Odor dilution sorting as a clinical test of olfactory function: normative values and reliability data.

Clinical assessment of an individual's sense of smell has gained prominence, but its resource-intensive nature necessitates the exploration of self-administered methods. In this study, a cohort of 68 patients with olfactory loss and 55 controls were assessed using a recently introduced olfactory test. This test involves sorting 2 odorants (eugenol and phenylethyl alcohol) in 5 dilutions according to odor intensity, with an average application time of 3.5 min. The sorting task score, calculated as the mean of Kendall's Tau between the assigned and true dilution orders and normalized to [0,1], identified a cutoff for anosmia at a score ≤ 0.7. This cutoff, which marks the 90th percentile of scores obtained with randomly ordered dilutions, had a balanced accuracy of 89% (78% to 97%) for detecting anosmia, comparable to traditional odor threshold assessments. Retest evaluations suggested a score difference of ±0.15 as a cutoff for clinically significant changes in olfactory function. In conclusion, the olfactory sorting test represents a simple, self-administered approach to the detection of anosmia or preserved olfactory function. With balanced accuracy similar to existing brief olfactory tests, this method offers a practical and user-friendly alternative for screening anosmia, addressing the need for resource-efficient assessments in clinical settings.

Palmitoylethanolamide and Luteolin for Postinfectious Olfactory Disorders: How Clinically Meaningful Is Its Effect?

INTRODUCTION: The prevalence of post-viral olfactory dysfunction has increased significantly during the COVID-19 pandemic, posing a major challenge for patients and practitioners. While olfactory training (OT) is a common approach to therapy, there has been increasing interest in supplementing therapy with a combination of palmitoylethanolamide (PEA) and luteolin (LUT), which are known for their anti-inflammatory properties. In this study, their efficacy in the treatment of patients with olfactory loss following upper respiratory tract infections, mainly COVID-19, was investigated in an outpatient clinic. METHODS: Fifty patients with persistent olfactory dysfunction were randomized to two groups: one receiving OT and PEA-LUT, the other OT alone. Olfactory function was evaluated before and after treatment. RESULTS: The study group showed significant improvements in odor discrimination and overall olfactory function (TDI score) after treatment with PEA-LUT and OT, while the control group did not. However, when clinically meaningful improvements were considered, there was no significant difference between the groups. CONCLUSION: The present study suggests that while PEA-LUT may have the potential to improve olfactory function in post-viral dysfunction, the additional benefit over OT alone may be limited. These results contrast with some previous studies.

Assessment of postviral qualitative olfactory dysfunction using the short SSParoT in patients with and without parosmia.

PURPOSE: To examine if the short formed Sniffin Sticks Parosmia Test (SSParoT), a test for parosmia can distinguish cases with parosmia from cases without parosmia. METHODS: In this study, 63 patients with postviral olfactory dysfunction were investigated including both COVID and non-COVID cases. The age, symptom duration, degree of parosmia/phantosmia was collected. For olfactory function, the Sniffin Sticks olfactory score was obtained including scores for odor threshold, discrimination and identification. For assessment of parosmic changes, the short SSParoT was adopted and both hedonic range (HedRang) and direction (HedDir) was calculated. RESULTS: The mean HedRang of patients with parosmia (2.35, standard deviation, SD = 1.40) and without parosmia (2.78, SD = 1.09) was smaller than that in controls (4.5, SD = 2.15). However, the mean HedDir of both parosmia (- 0.32, SD = 0.98) and non-parosmia patients (0.04, SD = 1.07) was similar to controls (- 0.1, SD = 1.55). When considering that the 10th percentile of the distribution of SSParoT score should distinguish between patients with and without parosmia, the sensitivity of the HedRang was 29% and specificity was 67%. For HedDir, the sensitivity was 6% and specificity was 100%. Only the odor identification score (r = 0.34, p = 0.01) discriminated parosmia and non-parosmia while other measures including HedRang and HedDir did not. CONCLUSION: The present study showed that the short SSParoT score could not distinguish patients with parosmia from patients without parosmia. Although the SSParoT represents an innovative approach to assess parosmia, and could be useful in the tracking of parosmic changes, the development of measures to diagnose parosmia in an objective way remains a challenge.

Acupuncture is associated with a positive effect on odour discrimination in patients with postinfectious smell loss-a controlled prospective study.

