Predicting Post-Mortem α-Synuclein Pathology by the Combined Presence of Probable REM sleep behavior disorder and Hyposmia.

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (RBD) is a strong known predictor of a final clinicopathological diagnosis of a Lewy type α-synucleinopathy (LTS). Olfactory dysfunction is an early symptom of synucleinopathies and has been repeatedly associated with the presence of post-mortem LTS. OBJECTIVE: To assess the combined value of a clinician diagnosis of probable RBD (PRBD) and hyposmia in predicting the post-mortem presence of LTS in a broader, less-selected, volunteer elderly population. METHODS: We studied 652 autopsied subjects from the Arizona Study of Aging and Neurodegenerative Disorders, which were evaluated for PRBD, had completed annual movement and cognitive assessments, and had at least one the University of Pennsylvania Smell Identification Test (UPSIT) olfactory test. RESULTS: Histological evidence of LTS was significantly more frequent in those who had PRBD (112/152: 73.7%) than those without (177/494: 35.8%) (P < 0.001). LTS was more frequent in cases with PRBD and a low UPSIT score (90.8%) compared to cases with PRBD only (73.7%) (P < 0.001) or cases with a low UPSIT score only (69.4%) (P < 0.001). Sensitivity of PRBD diagnosis for predicting LTS was 38.8% and specificity 88.8%, whereas sensitivity of a low UPSIT score was 74.4% and specificity 73.4% (Youden's index = 0.276 for PRBD, 0.478 for UPSIT). When combining both measures, sensitivity was 34.3% and specificity increased to 97.2%. CONCLUSION: PRBD, diagnosed without sleep study confirmation, combined with a reduced olfactory performance is highly specific for predicting post-mortem presence of LTS. The combination of both measures may provide a cost-effective means of predicting LTS in a broader community.

Association between urinary mixture metal levels and olfactory function in coal miners.

Background: Exposure to occupational metallic mixtures has a potential impact on olfactory function. However, research evidence is limited on the potential impact of exposure to metallic mixtures and olfactory dysfunction. Furthermore, the coal dust generated contains multiple various metals during coal mining, and no study yet has focus on the olfactory dysfunction of coal miners. Objectives: In this study, we evaluate the association between urinary metallic mixtures and olfactory function in coal miners, while also exploring the potential applicability of plasma olfactory marker protein (OMP) as a biomarker for assessing olfaction. Methods: From July to October 2023, coal workers from seven different coal mining enterprises were recruited for the survey when they come for the employee health checkup. Ultimately, 376 participants were met the inclusion criteria and, respectively, determined with the concentrations of urine (16 metals) and plasma (OMP). Meanwhile, applying UPSIT to access their olfactory function. Binary logistic regression and restricted cubic spline (RCS) model were used to estimate the association of individual metals with olfactory function. Bayesian kernel machine regression (BKMR) and Quantile g-computation (QG-C) regression were employed to assess the overall association between metal mixtures and olfactory function and identify the major contributing elements. Results: In a single-metal model, two metals in urine were found to be significantly associated with olfactory function. RCS analysis further revealed that the association between Iron (Fe) and olfactory function was linear, while Lead (Pb) exhibited a non-linear. The BKMR model demonstrated a significant positive association between metal mixture concentration and olfactory function. Combined QG-C regression analysis suggested that metals Cr, Fe, Se, Sb, and Pb could impact the performance of the olfactory test (UPSIT), with Pb being identified as the most influential contributor. The correlation between plasma OMP protein levels and urinary metal concentrations was weak. Conclusion: Multiple metals are associated with olfactory function in the coal miners. A significant positive association was observed between metal mixture concentrations and olfactory function, with Pb being the most important contributor. In this study, plasma OMP has not been demonstrated to serve as a biomarker for olfactory function.

[Development and validation of Russian olfactory test]. / Otechestvennyi obonyatel'nyi test: razrabotka i validizatsiya.

