Odor identification dysfunction in late-life depression with suicidal ideation.

BACKGROUND: Suicide is more prevalent among older adults compared to younger individuals. Late-life depression (LLD) poses the highest risk for suicide. However, early recognition of suicidal ideation is challenging. Dysfunction in odor identification (OI), a characteristic of LLD, may hold potential for early identification of suicidal ideation. This study aims to compare OI between LLD patients with suicidal ideation (LLD-S) and LLD patients without suicidal ideation (LLD-NS), and examine its relationship with cognitive function. METHODS: A total of 262 LLD-NS patients, 63 LLD-S patients, and 316 healthy normal older adults (HOAs) underwent OI testing, standardized clinical interviews, and comprehensive neuropsychological assessments. RESULTS: (1) LLD-S patients exhibited lower OI scores and poorer cognitive performance (including global cognition, information processing speed, memory, language, executive function, and visuospatial ability) compared to LLD-NS patients and HOAs. (2) There were interactive effects between suicidal ideation and OI dysfunction, leading to lower scores in information processing speed and visuospatial ability. (3) OI dysfunction mediated the differences in cognition between the LLD-NS and LLD-S groups. LIMITATIONS: The present study was a cross-sectional design. CONCLUSIONS: LLD-S patients had worse odor identification than LLD-NS patients and HOAs, suggesting that OI testing could be a valuable approach for identifying suicidal ideation in LLD and screening for suicide risk. The presence of both OI impairment and suicidal ideation was associated with poorer cognitive performance in LLD.

The digital scent device 20: an automated, self-administered odor identification test.

PURPOSE: Assessing olfactory function is highly significant in clinical practice, particularly in the context of the recent COVID-19 pandemic. Recent approaches in this field emphasize the importance of reducing the time and cost devoted to olfactory testing procedures. Hence, the aim of the present study was to examine the reliability and basic characteristics of Digital Scent Device 20 (DSD-20), an innovative olfactory test consisting of 20 "universal odors", in a European population. METHODS: A total of 88 participants (mean age = 45.1, SD = 20.3) volunteered for the study. The sample consisted of 37 normosmic controls and 51 dysosmic patients. RESULTS: The correlation between DSD-20 and the total score in Sniffin' Sticks was high (TDI; R = .80, p < .001), and the test correlated with the individual components of the Sniffin' Sticks test. Furthermore, the correlation coefficient between DSD-20 test and retest was very high (R = .88, p < .001), which was additionally confirmed by a Bland-Altman plot. Essential characteristics of the DSD-20 are its simplicity in self-administration, speed of application, portability, and the fact that it can be reused. CONCLUSION: Overall, the present study confirms previous notions on DSD-20 by demonstrating its high reliability and usefulness in separating patients with hyposmia/anosmia and normosmic controls.

Factors influencing olfactory function in an adult general population sample: the CHRIS study.

The sense of smell allows for the assessment of the chemical composition of volatiles in our environment. Different factors are associated with reduced olfactory function, including age, sex, as well as health and lifestyle conditions. However, most studies that aimed at identifying the variables that drive olfactory function in the population suffered from methodological weaknesses in study designs and participant selection, such as the inclusion of convenience sample or only of certain age groups, or recruitment biases. We aimed to overcome these issues by investigating the Cooperative Health Research in South Tyrol (CHRIS) cohort, a population-based cohort, by using a validated odor identification test. Specifically, we hypothesized that a series of medical, demographic and lifestyle variables is associated with odor identification abilities. In addition, our goal was to provide clinicians and researchers with normative values for the Sniffin' Sticks identification set, after exclusion of individuals with impaired nasal patency. We included 6,944 participants without acute nasal obstruction and assessed several biological, social, and medical parameters. A basic model determined that age, sex, years of education, and smoking status together explained roughly 13% of the total variance in the data. We further observed that variables related to medical (positive screening for cognitive impairment and for Parkinson's disease, history of skull fracture, stage 2 hypertension) and lifestyle (alcohol abstinence) conditions had a negative effect on odor identification scores. Finally, we provide clinicians with normative values for both versions of the Sniffin' Sticks odor identification test, i.e. with 16 items and with 12 items.

The "Sniffin' Kids-PT" test: A smell test variant for Portuguese children.