INTRODUCTION: Smell disorders are common in the general population and occur e.g., after infections, trauma or idiopathically Treatment strategies for smell loss range from surgery, medication to olfactory training, depending on the pathology, but they are limited This study examined the effect of acupuncture on olfactory function. METHODS: Sixty patients with smell loss following infections of the upper respiratory tract were included in this investigation Half of the study group were randomly assigned to verum acupuncture and the other half to sham acupuncture Olfaction was measured by means of the "Sniffin' Sticks" test battery (odour threshold, discrimination and identification). RESULTS: Compared to sham acupuncture, verum was associated with an improvement of smell function as measured by the TDI score (p = 0.039) The improvement was largely determined by improvement in odour discrimination, and was significantly better in patients with a shorter duration of the disorder. CONCLUSION: The present results suggest that acupuncture is an effective supplementary treatment option for patients with olfactory loss.

Functional improvement in children and adolescents with primary headache after an interdisciplinary multimodal therapy program: the DreKiP study.

BACKGROUND: More than 2/3 of children and adolescents in Germany regularly suffer from headaches. Headache-related limitations in everyday life, school drop-out and educational impairment are common. Structured therapy programs for young headache patients are widely missing. METHODS: One hundred eleven patients with frequent migraine and/or tension type headache were treated in a 15 hour group program in afternoons, parallel with school, parents received 7 hours of therapy. At the beginning of the program (T0), 6 (T1) and 12 months (T2) after completion, data on headache related disability (PedMidas), headache frequency, intensity, and pediatric pain disability score (PPDI) were prospectively collected to investigate the effects of the therapy. RESULTS: Seventy-five patients (9-19 years, median = 14; 66.7% female) and their parents provided patient reported outcome measures showing at T1 (65 patients) and T2 (47 patients) reduced headache frequency (last 3 months headache days median T0: 30 days; T1: 18 days, reduction of median 12 days since T0; T2: 13 days, reduction of median 17 days since T0). Linear mixed models revealed significant reduction (T0/T1 p = 0,002; T0/T2 p = 0,001). Reduced headache disability has been reported at T1 and T2 (PedMidas median T0 = 30, T1 = 15, T2 = 7; p < 0,001, p < 0,001 respectively). Follow up data of a subgroup of patients 24 months after the treatment point to sustainable effects. CONCLUSIONS: The interdisciplinary multimodal headache therapy program DreKiP reduces headache frequency and headache related disability significantly 6-12 months following its completion. TRIAL REGISTRATION: DRKS00027523, retrospectively registered.

Olfactory impairment as an early marker of Parkinson's disease in REM sleep behaviour disorder: a systematic review and meta-analysis.

Olfactory impairment and rapid eye movement sleep behaviour disorder (RBD) are prodromal symptoms of Parkinson's disease (PD) that may be associated with each other. This review aims to investigate the significance of olfaction in the diagnosis and prognosis of patients with RBD and to assess moderating factors affecting olfactory performance. We searched articles on olfaction in RBD and PD in five electronic databases. We identified 32 studies for the systematic review and used 28 of those, including 2858 participants for meta-analysis. Results revealed significant deficits in odour identification (g=-1.80; 95% CI: -2.17 to -1.43), threshold (g=-1.29; 95% CI: -1.67 to -0.91), discrimination (g=-1.08; 95% CI: -1.28 to -0.87) and overall olfactory function (g=-1.64; 95% CI: -1.94 to -1.35) in patients with RBD. Except for the Unified Parkinson's Disease Rating Scale Part III scores, none of the known moderating variables (including age, sex, disease duration and years of education) accounted for the olfactory function heterogeneity in patients with RBD. We identified similar olfactory impairments in patients with RBD and patients with PD (either with or without underlying RBD). These findings suggest that olfactory impairment may be a sensitive and stable diagnostic biomarker of RBD and appears to be useful for identifying patients with idiopathic RBD at high risk for early conversion to PD.

