University Of Pennsylvania Smell Identification Test Scores Research Articles

Long-Term Taste and Smell Outcomes After COVID-19

Self-report surveys suggest that long-lasting taste deficits may occur after SARS-CoV-2 infection, influencing nutrition, safety, and quality of life. However, self-reports of taste dysfunction are inaccurate, commonly reflecting deficits due to olfactory not taste system pathology; hence, quantitative testing is needed to verify the association of post-COVID-19 condition with taste function. To use well-validated self-administered psychophysical tests to investigate the association of COVID-19 with long-term outcomes in taste and smell function. This nationwide cross-sectional study included individuals with and without a prior history of COVID-19 recruited from February 2020 to August 2023 from a social media website (Reddit) and bulletin board advertisements. In the COVID-19 cohort, there was a mean of 395 days (95% CI, 363-425 days) between diagnosis and testing. History of COVID-19. The 53-item Waterless Empirical Taste Test (WETT) and 40-item University of Pennsylvania Smell Identification Test (UPSIT) were used to assess taste and smell function. Total WETT and UPSIT scores and WETT subtest scores of sucrose, citric acid, sodium chloride, caffeine, and monosodium glutamate were assessed for groups with and without a COVID-19 history. The association of COVID-19 with taste and smell outcomes was assessed using analysis of covariance, χ2, and Fisher exact probability tests. Tests were completed by 340 individuals with prior COVID-19 (128 males [37.6%] and 212 females [62.4%]; mean [SD] age, 39.04 [14.35] years) and 434 individuals with no such history (154 males [35.5%] and 280 females [64.5%]; mean (SD) age, 39.99 [15.61] years). Taste scores did not differ between individuals with and without previous COVID-19 (total WETT age- and sex-adjusted mean score, 33.41 [95% CI, 32.37-34.45] vs 33.46 [95% CI, 32.54-34.38]; P = .94). In contrast, UPSIT scores were lower in the group with previous COVID-19 than the group without previous COVID-19 (mean score, 34.39 [95% CI, 33.86-34.92] vs 35.86 [95% CI, 35.39-36.33]; P < .001]); 103 individuals with prior COVID-19 (30.3%) and 91 individuals without prior COVID-19 (21.0%) had some degree of dysfunction (odds ratio, 1.64 [95% CI, 1.18-2.27]). The SARS-CoV-2 variant present at the time of infection was associated with smell outcomes; individuals with original untyped and Alpha variant infections exhibited more loss than those with other variant infections; for example, total to severe loss occurred in 10 of 42 individuals with Alpha variant infections (23.8%) and 7 of 52 individuals with original variant infections (13.5%) compared with 12 of 434 individuals with no COVID-19 history (2.8%) (P < .001 for all). In this study, taste dysfunction as measured objectively was absent 1 year after exposure to COVID-19 while some smell loss remained in nearly one-third of individuals with this exposure, likely explaining taste complaints of many individuals with post-COVID-19 condition. Infection with earlier untyped and Alpha variants was associated with the greatest degree of smell loss.

Longitudinal brain changes in Parkinson's disease with severe olfactory deficit

IntroductionOlfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying neurobiology for this relationship remains unclear but may involve distinct patterns of neurodegeneration. This study aimed to examine longitudinal cortical atrophy and thinning in early-stage PD with severe olfactory deficit (anosmia) without and with concurrent probable RBD. MethodsLongitudinal MRI data over four years of 134 de novo PD and 49 healthy controls (HC) from the Parkinson Progression Marker Initiative (PPMI) cohort were analyzed using a linear mixed-effects model. Patients were categorized into those with anosmia by the University of Pennsylvania Smell Identification Test (UPSIT) score ≤ 18 (AO+) and those without (UPSIT score > 18, AO-). The AO+ group was further subdivided into AO+ with probable RBD (AO+RBD+) and without (AO+RBD-) for subanalysis. ResultsCompared to subjects without baseline anosmia, the AO+ group exhibited greater longitudinal declines in both volume and thickness in the bilateral parahippocampal gyri and right transverse temporal gyrus. Patients with concurrent anosmia and RBD showed more extensive longitudinal declines in cortical volume and thickness, involving additional brain regions including the bilateral precuneus, left inferior temporal gyrus, right paracentral gyrus, and right precentral gyrus. ConclusionsThe atrophy/thinning patterns in early-stage PD with severe olfactory dysfunction include regions that are critical for cognitive function and could provide a structural basis for previously reported associations between severe olfactory deficit and cognitive decline in PD. Concurrent RBD might enhance the dynamics of cortical changes.

