The role of olfactory dysfunction in mild cognitive impairment and Alzheimer's disease: A meta-analysis.

PURPOSE: This comprehensive meta-analysis investigates the association between olfactory deficits in mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: A thorough search across databases identified articles analyzing olfactory status in MCI or AD patients. Methodological quality assessment followed PRISMA guidelines. Hedges' g effect size statistic computed standard mean differences and 95% confidence intervals. Moderator analysis was conducted. RESULTS: Among the included studies (65 for MCI and 61 for AD), odor identification exhibited larger effect sizes compared to odor threshold and discrimination, in both MCI and AD samples. Moderate effect size is found in OI scores in MCI (k = 65, SE = 0.078, CI 95% = [-1.151, -0.844]). Furthermore, compared to MCI, AD had moderate to large heterogeneous effects in olfactory identification (k = 61, g = -2.062, SE = 0.125, CI 95% = [-2.308, -1.816]). Global cognitive status is positively related to olfactory identification impairment in both MCI (k = 57, Z = 2.74, p = 0.006) and AD (k = 53, Z = 5.03, p < 0.0001) samples. CONCLUSION: Olfactory impairments exhibit a notable and substantial presence in MCI. Among these impairments, odor identification experiences the greatest decline in MCI, mirroring the primary sensory deficit observed in AD. Consequently, the incorporation of a straightforward odor identification test is advisable in the evaluation of individuals vulnerable to the onset of AD, offering a practical screening tool for early detection.

Impact of post-COVID-19 olfactory disorders on quality of life, hedonic experiences and psychiatric dimensions in general population.

BACKGROUND AND OBJECTIVE: Olfactory disorders in COVID-19 impact quality of life and may lead to psychological impairments. Prevalence ranges from 8 to 85%, persisting in about 30% of cases. This study aimed to evaluate the 6-month post-COVID-19 impact on quality of life, hedonic experiences, anxiety and depression due to olfactory disorders. Additionally, it sought to compare psychophysical tests and self-perceived olfactory evaluations. METHODS: A prospective, longitudinal study was conducted over baseline (T0) and 6 months (T1) on individuals with persistent olfactory disorders post-COVID-19 for more than 6 weeks. Psychophysical tests employed the Sniffin' Sticks Test® (TDI score), and self-perceived olfactory evaluation used a Visual Analogue Scale. Quality of life was assessed with an Olfactive Disorder Questionnaire and the French version of the Quality of Life and Diet Questionnaire. Hedonic experiences were gauged using the Snaith-Hamilton Pleasure Scale, while anxiety and depression dimensions were measured by The State-Trait Anxiety Inventory, The Post Traumatic Stress Checklist Scale, and Hamilton Rating Scale for Depression. Participants were classified into the "normosmic group" (NG) and the "olfactory disorders group" (ODG) at T0 and T1 based on the TDI score. RESULTS: Were included 56 participants (58.93% women, 41.07% men) with a mean age of 39.04 years and a mean duration of post-COVID-19 olfactory disorders of 5.32 months. At T1, ODG had a significantly lower quality of life and hedonic experiences than NG. No significant differences in anxiety and depression dimensions were observed between groups. At T0, psychophysical tests and self-perceived olfactory evaluations were significantly correlated with quality of life and hedonic experiences in both groups. At T1, self-perceived olfactory evaluation in NG correlated significantly with quality of life, hedonic experiences, anxiety and depression dimensions, whereas ODG only correlated with hedonic experiences. CONCLUSION: Individuals with persistent post-COVID-19 olfactory disorders after six months demonstrated compromised quality of life and hedonic experiences. Self-perceived olfactory evaluation played a more significant role in influencing quality of life and the dimension of anxiety and depression than the psychophysical presence of olfactory disorders. These findings emphasize the importance of considering patients' perceptions to comprehensively assess the impact of olfactory disorders on their well-being. TRIAL REGISTRATION: ClinicalTrials.gov number (ID: NCT04799977).

