after symptom onset), 7.2 per cent of the patients still had severe dysfunctions. The risk of developing a long-lasting disorder becomes significant at 10 days for taste (odds ratio = 40.2, 95 per cent confidence interval = 2.204–733.2, p = 0.013) and 20 days for smell (odds ratio = 58.5, 95 per cent confidence interval = 3.278–1043.5, p = 0.005).
Conclusion
Chemosensitive disturbances persisted in 7.2 per cent of patients 60 days after clinical onset. Specific therapies should be initiated in patients with severe olfactory and gustatory disturbances 20 days after disease onset.