Olfactory disorders is one of the first symptoms of diseases from various departments of medicine (otorhinolaryngology, psychology, neurology, etc.). Based on international clinical recommendations, olfactory tests are the gold standard for the diagnosis of olfactory disorders. There are many different psychophysical tests: UPSIT (USA, Pennsylvania), Sniffin' Sticks test (Germany), BAST-24 (Spain), etc. Currently, there is an acute shortage of olfactory tests available for clinical practice In Russia. This problem is related to the fact that there are no olfactory tests registered as medical devices on the territory of the Russian Federation. Also, a significant limitation is the unrecognizability of odors by the population of our country, which include foreign analogues (licorice, anise, turpentine, etc.). OBJECTIVE: To develop and validate the national olfactory test on healthy volunteers. MATERIAL AND METHODS: The development and validation of the olfactory test included several stages. First, the development of an olfactory test was carried out, the selection of aromas to assess the threshold and identification ability of olfaction. 25 dilutions of n-butanol were used for the assessment of the threshold olfactory ability. For the stage of assessing the identification ability of the sense of smell, in our previous study, an assessment of the recognition of odor names in the territory of the Russian Federation was carried out. A total of 3.000 people from 8 federal districts of the Russian Federation were interviewed. During the development of the test, 20 names of flavors with the highest rating were used. By the 8th, the selection of monocomponent substances was carried out. Commercially available certified food and perfume flavorings have been used for fragrances whose equivalent in the test cannot be a monocomponent substance. A group of 25 healthy volunteers selected a flavor or a monocomponent for each of the 20 positions. To carry out the identification stage of testing, a booklet was developed with answer options for each fragrance, including 80 images associated with the smell. A methodology for conducting diagnostics has been created. Next, the validation of the developed olfactory test was carried out on 150 healthy volunteers. The study included an assessment of the threshold and identification ability of the sense of smell using the developed test and conducting a comparative analysis with a set of flavors and descriptors corresponding to the Sniffin' Sticks test. RESULTS: The developed test includes: 2 panels - panel 1 to assess the threshold ability of smell, panel 2 to assess the identification ability of smell, a booklet with 80 images and captions to them. The norms of threshold and identification olfactory abilities were also determined in the developed test. The domestic test was validated against the relative foreign Sniffin' Sticks test. Spearman's correlation between the accuracy values of the domestic test (17-20; 85.00-100.00%) and the values of the foreign test (11-16; 68.75-100.00%) did not reveal statistically significant differences (rs=0.065, p=0.432), which confirms the equally effective assessment of olfactory ability by the domestic olfactory test in comparison with its foreign counterpart. CONCLUSION: In this work, a methodology for the use of Russian olfactory test was developed and validated on healthy volunteers. The features of the developed test are an assessment of the threshold and identification ability of smell, an adapted set of odors for the Russian population, the use of paper blotters when applying flavor and visual images of descriptors. Despite the wide variety of psychophysical tests, this problem requires further study and comparative analysis of olfactory tests available In Russia and foreign analogues in order to obtain a universal and effective diagnostic method for the populations of our country.This work was supported by the Russian Foundation for Basic Research (Project No. 24-25-00415).

Self-Reported Hypersensitivity to Smells: Objective Evidence for Hyposmia, not Hyperosmia.