Olfactory training effects in children after mild traumatic brain injury.

OBJECTIVE: Mild traumatic brain injury (mTBI) might impair the sense of smell and cognitive functioning. Repeated, systematic exposure to odors, i.e., olfactory training (OT) has been proposed for treatment of olfactory dysfunctions, including post-traumatic smell loss. Additionally, OT has been shown to mitigate cognitive deterioration in older population and enhance selected cognitive functions in adults. We aimed to investigate olfactory and cognitive effects of OT in the pediatric population after mTBI, likely to exhibit cognitive and olfactory deficits. METHODS: Our study comprised 159 children after mTBI and healthy controls aged 6-16 years (M = 9.68 ± 2.78 years, 107 males), who performed 6-months-long OT with a set of 4 either high- or low-concentrated odors. Before and after OT we assessed olfactory functions, fluid intelligence, and executive functions. RESULTS: OT with low-concentrated odors increased olfactory sensitivity in children after mTBI. Regardless of health status, children who underwent OT with low-concentrated odors had higher fluid intelligence scores at post-training measurement, whereas scores of children performing OT with high-concentrated odors did not change. CONCLUSION: Our study suggests that OT with low-concentrated odors might accelerate rehabilitation of olfactory sensitivity in children after mTBI and support cognitive functions in the area of fluid intelligence regardless of head trauma.

Cognitive impairment is correlated with olfactory identification deficits in older Japanese adults: A cross-sectional study using objective and subjective olfactory measures.

AIM: Olfactory impairment is associated with cognitive impairment. However, differences between subjective and objective olfactory impairment measurements in older adults and their relationship with cognitive impairment are unclear. METHODS: We assessed the relationship between cognitive and olfactory impairments via a single-center observational study in 2020. Forty-seven individuals who visited our memory clinic were enrolled and asked to complete objective and subjective olfactory tests. Participants had dementia, mild cognitive impairment, or normal cognition. We administered the Open Essence (a simple card-type odor identification test) and self-administered odor questionnaire to assess objective and subjective olfaction, respectively, and the Mini-Mental State Examination to assess cognitive function. RESULTS: Older age was related to decreased Open Essence scores (P < 0.001). Compared with the mild cognitive impairment and normal cognition groups, the dementia group had significantly lower Open Essence scores (P < 0.001). Cognitive impairment was also associated with decreased Open Essence scores after adjusting for age, sex, and education (P < 0.001). Participants with dementia did not obtain lower self-administered odor questionnaire scores than those with normal cognition, and they tended to be unaware of their olfactory impairment. CONCLUSION: Open Essence scores significantly decreased according to the degree of cognitive impairment. Participants with dementia were unaware of their olfactory impairment, as indicated by odor questionnaire scores. Objective and subjective scores of olfaction differed in participants with dementia. Concomitant assessment of objective and subjective olfaction is useful to screen older adults with both olfactory and cognitive impairments. Geriatr Gerontol Int 2022; 22: 924-929.

The Neuroanatomic Correlates of Olfactory Identification Impairment in Healthy Older Adults and in Persons with Mild Cognitive Impairment.

BACKGROUND: Olfactory identification (OI) impairment appears early in the course of Alzheimer's disease dementia (AD), prior to detectable cognitive impairment. However, the neuroanatomical correlates of impaired OI in cognitively normal older adults (CN) and persons with mild cognitive impairment (MCI) are not fully understood. OBJECTIVE: We examined the neuroanatomic correlates of OI impairment in older adults from the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). METHODS: Our sample included 1,600 older adults without dementia who completed clinical assessment and structural brain imaging from 2011 to 2013. We characterized OI impairment using the 12-item Sniffin' Sticks odor identification test (score ≤6). We used voxel-based morphometry (VBM) and region of interest (ROI) analyses to examine the neuroanatomic correlates of impaired OI in CN and MCI, after adjusting for potential confounders. Analyses were also separately stratified by race and sex. RESULTS: In CN, OI impairment was associated with smaller amygdala gray matter (GM) volume (p < 0.05). In MCI, OI impairment was associated with smaller GM volumes of the olfactory cortex, amygdala, entorhinal cortex, hippocampus, and insula (ps < 0.05). Differential associations were observed by sex in MCI; OI impairment was associated with lower insular GM volumes among men but not among women (p-interaction = 0.04). There were no meaningful interactions by race. CONCLUSION: The brain regions associated with OI impairment in individuals without dementia are specifically those regions known to be the primary targets of AD pathogenic processes. These findings highlight the potential utility of olfactory assessment in the identification and stratification of older adults at risk for AD.