OBJECTIVE: Olfactory tests tailored for children are essential, as diagnosing olfactory dysfunction at these ages can be challenging. The 16-item "Sniffin' Sticks" is reliable and easy to perform. To the best of our knowledge, there is currently no validated olfactory test for the Portuguese pediatric population. This study aimed to adapt and validate the "Sniffin' Sticks" olfactory test for the Portuguese pediatric population. METHODS: Between August 2020 and September 2021, 354 children aged between 6 and 17years old enrolled in the study, 336 healthy children with a normal sense of smell, and 18 anosmic children with Kallmann syndrome. The study consisted of two parts. Firstly, the "Sniffin' Sticks" olfactory identification test was applied to healthy children and the odors with statistically significant low identification rates were excluded. A modified version of "Sniffin' Sticks" was defined and named "Sniffin' Kids-PT" test. Secondly, normative data were assessed and test-retest and validation tests were performed. RESULTS: Apple and Cloves odors were identified with a low rate and were excluded from the "Sniffin' Sticks" olfactory test. In the modified 14-item "Sniffin' Kids-PT", scoring <6 (from 6-8years old), <7 (from 9-11years old) or <8 (from 12-14years old and 15-17years old) was indicative of olfactory dysfunction. The test-retest reliability was good (r=0.81; P<0.001) and the differences between scores of healthy children and anosmic children were statistically significant (U213=13.00; P<0.001). CONCLUSION: The modified "Sniffin' Kids-PT" is a reliable test to discriminate between normosmia and olfactory dysfunction in Portuguese children over 5years old.

qU-Sniff - the development of a short version of the Universal "Sniffin' Sticks" test.

OBJECTIVES: Extensive olfactory testing is sparsely applied in pediatric patients in clinical routine especially because of its time taking nature. Therefore a 5-item odor identification test (quick "U-Sniff", "qU-Sniff") from the 12-item "U-Sniff" test was developed. METHODS: A total of 724 normosmic children between 6 and 17 years of age, divided in four age groups, were included in this retrospective study. Additionally, 17 children with congenital anosmia in the same age range were included. To calculate test-retest reliability 90 participants from the healthy group were tested twice. RESULTS: The five most correctly identified odors from the 12-item "U-Sniff" test were: coffee (98 %), peach (95 %), flower (90 %), fish (88 %) and onion (84 %). Normosmic participants scored 4.71 ± 0.62 points on the "qU-Sniff" test. A significant correlation between results of the 12-item and 5-item test (n = 724; rs = 0.580; p < 0.001) and a significant test-retest reliability (rs = 0.626, p < 0.001) were shown. For "qU-Sniff" validation a ROC analysis to distinguish between anosmic patients and healthy controls was conducted for each age group separately. AUCs were as followed: i) 0.963 ± 0.018, p < 0,001; ii) 0.978 ± 0.013, p < 0.001; iii) 0.992 ± 0.006, p < 0.001; iv) 0.994 ± 0.005, p < 0.001. The cut-off value to determine anosmic and normosmic participants was <4 points. CONCLUSION: With the "qU-Sniff" test, we present a short screening tool for clinical routine with <4 points as cut-off to initiate more detailed olfactory testing.

Odor Identification Across Time in Mutation Carriers and Non-Carriers in Autosomal-Dominant Alzheimer's Disease.

BACKGROUND: Impaired odor identification is a characteristic of sporadic Alzheimer'sdisease(AD), but its presence in autosomal-dominantAD (adAD) remains uncertain. OBJECTIVE: To investigate odor identification ability in mutation carriers (MC) and non-carriers (NC) of adAD in relation to years to estimated clinical onset clinical onset (YECO) of disease. METHODS: Participants from six families with autosomal-dominant mutations (APP Swedish, APP Arctic, and PSEN1 mutations) included 20 MC and 20 NC. The groups were comparable in age, gender, education, number of APOE ɛ4 alleles, and YECO, but differed in global cognition (Mini-Mental State Examination). The MC group included individuals in asymptomatic, symptomatic cognitively unimpaired, mild cognitive impairment, and dementia stages of disease, spanning approximately 40 years of the AD continuum. All NC were asymptomatic. Olfactory function was assessed by means of free and cued identification of common odors summarized as total identification. RESULTS: MC performed poorer than NC in free and total identification. Four MC and none of the NC were anosmic. Olfactory functions in MC and NC were significantly and inversely related to time course (YECO) for both free and total identification. The decline in free identification began approximately 10 years prior to the estimated clinical onset of AD in MC. Odor identification proficiency was associated with episodic memory and executive function in MC and NC. CONCLUSIONS: Impaired odor identification is present well before the clinical diagnosis of AD in MC and is associated with disease progression. Odor identification ability may be a useful early biomarker for adAD.