Brain response to odors presented inside the nose, directly in front of the nose or with ambient air.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) allows the measurement of changes in blood flow in association with changes in brain activity. This technique has been used frequently to study brain activation in response to odorous stimuli. The aim of this study was to evaluate the effects of odor delivery conditions on brain responses obtained with fMRI. STUDY DESIGN: Prospective cohort study SETTING: Academic institution. METHODS: Twenty healthy volunteers (mean age = 29.5 years; 9 women, 11 men) participated. Three odor delivery methods were used: "tube" (odor presented intranasally with separate tubing for each nostril), "mask" (odor presented in a face mask covering the subject's nose) and "vacuum" (odor presented into the ambient air). Presentation of the pleasant "peach" odor was performed using a computer-controlled olfactometer. Subjects were asked to evaluate the intensity of the odors after each fMRI run. RESULTS: "Tube" showed higher self-rated odor intensity compared to "mask" and "vacuum" (F = 18.4, p < 0.001). Odor intensity had a positive correlation (r = 0.6, p < 0.05) with percent signal change extracted from the secondary olfactory cortex region in the mask condition. In the tube condition, several selected regions of interest (Amygdala, Insula, Thalamus) showed lower activations compared to the other two conditions (puncorrected < 0.001, mask > tube, vacuum > tube). CONCLUSION: Activations of region of interests (ROIs) in response to the odorous stimuli showed differences under the three conditions (mask, tube, vacuum). In this passive fMRI paradigm, this may partly reflect the differences in odor intensity, but also in attention and contextual variables related to odor perception.

Apparently Minor Head Trauma Can Lead to Anosmia: A Case Report.

We report the case of a 49-year-old female patient who suffered from anosmia following an apparently mild head trauma when bumping into a door at her home. She reported no other accompanying symptoms after the injury that day. Olfactory function was completely lost, which was noted the day after the trauma. Gustatory function remained normal. Magnetic resonance imaging indicated lesions/bleeding in the right frontal lobe and in the area of the olfactory sulcus/bulb. The present case indicates that in case of apparently mild head trauma with anosmia, an MRI scan of the head should be performed because of suspect brain damage. This case also points to the deeper question how to gauge severity of head trauma.

Chemosensory function is decreased in rheumatoid arthritis.

PURPOSE: Research indicates that rheumatic disorders are accompanied by decreased chemosensory function. The present study aimed to specifically evaluate this issue in patients with rheumatoid arthritis (RA). METHODS: 212 RA patients (43 men, 169 women, mean age 59 ± 13.3 years), and 30 healthy controls (10 men, 20 women, mean age 40 ± 15.3 years), were included in this study. Chemosensory measurements consisted of olfactory testing using the "Sniffin' Sticks" test battery (with odor thresholds, odor discrimination and odor identification; OT, OD, OI) and gustatory testing on a suprathreshold and a quasi-threshold level using "taste sprays" and "taste strips", respectively. In addition, inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) and RA autoantibodies (anti-cyclic citrullinated peptides, RA factors) were evaluated. RESULTS: Olfactory measurements showed 4% of the RA patients functionally anosmic and 40% hyposmic. RA patients scored significantly lower in suprathreshold olfactory tests (OD, OI) compared to controls (OI: 12.5 ± 2.5 vs. 14.1 ± 1.3; OD: 11.3 ± 2.7 vs. 12.9 ± 1.7). In addition, RA patient had decreased taste function compared to healthy individuals (10.4 ± 2.6 vs. 11.7 ± 1.7). Chemosensory function did not correlate with parameters related to the severity of disease. CONCLUSION: Chemosensory function (taste, OD and OI) appears to be decreased in RA patients. In contrast, OT was not affected. Changes in chemosensory function seem to be independent of disease parameters such as duration of disease or disease activity.

Quality of Life in Patients With Olfactory Loss Is Better Predicted by Flavor Identification Than by Orthonasal Olfactory Function.

To date, most studies on the relationship between chemosensory performance and quality of life have focused on orthonasal measures of olfactory function. In the current investigation, we examined the predictive value of orthonasal and flavor identification indices of olfactory function on a wide spectrum of health and sociopsychological factors, including quality of life, life satisfaction, overall health, and depressive symptoms. Participants were 178 ENT patients (Mage = 58 ± 1), representing various causes of olfactory loss: idiopathic smell loss (n = 51; Mage = 63 ± 2), sinunasal disease (n = 27; Mage = 56 ± 3), head trauma (n = 33; Mage = 51 ± 2), and infections of the upper respiratory tract (n = 67; Mage = 59 ± 2). They completed self-report questionnaires and underwent olfactory testing using Sniffin' Sticks (orthonasal olfactory testing) and "Taste Powder" (intraorally applied flavors for retronasal olfactory testing, additionally inducing taste sensation). Data were analyzed with hierarchical regression models wherein the first step included subjects' sex, age, and orthonasal olfaction score. In the second step, we included the "Taste Powder" score. Tested models revealed that the first step was not significantly predicting variables of interest; however, there was an improvement of the model's predictive value when the "Taste Powder" score was added. Results of this study suggest that flavor identification significantly improves predictions of health and sociopsychological functioning of ENT patients with various etiologies.