Reliability and validity of a brief version of the Questionnaire of Olfactory Disorders (brief QOD) in patients with olfactory dysfunction.

BACKGROUND: The aim of this study was to determine the reliability and validity of the brief version of Questionnaire of Olfactory Disorders (brief QOD). METHODS: A total of 372 patients participated in this study. Olfactory function was examined using the Sniffin' Sticks test. The brief version of QOD, including 4 items concerning parosmia (QOD-P), 7 items concerning quality of life (QOD-QOL), and 3 visual analog scales to rate disease burden, awareness of the disorder and issues related to professional life (QOD-VAS), was used to assess subjective information on olfactory dysfunction. We evaluated the split-half reliability, internal consistency and validity of the brief QOD. RESULTS: The split-half reliability was 0.60 (QOD-P), 0.87 (QOD-QOL), and 0.66 (QOD-VAS), respectively. The Cronbach's coefficient was 0.63 (QOD-P), 0.87 (QOD-QOL), and 0.71 (QOD-VAS), respectively. Olfactory function was found to be associated with QOD-P, QOD-QOL and QOD-VAS. CONCLUSIONS: The brief QOD is a suitable scale for the assessment of subjective severity of olfactory dysfunction for purposes such as treatment counseling, disability assessment, treatment control, and research in patients with olfactory disorder.

Olfactory impairment in mild cognitive impairment with Lewy bodies and Alzheimer's disease.

OBJECTIVES: Impaired olfaction may be a biomarker for early Lewy body disease, but its value in mild cognitive impairment with Lewy bodies (MCI-LB) is unknown. We compared olfaction in MCI-LB with MCI due to Alzheimer's disease (MCI-AD) and healthy older adults. We hypothesized that olfactory function would be worse in probable MCI-LB than in both MCI-AD and healthy comparison subjects (HC). DESIGN: Cross-sectional study assessing olfaction using Sniffin' Sticks 16 (SS-16) in MCI-LB, MCI-AD, and HC with longitudinal follow-up. Differences were adjusted for age, and receiver operating characteristic (ROC) curves were used for discriminating MCI-LB from MCI-AD and HC. SETTING: Participants were recruited from Memory Services in the North East of England. PARTICIPANTS: Thirty-eight probable MCI-LB, 33 MCI-AD, 19 possible MCI-LB, and 32HC. MEASUREMENTS: Olfaction was assessed using SS-16 and a questionnaire. RESULTS: Participants with probable MCI-LB had worse olfaction than both MCI-AD (age-adjusted mean difference (B) = 2.05, 95% CI: 0.62-3.49, p = 0.005) and HC (B = 3.96, 95% CI: 2.51-5.40, p < 0.001). The previously identified cutoff score for the SS-16 of ≤ 10 had 84% sensitivity for probable MCI-LB (95% CI: 69-94%), but 30% specificity versus MCI-AD. ROC analysis found a lower cutoff of ≤ 7 was better (63% sensitivity for MCI-LB, with 73% specificity vs MCI-AD and 97% vs HC). Asking about olfactory impairments was not useful in identifying them. CONCLUSIONS: MCI-LB had worse olfaction than MCI-AD and normal aging. A lower cutoff score of ≤ 7 is required when using SS-16 in such patients. Olfactory testing may have value in identifying early LB disease in memory services.