Olfactory function assessment of migraine patients by using the Sniffin' sticks test: A clinical study.

OBJECTIVE: This as a cross-sectional controlled clinical study. We hypothesis that the olfactory functions in migraine patients may differ from the healthy controls. In this study, we evaluated the olfactory functions by using a Sniffin' Sticks test battery, which is a reliable and semi quantitative test to evaluate for olfactory dysfunction. METHODS: Patients above 18 years of age who had migraine received a definitive diagnosis of migraine from experienced headache specialists based on the criteria of The International Classification of Headache Disorders-3 were included. Odor threshold, discrimination, and identification parameters were assessed using the "Sniffin' Sticks" test. RESULTS: One-hundred and one migraine patients (age [mean ± SD], 36.9 ± 10.4 years; range, 18-60 years) and sixty healthy volunteers (age 34.5 ± 13.2 years, range 18-65 years) participated in our study. The median odor threshold score [percentiles 25th-75th] was 8.3 [6.5-9.8] for the migraine group during attack free period and 4.5[3.6-6.0] for the control group. It was found that the migraine group had a median odor discrimination score of 10.0 [10.0-13.0] and the control group 12.0 [11.0-13.0]. These differences were statistically significant (p < 0.001 and p = 0.032 respectively). The median odor discrimination and identification scores were statistically significant higher for the participants with higher educational level group than in those of lower educational group (p < 0.0001). The median odor discrimination and identification scores of those without allodynia (12.0 [10.0-14.0] and 13.0 [10.0-13.0] respectively) were higher than that of those with allodynia (11.0 [9.0-12.0] and 11.0 [10.0-13.0] respectively) (p = 0.037 and p = 0.034 respectively). CONCLUSIONS: We found that the odor thresholds, discrimination and identification scores of the migraine group demonstrate differences from those of the healthy group and in relation to allodynia.

Association Between Olfactory Dysfunction and Cognitive Impairment in Dementia-Free Older Adults: A Prospective Cohort Study in Taiwan.

BACKGROUND: Previous studies assessing olfactory function and cognition have mostly been cross-sectional, and few have investigated the Asian geriatric population. OBJECTIVE: To examine the relationships of olfaction with global or domain-specific cognitive function in Taiwanese community-dwelling older adults. METHODS: This cohort study (2015-2019) is part of the Taiwan Initiative for Geriatric Epidemiological Research. The Taiwanese version of the Montreal Cognitive Assessment (MoCA-T) and a battery of neuropsychological tests were assessed at baseline and at a two-year follow-up. The cross-culture modified Sniffin' Sticks Identification Test (SSIT) was utilized to measure olfactory function. Generalized linear mixed models were used to examine the association of olfaction with cognitive performance over two years. RESULTS: Data were collected from 376 participants (55.1% women), with a mean age of 75.6 years. A one-point decrease in the SSIT score (worsening of olfaction) was associated with worse global cognition (MoCA-T: ߈= -0.13), memory (߈= -0.08 to -0.06), and verbal fluency (߈= -0.07). Compared with an SSIT score ≥ 11 (normosmia), an SSIT score < 8 (anosmia) was associated with worse global cognition (MoCA-T: ߈= -0.99), memory (߈= -0.48 to -0.42), executive function (Trail Making Test A: ߈= -0.36), attention (digit span backward: ߈= -0.34), and verbal fluency (߈= -0.45). After stratified analyses, the associations remained in older adults ≥ 75 years, males, and non-carriers of apolipoprotein E ɛ4 in terms of global cognition, memory, and verbal fluency. CONCLUSIONS: Odor identification deficits were associated with poor global or domain-specific cognitive function in a four-year cohort of community-dwelling older adults. Cognitive assessments should be conducted in dementia-free elderly individuals with impaired odor identification.