OBJECTIVE: To compare, using state-of-the-art psychophysical tests, the olfactory function of patients complaining and not complaining of olfactory hypersensitivity. STUDY DESIGN: Retrospective cross-sectional. SETTING: The Smell and Taste Center at the University of Pennsylvania. METHODS: University of Pennsylvania Smell Identification Test (UPSIT) scores were obtained from 148 patients complaining of hyperosmia and 494 patients with no such complaints; detection threshold test scores were obtained from 77 and 483 patients of these respective groups. The effects of subject group, age, and sex on the test scores were assessed using analyses of variance. Categorical variables were evaluated by χ2. Responses to items within a detailed intake questionnaire, for example, the Beck Depression Inventory (BDI-II), were also evaluated. RESULTS: Unexpectedly, those complaining of hyperosmia had lower olfactory test scores than those with no such complaints (respective UPSIT means [95% confidence interval [CIs]] = 27.86 (26.85, 28.87) and 32.19 (31.67, 32.71); P < .001; respective threshold means (log vol/vol) = -4.49 (-4.89, -4.09) and -5.22 (-5.36, -5.06); P < .001). Remarkably, 70.95% of the self-identified hyperosmics exhibited mild to severe microsmia. The hyposmia complainers also exhibited elevated BDI scores (11.02 [9.53, 12.51] vs 7.58 [6.80, 8.34]). CONCLUSION: When objectively tested, many patients who complain of hypersensitivity to odors are actually less sensitive to them. The basis of this phenomenon is unclear. It could reflect the presence of emotionally disturbing altered smell sensations, or one or more comorbidities, such as hypochondria or osmophobia. These findings point to the importance of objective testing of persons with complaints of chemosensory dysfunction and reiterate the inaccuracy of self-reports.

The relationship between survey-based subjective olfactory awareness and objective olfactory function.

KEY POINTS: Correlation between symptom-based surveys and objective olfactory testing is variable. For diagnosis and symptom monitoring, surveys should correlate with objective testing. The Odor Awareness Scale (OAS) and Affective Importance of Odor Scale (AIO) showed significant but moderate positive correlations with University of Pennsylvania Scent Identification Test (UPSIT) score.

RNA sequencing of olfactory bulb in Parkinson's disease reveals gene alterations associated with olfactory dysfunction.

The olfactory bulb is involved early in the pathophysiology of Parkinson's disease (PD), which is consistent with the early onset of olfactory dysfunction. Identifying the molecular mechanisms through which PD affects the olfactory bulb could lead to a better understanding of the pathophysiology and etiology of olfactory dysfunction in PD. We specifically aimed to assess gene expression changes, affected pathways and co-expression network by whole transcriptomic profiling of the olfactory bulb in subjects with clinicopathologically defined PD. Bulk RNA sequencing was performed on frozen human olfactory bulbs of 20 PD and 20 controls without dementia or any other neurodegenerative disorder, from the Arizona Study of Aging and Neurodegenerative disorders and the Brain and Body Donation Program. Differential expression analysis (19 PD vs 19 controls) revealed 2164 significantly differentially expressed genes (1090 upregulated and 1074 downregulated) in PD. Pathways enriched in downregulated genes included oxidative phosphorylation, olfactory transduction, metabolic pathways, and neurotransmitters synapses while immune and inflammatory responses as well as cellular death related pathways were enriched within upregulated genes. An overrepresentation of microglial and astrocyte-related genes was observed amongst upregulated genes, and excitatory neuron-related genes were overrepresented amongst downregulated genes. Co-expression network analysis revealed significant modules highly correlated with PD and olfactory dysfunction that were found to be involved in the MAPK signaling pathway, cytokine-cytokine receptor interaction, cholinergic synapse, and metabolic pathways. LAIR1 (leukocyte associated immunoglobulin like receptor 1) and PPARA (peroxisome proliferator activated receptor alpha) were identified as hub genes with a high discriminative power between PD and controls reinforcing an important role of neuroinflammation in the olfactory bulb of PD subjects. Olfactory identification test score positively correlated with expression of genes coding for G-coupled protein, glutamatergic, GABAergic, and cholinergic receptor proteins and negatively correlated with genes for proteins expressed in glial olfactory ensheathing cells. In conclusion, this study reveals gene alterations associated with neuroinflammation, neurotransmitter dysfunction, and disruptions of factors involved in the initiation of olfactory transduction signaling that may be involved in PD-related olfactory dysfunction.

The greatest loss of unpleasant smells may be related to the risk of more severe PD symptoms.