Psychophysical assessments of olfaction after endoscopic unilateral resection with post-operative radiotherapy in olfactory neuroblastomas.

Endoscopic resection with post-operative radiotherapy has been included in the standard therapeutic options for olfactory neuroblastomas (ONBs). Recent publications have indicated the feasibility of olfactory preservation after endoscopic unilateral resection of ONBs. This study validated residual olfaction using the psychophysical assessment, T & T olfactometer, in patients who underwent endoscopic unilateral resection with post-operative radiotherapy. A single-institutional retrospective review was performed to identify patients who underwent endoscopic unilateral resection of ONBs with olfaction monitoring using T & T olfactometer between 2009 and 2020. T & T olfactometry was performed before surgery, after surgery, before radiotherapy, and after completion of radiotherapy. Four patients (one female and three males) were identified. The mean observation period was 41.9 months, and all patients showed no evidence of disease. Three patients exhibited residual olfactory function with two patients having normal or pre-operative level olfaction, although T & T olfactometer results showed a temporary increase in recognition thresholds after surgery. As consequence, endoscopic unilateral resection can achieve satisfactory olfactory preservation in patients with early-stage ONBs.

A study of depression, partnership and sexual satisfaction in patients with post-traumatic olfactory disorders.

Post-traumatic olfactory dysfunction (PTOD) is associated with a significant decrease in quality of life. The present study aimed to explore whether PTOD is associated with depression and changes in sexuality. There were two groups in this case-control study. The patient group consisted of patients with PTOD (n = 55), and the control group comprised healthy individuals without the olfactory disorder (n = 115). Olfactory function, depression, partnership, and sexual satisfaction were assessed using the Iranian version of the Sniffin' Sticks test (Ir-SST), Beck Depression Inventory (BDI), Enrich Couple Scale (ECS) and Sexual Satisfaction Scale for Women (SSSW). The BDI scores were higher in the patient group than in the control group (p < 0.001). The SSSW score was lower in the patient group than in controls (p < 0.01), although the ECS score was not significantly different between patients and controls. Also, there was no significant difference in the severity of trauma between marital satisfaction and sexual satisfaction. However, the analysis showed a statistically significant difference in depression scores in connection with the head trauma severity. In the PTOD group, depression was increased and sexual satisfaction declined. Understanding the association of olfactory dysfunction with depression and sexuality allows patients and doctors to deal with less notable consequences of this disorder.

Olfactory Impairment and Close Social Relationships. A Narrative Review.

Olfactory impairment is one of the more unique symptoms of COVID-19 infection and has therefore enjoyed increased public attention in recent months. Olfactory impairment has various implications and consequences ranging from difficulty detecting dangerous pathogens to hindering social functioning and social behaviors. We provide an overview of how olfactory impairment can impact 3 types of close social relationships: family relationships, friendships, and romantic relationships. Evidence is divided into several categories representing potential mechanisms by which olfactory impairment can impact close social relationships: bonding disruptions, decreased social support, missed group-eating experiences, hygiene concerns, and altered sexual behaviors. We conclude with a discussion of emerging future research questions.

Impact of olfactory dysfunction on quality of life in coronavirus disease 2019 patients: a systematic review.

OBJECTIVE: To outline the impact on quality of life in coronavirus disease 2019 patients with olfactory dysfunction. METHODS: Five databases were searched for articles referring to the impact on quality of life in coronavirus disease 2019 patients with olfactory dysfunction. The search was conducted for the period from November 2019 to April 2021. The search was conducted over one month (May 2021). RESULTS: Four studies that met the objective were included. Altogether, there were 1045 patients. Various questionnaires were used to assess quality of life. Overall, the quality of life deficit affected 67.7 per cent of patients. Quality of life domains investigated include overall quality of life (four studies), food and taste dysfunction (two studies), mental health (two studies), cognitive function (one study), functional outcome (one study) and safety domains (one study). CONCLUSION: Quality of life deficit was reported to be 67.7 per cent among coronavirus disease 2019 patients with olfactory dysfunction. The high prevalence of persistent olfactory dysfunction prompts more serious research, as the long-standing consequences of olfactory dysfunction are detrimental.