Nocturnal Olfactory Stimulation for Improvement of Sleep Quality in Patients With Posttraumatic Stress Disorder: A Randomized Exploratory Intervention Trial.

Posttraumatic stress disorder (PTSD) is characterized by sleep impairment and nightmares. As pleasant odors presented during sleep affect the emotional tone of dreams without inducing arousal, we investigated whether sleep patterns in PTSD can be improved via nocturnal olfactory stimulation. Participants were 40 inpatients with PTSD (n = 35 women; age range: 20-59 years) who completed a randomized, patient-blind, placebo-controlled trial. Baseline measurement for 5 consecutive nights was followed by a 5-night experimental intervention or placebo trial. During the intervention, patients received nocturnal stimulation with a pleasant odor (odor condition) or clean air (placebo condition) via an olfactometer that delivered inspiration-triggered stimuli in a nasal tube or via an odorized nasal clip. After each night, the patients completed standardized questionnaires that assessed sleep parameters and dream content. Each night, sleep efficiency, sleep onset latency, and wakefulness after sleep onset were monitored with a motion biosensor. Baseline assessment revealed that PTSD severity was associated with poorer sleep outcomes. An interaction effect showed that nocturnal odorization affected dream intensity. Post hoc tests revealed an improvement in the group that used the nasal clip as compared to baseline, d = 0.68. No negative effects were observed after odorization with the nasal clip. Considering the limited sample size, the study indicates that nocturnal olfactory stimulation may serve as a low-cost concomitant intervention to improve sleep quality in PTSD.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Estimulación Olfatoria Nocturna para Mejorar la Calidad del Sueño en pacientes con Trastorno por Estrés Postraumático: Un ensayo de intervención exploratorio aleatorizado ESTIMULACIÓN OLFATORIA NOCTURNA EN PTSD El trastorno de estrés postraumático (TEPT) se caracteriza por trastornos del sueño y pesadillas. Como los olores agradables que se presentan durante el sueño afectan el tono emocional de los sueños sin inducir alerta, exploramos si los patrones de sueño en el TEPT pueden mejorarse a través de la estimulación olfatoria nocturna. Los participantes fueron 40 pacientes hospitalizados con TEPT (n = 35 mujeres; rango de edad: 20-59 años) que completaron un ensayo aleatorizado, ciego para los pacientes, controlado con placebo. La medición de línea base durante cinco noches consecutivas fue seguida por una intervención experimental de 5 noches o un ensayo con placebo. Durante la intervención, los pacientes recibieron estimulación nocturna con un olor agradable (condición de olor) o aire limpio (condición de placebo) a través de un olfatómetro que administró estímulos que gatillan-inspiración en un tubo nasal o mediante un clip nasal odorizado. Después de cada noche, los pacientes completaron cuestionarios estandarizados que evaluaron los parámetros de la calidad del sueño y del contenido de los sueños. Cada noche, la eficacia del sueño, la latencia del inicio del sueño y la vigilia después del inicio del sueño se controlaron con un biosensor de movimiento. La evaluación de línea base reveló que la gravedad del TEPT se asoció con resultados de sueño más deficientes. Un efecto de interacción mostró que la odorización nocturna afectó la intensidad del sueño. Pruebas post hoc revelaron una mejoría en el grupo que usó el clip nasal en comparación con la línea base, d = 0.68. No se observaron efectos negativos después de la odorización con el clip nasal. Teniendo en cuenta el tamaño limitado de la muestra, el estudio indica que la estimulación olfatoria nocturna puede servir como una intervención concomitante de bajo costo para mejorar la calidad del sueño en el TEPT.

Olfactory cleft evaluation: a predictor for olfactory function in smell-impaired patients?