Background: Limited research has explored the relationship between the valence of olfactory dysfunction and PD clinical symptoms. This study aimed to investigate correlations between the emotional valence of olfactory impairment and different domains of PD symptoms. Methods: PD patients who fulfilled the clinically probable PD diagnostic criteria of the International Parkinson and Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease were recruited from the Center for Parkinson and Movement Disorders at Taichung Veterans General Hospital between October 2016 and April 2022. Demographic data and serial clinical assessments were collected, including the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC) and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Thirty-five odors from the UPSIT-TC were classified into neutral, pleasant or unpleasant groups. Group comparisons, correlation analyses, and linear regression analyses were conducted to examine the relationship between olfactory impairment of UPSIT-TC odors, considering emotional valence, and MDS-UPDRS subscores across various domains. Results: A total of 176 PD patients were recruited for analysis. Patients in the predominantly neutral/unpleasant odor impairment groups had higher MDS-UPDRS part III scores compared to those in the predominantly pleasant odor impairment group (pleasant vs. neutral vs. unpleasant odor impairment groups: 26.79 ± 13.59 vs. 35.33 ± 16.36 vs. 31.57 ± 12.37, p = 0.009). This trend was also noted in MDS-UPDRS rigidity, bradykinesia, and akinetic-rigid subscores (p = 0.003, p = 0.012, and p = 0.001, respectively). Correlation analysis revealed a weak but significant correlation between rigidity/akinetic-rigid subscores and misidentification numbers for neutral/unpleasant odors (all p < 0.05), with age, gender, LEDD, and disease duration as covariates. All significances were retained in the linear regression analysis. Conclusion: Our results emphasize the link between olfactory impairment of specific emotional valence, neutral/unpleasant odors, and PD severity, particularly with respect to akinetic-rigid symptoms. A concise olfactory test that focuses on both neutral and unpleasant odors may offer deeper insights into PD symptoms.

Development of parallel forms of a brief smell identification test useful for longitudinal testing.

Although there are numerous brief odor identification tests available for quantifying the ability to smell, none are available in multiple parallel forms that can be longitudinally administered without potential confounding from knowledge of prior test items. Moreover, empirical algorithms for establishing optimal test lengths have not been generally applied. In this study, we employed and compared eight machine learning algorithms to develop a set of four brief parallel smell tests employing items from the University of Pennsylvania Smell Identification Test that optimally differentiated 100 COVID-19 patients from 132 healthy controls. Among the algorithms, linear discriminant analysis (LDA) achieved the best overall performance. The minimum number of odorant test items needed to differentiate smell loss accurately was identified as eight. We validated the sensitivity of the four developed tests, whose means and variances did not differ from one another (Bradley-Blackwood test), by sequential testing an independent group of 32 subjects that included persons with smell dysfunction not due to COVID-19. These eight-item tests clearly differentiated the olfactory compromised subjects from normosmics, with areas under the ROC curve ranging from 0.79 to 0.83. Each test was correlated with the overall UPSIT scores from which they were derived. These brief smell tests can be used separately or sequentially over multiple days in a variety of contexts where longitudinal olfactory testing is needed.

A characteristic of olfactory function in four types of dementia and non-dementia subjects using smell identification test.

BACKGROUND: For those outpatients who were consulted for memory loss, the Japanese version of University of Pennsylvania Smell Identification Test (UPSIT-J) was performed to examine olfactory function. In the same way, the revised version of Hasegawa Dementia Scale, Mini Mental State Examination, Clinical Dementia Rating and brain magnetic resonance imaging were used to investigate the cognitive function. In the present study, we evaluated the olfactory function of elderly subjects, including those with dementia, by means of UPSIT-J and we examined their characteristics. METHODS: The characteristics of dementia as Alzheimer type group (AD.G), mixed type group (MixD.G), vascular type group (VaD.G), dementia with Lewy bodies group (DLB.G) and the groups which had no dementia as low score group (LS.G), high score group (HS.G), and healthy group (H.G), were examined. RESULTS: The numbers of olfactory discriminating scores (nODS) were significantly lower in all the dementia groups than in all the LS.G, HS.G and the H.G. No significant difference was observed in nODS between AD.G and DLB.G. The rate of nODS with less than five scores were as follows: AD.G (80.1%), MixD.G (91.5%), VaD.G (63.1%), DLB.G (89.6%), LS.G (50.8%), HS.G (18.6%), H.G (15.6%). A significant positive correlation was found between nODS and Hasegawa Dementia Scale and Mini Mental State Examination scores (r = 0.567, r = 0.532, respectively), which was significant negatively correlated for Clinical Dementia Rating (r = -0.578). A significant negative correlation was observed between nODS and Z score of voxel-based specific regional analysis for Z score of Alzheimer's disease (VSRAD) (r = 0.463). CONCLUSION: nODS showed a significant correlation between cognitive function tests and brain atrophy level. These results indicate that UPSIT-J is considered a psycho-physiological index useful for the diagnosis and early detection of dementia.