Olfactory and cognitive decrements in 1991 Gulf War veterans with gulf war illness/chronic multisymptom illness

BackgroundGulf War illness (GWI)/Chronic Multisymptom Illness (CMI) is a disorder related to military service in the 1991 Gulf War (GW). Prominent symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. Although anosmia is not a typical GWI/CMI symptom, anecdotally some GW veterans have reported losing their sense smell shortly after the war. Because olfactory deficit is a prodromal symptom of neurodegenerative diseases like Parkinson’s and Alzheimer’s disease, and because we previously reported suggestive evidence that deployed GW veterans may be at increased risk for Mild Cognitive Impairment (MCI) and dementia, the current study examined the relationship between olfactory and cognitive function in deployed GW veterans.MethodsEighty deployed GW veterans (mean age: 59.9 ±7.0; 4 female) were tested remotely with the University of Pennsylvania Smell Identification Test (UPSIT) and the Montreal Cognitive Assessment (MoCA). Veterans also completed self-report questionnaires about their health and deployment-related exposures and experiences. UPSIT and MoCA data from healthy control (HC) participants from the Parkinson’s Progression Markers Initiative (PPMI) study were downloaded for comparison.ResultsGW veterans had a mean UPSIT score of 27.8 ± 6.3 (range 9–37) and a mean MoCA score of 25.3 ± 2.8 (range 19–30). According to age- and sex-specific normative data, 31% of GW veterans (vs. 8% PPMI HCs) had UPSIT scores below the 10th percentile. Nearly half (45%) of GW veterans (vs. 8% PPMI HCs) had MoCA scores below the cut-off for identifying MCI. Among GW veterans, but not PPMI HCs, there was a positive correlation between UPSIT and MoCA scores (Spearman’s ρ = 0.39, p < 0.001). There were no significant differences in UPSIT or MoCA scores between GW veterans with and without history of COVID or between those with and without Kansas GWI exclusionary conditions.ConclusionsWe found evidence of olfactory and cognitive deficits and a significant correlation between UPSIT and MoCA scores in a cohort of 80 deployed GW veterans, 99% of whom had CMI. Because impaired olfactory function has been associated with increased risk for MCI and dementia, it may be prudent to screen aging, deployed GW veterans with smell identification tests so that hypo- and anosmic veterans can be followed longitudinally and offered targeted neuroprotective therapies as they become available.

Vitamin D levels and olfactory dysfunction in multiple sclerosis patients

Objective The objective was to explore the possible relationship between the serum vitamin D level and olfactory impairment in a population of multiple sclerosis (MS) patients in Guizhou, China. Methods We included 25 patients with MS and 18 healthy controls (HCs) who were recruited from the Affiliated Hospital of Guizhou Medical University from February 2021 to September 2021. The University of Pennsylvania Smell Identification Test (UPSIT) was used to test the patients’ sense of smell, and the level of serum 25-hydroxyethylene polyprotein D was measured. Results Serum vitamin D levels and UPSIT scores were significantly different between the MS group and the control group (both p < 0.001). Moreover, a significant positive correlation emerged between vitamin D levels and UPSIT scores in MS patients (r = 0.537, p = 0.021). Conclusions The serum vitamin D level may be involved in the regulation of olfactory dysfunction in MS patients in Guizhou, China.

Validation of Minimal Clinically Important Difference (MCID) for University of Pennsylvania Smell Identification Test (UPSIT).

The University of Pennsylvania Smell Identification Test is widely used to measure change in olfactory function, but a minimal clinically important difference (MCID) has not been well-established. A study published in 1997 regarding patients with head trauma reported an MCID of 4 but did not detail the methods used in the calculation. To validate the MCID for UPSIT in patients with postviral, sinusitis, and procedure-associated olfactory loss. This was a secondary analysis of prospectively collected data from 5 clinical research studies related to olfactory function. Three studies included subjects with COVID-19-related olfactory dysfunction, one with chronic sinusitis subjects, and one with subjects undergoing transsphenoidal surgery. All subjects had completed a baseline and follow-up UPSIT, baseline and follow-up Clinical Global Impression-Severity (CGI-Severity), and a follow-up CGI-Improvement. Both distribution- and anchor-based methods were used to determine the MCID of UPSIT. Distribution-based method calculated MCID using half standard deviation of baseline UPSIT and delta UPSIT scores. Clinical-anchor method determined MCID by comparing delta UPSIT scores between consecutive CGI-I clinical categories ranging from very much better to very much worse. The study population comprised 295 subjects. Subjects had a mean (SD) baseline UPSIT score of 27 (7.5), and follow-up score of 28 (7.9), and a mean UPSIT change of 0.6 (5.8). Half the baseline UPSIT SD was 3.75 and half the delta UPSIT SD was 2.9. With the anchor-based approach, an MCID of 4 was defined as clinically meaningful by exploring the relationship between delta UPSIT and CGI-Improvement. Using a more conservative approach based on the MCID values identified from both methods, we determined that a change of 4 or greater is the appropriate MCID for UPSIT. Investigators in the future should use 4 as MCID for UPSIT and report the percentage of study subjects who achieve a clinically meaningful difference. III.