OBJECTIVE: In this study, we introduce an extension of previous work by Soler et al. (Int Forum Allergy Rhinol 6(3):293-298, 2016) on a modified endoscopic scoring system of the Lund-Kennedy Score (focusing on the olfactory cleft) to evaluate its correlation with the olfactory function in patients with various smell disorders. STUDY DESIGN: A prospective cohort study. METHODS: Two-hundred and eighty-eight participants were included and categorized in five groups according to the cause of their olfactory disorder: (0) control, (1) idiopathic, (2) sino-nasal, (3) postinfectious and (4) post traumatic olfactory loss. Olfaction was evaluated using the "Sniffin' Sticks" test. The classical Lund-Kennedy scoring and a new olfactory cleft specific Lund-Kennedy scoring (OC-LK) were performed to evaluate mucosal changes. RESULTS: Significantly higher OC-LK scores on both sides were found in smell-impaired patients as compared to normosmic controls. When comparing the 4 groups, a significant difference of the OC-LK score were present between the sino-nasal and all other groups. Most importantly, significant negative correlations with strong effects were shown in the sino-nasal group between the OC-LK score and odor discrimination and odor identification. However, no such correlation emerged between the classical LK score and smell function. CONCLUSION: Olfactory cleft evaluation using the OC-LK score correlates with the olfactory function in patients with sino-nasal smell disorder. This diagnostic tool may reflect the underlying pathophysiological mechanism of sino-nasal smell loss, and therefore, should complement olfactory diagnostics in patients with sino-nasal smell disorder.

Effects of "trigeminal training" on trigeminal sensitivity and self-rated nasal patency.

PURPOSE: Patients with the feeling of a congested nose not always suffer from an anatomical obstruction but might just have a low trigeminal sensibility, which prevents them from perceiving the nasal airstream. We examined whether intermittent trigeminal stimulation increases sensitivity of the nasal trigeminal nerve and whether this effect is accompanied by subjective improvement of nasal breathing. METHOD: Thirty-five patients (Mage = 58.4 years; SD = 14.8; Minage = 21 years; Maxage = 79 years; 43% females) and 30 healthy controls (Mage = 36.7 years, SD = 14.5; Minage = 20 years; Maxage = 73 years; 60% females) participated in a study comprised of two sessions separated by "trigeminal training". During each session, trigeminal sensitivity towards CO2, trigeminal lateralization abilities and ratings of nasal patency were assessed. Age and training compliance were controlled. RESULTS: "Trigeminal training" had a positive effect on trigeminal sensitivity in both groups, (p = .027) and this effect depended on the training compliance (p < .001). "Trigeminal training" had no effect on lateralization abilities of the subjects (p > .05). Ratings of nasal patency increased in patients (p = .03), but not in controls. CONCLUSIONS: "Trigeminal training" consisting of intermittent presentation of diverse stimulants leads to an increase of trigeminal sensitivity, but this effect depended on the training compliance. Importantly, in patients, this training is also associated with an increase in self-rated nasal patency.

Differences in the Density of Fungiform Papillae and Composition of Saliva in Patients With Taste Disorders Compared to Healthy Controls.

This study investigated the relation of the fungiform taste papillae density and saliva composition with the taste perception of patients suffering from diagnosed taste disorders. For this purpose, 81 patients and 40 healthy subjects were included. Taste was measured by means of regional and whole mouth chemosensory tests, and electrogustometry. Olfaction was assessed using the Sniffin Sticks. Fungiform papillae were quantified using the "Denver Papillae Protocol for Objective Analysis of Fungiform Papillae". In addition, salivary parameters [flow rate, total proteins, catalase, total anti-oxidative capacity (TAC), carbonic anhydrase VI (caVI), and pH] were determined and the Beck Depression Inventory was administered. Patients showed less taste papillae compared to healthy subjects. The number of papillae correlated with total taste strip score and salivary flow rate. Regarding salivary parameters, the flow rate, protein concentration, and TAC of patients were higher compared to controls. In addition, salivary flow rate, protease, caVI, and catalase values correlated with the summed taste strip score. Regarding various taste disorders, salty-dysgeusia patients showed the lowest taste test scores compared to those with bitter or metal-dysgeusia. Olfactory function of patients was significantly worse compared to healthy controls. This difference was most pronounced for ageusia patients. Compared to controls, patients also exhibited higher depressive symptoms. The density of fungiform papillae seemed to be positively associated with taste perception. Furthermore, patients exhibited changes in saliva composition (higher salivary flow rate, increased protein concentration, proteolysis, and TAC) compared to controls indicating that assessment of saliva may be critical for the diagnostic procedure in taste disorders.