Quality of life and safety impact of COVID-19 associated smell and taste disturbances.

OBJECTIVE: The association between COVID-19 and chemosensory loss has garnered substantial attention, however to date little is known about the real-life consequences of impairment in this unique patient population. The aim of this study is to evaluate the quality of life (QOL) and personal safety deficits experienced by patients with COVID-19 infection. STUDY DESIGN: Prospective, longitudinal questionnaires. SETTING: National survey. METHODS: A longitudinal web-based nationwide survey of adults with COVID-19 and/or a sudden change in smell and taste was launched April 10, 2020. Previously published questions on chemosensory-related QOL and safety events were asked at the 6-month follow-up survey. RESULTS: As of February 10, 2021, 480 eligible respondents took the 6-month questionnaire, of whom 322 were COVID-19 positive. Impact on QOL was substantial with 96% of subjects reporting at least one of the defined deficits, and over 75% reporting at least 3 of these. "Reduced enjoyment of food" was the most common complaint (87%), while 43% of subjects self-reported depression. The prevalence of safety-related issues was common in this population, with over 57% reporting at least one, and 36% reporting 2 or more events. Of the events asked, the inability to smell smoke that others could perceive was the most common at 45%. CONCLUSIONS: COVID-19 associated chemosensory losses have a real and substantial impact on both quality of life and safety, beyond mere inconvenience. The high prevalence of these issues despite a relatively short period of olfactory deficit should alert clinicians to the serious risks to an already vulnerable patient population.

Differences in taste and smell perception between type 2 diabetes mellitus patients and healthy controls.

BACKGROUND AND AIMS: The senses of taste and smell are essential determinants of food choice, which in turn may contribute to the development of chronic diseases, including diabetes. Although past studies have evaluated the relationship between type 2 diabetes mellitus (DM2) and senses disorders, this relationship remains controversial. In this study, we evaluated taste and smell perception in DM2 patients and healthy controls (HC). Moreover, we analyzed the association of chemosensory impairments with anthropometric and clinical outcomes (e.g. Body Mass Index (BMI), Fasting blood glucose (FBG), drugs, cardiovascular diseases (CVD), and hypertension) in DM2 patients. METHODS AND RESULTS: The study included 94 DM2 patients and 244 HC. Taste recognition for 6-n-propylthiouracil (PROP), quinine, citric acid, sucrose, and sodium chloride (NaCl) compounds was assessed using a filter paper method, while smell recognition of 12 odorants was performed using a Sniffin' sticks test. We found that a higher percentage of DM2 patients showed identification impairment in salt taste (22% vs. 5%, p-value<0.0009) and smell recognition (55% vs. 27%, p-value = 0.03) compared to HC. We also observed that 65% of hypertensive DM2 subjects presented smell identification impairment compared to 18% of non-hypertensive patients (p-value = 0.019). Finally, patients with impairments in both taste and smell showed elevated FBG compared to patients without impairment (149.6 vs.124.3 mg/dL, p-value = 0.04). CONCLUSION: The prevalence of taste and smell identification impairments was higher in DM2 patients compared to HC, and a possible relationship with glycemic levels emerged.

Intranasal administration of white tea alleviates the olfactory function deficit induced by chronic unpredictable mild stress.

