Measures Of Olfactory Function Research Articles

Efficacy of Gabapentin For Post–COVID-19 Olfactory Dysfunction

The COVID-19 pandemic affected millions of people and has become a dominant etiology of olfactory dysfunction (OD). No interventions with definitive clinical utility exist. Gabapentin represents a potential therapy for COVID-19-induced OD. To evaluate the efficacy of oral gabapentin on olfactory function and olfaction-related quality of life in patients with COVID-19-induced OD. This pilot double-blinded, placebo-controlled randomized clinical trial (RCT) was conducted at Washington University School of Medicine in St Louis from January 7, 2022, to February 3, 2023. Adults with at least 3 months of OD after COVID-19 infection were eligible for inclusion. Participants with a history of other causes of OD or contraindications to gabapentin were excluded. Patients were randomized 1:1 to oral gabapentin or placebo. All patients underwent titration to a maximum tolerable dose, which was maintained during an 8-week fixed-dose (FD) phase then tapered off. Participants were monitored for 4 weeks following cessation of study medication. Outcomes were assessed following the 8-week FD phase and 4 weeks after taper completion. The primary outcome measure was the response rate determined by subjective improvement in OD on the Clinical Global Impression of Improvement (CGI-I) after the FD phase. Other subjective and objective measures of olfactory function were also assessed as secondary outcome measures. Sixty-eight participants were enrolled (34 randomized to each arm), a total of 44 participants completed the FD period and 20 (45.4%) reported response to treatment with at least slight improvement in olfaction from baseline. Of those randomized, 51 (75%) were women and 56 were White (82%) with a mean (SD) age of 43 (13.5) years. Baseline demographic features including age, sex, and race and ethnicity were not significantly different between the groups. Of the 18 participants in the gabapentin group, 8 (44%) were responders and of the 26 participants in the placebo group, 12 (46%) reported response to treatment (percent difference, 1.7%; 95% CI, -31.6% to 28.2%). Mixed-model analysis of all secondary outcome measures demonstrated no clinically meaningful or statistically significant difference between the gabapentin and placebo groups throughout the trial. There were no serious adverse events. In this randomized clinical trial, gabapentin was not associated with statistically significant or clinically meaningful benefit over placebo and likely is not an efficacious therapy for COVID-19-induced OD. ClinicalTrials.gov Identifier: NCT05184192.

Olfactory function reflects episodic memory performance and atrophy in the medial temporal lobe in individuals at risk for Alzheimer’s disease

We examined cognitive domains and brain regions associated with olfactory performance in cognitively unimpaired older adults (CU-OAs) and individuals with or at risk for Alzheimer’s Disease (AD). We compared CU-OAs (N = 55), individuals with subjective cognitive decline (SCD, N = 55), mild cognitive impairment (MCI, N = 101), and AD (N = 45) on measures of olfactory function (Brief Smell Identification Test), cognition (episodic and semantic memory), and medial temporal lobe thickness and volume. Analyses controlled for age, sex, education, and total intracranial volume. Olfactory function decreased from SCD to MCI to AD. CU-OAs outperformed all groups except SCDs on tests of cognition and olfaction. Although these measures did not differ between the CU-OAs and SCDs, olfactory function correlated with episodic memory tests and with entorhinal cortex atrophy only in the SCD group. Olfactory function also correlated with hippocampal volume and right-hemisphere entorhinal cortex thickness in the MCI group. Olfactory dysfunction reflects medial temporal lobe integrity and memory performance in a group at risk for AD with normal cognition and olfaction.

Visual Analog Scale and Olfactory Objective Tests in Hyposmia Patients: Is There a Link?