Odor Identification Moderates Relationship Between Cognitive Training and Cognitive Decline

AbstractBackgroundOlfactory deficits have been shown to predict cognitive decline. Recent findings suggest that computerized cognitive training may reduce the risk of cognitive decline and dementia. However, the impact of olfaction deficits on cognitive training outcomes is unclear. In this study, we investigate how lower odor identification may moderate the relationship between treatment assignment (cognitive games versus crossword puzzles) and cognitive outcomes in older adults diagnosed with mild cognitive impairment (MCI).MethodData were drawn from the Cognitive Training and Neuroplasticity in Mild Cognitive Impairment (COG‐IT) Trial (NCT03205709). In this two‐site, single‐blinded, 78‐week trial, participants with MCI — stratified by age, severity (early/late MCI), and site — were randomly assigned to 12 weeks of intensive, home‐based, Computerized Cognitive Training (CCT) or computerized Crossword Puzzle Training (CPT), followed by six booster sessions. 106 patients received neuropsychological and olfactory assessments through the 11‐item Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog) and the 40‐item University of Pennsylvania Smell Identification Test (UPSIT). In linear mixed‐model analyses, the effect of baseline UPSIT score on change in the ADAS‐Cog score from baseline over 78 weeks by treatment group, adjusted for age and baseline ADAS‐Cog, was assessed.ResultAmong 106 older adults (n = 50 [games]; n = 56 [crosswords]), higher baseline UPSIT scores predicted improved ADAS‐Cog performance at week 78 for all patients randomized to CPT (beta coefficient, 0.15, 95% confidence interval [CI], 0.02 to 0.27; P = 0.02). Greater baseline UPSIT score predicted improved ADAS‐Cog performance at weeks 12, 52, and 78 for early MCI patients randomized to CPT (Week 12: beta coef. 0.26, 95% CI 0.09 to 0.43; Week 52: beta coef. 0.23, 95% CI 0.05 to 0.40; Week 78: beta coef. 0.22, 95% CI 0.05 to 0.39). This was not shown in early MCI patients randomized to CCT. Higher baseline UPSIT predicted significant improvement in ADAS‐Cog for late MCI patients randomized to CCT at week 78 (beta coefficient, 0.24, 95% CI 0.05 to 0.42; P = 0.01).ConclusionOur results are consistent with literature, suggesting that impaired olfaction moderates memory decline. Our preliminary results show that individuals with less impaired olfaction may experience greater cognitive improvement following cognitive training.

Olfactory dysfunction and training in children with COVID-19 infection: A prospective study Post-COVID pediatric olfactory training

ObjectivePostviral olfactory dysfunction (OD) including corona 2019 viral disease (COVID-19) OD occurs in both adults and children. Despite limited reports of efficacy in treating adult postviral including COVID-19 OD with olfactory training (OT), its effects on children in general, and post-COVID-19 in specific, is unknown. The study aimed at evaluating the effects of OT in a COVID-19 OD pediatric cohort. MethodsA single-arm prospective study of pediatric COVID-19 OD subjects confirmed by the University of Pennsylvania Smell Identification Test (UPSIT), was conducted. All subjects underwent OT by sniffing 4 odorants (lavender, orange, peppermint, and eucalyptus) for 1 min twice a day for 3 months. Subjects underwent an odorant identification test (OIT) of the 4 odorants each visit. A repeat UPSIT was administered at the 4th visit. ResultsThe study enrolled a total of 37 subjects [11 males/26 females with mean age/standard deviation (std) of 15.6(2.1) years]. The time interval between COVID-19 and entry was 5.3(2.4) months. The mean pre/post study UPSIT score improvement was 2.3(4.7), p = .09. OIT scores between entry and 3 subsequent visits showed a mean improvement of 1.8(1.5), 1.8(1.9) and 2.3(1.9) odorants, respectively, with P < .001 for all 3 comparisons. ConclusionsOT subjects were predominantly female teens with substantial OD lasting greater than 5 months. OT did not affect OD as measured by UPSIT but OIT scores improved during OT. We postulate that OT likely has a role in pediatric post-COVID OD recovery, but UPSIT likely is too rigid to detect disparate odorant improvement.

Stellate Ganglion Block for the Treatment of COVID-19-Induced Olfactory Dysfunction: A Prospective Pilot Study.