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

BACKGROUND: 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. OBJECTIVE: To validate the MCID for UPSIT in patients with postviral, sinusitis, and procedure-associated olfactory loss. METHODS: 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. RESULTS: 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. CONCLUSION: Investigators in the future should use 4 as MCID for UPSIT and report the percentage of study subjects who achieve a clinically meaningful difference. LEVEL OF EVIDENCE: III.

Local cytokine levels associate with SNOT-22 and UPSIT scores in chronic rhinosinusitis.

KEY POINTS: Elevated IL-5, IL-13, IL-33, and CCL2 correlate with lower UPSIT scores in CRS and AERD patients. Elevated IL-5, IL-13, TNF-α, CCL2, and CXCL-8 correlate with higher SNOT-22 scores in CRS and AERD patients.

UPSIT subitems may predict motor progression in Parkinson's disease.

Background: The relationship between hyposmia and motor progression is controversial in Parkinson's disease (PD). The aim of this study was to investigate whether preserved identification of Chinese-validated University of Pennsylvania Smell Identification Test (UPSIT) odors could predict PD motor progression. Methods: PD patients with two consecutive clinical visits while taking medication were recruited. Based on mean changes in Movement Disorder Society Unified Parkinson's Disease Rating Scale part 3 score and levodopa equivalent daily dosage, the participants were categorized into rapid progression, medium progression, and slow progression groups. Odors associated with the risk of PD motor progression were identified by calculating the odds ratios of UPSIT item identification between the rapid and slow progression groups. Receiver operating characteristic curve analysis of these odors was conducted to determine an optimal threshold for rapid motor progression. Results: A total of 117 PD patients were screened for group classification. Preserved identification of neutral/pleasant odors including banana, peach, magnolia, and baby powder was significantly correlated with rapid motor progression. The risk of rapid progression increased with more detected risk odors. Detection of ≥1.5 risk odors could differentiate rapid progression from slow progression with a sensitivity of 85.7%, specificity of 45.8%, and area under the receiver operating characteristic curve of 0.687. Conclusion: Preserved identification of neutral/pleasant odors may help to predict PD motor progression, and detection of ≥1.5 UPSIT motor progression risk odors could improve the predictive power. In PD patients with a similar level of motor disability during initial screening, preserved pleasant/neutral odor identification may imply relatively better cortical odor discriminative function, which may suggest the body-first (caudo-rostral) subtype with faster disease progression.

Sequential change in olfaction and (non) motor symptoms: the difference between anosmia and non-anosmia in Parkinson's disease.

Introduction: Hyposmia is a common prodrome in patients with Parkinson's disease (PD). This study investigates whether olfactory changes in PD differ according to the degree of olfactory dysfunction and whether there are changes in motor and non-motor symptoms. Methods: The 129 subjects with PD were divided into two groups: anosmia and non-anosmia. All cases were reassessed within 1-3 years after the initial assessment. The assessment included the MDS-Unified PD Rating Scale (MDS-UPDRS), the University of Pennsylvania Smell Identification Test (UPSIT), Beck's Depression Inventory-II (BDI-II), Montreal Cognitive Assessment (MoCA), and equivalence dose of daily levodopa (LEDD). The generalized estimating equation (GEE) model with an exchangeable correlation structure was used to analyze the change in baseline and follow-up tracking and the disparity in change between these two groups. Results: The anosmia group was older and had a longer disease duration than the non-anosmia group. There was a significant decrease in UPSIT after follow-up in the non-anosmia group (ß = -3.62, p < 0.001) and a significant difference in the change between the two groups (group-by-time effect, ß = 4.03, p < 0.001). In the third part of the UPDRS motor scores, there was a tendency to increase the score in the non-anosmia group compared to the anosmia group (group-by-time effect, ß = -4.2, p < 0.038). There was no significant difference in the group-by-time effect for UPDRS total score, LEDD, BDI-II, and MoCA scores. Discussion: In conclusion, this study found that olfactory sensation may still regress in PD with a shorter disease course without anosmia, but it remains stable in the anosmia group. Such a decline in olfaction may not be related to cognitive status but may be associated with motor progression.