A tool developed for Chinese olfactory screening: culturally adapted version of "Quick olfactory Sniffin' Sticks Test (Q-Sticks)".

BACKGROUND: The odor identification test is culture-dependent. OBJECTIVES: This study aimed to develop a culturally adapted version of the 5-item Quick olfactory Sniffin' Sticks Test (Q-Stick) to adapt to the clinical environment in China. METHODS: The study included 3 phases: (1) develop a culturally adapted version of Q-Stick by replacing unfamiliar odors in the original Q-Stick test (N = 344); (2) validate the culturally adapted version of Q-Stick against two widely used olfactory tests: the Sniffin' Sticks olfactory test and the 12-item Cross-Cultural Smell Identification Test (CC-SIT) (N = 286); 3) evaluate the test-retest reliability of the culturally adapted version of Q-Stick (N = 60). RESULTS: After modification of the interference items, the correct recognition rate of leather was changed from 54.65% to 90.00%. The adapted version of the Q-Stick score significantly correlated with both the Sniffin' Sticks score (r = 0.7642, p < .0001) and CC-SIT score (r = 0.7403, p < .0001). Normal olfaction is indicated if the culturally adapted version of the Q-Stick score > 4 (specificity 70.00%, sensitivity 83.33%, Youden index 0.533) and Q-Stick score ≤ 4 indicates olfactory dysfunction. The 3-month test-retest reliability coefficient was as high as 0.96. CONCLUSIONS AND SIGNIFICANCE: The culturally adapted version of Q-Stick is an effective and stable screening tool to identify patients with olfactory dysfunction in China.

Evaluating cognitive impairment in the early stages of Parkinson's disease using the Cambridge brain sciences-cognitive platform.

BACKGROUND: Non-motor symptoms (NMS) such as cognitive impairment are among common presentations in patients with Parkinson's disease (PD). In parallel with motor symptoms, these impediments can affect PD patients' quality of life. However, cognitive impairment has received less attention in early PD. On the other hand, the relationship between olfactory symptoms and cognitive impairment is unclear in early PD. Considering the importance of accurate and timely assessment of cognitive function in PD patients using readily available/validated tests, this study has employed the Cambridge Brain Sciences-Cognitive Platform (CBS-CP) as a computer-based tool to assess cognitive presentations in early PD patients. METHODS: Thirty-four eligible males and females were assigned to PD and healthy controls (HCs). The cognitive performance was assessed using CBS-CP and Mini-Mental State Examination (MMSE), and olfactory function was measured through the standardized olfactory Quick Smell test (QST). RESULTS: PD patients had poorer performance in all CBS-CP tasks, including short-term memory, attention, and reasoning domains than HCs. Meanwhile, the verbal domain task scores showed no significant difference between groups. PD MMSE results were in the normal range (mean=26.96), although there was a significant difference between the PD and HCs groups (P = 0.000). Our results revealed no correlation between cognitive impairment and olfactory function in PD patients. CONCLUSION: Given the widely studied features of CBS-CP and its reliability across published evidence, CBS-CP appears to be a suitable measurement to evaluate cognitive impairment in early PD with normal MMSE scores. It seems cognitive and olfactory impairments are independent in early PD. DATA AVAILABILITY STATEMENT: The datasets generated during the current study are available from the corresponding author upon reasonable request.

"Mmm, Smells like Coffee!": How a Brief Odor Identification Test Could Help to Identify People with Mild Cognitive Impairment and Dementia.

(1) Background: Dementia and mild cognitive impairment (MCI) are still underdiagnosed in the general population. Impaired odor identification has been identified as an early marker of MCI and dementia. We aimed to compare the additional diagnostic value of two odor identification tests to a cognitive screening test in detecting MCI or dementia. (2) Methods: The Sniffin' Sticks odor identification test (SS-OIT), a brief odor identification test (B-OIT) requiring the identification of coffee scent, and the Mini-Mental State Exam (MMSE) were administered to a consecutive series of 174 patients (93 with dementia, 42 with mild cognitive impairment, and 39 without cognitive impairment) referred for neuropsychological testing. (3) Results: Both participants with dementia and with MCI exhibited impairments in odor identification. The SS-OIT and the B-OIT were substantially correlated. Complementing MMSE scores with the SS-OIT or the B-OIT similarly improved the diagnostic accuracy of individuals with dementia and MCI. (4) Conclusions: People with suspected dementia or MCI may already benefit from brief odor identification tests. Although these tests require little additional time, they can notably increase sensitivity for dementia or MCI.