Introduction Olfactory dysfunction (OD) is often a devaluated sensorial affection. The objective evaluation of this dysfunction does not evaluate its compromise in patients' daily life.It is unclear to what extent there is a correlation between the objective evaluation of OD and patient-reported impairment. Objective We aim to search if Sniffin Sticks® correlates with the Visual Analog Scale (VAS) of Hyposmia Symptoms, and therefore if it is a useful method for clinical use. Methods A prospective study was carried out to evaluate and compare consecutive patients who had olfactory impairment due to COVID-19 that were referred to an otolaryngology office. The variables evaluated were gender, age, co-morbidities, and olfactory thresholds (measured according to Sniffin Sticks®). Patients were also enquired about their sense of impairment according to VAS from 1 (worst possible) to 10 (best possible). Statistical analysis was performed using SPSS (IBM SPSS Statistics 26). Normal distribution was checked using both skewness and kurtosis and Kolmogorov-Smirnov tests. Pearson correlation test was used to seek a correlation between VAS and olfactory thresholds. All reported p-values are two-tailed, with a p-value ≤ 0.05 indicating statistical significance. Results Our sample of 47 patients was composed of 30 females (63.8%) and 17 females (36.2%). We found a mean variation between olfactory thresholds before and after the intervention of 3.91±2.466, and an average improvement of 2.29±2.93 in the visual analog scale for subjective evaluation of olfactory impairment. According to the Pearson correlation test, with 95% confidence, there is evidence to claim a moderate association (0.512) between an improvement in olfactory thresholds and VAS (p=0.05). Conclusions There was a moderate correlation between ratings and measures of olfactory function. On an individual basis, there were remarkable differences between measures and ratings of olfactory function. VAS should be considered in the evaluation of the hyposmic patient, due to its simplicity and quick applicability.

Olfactory Dysfunction in Familial and Sporadic Parkinson's Disease.

This minireview discusses our current understanding of the olfactory dysfunction that is frequently observed in sporadic and familial forms of Parkinson's disease and parkinsonian syndromes. We review the salient characteristics of olfactory dysfunction in these conditions, discussing its prevalence and characteristics, how neuronal processes and circuits are altered in Parkinson's disease, and what is assessed by clinically used measures of olfactory function. We highlight how studies of monogenic Parkinson's disease and investigations in ethnically diverse populations have contributed to understanding the mechanisms underlying olfactory dysfunction. Furthermore, we discuss how imaging and system-level approaches have been used to understand the pathogenesis of olfactory dysfunction. We discuss the challenging, remaining gaps in understanding the basis of olfactory dysfunction in neurodegeneration. We propose that insights could be obtained by following longitudinal cohorts with familial forms of Parkinson's disease using a combination of approaches: a multifaceted longitudinal assessment of olfactory function during disease progression is essential to identify not only how dysfunction arises, but also to address its relationship to motor and non-motor Parkinson's disease symptoms. An assessment of cohorts having monogenic forms of Parkinson's disease, available within the Genetic Epidemiology of Parkinson's Disease (GEoPD), as well as other international consortia, will have heuristic value in addressing the complexity of olfactory dysfunction in the context of the neurodegenerative process. This will inform our understanding of Parkinson's disease as a multisystem disorder and facilitate the more effective use of olfactory dysfunction assessment in identifying prodromal Parkinson's disease and understanding disease progression.

Unawareness of Olfactory Dysfunction in Older Adults

Deterioration of olfaction is a common phenomenon observed in the senior population. A number of factors may cause this deficit including infections, aging and neurodegenerative diseases. The aim of this study was to evaluate the reliability of the self-report as a measure of olfactory function in seniors. A total of 93 community-dwelling participants (43 men and 50 women) from the Quebec NuAge cohort on Nutrition and Successful Aging participated in the Olfactory Response and Cognition in Aging (ORCA) study. The age range was 80-95 years and all subjects had a telephone mini mental state examination (t-MMSE) score > 18. Individuals were interviewed using a self-report ('do you suffer from smell problems?') and quantitative (University of Pennsylvania Smelling Identification Test (UPSIT)) olfactory tests. Based on the self-report, 81% of the participants claimed to have a normal sense of olfaction. However, based on the UPSIT, 95% of them showed different forms of microsmia. These results reveal that most senior citizens are unaware of their olfactory dysfunction and indicate that an self-report questionnaire is not a valid instrument to assess olfactory function in the aging population.