CONTEXT: White tea [Camellia sinensis (L) O.Ktze. (Theaceae)] is popular in Asia, but its benefits on olfactory injury are unknown. OBJECTIVE: The present study explores the effects of white tea on the olfactory injury caused by chronic unpredictable mild stress (CUMS). MATERIALS AND METHODS: C57BL/6J mice (WT) were exposed to CUMS. CUMS mice (CU) were intranasally treated with white tea extract [low tea (LT), 20 mg/kg; high tea (HT), 40 mg/kg] and fluoxetine (CF, 20 mg/kg) for 7 days. Several behavioural tests were conducted to assess depression and olfactory function. The transmission electron microscope (TEM) and semi-quantitative reverse transcription PCR were performed separately to observe the changes of related structures and genes transcription level. RESULTS: The depressive behaviours of the LT and HT mice were reversed. The latency time of the buried food pellet test decreased from 280 s (CU) to 130 s (HT), while the olfactory sensitivity and olfactory avoidance test showed that the olfactory behaviours disorder of LT and HT mice were alleviated. The white tea increased the A490 nm values of the cortisol treated cells from 0.15 to 1.4. Reduced mitochondrial and synaptic damage in the olfactory bulb (OB), enhanced expression of the brain-derived neurotrophic factor (BDNF) and olfactory marker protein (OMP) were observed in the LT and HT mice. CONCLUSIONS AND DISCUSSION: White tea has the potential in curing the olfactory deficiency related to chronic stress. It lays the foundation for the development of new and reliable drug to improve olfactory.

Assessment of odor hedonic perception: the Sniffin' sticks parosmia test (SSParoT).

Qualitative olfactory dysfunction is characterized as distorted odor perception and can have a profound effect on quality of life of affected individuals. Parosmia and phantosmia represent the two main subgroups of qualitative impairment and are currently diagnosed based on patient history only. We have developed a test method which measures qualitative olfactory function based on the odors of the Sniffin' Sticks Identification subtest. The newly developed test is called Sniffin' Sticks Parosmia Test (SSParoT). SSParoT uses hedonic estimates of two oppositely valenced odors (pleasant and unpleasant) to assess hedonic range (HR) and hedonic direction (HD), which represent qualitative olfactory perception. HR is defined as the perceivable hedonic distance between two oppositely valenced odors, while HD serves as an indicator for overall hedonic perception of odors. This multicenter study enrolled a total of 162 normosmic subjects in four consecutive experiments. Cluster analysis was used to group odors from the 16-item Sniffin' Sticks Identification test and 24-additional odors into clusters with distinct hedonic properties. Eleven odor pairs were found to be suitable for estimation of HR and HD. Analysis showed agreement between test-retest sessions for all odor pairs. SSparoT might emerge as a valuable tool to assess qualitative olfactory function in health and disease.

Increased prediction value of biomarker combinations for the conversion of mild cognitive impairment to Alzheimer's dementia.

BACKGROUND: Progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia can be predicted by clinical features and a combination of biomarkers may increase the predictive power. In the present study, we investigated whether the combination of olfactory function and plasma neuronal-derived exosome (NDE) Aß1-42 can best predict progression to AD dementia. METHODS: 87 MCI patients were enrolled and received the cognitive assessment at 2-year and 3-year follow-up to reevaluate cognition. In the meanwhile, 80 healthy controls and 88 AD dementia patients were enrolled at baseline as well to evaluate the diagnose value in cross-section. Olfactory function was evaluated with the sniffin sticks (SS-16) and Aß1-42 levels in NDEs were determined by ELISA. Logistic regression was performed to evaluate the risk factors for cognitive decline in MCI at 2-year and 3-year revisits. RESULTS: In the cross cohort, lower SS-16 scores and higher Aß1-42 levels in NDEs were found in MCI and AD dementia compared to healthy controls. For the longitudinal set, 8 MCI individuals developed AD dementia within 2 years, and 16 MCI individuals developed AD dementia within 3 years. The two parameter-combination of SS-16 scores and Aß1-42 level in NDEs showed better prediction in the conversion of MCI to AD dementia at 2-year and 3-year revisit. Moreover, after a 3-year follow-up, SS-16 scores also significantly predicted the conversion to AD dementia, where lower scores were associated with a 10-fold increased risk of developing AD dementia (p = 0.006). Similarly, higher Aß1-42 levels in NDEs in patients with MCI increased the risk of developing AD dementia by 8.5-fold (p = 0.002). CONCLUSION: A combination of two biomarkers of NDEs (Aß1-42) and SS-16 predicted the conversion of MCI to AD dementia more accurately in combination. These findings have critical implications for understanding the pathophysiology of AD dementia and for developing preventative treatments for cognitive decline.