The objective of this study was to explore the safety and feasibility of stellate ganglion blocks (SGBs) to treat persistent COVID-19-induced olfactory dysfunction (OD). Secondarily, the goal was to determine effect sizes to plan a future randomized clinical trial. Prospective case series. Quaternary Care Academic Medical Center. In this single-arm pilot trial, adult participants with a COVID-19 diagnosis ≥ 12 months prior to enrollment with OD underwent bilateral SGBs. Subjects were followed for 1 month after completion of SGB. The primary outcome measure was the change in the Clinical Global Impression-Improvement Scale for smell loss. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT) and Olfactory Dysfunction Outcomes Rating (ODOR). Twenty participants were enrolled with a mean (SD) age of 46 (11) years and a mean (SD) duration of OD of 21 (5) months. At 1 month, 10 (50%) participants experienced at least slight subjective improvement in their OD, 11 (55%) attained a clinically meaningful improvement in smell identification using the UPSIT, and 7 (35%) achieved a clinically meaningful improvement in olfactory-specific quality of life (QoL) measured by the ODOR. The median difference between UPSIT scores at baseline and 1 month was 6 (95% confidence interval: 3-11), exceeding the minimal clinically important difference of 4. There were no serious adverse events. Sequential SGBs for COVID-19-associated OD were safe and associated with modest improvements in subjective olfaction, odor identification, and olfactory-specific QoL. A placebo-controlled trial is warranted to determine the efficacy of SGBs for COVID-19-associated OD.

The longitudinal progression of autonomic dysfunction in Parkinson's disease: A 7-year study.

Autonomic dysfunction, including gastrointestinal, cardiovascular, and urinary dysfunction, is often present in early Parkinson's Disease (PD). However, the knowledge of the longitudinal progression of these symptoms, and the connection between different autonomic domains, is limited. Furthermore, the relationship between the presence of autonomic symptoms in early-stage PD and olfactory dysfunction, a possible marker of central nervous system involvement, has not been fully investigated. We aimed to investigate the occurrence and progression of autonomic dysfunction in recently diagnosed (< 2 years) untreated PD patients and determine any coexistence of symptoms in individual patients. We also investigated the relationship between autonomic symptoms, olfactory dysfunction, and motor impairment. Data were obtained from the Parkinson's Progression Markers Initiative (PPMI) database. Autonomic dysfunction was measured using the Scales for Outcomes in Parkinson's Disease (SCOPA-AUT). Symptom frequency and mean scores over 7 years were determined. The simultaneous occurrence of different autonomic symptoms was also examined. Finally, the relationships between SCOPA-AUT scores, olfactory dysfunction, and motor impairment were investigated using the University of Pennsylvania Smell Identification Test (UPSIT) and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), respectively. Follow-up data were available for 7 years for 171 PD patients and for 5 years for 136 HCs. Mean SCOPA-AUT score increased significantly from baseline to the 7-year follow-up for each autonomic domain, except for female sexual dysfunction. Most patients reported three or more autonomic symptoms. Common clusters of symptoms were composed of combinations of gastrointestinal, urinary, thermoregulatory, and sexual dysfunction. At baseline, greater SCOPA-AUT total score was associated with lower UPSIT scores (r = -0.209, p = 0.006) and with greater total MDS-UDPRS III score (r = 0.218, p = 0.004). Autonomic dysfunction, often with coexistence of autonomic manifestations, is common in early PD and progressively worsens over the first 7 years of disease, suggesting that these symptoms should be addressed with appropriate treatments early in the disease. The association between greater autonomic dysfunction and greater olfactory impairment, coupled with the association with more severe motor scores at baseline, indicates that patients who show more severe autonomic dysfunction could also have more severe involvement of the central nervous system at the time of diagnosis.

Olfactory Impairment Is the Main Predictor of Higher Scores at REM Sleep Behavior Disorder (RBD) Screening Questionnaire in Parkinson's Disease Patients.

Olfactory impairment and REM sleep behavior disorder (RBD) are common non-motor symptoms in Parkinson's disease (PD) patients, often preceding the onset of the specific motor symptoms and, thus, crucial for strategies directed to anticipate PD diagnosis. In this context, the specific interaction between olfactory impairment and RBD has not been clearly defined. The aim of this study was to determine the possible role of olfactory impairment and other clinical characteristics as possible predictors of higher scores at RBD screening questionnaire (RBDSQ) in a large population of PD patients. In this study, 590 PD patients were included from the Parkinson's Progression Markers Initiative. Demographic and clinical features were registered. All participants completed motor and non-motor evaluations at the baseline visit. For motor assessments, the disease severity was evaluated by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) pars III. Regarding non-motor symptoms assessment, Montreal Cognitive Assessments (MoCA), University of Pennsylvania Smell Identification Test (UPSIT) and RBD screening questionnaire (RBDSQ) were registered. Among 590 PD patients included in this study, 111 patients with possible RBD were found (18.8%). RBD was less frequent in female PD patients (p ≤ 0.011). Among patients with or without possible RBD diagnosis, statistically significant differences in MDS-UPDRS III (23.3 ± 11.4 vs. 19.7 ± 9.1, respectively, p ≤ 0.002) and in UPSIT score (19.7 ± 8.3 vs. 22.6 ± 8.0, respectively, p ≤ 0.001) were found. Moreover, significant correlations between RBDSQ versus UPDRS III score and versus UPSIT score were observed. Multivariate linear regression analysis showed that UPSIT was the most significant predictor of higher scores at RBDSQ, while the other significant predictors were UPDRS III and age. The severity of olfactory impairment appears tightly correlated to RBD symptoms, highlighting the role of these biomarkers for PD patients. Additionally, according to this large study, our data confirmed that RBD in PD patients exhibits peculiar gender differences.