Olfactory Performance Can Be Influenced by the Presentation Order, Background Noise, and Positive Concurrent Feedback.

Sniffin' Sticks have become a popular procedure to measure overall olfactory functionality with 3 subtest: phenyl ethyl alcohol threshold test (T), discrimination (D), and identification (I). However, several procedural components specified by the original paper have not been tested nor has the impact of deviations been measured. The aim of the present work was to measure olfactory performance under modified testing procedures. First, the reverse order of subtests (IDT) was compared with more standard practices (TDI). Next, the possible impact of background noise and positive concurrent feedback were assessed. A total of 120 individuals participated in the study where the 3 conditional experiments, each involving 40 participants, were completed. Testing procedures that reversed the presentation order of subtests (I->D->T) scored a significantly lower overall TDI score than standard testing order with the threshold subtest being the most influenced. Additionally, nonverbal background noise lowered overall olfactory performance while concurrent feedback modulated threshold performance. These results emphasize the importance of testing parameters where olfactory perception and tasks may be modulated by adaptation and attentional distraction, respectively. This study helped furthermore to demonstrate that the investigated 3 deviations from the standard procedure revealed a significant impact on the performance outcome in olfactory assessment using the Sniffin' Sticks.

Short-term effect of caffeine on olfactory function in hyposmic patients.

The purpose of this study was to investigate the potential effects of caffeine in patients with olfactory loss. The suggested mechanisms of action consist in the non-selective blocking of adenosine receptors as well as inhibition of the phospodiesterase. Olfactory function was tested twice in 76 hyposmic patients either because of URTI or because of sinunasal causes. For definition of hyposmia and for later assessment of phenyl ethyl alcohol odor threshold, and odor discrimination the Sniffin Sticks data test was used. Using a double-blinded design, the participants were divided into two groups: one received a cup of espresso with caffeine (65 mg/cup), the other a cup of espresso without caffeine (placebo). Before and approximately 45 min after espresso consumption olfactory function was assessed. Across all participants, in comparison to placebo there was no significant effect of caffeine on olfactory function, regardless whether it was caused by an acute infection of the upper respiratory tract or sinunasal disease. These results indicate that-under the current conditions-the phosphodiesterase-inhibitor/adenosine-receptor agonist caffeine has little or no short-term effect on olfactory function in patients with olfactory loss.

Drug-target based cross-sectional analysis of olfactory drug effects.

BACKGROUND: Drug effects on the human sense of smell attract increasing interest, yet systematic evidence from controlled studies is sparse. The present cross-sectional approach to olfactory drug effects made use of the recent developments in informatics, knowledge discovery, and data mining allowing connecting drug-related information from humans with underlying molecular drug targets. METHODS: In this prospective cross-sectional study, n = 1008 outpatients at a general practitioner were enrolled. All currently taken medications were obtained, and olfactory function was assessed by means of a clinically established 12-item odor identification test. The association between the patients' sense of smell and the administered medications was based (i) on the active pharmacological substances and (ii) on the molecular targets queried from the publicly accessible DrugBank database. RESULTS: Of the 168 different substances, six were taken sufficiently often to be analyzed. The administration of levothyroxine was associated with a higher olfactory score (p = 0.033). For the 168 drugs, 323 different targets could be queried. Thirty-one gene products were addressed sufficiently often to be analyzed. Besides agonistic targeting of thyroid hormone receptors (genes THRA1, THRB1) agreeing with the above result, antagonistically targeting the adrenoceptor alpha 1A (gene ADRA1A) by several unrelated medications was associated with a significantly higher olfactory score (p = 0.012). CONCLUSIONS: The identified drug effects on olfaction are both biologically plausible based on supportive information from basic science studies. The novel molecular target-based approach suggested clear advantages over the classical drug or drug class-based approach. It increased the analyzable data volume fivefold and provided plausible hypotheses about mechanistic drug effects opening possibilities for drug discovery and repurposing.

Accurate detection of Parkinson's disease in tremor syndromes using olfactory testing.