Mood, Anxiety and Olfactory Dysfunction in COVID-19: Evidence of Central Nervous System Involvement?

OBJECTIVE: The objective of this study was to determine the burden of depressed mood and anxiety in COVID-19, and associated disease characteristics. MATERIALS AND METHODS: This is a prospective, cross-sectional study of 114 COVID-19 positive patients diagnosed using RT-PCR-based testing over a 6-week period. The two-item Patient Health Questionnaire (PHQ-2) and the two-item Generalized Anxiety Disorder questionnaire (GAD-2) were used to measure depressed mood and anxiety level, respectively, at enrollment and for participants' baseline, pre-COVID-19 state. Severity of smell loss, loss of taste, nasal obstruction, rhinorrhea/mucus production, fever, cough, and shortness of breath (SOB) during COVID-19 were assessed. RESULTS: PHQ-2 and GAD-2 significantly (P < .001) increased from baseline to enrollment. PHQ-2 was associated with smell loss (adjusted incidence rate ratio [aIRR] = 1.40, 95% CI, 1.10-1.78, P = .006), age (aIRR = 1.02, 95% CI, 1.01-1.04, P = .006), and baseline PHQ-2 score (aIRR = 1.39, 95% CI, 1.09-1.76, P = .007). GAD-2 score was associated with smell loss (aIRR = 1.29, 95% CI, 1.02-1.62, P = .035), age (aIRR = 1.02, 95% CI, 1.01-1.04, P = .025) and baseline GAD-2 score (aIRR = 1.55, 95% CI, 1.24-1.93, P < .001). Loss of taste also exhibited similar associations with PHQ-2 and GAD-2. PHQ-2 and GAD-2 scores were not associated with severities of any other symptoms during the COVID-19 course. CONCLUSIONS: Despite the occurrence of symptoms-such as SOB-associated with severe manifestations of COVID-19, only the severities of smell and taste loss were associated with depressed mood and anxiety. These results may raise the novel possibility of emotional disturbance as a CNS manifestation of COVID-19 given trans-olfactory tract penetration of the central nervous system (CNS) by coronaviruses. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:2520-2525, 2020.

Association Between Orthonasal Olfaction and Chemosensory Perception in Patients With Smell Loss.

OBJECTIVES: Self-ratings seem to be the most effortless strategy for assessment of patients' chemical senses. Notably, although flavor perception strongly relies on olfaction, the relationship between self-reported flavor perception and orthonasal olfactory tests have hitherto not been considered. The aim of this study was to investigate the relationship between self-perceived olfactory function (SO), taste (ST), and flavor perception (SF) and smell test results in patients with olfactory dysfunction (OD). METHODS: We included 203 patients with quantitative OD. Group comparison, bivariate correlation, and ordinal logistic regression were employed to quantify the relationships between predictor variables (age, gender, reason for OD, and orthonasal olfaction-summed scores of threshold, discrimination, and identification [TDI]) and outcomes of SO and SF ("impaired," "average," or "good"). RESULTS: Group comparison revealed significant differences between SO and SF (P < .001). Stronger correlations were found between SO and TDI (r = 0.64), compared to SF and TDI (r = 0.27). No relevant correlation was found between ST and TDI (r = 0.10). Higher TDI was associated with odds of higher SO in univariate (odds ratio = 1.25) and multivariable analyses (adjusted odds ratio = 1.23), and both models showed good fit of data. Conversely, regression models on the associations between TDI and changes in SF did not meet the assumption of goodness of fit. CONCLUSION: We found that higher orthonasal olfactory performance was associated with odds of higher SO in patients with OD, even after controlling for olfactory-relevant factors. To the contrary, similar models based on flavor perception failed to describe these relationships. This indicates for SF and ST to be less represented by the TDI compared to SO. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2213-2219, 2020.