Impact of Reverse Septal Flap on Morbidity of Nasoseptal Flap Reconstruction of Skull Base Defects.

The workhorse for endonasal reconstruction of skull base defects is the posteriorly-based nasoseptal flap (NSF). Postoperative nasal deformities and decreased olfaction are potential complications of NSF. The reverse septal flap (RSF) minimizes the donor site morbidity of the NSF by covering the exposed cartilage of the anterior septum. Currently, there are minimal data examining its effect on outcomes including nasal dorsum collapse and olfaction. Our study aims to clarify whether the RSF should be utilized when the option exists. Adult patients undergoing endoscopic endonasal approach (EEA) surgery of the skull base (transsellar/transplanum/transclival approaches) with NSF reconstruction were identified. Data from 2 separate cohorts, one retrospective and one prospective, were collected. Follow-up was at least 6 months. Patients were photographed preoperatively and postoperatively using standard rhinoplastic nasal views. Patients completed the University of Pennsylvania Smell Identification Test (UPSIT) and the 22-item Sino-Nasal Outcome Test (SNOT-22) preoperatively and postoperatively and were also queried regarding subjective changes in nasal appearance and plans for cosmetic surgery following EEA. There were no statistically significant differences in the change in UPSIT and SNOT-22 scores between patients receiving RSF and other reconstructive groups (either NSF without RSF or no NSF). One of 25 patients who were reconstructed with an NSF with RSF reported a change in nasal appearance; none were considering reconstructive surgery. The proportion of patients reporting changes in appearance was significantly lower in the NSF with RSF group as compared to the NSF without RSF group (P = .012). The use of an RSF to limit donor site morbidity of the NSF was shown to significantly decrease the proportion of patients who reported nasal deformities and did not show a significant difference in patient-reported sinonasal outcomes. Given these findings, RSF should be considered whenever an NSF is used for reconstruction.

Updated Percentiles for the University of Pennsylvania Smell Identification Test in Adults 50 Years of Age and Older.

The University of Pennsylvania Smell Identification Test (UPSIT) is commonly used to assess olfaction and screen for early detection of disorders including Parkinson (PD) and Alzheimer disease. Our objective was to develop updated percentiles, based on substantially larger samples than previous norms, to more finely discriminate age- and sex-specific UPSIT performance among ≥50-year-old adults who may be candidates for studies of prodromal neurodegenerative diseases. The UPSIT was administered cross-sectionally to participants recruited between 2007-2010 and 2013-2015 for the Parkinson Associated Risk Syndrome (PARS) and Parkinson's Progression Markers Initiative (PPMI) cohort studies, respectively. Exclusion criteria included age <50 years and a confirmed or suspected PD diagnosis. Demographics, family history, and prodromal features of PD including self-reported hyposmia were collected. Normative data including mean, SDs, and percentiles were derived by age and sex. The analytic sample included 9,396 individuals (5,336 female and 4,060 male), aged 50-95 years, who were predominantly White, non-Hispanic US residents. UPSIT percentiles were derived and are provided across 7 age categories (50-54, 55-59, 60-64, 65-69, 70-74, 75-79, and ≥80 years) for female and male participants separately; relative to existing norms, subgroups included between 2.4 and 20 times as many participants. Olfactory function declined with age and was better among women than men; accordingly, the percentile corresponding to a given raw score varied markedly by age and sex. UPSIT performance was comparable among individuals with vs without first-degree family history of PD. Comparisons of self-reported hyposmia vs UPSIT percentiles indicated a strong association (χ2 p < 0.0001) but minimal agreement (Cohen simple kappa [95% CI]: = 0.32 [0.28-0.36] for female participants; 0.34 [0.30-0.38] for male participants). Updated age/sex-specific UPSIT percentiles are provided for ≥50-year-old adults who reflect a population likely to be recruited into studies of prodromal neurodegenerative diseases. Our findings highlight the potential advantages of evaluating olfaction relative to age and sex instead of in absolute terms (i.e., based on raw UPSIT scores) or based on subjective (i.e., self-reported) measures. This information addresses the need to support studies of disorders including PD and Alzheimer disease by providing updated normative data from a larger sample of older adults. NCT00387075 and NCT01141023.

A quick test to objectify smell and taste dysfunction at home: a proof of concept for the validation of the chemosensory perception test.