A mobile APP-based, customizable automated device for self-administered olfactory testing and an implementation of smell identification test.

Olfactory tests are used for the evaluation of ability to detect and identify common odors in humans psychophysically. Olfactory tests are currently administered by professionals with a set of given odorants. Manual administration of such tests can be labor and cost intensive and data collected as such are confounded with experimental variables, which adds personnel costs and introduces potential errors and data variability. For large-scale and longitudinal studies, manually recorded data must be collected and compiled from multiple sites. It is difficult to standardize the way data are collected and recorded. There is a need for a computerized smell test system for psychophysical and clinical applications. A mobile digital olfactory testing system (DOTS) was developed, consisting of an odor delivery system (DOTS-ODD) and a mobile application program (DOTS-APP) connected wirelessly. The University of Pennsylvania Smell Identification Test was implemented in DOTS and compared to its commercial product on a cohort of 80 normosmic subjects and a clinical cohort of 12 Parkinson's disease patients. A test-retest was conducted on 29 subjects of the normal cohort. The smell identification scores obtained from the DOTS and standard UPSIT commercial test are highly correlated (r = 0.714, P < 0.001), and test-retest reliability coefficient was 0.807 (r = 0.807, P < 0.001). The DOTS is customizable and mobile compatible, which allows for the implementation of standardized olfactory tests and the customization of investigators' experimental paradigms. The DOTS-APP on mobile devices offers capabilities for a broad range of on-site, online, or remote clinical and scientific chemosensory applications.

Odor Perception and Descriptions of Rose-Scented Geranium Pelargonium graveolens 'Dr. Westerlund'-Sensory and Chemical Analyses.

A recent study found that the natural scent from the rose-scented geranium Pelargonium graveolens 'Dr. Westerlund' had positive effects on stress reduction. Essential oils from many pelargonium species are known to have phytochemical properties and pharmacological activities. No study has, so far, explored and identified the chemical compounds and the sensory perception of these compounds in 'Dr. Westerlund' plants. Such knowledge would be an important contribution to an increased understanding of the effects of plants' chemical odor properties on human well-being, and link this to the expressed perceived scents. This study aimed to identify the sensory profile and suggest responsible chemical compounds of Pelargonium graveolens 'Dr. Westerlund'. The sensory and chemical analysis results revealed sensory profiles of Pelargonium graveolens 'Dr. Westerlund's and provided suggestions for the chemical compounds attributed to the sensory profiles. Further studies are recommended to investigate the correlation between volatile compounds and possible stress reduction in humans.

Flavor characteristics of peeled walnut kernels under two-steps roasting processes.

Currently, the effects of roasting methods on the flavor profile of peeled walnut kernels (PWKs) remain unknown. The effects of hot air binding (HAHA), radio frequency (HARF), and microwave irradiation (HAMW) on PWK were evaluated using olfactory, sensory, and textural techniques. Solvent Assisted Flavor Evaporation-Gas Chromatography-Olfactometry (SAFE-GC-O) identified 21 odor-active compounds with total concentrations of 229 µg/kg, 273 µg/kg and 499 µg/kg due to HAHA, HARF, and HAMW, respectively. HAMW exhibited the most prominent nutty taste, with the highest response among roasted milky sensors with the typical aroma of 2-ethyl-5-methylpyrazine. HARF had the highest values for chewiness (5.83 N·mm) and brittleness (0.68 mm); however, these attributes did not contribute to the flavor profile. The partial least squares regression (PLSR) model and VIP values showed 13 odor-active compounds were responsible for the sensory differences from different processes. The two-step treatment with HAMW improved the flavor quality of PWK.

Could olfactory identification be a prognostic factor in detecting cognitive impairment risk in the elderly?