The 8-item NHANES pocket smell test®: Normative data.

This study provides normative data useful for interpreting scores from the Pocket Smell Test® (PST®), a brief "scratch & sniff" neuropsychological olfactory screening test comprised of 8 items from the 40-item University of Pennsylvania Smell Identification Test (UPSIT®). We combined 3,485 PST® scores from the 2013 to 2014 National Health and Nutrition Survey (NHANES) of persons 40 years of age and older with equivalent PST® items extracted from an UPSIT® database of 3,900 persons ranging in age from 5 to 99 years. Decade-related age- and gender-adjusted percentile normative data were established across the entire age spectrum. Cut-points for defining clinically useful categories of anosmia, probable microsmia, and normosmia were determined using receiver operating characteristic (ROC) curve analyses. An age-related decline in test scores was evident for both sexes after the age of 40 years, with women outperforming men. Based on the ROC analyses, subjects scoring 3 or less (AUC = 0.81) defines anosmia. Regardless of sex, a score of 7 or 8 on the N-PST® signifies normal function (AUC of 0.71). Probable microsmia is classified as scores extending from 3 to 6. These data provide an accurate means for interpreting PST® scores within a number of clinical and applied settings.

Specific olfactory deficit patterns observed in seniors and associated with cognitive decline.

Olfactory dysfunction is a common symptom in neurodegenerative disorders and is regarded as a potential early predictor of impending cognitive decline. This study was undertaken in order to determine if olfactory dysfunction observed in the elderly is due to a general loss of smell or the inability to detect specific odours, and if misidentification of odours correlates with cognitive scores. Seniors for the Olfactory Response and Cognition in Aging (ORCA) sub-study were recruited from the Quebec Nutrition and Successful Aging (NuAge) cohort. The University of Pennsylvania smell identification test (UPSIT) was performed to measure olfactory function and the telephone Mini Mental State Examination (t-MMSE) and the French version of the Telephone Interview for Cognitive Status Modified (F-TICS-m) for cognitive status. The results demonstrate that seniors exhibit specific olfactory loss and had severe difficulty in particular in identifying lemon, pizza, fruit punch, cheddar cheese and lime. Furthermore, there was a significant difference in the ability to detect certain odours between the sexes. Results also showed that misidentification of certain scents was associated with cognitive scores, and when the sexes were assessed separately sex-specific misidentification of cognitive-associated odours was observed. The relationship between the cognitive scores and scent misidentification suggests that impending cognitive decline may be highlighted by the inability to smell specific odours. Our study provides additional support for the testing of olfactory function in the elderly and suggests that loss of smell for particular scents may become a useful diagnostic tool.

Comparison between olfactory training and curcumin therapy in improving olfactory dysfunction in patients with chronic kidney disease.