Recent studies have shown the efficacy of a home test for the self-evaluation of olfactory and gustatory functions in quarantined coronavirus disease-2019 (COVID-19) patients. However, testing was often limited to COVID-19 participants, and the accuracy of home test kits was rarely compared to standardized testing. This study aims at providing proof of concept for the validation of the new Chemosensory Perception Test (CPT) developed to remotely assess orthonasal olfactory, retronasal olfactory, and gustatory functions in various populations using common North American household items. In the 2 experiments, a total of 121 participants irrespective of having olfactory and/or gustatory complaints from various causes (COVID-19, sinunasal, post-viral, idiopathic) were tested first, with one or many of the following tests: (i) a brief chemosensory questionnaire, (ii) an olfactory test-Sniffin' Sticks Test (SST) or University of Pennsylvania Smell Identification Test (UPSIT), and/or (iii) a gustatory test-Brief Waterless Empirical Taste Test (B-WETT). We then applied the CPT which yielded 3 different subscores, namely orthonasal, retronasal, and gustatory CPT scores. The orthonasal CPT score was significantly correlated with SST (ρ = 0.837, P < 0.001) and UPSIT (ρ = 0.364, P < 0.001) scores, and exhibited an excellent accuracy to identify olfactory dysfunction (OD) as compared to SST (area under the curve [AUC]: 0.923 [95% confidence interval {CI}, 0.822-1.000], P < 0.001). The retronasal CPT score but not the gustatory CPT score allowed to distinguish between participants with or without subjective gustatory complaint (AUC: 0.818 [95% CI, 0.726-0.909], P < 0.001). The CPT has the ability to identify OD and to quantify subjective gustatory complaints.

Enhancement of taste by retronasal odors in patients with Wolfram syndrome and decreased olfactory function.

Wolfram syndrome is a rare disease characterized by diabetes, neurodegeneration, loss of vision, and audition. We recently found, in a young sample of participants (mean age 15 years), that Wolfram syndrome was associated with impairment in smell identification with normal smell sensitivity and whole-mouth taste function. However, these senses were assessed separately, and it is unknown whether smell-taste interactions are altered in Wolfram syndrome, which was the focus of this study. Participants with Wolfram syndrome (n = 36; 18.2 ± 6.8 years) and sex-age-equivalent healthy controls (n = 34) were assessed with a battery of sensory tests. Using sip-and-spit methods, participants tasted solutions containing gustatory and olfactory stimuli (sucrose with strawberry extract, citric acid with lemon extract, sodium chloride in vegetable broth, and coffee) with and without nose clips, and rated perceived taste and retronasal smell intensities using the generalized Labeled Magnitude Scale. Participants also completed n-butanol detection thresholds and the University of Pennsylvania Smell Identification Test (UPSIT). Retronasal smell increased taste intensity of sucrose, sodium chloride, and coffee solutions similarly in both groups (P values <0.03). Compared with the control group, participants in the Wolfram group had lower UPSIT scores and reduced smell sensitivity, retronasal intensity, and saltiness (P values <0.03), but rated other taste intensities similarly when wearing the nose clip. Despite impairments in orthonasal smell identification, odor-induced taste enhancement was preserved in participants with Wolfram syndrome who still had some peripheral olfactory function. This finding suggests that odor-induced taste enhancement may be preserved in the presence of reduced olfactory intensity.

Efficacy of Combined Visual-Olfactory Training With Patient-Preferred Scents as Treatment for Patients With COVID-19 Resultant Olfactory Loss

The number of olfactory dysfunction cases has increased dramatically because of the COVID-19 pandemic. Identifying therapies that aid and accelerate recovery is essential. To determine the efficacy of bimodal visual-olfactory training and patient-preferred scents vs unimodal olfactory training and physician-assigned scents in COVID-19 olfactory loss. This was a randomized, single-blinded trial with a 2-by-2 factorial design (bimodal, patient preferred; unimodal, physician assigned; bimodal, physician assigned; unimodal, patient preferred) and an independent control group. Enrollment occurred from February 1 to May 27, 2021. Participants were adults 18 to 71 years old with current olfactory loss defined as University of Pennsylvania Smell Identification Test (UPSIT) score less than 34 for men and less than 35 for women and duration of 3 months or longer. Olfactory loss was initially diagnosed within 2 weeks of COVID-19 infection. Participants sniffed 4 essential oils for 15 seconds with a 30-second rest in between odors for 3 months. Participants in the physician-assigned odor arms trained with rose, lemon, eucalyptus, and clove. Participants randomized to the patient-preferred arms chose 4 of 24 available scents. If assigned to the bimodal arm, participants were shown digital images of the essential oil they were smelling. The primary end point was postintervention change in UPSIT score from baseline; measures used were the UPSIT (validated, objective psychometric test of olfaction), Clinical Global Impressions Impression-Improvement (CGI-I; self-report improvement scale), and Olfactory Dysfunction Outcomes Rating (ODOR; olfaction-related quality-of-life questionnaire). Among the 275 enrolled participants, the mean (SD) age was 41 (12) years, and 236 (86%) were female. The change in UPSIT scores preintervention to postintervention was similar between the study arms. The marginal mean difference for change in UPSIT scores preintervention to postintervention between participants randomized to patient-preferred vs physician-assigned olfactory training was 0.73 (95% CI, -1.10 to 2.56), and between participants randomized to bimodal vs unimodal olfactory training was 1.10 (95% CI, -2.92 to 0.74). Five (24%) participants in the control arm had clinically important improvement on UPSIT compared with 18 (53%) in the bimodal, patient-preferred arm for a difference of 29% (95% CI, 4%-54%). Four (19%) participants in the control group self-reported improvement on CGI-I compared with 12 (35%) in the bimodal, patient-preferred arm for a difference of 16% (95% CI, -7% to 39%). The mean change in ODOR score preintervention to postintervention was 11.6 points (95% CI, 9.2-13.9), which was not deemed clinically important nor significantly different between arms. Based on the change in UPSIT scores, this randomized clinical trial did not show any difference between intervention arms, but when exploring within-patient change in UPSIT as well as self-reported impression of improvement, active interventions were associated with larger improvement than controls with a potential advantage of bimodal intervention. While not definitive, these results suggest that patients with COVID-19 olfactory loss may benefit from bimodal visual-olfactory training with patient-preferred scents. ClinicalTrials.gov Identifier: NCT04710394.