Aging contributes to the deterioration of the olfactory system in humans. Several studies indicate that the olfactory identification test alone may function as a screening test for olfactory dysfunction and they are more feasible to apply in clinical practice. Olfactory identification may be a predictor for cognitive impairment. Multiple studies have considered the use of odor identification as a measure to identify the conversion from normality to mild cognitive impairment or dementia. The objectives were (i) to elucidate the associations between cognitive status and olfactory identification performance in aging; (ii) understand the predictive value of olfactory capacity in identifying subjects with cognitive impairment risk; and (iii) to study how cognitive status and olfactory identification relate with other variables of wellness in aging, such as functional capabilities and clinical measures. For this purpose, a group of 149 participants (77.15 ± 7.29 years; 73 women of 76.7 ± 8 years and 76 men of 77.6 ± 6.52 years) were recruited and were subjected to a sociodemographic questionnaire, a psychological screening tool of general cognitive status, an olfactory identification evaluation, and clinical measures. The participants were divided into groups based on their cutoff scores of previous scientific reports about the Spanish version of Montreal Cognitive Assessment. Our results indicate an age-associated decline in olfactory identification ability and intensity of odor perception. The predictive ability of olfactory identification scores for the risk of mild and severe impairment is around 80%. Olfactory identification decreases with cognitive function. Performance in odor identification is associated with impairment of episodic memory and executive functions. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia.

Odor identification errors reveal cognitive aspects of age-associated smell loss.

Human olfaction can be extraordinarily sensitive, and its most common assessment method is odor identification (OID), where everyday odors are matched to word labels in a multiple-choice format. However, many older persons are unable to identify familiar odors, a deficit that is associated with the risk of future dementia and mortality. The underlying processes subserving OID in older adults are poorly understood. Here, we analyzed error patterns in OID to test whether errors could be explained by perceptual and/or semantic similarities among the response alternatives. We investigated the OID response patterns in a large, population-based sample of older adults in Sweden (n = 2479; age 60-100 years). Olfaction was assessed by a 'Sniffin ́ TOM OID test with 16 odors; each trial involved matching a target odor to a correct label among three distractors. We analyzed the pattern of misidentifications, and the results showed that some distractors were more frequently selected than others, suggesting cognitive or perceptual factors may be present. Relatedly, we conducted a large online survey of older adults (n = 959, age 60-90 years) who were asked to imagine and rate the perceptual similarity of the target odors and the three corresponding distractors (e.g. "How similar are these smells: apple and mint?"). We then used data from the Swedish web corpus and the Word2Vec neural network algorithm to quantify the semantic association strength between the labels of each target odor and its three distractors. These data sources were used to predict odor identification errors. We found that the error patterns were partly explained by both the semantic similarity between target-distractor pairs, and the imagined perceptual similarity of the target-distractor pair. Both factors had, however, a diminished prediction in older ages, as responses became gradually less systematic. In sum, our results suggest that OID tests not only reflect olfactory perception, but also likely involve the mental processing of odor-semantic associations. This may be the reason why these tests are useful in predicting dementia onset. Our insights into olfactory-language interactions could be harnessed to develop new olfactory tests that are tailored for specific clinical purposes.

The Effect of Chinese Herbal Medicine on Traumatic Anosmia: A Prospective, Randomized Clinical Trial.

OBJECTIVE: Chinese herbal medicine (CHM) has been implemented as a form of treatment for olfactory dysfunction. In this study, we aimed to use a tailored Guizhi decoction for the treatment of traumatic olfactory dysfunction. METHODS: Patients who had lost olfactory function after experiencing head trauma and whose olfactory function was anosmic were selected. The eligible patients were randomly assigned to two groups. In the CHM group, a tailored Guizhi decoction was prescribed, with patients also undergoing olfactory training (OT). In the OT group, patients performed OT only. The olfactory function of each patient was evaluated by both the phenyl ethyl alcohol (PEA) odor detection threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test (TC-UPSIT), at both 3 and 6 months after the completion of treatment. RESULTS: A total of 38 patients in the CHM group and 40 in the OT group completed the study. The TC-UPSIT scores of patients slightly rose after treatment in both the CHM and OT groups. Nevertheless, there were no significant differences in TC-UPSIT scores before and after treatment in both groups. However, the PEA thresholds improved significantly in both CHM and OT groups (p = 0.005 and 0.016, respectively). Of note, there were no significant differences in threshold or identification scores between the CHM and OT groups. CONCLUSION: Our results show that adding a tailored Guizhi decoction to OT conferred a limited benefit to the olfactory function of patients experiencing traumatic anosmia. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:1473-1479, 2023.