Awareness of Olfactory Dysfunction in Subjective Cognitive Decline, Mild Cognitive Decline, and Alzheimer\u2019s Disease

IntroductionHyposmia and metacognitive errors are related to aging, depression, male gender, and cognitive decline. The current study investigated the awareness of olfactory dysfunction in subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer’s disease (AD), as well as the influence of additional factors.MethodsA sample of 641 patients, including controls, SCD, non-amnestic MCI (naMCI), amnestic MCI (aMCI), and AD patients, was assessed with the Sniffin’ Sticks odor identification test (OIT) and the subjective olfactory capability (SOC) scale, in addition to measures of depressive symptoms, verbal memory, and executive functioning. Olfactory awareness groups were formed by means of the cutoffs of the OIT and the SOC.ResultsModerate and small, although significant, correlations between the OIT and the SOC were found among the study groups, with a significant discrimination of measured olfactory function via subjective assessment existing among controls but not among patients with AD. Of all AD patients, 34% overrated their sense of smell while 21% correctly identified themselves as being hyposmic, as opposed to corresponding 6% and 1% of healthy elderly. Overraters and correct hyposmic participants showed higher age and worse verbal memory and executive functions.ConclusionsReduced odor identification might underlie the same pathological changes within the brain as cognitive impairment and could serve as an additional marker for the development of AD.ImplicationsAlthough people with AD are aware of hyposmia to some extent, the majority is affected by overestimation of the ability to smell, making the combination of subjective ratings and measures of olfactory function an interesting topic for further research.

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.

Severity of olfactory deficits is reflected in functional brain networks-An fMRI study.

Even though deficits in olfactory function affect a considerable part of the population, the neuronal basis of olfactory deficits remains scarcely investigated. To achieve a better understanding of how smell loss affects neural activation patterns and functional networks, we set out to investigate patients with olfactory dysfunction using functional magnetic resonance imaging (fMRI) and olfactory stimulation. We used patients' scores on a standardized olfactory test as continuous measure of olfactory function. 48 patients (mean olfactory threshold discrimination identification (TDI) score = 16.33, SD = 6.4, range 6 - 28.5) were investigated. Overall, patients showed piriform cortex activation during odor stimulation compared to pure sniffing. Group independent component analysis indicated that the recruitment of three networks during odor stimulation was correlated with olfactory function: a sensory processing network (including regions such as insula, thalamus and piriform cortex), a cerebellar network and an occipital network. Interestingly, recruitment of these networks during pure sniffing was related to olfactory function as well. Our results support previous findings that sniffing alone can activate olfactory regions. Extending this, we found that the severity of olfactory deficits is related to the extent to which neural networks are recruited both during olfactory stimulation and pure sniffing. This indicates that olfactory deficits are not only reflected in changes in specific olfactory areas but also in the recruitment of occipital and cerebellar networks. These findings pave the way for future investigations on whether characteristics of these networks might be of use for the prediction of disease prognosis or of treatment success.

The Influence of Sniffing on Airflow and Odorant Deposition in the Canine Nasal Cavity.

Nasal airflow plays a critical role in olfaction by transporting odorant from the environment to the olfactory epithelium, where chemical detection occurs. Most studies of olfaction neglect the unsteadiness of sniffing and assume that nasal airflow and odorant transport are "quasi-steady," wherein reality most mammals "sniff." Here, we perform computational fluid dynamics simulations of airflow and odorant deposition in an anatomically accurate model of the coyote (Canis latrans) nasal cavity during quiet breathing, a notional quasi-steady sniff, and unsteady sniffing to: quantify the influence of unsteady sniffing, assess the validity of the quasi-steady assumption, and investigate the functional advantages of sniffing compared to breathing. Our results reveal that flow unsteadiness during sniffing does not appreciably influence qualitative (gross airflow and odorant deposition patterns) or quantitative (time-averaged olfactory flow rate and odorant uptake) measures of olfactory function. A quasi-steady approximation is, therefore, justified for simulating time-averaged olfactory function in the canine nose. Simulations of sniffing versus quiet breathing demonstrate that sniffing delivers about 2.5 times more air to the olfactory recess and results in 2.5-3 times more uptake of highly- and moderately-soluble odorants in the sensory region per unit time, suggesting one reason why dogs actively sniff. Simulations also reveal significantly different deposition patterns in the olfactory region during inspiration for different odorants, and that during expiration there is little retronasal odorant deposition in the sensory region. These results significantly improve our understanding of canine olfaction, and have several practical implications regarding computer simulation of olfactory function.