BACKGROUND/AIMS: The diagnostic value of olfactory testing for the discrimination of tremor-dominant Parkinson's disease (PD) from other tremor disorders remains enigmatic. We evaluated whether olfactory testing can accurately detect PD in tremor patients. METHODS: A retrospective analysis of 299 consecutive subjects referred for the differential diagnosis of a tremor disorder was done. Olfactory testing was performed using 'Sniffin' Sticks', resulting in a composite TDI score of odor threshold (T), discrimination (D), and identification (I). Receiver operating curve (ROC) plots were used to calculate sensitivity/specificity for the detection of PD. RESULTS: Of all subjects, 167 (55.9%) had PD and 85 (28.4%) had essential tremor (ET). The mean TDI score in PD was significantly reduced compared to those in ET and other tremor disorders with no differences between ET and other tremor disorders. ROC analysis revealed strong correlations of TDI scores with PD [area under the curve: 0.85 (95% CI: 0.80-0.89); p < 0.001]. The highest Youden index was observed for a TDI score <25 (Youden index: 0.58). Using this cutoff score and that generated from normative data of healthy controls, the TDI score provided high sensitivity (negative predictive value) and specificity (positive predictive value) of approximately 80% for detecting PD. CONCLUSION: Olfactory testing is a useful, easily applied and inexpensive diagnostic test which is helpful to detect PD among tremor patients.

Pronounced Olfactory Habituation with Age.

OBJECTIVES: Olfactory habituation is a transient decrease in olfactory sensitivity caused by prolonged odor exposure, aiding in the discernment of new olfactory stimuli against the background. We explored the impact of subclinical olfactory impairment on odor habituation using age as a proxy. METHODS: Before the actual experiment, the individual olfactory threshold for the rose-like odorant phenylethyl alcohol (PEA) was assessed separately for the left and right nostril using the "Sniffin' Sticks" test, and ratings for odor intensity and pleasantness were collected. After applying a nasal clip continuously delivering PEA odor to one nostril for 10 min and 2 h, respectively, threshold, intensity, and pleasantness were reassessed immediately after clip removal. RESULTS: In the group of 80 participants (younger adults-mean age 27.7 ± 4.5 years; older adults-mean age 61.5 ± 4.7 years), olfactory thresholds were already significantly elevated after just 10 min, and this habituation was even more pronounced after 2 h. This effect could be observed bilaterally even though significantly more distinct on the exposed side. Older participants generally exhibited a more pronounced habituation on the exposed side after 2 h compared to the younger participants. CONCLUSION: The results indicate that older people experience more notable habituation after extended exposure to odors. This is most likely due to the compromised olfactory function in age. Although older and younger subjects scored in the normosmic range when tested with standardized olfactory tests, the stress on the system after exposure to an odor clearly revealed the lower functionality of the aging sense of smell. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3765-3768, 2024.

Patients with parosmia respond faster to unpleasant odors than patients with hyposmia: Insights from olfactory event-related potentials.

BACKGROUND: Diagnosing parosmia is a challenge. The present study aimed to explore the distinctions between hyposmic patients with and without parosmia utilizing electroencephalography-derived olfactory event-related potentials (ERP). METHODS: Forty-four patients with hyposmia were enrolled and divided into a group with parosmia (n = 23, mean age ± standard deviation = 48 ± 14 years, seven men) and a group without parosmia (n = 21, age = 52 ± 12 years, seven men) based on the clinical interview. Additionally, 21 healthy controls (mean age = 45 ± 14 years, six men) were included. Various measurements were obtained, including the Sniffin' Stick test, threshold tests for the odorants furfural mercaptan and 2,6-nonadienal, a modified Sniffin' Stick parosmia test, and well-being ratings. Chemosensory ERPs were recorded separately for each nostril using high-precision, computer-controlled air-dilution olfactometry. RESULTS: Patients with parosmia had a decreased olfactory function similar to that observed in patients with hyposmia, although the odor sensitivity of patients with severe parosmia remained relatively unaffected. Patients with parosmia reported a decrease in well-being compared to controls. The severity of parosmia was positively correlated with odor sensitivity. Furthermore, patients with severe parosmia exhibited faster responses to unpleasant odors than patients without parosmia. CONCLUSION: Overall, the present findings support the idea that parosmia predominantly occurs during olfactory recovery, significantly disturbing patients and warranting the development of effective treatments. Notably, the relatively faster responses of hyposmic patients with severe parosmia suggest that the generation of distorted olfactory responses may involve early stages of the processing of olfactory information.