DUPILAMAB FOR POST-VIRAL SMELL LOSS IN ALLERGIC RHINITIS AND CHRONIC RHINOSINUSITIS WITHOUT NASAL POLYPOSIS

<h3>Introduction</h3> Evaluate effectiveness of dupilamab for post-viral smell loss with allergic rhinitis (AR), and chronic rhinosinusitis without nasal polyposis (CRSsNP). <h3>Case Description</h3> 76-year-old male presented with AR, rhinosinusitis, wheezing, treated with oral/inhaled steroids, nebulized albuterol, and antibiotics. Two weeks later he developed anosmia that did not respond to 2 weeks of prednisone or 6 months of intranasal theophylline. No history of nasal polyps, aspirin sensitivity, whiplash injury/head trauma, neurodegenerative disease. Exam remarkable for normal nares, no polyps, expiratory wheezing. Nasopharyngolaryngoscopy: septal deviation, edematous turbinates. LABS: University of Pennsylvania Smell Identification Test (UPSIT) score of 17 of 40, normal >34; negative CXR; sinus CT: chronic ethmoiditis; reactive allergy testing to pollens/dust mites/molds. PFT: reversible small airways obstruction, positive methacholine challenge. Thyroid functions/antibodies, IgE, CRP/ESR, CBC with differential, chemistries, serum/urine immunofixation/immunoelectrophoresis, ANA/ANCA, immunoglobulins, B6/B2, zinc were normal. Dual maintenance controller treatment failed to completely improve wheezing or PFT and he was started on dupilamab. After 8 months of dupilamab self-administered 300 mg bimonthly, improvement in smell and UPSIT score rose to 21. Wheezing and PFT improved. After 22 months of dupilamab, smell subjectively improved. UPSIT rose to 33 (Figure 1). <h3>Discussion</h3> First case report of post-viral smell loss with AR and CRSsNP with significant subjective and objective improvement in smell with dupilamab. Improvement noted objectively within 8 months of treatment and showed progressive improvement through 22 months of therapy. Based on this case report, further research using dupilamab in individuals with post-viral smell loss with AR and CRSsNP should be considered.

Olfactory and neurological outcomes of SARS-CoV-2 from acute infection to recovery

To investigate the impact of SARS-CoV-2 on sinonasal quality of life, olfaction, and cognition at different stages of viral infection and evaluate the association between olfaction and cognition in this population cohort. While olfactory dysfunction (OD) is a frequently reported symptom of COVID-19 (98% prevalence), neurocognitive symptoms are becoming more apparent as patients recover from infection. This study aims to address how different stages of infection [active infection (positive PCR test, symptomatic) vs. recovered (7 days post-symptoms)] compared to healthy control patients influence sinonasal quality of life, olfactory function, and cognition. Prospective, longitudinal, case-control. Participants completed the SNOT-22, University of Pennsylvania Smell Identification Test (UPSIT) and validated cognitive examinations to assess degree of smell loss and neurocognitive function at baseline and at 1 and 3 months for the active group and 3 months for the recovered group. Self-reported olfactory function and overall health metrics were also collected. The recovered group had the lowest average UPSIT score of 27.6 compared to 32.7 (active) and 32.6 (healthy control). 80% (n = 24) of the recovered patients and 56.3% (n = 9) of the active patients suffered from smell loss. In follow-up, the active group showed improvement in UPSIT scores while the recovered group scores worsened. In terms of neurocognitive performance, recovered patients had lower processing speed despite an improving UPSIT score. SARS-CoV-2 infection was found to impact olfactory function in a delayed fashion with significant impact despite recovery from active infection. Although olfactory function improved, decrements in cognitive processing speed were detected in our cohort.