EPV 12. Objective measurements of olfactory function in infants

Objectives To objectively measure olfactory function in adults, olfactory event-related potentials (OERP) are widely used in clinical and scientific settings. So far this method has not been applied to infants. Previous studies relied on observations like grimacing or head turning to assess olfactory function of infants. Aim of this study was to evaluate olfactory event-related potentials as an objective measurement of olfactory function in infants. Materials & methods Thirteen infants, between 23 and 41 days of age, were included in the study. OERP to phenylethylalcohol were measured. The odor was delivered with a computer-controlled olfactometer. Recording electrodes were applied using the 10–20 system. Data from electrodes Fz, Cz, Pz, C3 and C4 was analyzed by Matlab’s “Letswave” toolbox using the canonical time-domain averaging as well as the time-frequency analyzing method. Results Ten out of 13 infants finished the recording session. In seven out of these ten infants we were able to observe OERP. Recordings were best in electrodes Fz and Cz. The N1 peak was visible at 328 ms followed by P2 at 505 ms. In addition the time-frequency analysis revealed an increase in low frequencies (4–7 Hz) around 550 ms after odor presentation. Conclusions In this study we were able to record OERP in infants. For data analysis both methods, the time-domain averaging as well as the time-frequency analysis proofed to be of value. Further studies are needed to evaluate the clinical relevance of measuring OERPs e.g. in the diagnosis of asphyxia or traumatic brain injury.

Olfactory Function in Head Trauma Patients a Link to Frontal Brain Damage?

Aims: In the recent years, the olfactory system gained more attention because of its unique characteristics of continuous regeneration and neurogenesis in adults. This is necessary for maintaining an intact olfactory function throughout life. Nevertheless, several diseases with olfactory dysfunction have been identified. Especially head trauma has shown to be linked to olfactory impairment. This is of interest because it is believed that measurement of olfactory function after head trauma represents a sensitive tool for measuring frontal brain damage. Most of the studies regarding this topic were conducted in adults. The aim of this study, therefore, is to evaluate the effect of mild head trauma in children on olfactory function over a time period of up to 1 year after head trauma.

Diagnosis of olfactory disorders

Alongside a structured case history, the measurement of olfactory function and diagnosis of olfactory dysfunction is of great clinical importance. Validated and established methods have been developed to this aim. The "Sniffin' Sticks" test battery is an easy-to-use tool for assessing olfactory function. Recording of olfactory event-related potentials is a more objective approach, which is particularly important in medicolegal cases. Imaging techniques such as MRI and CT provide additional information in the diagnosis of olfactory disorders. The latter techniques enable the anatomical structures of the skull and brain with the areas relevant to olfactory function to be evaluated.

Relation of the volume of the olfactory bulb to psychophysical measures of olfactory function.

The aim of this review is to investigate whether changes in olfactory bulb volume relate to changes in specific olfactory functions. We studied currently available peer-reviewed articles on the volume of the human olfactory bulb that also included a psychophysical measure of olfactory function. In the present review, we observed a very clear and consistent correlation between general olfactory function and olfactory bulb (OB) volume. We were not able to find a clear relationship between a specific smell component and OB volume, even when analyzing pathologic conditions separately. In some cases, changes were observed for different subtests, but these changes did not significantly correlate with OB volume or had only a borderline correlation. In other cases, we found contradictory data. Several factors may contribute to the difficulties in finding correlations with the different components of smell: (1) the OB volume may be influenced by information from olfactory receptor neurons (bottom-up effect), information from central nervous system (top-down effect) and by direct damage; (2) most pathologic conditions affect more than one area of the olfactory pathway; (3) small sample sizes of hyposmic subjects were used. We believe that it is necessary to do further studies with larger numbers of subjects to answer the currently investigated question.