Objective: Olfactory dysfunction can be seen in chronic kidney disease (CKD) patients. We aimed to investigate the effects of olfactory training and curcumin on olfactory dysfunction in CKD patients and compare their impact with a placebo. Methods: We conducted a double-blind, randomized, placebo-controlled trial in CKD patients, 2021-2022. We enrolled 60 participants in our study into three groups (curcumin, training, and control). Participants were randomized into trials and control groups and assessed using the Iran-smell identification test (Iran-SIT), a questionnaire of olfactory disorders (QOD), and a self-assessment tool. P-value < 0.05 was considered statistically significant. Results: We gathered 58 participants (mean age of 56.1 ± 2.5, 56.9% men). All the tests showed that curcumin improved olfactory function after the trial, though it was significant in QOD (17.5 ± 11.8 vs. 13.1 ± 9.7, p = 0.045) and self-assessment results (8.5 ± 3.1 vs. 9.5 ± 4.0, p = 0.047). Moreover, compared to baseline, training patients experienced an increase in their olfactory function in Iran-SIT (15.3 ± 4.9 vs. 18.8 ± 2.7, p = 0.001), QOD (19.0 ± 10.4 vs. 12.2 ± 9.9, p = 0.003), and self-assessment tools (6.8 ± 1.8 vs. 8.2 ± 3.1, p = 0.027). In contrast, the olfactory function was unchanged in control in all the tests (p > 0.05). Also, the improved change of Iran-SIT and QOD scores during the trial was more significant in training compared to the curcumin group (p < 0.002). Conclusion: The findings of this study indicate that olfactory training, even more than curcumin, can improve olfactory function in CKD patients. This information may help manage olfactory dysfunction in the CKD population.

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.

Olfactory Training Impacts Olfactory Dysfunction Induced by COVID-19: A Pilot Study.

INTRODUCTION: Olfactory dysfunction is one of the main symptoms of COVID-19 and may last beyond resolution of the infection. The most promising intervention for post-viral olfactory dysfunction is olfactory training (OT), which involves exposing the olfactory system to a range of odors daily. This approach is thought of promoting the regeneration of olfactory receptor cells, but its effectiveness in patients with post-COVID-19 olfactory dysfunction has yet to be confirmed. METHODS: This double-blind randomized pilot study compared the effectiveness of OT versus placebo in the treatment of post-COVID-19 olfactory dysfunction. Twenty-five participants were recruited in each group. OT protocol consisted of sniffing 4 scents (rose, orange, clove, and eucalyptus) for 5 min twice daily for 12 weeks. Olfactory function was assessed before and after the training using (1) a validated odor identification test (UPSIT-40) and (2) a 10-point visual analog scale; we further assessed the presence of (3) parosmia. RESULTS: While we did not observe any effect of OT on olfactory test scores, we observed a significant improvement of subjective olfactory function in the intervention group, while no such effect was observed in the placebo group. Finally, the frequency of parosmia was significantly lower in the intervention group. CONCLUSIONS: This study highlights an increase in subjective but not objective olfactory function when performing OT for 12 weeks. Further, parosmia seems to be positively affected by OT. These results may serve as a starting point for larger scale studies to assess the efficacy of OT for treatment of post-COVID-19 olfactory dysfunction.

Correlation and agreement of olfactory perception assessed by the Connecticut Chemosensory Clinical Research Center olfactory test and the Brief-Smell Identification Test / Correlação e concordância da percepção olfativa avaliada pelos testes olfativos chemosensory clinical research center e brief-smell identification test,

Abstract Introduction: Assessing olfactory perception in olfactory disorders is of utmost importance in therapy management. However, the University of Pennsylvania Smell Identification Test and the Sniffin' Sticks are the only tests validated in Brazil. Objectives: To evaluate the correlation and agreement between the Chemosensory Clinical Research Center olfactory test and the Brief-Smell Identification Test - University of Pennsylvania Smell Identification Test - in healthy participants and in participants with olfactory disorders based on the results and technical aspects of both tests. Methods: Fifty participants without olfactory complaints and 50 participants with olfactory disorders who underwent the Chemosensory Clinical Research Center olfactory test and the Brief-Smell Identification Test were included. The following tests were used for statistical analysis: Mann-Whitney U test, Spearman's correlation, intraclass correlation coefficient and Bland-Altman plot. An alpha error (significance level) of 0.05 was considered in the statistical analysis. Results: Both tests were effective in distinguishing the groups without the presence of overlapping values for the measured markers. Additionally, there was a strong correlation between Spearman's correlation and intraclass correlation coefficient between the tests and for both nostrils. However, the correlations were lower when the groups were individually evaluated. The Bland-Altman plot showed no bias when all participants were simultaneously evaluated. Conclusions: The tests to assess olfactory perception presented a high level of agreement. In our sample, we could infer that the Connecticut Chemosensory Clinical Research Center olfactory test is similar to the Brief-Smell Identification Test and can be used in the routine diagnosis of patients with complaints of olfactory disorders, considering the advantage of its low cost.