Olfactory Dysfunction in Schizophrenia: Evaluating Olfactory Abilities Across Species.

Though understudied relative to perturbations in the auditory and visual domains, olfactory dysfunction is a common symptom of schizophrenia. Over the past two decades, the availability of standardized assessments to quantify human olfactory abilities, and enhance understanding of the neurophysiology supporting olfaction, has increased, enabling a more thorough characterization of these deficits. In contrast to other psychiatric conditions for which olfactory dysfunction has been observed (e.g., major depressive disorder, bipolar disorder, Alzheimer's disease), the impairments observed in schizophrenia are particularly global and profound. At this level, such deficits in olfactory abilities likely impact the enjoyment of food, detection of environmental hazards, and influence social relationships. More broadly, the study of olfactory phenotypes in schizophrenia presents new avenues for detection of those at-risk for the condition, identification of therapeutic targets for treatment development, and for the characterization of novel animal models relevant to schizophrenia and psychosis. This review will consider the olfactory performance of individuals with schizophrenia in domains for which standardized assessments are available (odor sensitivity, discrimination, identification, and memory). Paradigms available for assessing these abilities in rodents will also be discussed with the aim of facilitating translation. Thus, future studies will be able to include cross-species translation of mechanisms relevant to olfactory function and cognition, what has gone awry in the disease state, and test potential therapeutics.

Rapid olfactory decline during aging predicts dementia and GMV loss in AD brain regions.

INTRODUCTION: Longitudinal multivariable analyses are needed to determine if the rate of olfactory decline during normal cognition predicts subsequent Alzheimer's disease (AD) diagnoses and brain dysmorphology. METHODS: Older adults (n = 515) were assessed annually for odor identification, cognitive function and dementia clinical diagnosis (max follow-up 18 years). Regional gray matter volumes (GMV) were quantified (3T MRI) in a cross-sectional subsample (n = 121). Regression models were adjusted for APOE-ε4 genotype, dementia risk factors and demographics. RESULTS: Faster olfactory decline during periods of normal cognition predicted higher incidence of subsequent MCI or dementia (OR 1.89, 95% CI: 1.26, 2.90, p < 0.01; comparable to carrying an APOE-ε4 allele) and smaller GMV in AD and olfactory regions (ß = -0.11, 95% CI -0.21, -0.00). DISCUSSION: Rapid olfactory decline during normal cognition, using repeated olfactory measurement, predicted subsequent cognitive impairment, dementia, and smaller GMVs, highlighting its potential as a simple biomarker for early AD detection. HIGHLIGHTS: Rate of olfactory decline was calculated from olfactory testing over ≥3 time points. Rapid olfactory decline predicted impaired cognition and higher risk of dementia. Neurodegeneration on 3T magnetic resonance imaging was identical in those with olfactory decline and Alzheimer's disease.

Olfaction in pregnancy: systematic review and meta-analysis.

Little attention has been paid to olfactory changes during pregnancy with contemporary studies limited in number and sample size. We examined whether pregnancy is associated with differences in olfactory performance and if there were any specific gestational ages at which these differences occur through a comprehensive systematic review and meta-analysis of the current literature. An initial electronic database search identified 234 citations, which were screened at the abstract level. Twenty-three citations were germane for full-text review, and 13 met criteria for inclusion. Our review assessed 5 olfactory measures of interest: odor identification (n = 11 articles), threshold (n = 8), discrimination (n = 5), hedonics (n = 6), and intensity (n = 5). Nine of these 13 studies contained sufficient data for meta-analysis, and these studies included a total of 523 pregnant women and 365 non-pregnant controls. Despite previous subjective and objective reports of odor intolerances and odor hypersensitivity, we did not find any significant differences between pregnant and non-pregnant women in odor discrimination, thresholds, or hedonics. However, meta-analysis of 506 cases and 333 controls showed worse odor identification in pregnant women compared to controls in a random-effects model. Thus, we demonstrate worse performance at odor identification during pregnancy. In this review, we discuss the current evidence (and lack thereof) regarding olfaction in pregnancy as well as highlight current knowledge gaps in this field.