Olfactory Event-Related Potentials in Infants

To evaluate olfactory event-related potentials (OERPs) as an objective measurement of olfactory function in infants. OERPs to phenylethyl alcohol were measured in 13 infants, between 23 and 41days of age. The odor was delivered with a computer-controlled olfactometer. Recording electrodes were applied using the 10-20 system. Data from electrodes Fz, Cz, Pz, C3, and C4 were analyzed by MatLab's Letswave toolbox (André Mouraux, Brussels, Belgium) using the canonical time-domain averaging as well as the time-frequency analyzing method. Ten of 13 infants finished the recording session. We observed OERPs in 7 of these 10 infants. Recordings were best in electrodes Fz and Cz. The N1 peak was visible at 328ms followed by P2 at 505ms. In addition, the time-frequency analysis had an increase in low frequencies (4-7Hz) around 550ms after odor presentation. We were able to record OERPs in infants. The time-domain averaging as well as the time-frequency analysis was of value for data analysis.

Olfactory Function After Mild Head Injury in Children

Olfactory impairment has been shown to be linked to head injury. In addition, it is believed that measurement of olfactory function after head trauma represents a sensitive tool for measuring frontal brain damage. Aim of the study was to evaluate the effect of mild head trauma in children on olfactory function over a time period of up to 1 year after head trauma. The olfactory function of 114 children who suffered mild head trauma according to the Glasgow Coma Scale was assessed 3 times with an interval of 4 months. In addition, healthy, age-matched controls were tested for comparison of olfactory function. Patients scored significantly lower on the odor threshold test compared to the control group-but still within normal range. Between the 2 groups, no difference was found for suprathreshold testing. Neither olfactory threshold scores nor olfactory discrimination scores changed significantly over the study period of 1 year. This data prove an impact of mild head trauma on olfactory function of children. It seems unlikely that children who suffered mild head trauma will become hyposmic or anosmic.

Pregnancy Does Not Affect Human Olfactory Detection Thresholds

Hyperosmia is suspected in pregnancy; however, no empirical study using validated measures of olfactory function has clearly confirmed the anecdotal reports of this phenomenon. The goal of the current study is to compare the olfactory sensitivity of pregnant women to that of nonpregnant women and men. All participants rated their sense of smell and pregnant women listed the odors to which they were most sensitive. Detection thresholds were measured using a well-validated protocol. A group of pregnant and nonpregnant women was studied longitudinally using a signal detection procedure designed to detect small differences in sensitivity. Pregnant women, particularly in the 1st trimester, rated their sense of smell to be higher than nonpregnant women and men and indicated many (primarily unpleasant) odors to which they were more sensitive. Women rated their sense of smell higher than men. However, there was no sex difference in thresholds and neither thresholds nor signal detection measures of sensitivity were significantly affected by either sex or pregnancy status. The implications of the lack of relationship between self-report and measures of olfactory sensitivity, particularly in pregnancy, are discussed.

Candidate odours for a short form odorant identification test

Measurement of olfactory function is difficult and despite the availability of validated olfactory tests these are not in common use in general clinical practice. The mismatch between self-reported olfactory function and objective test response is well known, thus the need for adequate assessment of olfaction is not disputed. We aimed to determine which if any odour in a commercially available olfactory test could be identified by 70 % or more of normal subjects with a view to developing a shortened screening test for use in general otolaryngology and non-specialist clinics in the United Kingdom. Hospital staff and medical students, under 50 years of age were recruited. The tests were undertaken in a quiet room of neutral odour. Subjects were asked to self-identify 12 odorants presented consecutively and to record how strongly they perceived the odorants on a 4-point scale. One hundred and four participants correctly identified the odorant in 466 (37.3 %) of the 1,248 individual odorant identification tests. Peppermint, fish and coffee odours were identified by 88.5, 79.8 and 69.7 % of participants, respectively, without the advantage of a choice of name prompt. These supra-threshold test odour stimuli were perceived as present in all of the individual odour identification tests, but correct identification of the test odour was very much lower for the other nine test stimuli. Peppermint, fish and coffee are odours that should be evaluated further for inclusion in a short form olfactory identification test in a British population.