Longitudinal evaluation of olfactory function in individuals with Gaucher disease and GBA1 mutation carriers with and without Parkinson's disease.

Biallelic mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase, cause the lysosomal storage disorder Gaucher disease (GD). In addition, mutations in GBA1 are the most common genetic risk factor for future development of Parkinson's disease (PD). However, most mutation carriers will never develop parkinsonism. Olfactory dysfunction is often a prodromal symptom in patients with PD, appearing many years prior to motor dysfunction. The purpose of this study was to assess olfactory function longitudinally in individuals with and without parkinsonism who carry at least one GBA1 mutation. One hundred seventeen individuals who participated in a natural history study of GD at the National Institutes of Health were evaluated using the University of Pennsylvania Smell Identification Test (UPSIT) during a 16-year period. Seventy patients with GD (13 with PD) and 47 GBA1 carriers (9 with PD) were included. Fifty-six of the total (47.9%) were seen over multiple visits, and had UPSIT screening performed two to six times, with time intervals between testing ranging from 2 to 6 years. Comparative and control data were obtained from the Parkinson's Progression Markers Initiative (PPMI) database (519 individuals, including 340 with idiopathic PD and 179 healthy controls). Statistical analysis was performed using R. Severe hyposmia and anosmia was evident in both GBA1 heterozygotes and homozygotes with PD. 84% without parkinsonism had UPSIT scores >30, and those who underwent repeated testing maintained olfactory function over time. No statistically significant difference in UPSIT scores was found between mutation carriers with and without a family history of parkinsonism. A small group of individuals without PD scored in the moderate-severe microsmia range. No significant differences in olfaction were found among our GBA1-PD cohort and idiopathic PD cohort obtained from PPMI.

Olfactory dysfunction is common in classical infratentorial superficial siderosis of the central nervous system

BackgroundEstablished features of classical infratentorial superficial siderosis (iSS) include hearing loss, impaired balance, myelopathy and, less commonly, cognitive compromise. Olfactory function may be affected but dedicated studies are lacking. This study aimed to assess the prevalence of olfactory dysfunction in iSS and correlate it with auditory and cognitive functions.MethodsTen participants with iSS completed the University of Pennsylvania Smell Identification Test (UPSIT). The scores were compared with population norms; regression analysis was performed to evaluate associations between the scores and hearing thresholds (3-frequency average, 3FA) or the number of cognitive domains impaired. Imaging was reviewed for haemosiderin distribution and to exclude other causes of olfactory and hearing dysfunction.ResultsEight of ten participants were male; the mean (standard deviation, SD) age was 52.5 (14.5) years. Olfactory hypofunction was identified in all participants and in six (60%) was moderate or completely absent. The mean UPSIT score of 25.5 (7.8) was significantly worse than population norms (difference in means − 10.0; 95% CI − 15.6 to − 4.4). Linear regression identified an association between UPSIT and hearing thresholds (R = 0.75; p = 0.013). The score decreases by 0.157 units (95% CI − 0.31 to − 0.002; p = 0.048) per unit increase in 3FA, after adjusting for hearing loss risk factors. There was no statistically significant association between UPSIT and cognitive function (R = 0.383; p = 0.397).ConclusionWe report a high prevalence of olfactory dysfunction in iSS, the severity of which correlated with hearing loss. Olfaction appears to be a core feature of the iSS clinical syndrome that should be assessed routinely.

Intensive Olfactory Training in Post-COVID-19 Patients: A Multicenter Randomized Clinical Trial.

BackgroundOlfactory dysfunction (OD)—including anosmia and hyposmia—is a common symptom of COVID-19. Previous studies have identified olfactory training (OT) as an important treatment for postinfectious OD; however, little is known about its benefits and optimizations after SARS-CoV-2 infection.ObjectiveThis study aimed to assess whether olfactory training performance can be optimized using more fragrances over a shorter period of time in patients with persistent OD after COVID-19. In addition, we determined the presence of other variables related to OD and treatment response in this population.MethodsThis multicenter randomized clinical trial recruited 80 patients with persistent OD and prior COVID-19 infection for less than 3 months. The patients were divided into 2 groups receiving either 4 or 8 essences over 4 weeks. Subjective assessments and the University of Pennsylvania Smell Identification Test (UPSIT) were performed before and after the treatment.ResultsSignificant olfactory improvement was measured subjectively and using the UPSIT in both groups; however, no significant differences between the groups were observed. Additionally, the presence of olfactory fluctuations was associated with higher UPSIT scores.ConclusionThese data suggest that training intensification by increasing the number of essences for 4 weeks does not show superiority over the classical method. Moreover, fluctuant olfaction seems to be related to a higher score on the UPSIT.