Resumo Introdução: Avaliar a percepção olfativa em distúrbios olfativos é de extrema importância para a correta conduta terapêutica. No entanto, apenas o teste University of Pennsylvania smell identification test e o teste sniffin'sticks são validados no Brasil. Objetivos: Avaliar a correlação e concordância entre os testes Connecticut chemosensory clinical research center e do brief-smell identification test e University of Pennsylvania smell identification test em participantes saudáveis e em participantes com distúrbios olfativos de acordo com os resultados e aspectos técnicos dos dois testes. Método: Cinquenta participantes sem queixas olfativas e 50 participantes com distúrbios olfativos submetidos ao teste Connecticut chemosensory clinical research center e ao brief-smell identification test foram incluídos. Os seguintes testes foram usados para análise estatística: teste U de Mann-Whitney, correlação de Spearman, coeficiente de correlação intraclasse e plotagem de Bland-Altman. Um erro alfa (nível de significância) de 0,05 foi considerado nas análises estatísticas feitas no estudo. Resultados: Ambos os testes foram eficazes para diferenciar os grupos sem a presença de valores sobrepostos para os marcadores medidos. Além disso, houve uma forte correlação entre a correlação de Spearman e o coeficiente de correlação intraclasse entre os testes e para as duas narinas. Entretanto, as correlações foram menores quando os grupos foram avaliados individualmente. O gráfico de Bland-Altman não mostrou viés quando todos os participantes foram avaliados simultaneamente. Conclusões: Os testes para avaliar a percepção olfativa apresentaram um elevado nível de concordância. Em nossa amostra, podemos inferir que o Connecticut chemosensory clinical research center é equivalente ao brief-smell identification test e pode ser usado no diagnóstico de rotina de pacientes com queixas de distúrbios olfativos, considerando a vantagem de seu baixo custo.

Serial olfactory testing for the diagnosis of prodromal Parkinson's disease in the PARS study.

BACKGROUND: The Parkinson Associated Risk Syndrome (PARS) study was designed to evaluate whether screening with olfactory testing and dopamine transporter (DAT) imaging could identify participants at risk for developing Parkinson's disease (PD). OBJECTIVE: Hyposmia on a single test has been associated with increased risk of PD, but, taken alone, lacks specificity. We evaluated whether repeating olfactory testing improves the diagnostic characteristics of this screening approach. METHODS: Participants completed up to 10 years of clinical and imaging evaluations in the PARS cohort. Olfaction was assessed with the University of Pennsylvania Smell Identification Test at baseline and on average 1.4 years later. Multiple logistic regression and Cox proportional hazards regression were used to estimate the hazard of development of clinical PD or abnormal DAT imaging. RESULTS: Of 186 participants who were initially hyposmic, 28% reverted to normosmia on repeat testing (reverters). No initially normosmic subjects and only 2% of reverters developed DAT imaging progression or clinical PD, compared to 29% of subjects with persistent hyposmia who developed abnormal DAT and 20% who developed clinical PD. The relative risk of clinical conversion to PD was 8.3 (95% CI:0.92-75.2, p = 0.06) and of abnormal DAT scan was 12.5 (2.4-156.2, p = 0.005) for persistent hyposmia, compared to reversion. CONCLUSIONS: Persistent hyposmia on serial olfactory testing significantly increases the risk of developing clinical PD and abnormal DAT imaging, compared to hyposmia on a single test. Repeat olfactory testing may be an efficient and cost-effective strategy to improve identification of at-risk patients for early diagnosis and disease modification studies.