Olfaction in athletes with concussion

Moderate to severe traumatic brain injuries (TBIs) commonly lead to olfactory dysfunction; it is, however, unclear whether and to what degree mild TBI such as concussions, which are common sports injuries, affect olfactory function. We therefore aimed to evaluate smell function in athletes who sustained one or more sport concussions in a cross-sectional design. Twenty-two University-level football players with one or multiple concussions and 13 control athletes without a history of concussion participated. We measured olfactory function by using the Sniffin' Sticks test to assess subjects' ability to discriminate and identify odors as well as their detection thresholds. In addition, we assessed odor intensity and pleasantness. We used number of concussions and time since the last concussion as independent variables and measure of olfactory function as dependent variables. Although we did not observe any significant effect of the number of concussions, athletes with a longer delay from time of concussion scored significantly weaker than more recently concussed subjects on the odor identification test and on an aggregate olfactory score. Accordingly, we observed a significant negative linear correlation between the odor identification score and the time elapsed since the last concussion. These findings suggest a possible degenerative effect of concussions on olfactory function.

Olfactory function improves following hemodialysis

Olfactory function has been shown to be affected in chronic kidney disease; however, studies are contradictory and little is known on the effects of dialysis. To resolve these issues we tested olfactory function in 24 healthy controls and in 28 patients with chronic kidney disease receiving hemodialysis (20 patients) or peritoneal dialysis (the other 8). As assays for olfactory function we measured smell identification, n-butanol and acetic acid thresholds, Kt/V urea, percentage reduced urea, and weights before and after dialysis. Olfactory function was also self-rated by the participants. Compared to healthy controls, predialysis olfactory function was moderately but significantly decreased in the two dialysis groups, with hemodialysis patients being more affected. Patients self-rated olfactory function similar to that of healthy controls, suggesting that patients are unaware of the olfactory decrease. Olfactory function was significantly improved by one hemodialysis session. Neither body mass index, total volume loss, nor any other dialysis parameter correlated with olfactory function or its restitution following hemodialysis. The observed pattern of improvement suggests underlying mixed peripheral and central mechanisms. Thus, olfactory dysfunction in patients with chronic kidney disease is readily reversible by hemodialysis.

Self‐Ratings of Olfactory Function Reflect Odor Annoyance Rather than Olfactory Acuity

Self-ratings of olfactory function often correlates poorly with results of objective smell tests. We explored these ratings relative to self-rating of odor annoyance, to odor identification ability, and to mean perceived intensity of odors, and estimated relative genetic and environmental contributions to these traits. A total of 1,311 individual twins from the general population (62% females and 38% males, aged 10-83 years, mean age 29 years) including 191 monozygous and 343 dizygous complete twin pairs from Australia, Denmark, Finland, and the United Kingdom rated their sense of smell and annoyance caused by ambient smells (e.g., smells of foods) using seven categories, and performed odor identification and evaluation task for six scratch-and-sniff odor stimuli. The self-rating of olfactory function correlated with the self-rating of odor annoyance (r = 0.30) but neither correlated with the odor identification score. Quantitative genetic modeling revealed no unambiguously significant genetic contribution to variation in any of the studied traits. The results suggest that environmental rather than genetic factors modify the self-rating of olfactory function and support earlier findings of discrepancy between subjective and objective measures of olfactory function. In addition, the results imply that the self-rating of olfactory function arises from experienced odor annoyance rather than from actual olfactory acuity.