High prevalence of long-term olfactory disorders in healthcare workers after COVID-19: A case-control study.

BACKGROUND: More than a year after recovering from COVID-19, a large proportion of individuals, many of whom work in the healthcare sector, still report olfactory dysfunctions. However, olfactory dysfunction was common already before the COVID-19 pandemic, making it necessary to also consider the existing baseline prevalence of olfactory dysfunction. To establish the adjusted prevalence of COVID-19 related olfactory dysfunction, we assessed smell function in healthcare workers who had contracted COVID-19 during the first wave of the pandemic using psychophysical testing. METHODS: Participants were continuously tested for SARS-CoV-2 IgG antibodies since the beginning of the pandemic. To assess the baseline rate of olfactory dysfunction in the population and to control for the possibility of skewed recruitment of individuals with prior olfactory dysfunction, consistent SARS-CoV-2 IgG naïve individuals were tested as a control group. RESULTS: Fifteen months after contracting COVID-19, 37% of healthcare workers demonstrated a quantitative reduction in their sense of smell, compared to only 20% of the individuals in the control group. Fifty-one percent of COVID-19-recovered individuals reported qualitative symptoms, compared to only 5% in the control group. In a follow-up study 2.6 years after COVID-19 diagnosis, 24% of all tested recovered individuals still experienced parosmia. CONCLUSIONS: In summary, 65% of healthcare workers experienced parosmia/hyposmia 15 months after contracting COVID-19. When compared to a control group, the prevalence of olfactory dysfunction in the population increased by 41 percentage points. Parosmia symptoms were still lingering two-and-a half years later in 24% of SARS-CoV-2 infected individuals. Given the amount of time between infection and testing, it is possible that the olfactory problems may not be fully reversible in a plurality of individuals.

Tau propagation in the brain olfactory circuits is associated with smell perception changes in aging.

The direct access of olfactory afferents to memory-related cortical systems has inspired theories about the role of the olfactory pathways in the development of cortical neurodegeneration in Alzheimer's disease (AD). In this study, we used baseline olfactory identification measures with longitudinal flortaucipir and PiB PET, diffusion MRI of 89 cognitively normal older adults (73.82 ± 8.44 years; 56% females), and a transcriptomic data atlas to investigate the spatiotemporal spreading and genetic vulnerabilities of AD-related pathology aggregates in the olfactory system. We find that odor identification deficits are predominantly associated with tau accumulation in key areas of the olfactory pathway, with a particularly strong predictive power for longitudinal tau progression. We observe that tau spreads from the medial temporal lobe structures toward the olfactory system, not the reverse. Moreover, we observed a genetic background of odor perception-related genes that might confer vulnerability to tau accumulation along the olfactory system.

Olfactory Categorization Is Shaped by a Transmodal Cortical Network for Evaluating Perceptual Predictions.

Creating and evaluating predictions are considered important features in sensory perception. Little is known about processing differences between the senses and their cortical substrates. Here, we tested the hypothesis that olfaction, the sense of smell, would be highly dependent on (nonolfactory) object-predictive cues and involve distinct cortical processing features. We developed a novel paradigm to compare prediction error processing across senses. Participants listened to spoken word cues (e.g., "lilac") and determined whether target stimuli (odors or pictures) matched the word cue or not. In two behavioral experiments (total n = 113; 72 female), the disparity between congruent and incongruent response times was exaggerated for olfactory relative to visual targets, indicating a greater dependency on predictive verbal cues to process olfactory targets. A preregistered fMRI study (n = 30; 19 female) revealed the anterior cingulate cortex (a region central for error detection) being more activated by incongruent olfactory targets, indicating a role for olfactory predictive error processing. Additionally, both the primary olfactory and visual cortices were significantly activated for incongruent olfactory targets, suggesting olfactory prediction errors are dependent on cross-sensory processing resources, whereas visual prediction errors are not. We propose that olfaction is characterized by a strong dependency on predictive (nonolfactory) cues and that odors are evaluated in the context of such predictions by a designated transmodal cortical network. Our results indicate differences in how predictive cues are used by different senses in rapid decision-making.

Degeneration of the cholinergic system in individuals with subjective cognitive decline: A systematic review.

BACKGROUND: Subjective cognitive decline (SCD) is a risk factor for future cognitive impairment and dementia. It is uncertain whether the neurodegeneration of the cholinergic system is already present in SCD individuals. We aimed to review the current evidence about the association between SCD and biomarkers of degeneration in the cholinergic system. METHOD: Original articles were extracted from three databases: Pubmed, Web of Sciences, and Scopus, in January 2023. Two researchers screened the studies independently. RESULTS: A total of 11 research articles were selected. SCD was mostly based on amnestic cognitive complaints. Cholinergic system biomarkers included neuroimaging markers of basal forebrain volume, functional connectivity, transcranial magnetic stimulation, or biofluid. The evidence showed associations between basal forebrain atrophy, poorer connectivity of the cholinergic system, and SCD CONCLUSIONS: Degenerative changes in the cholinergic system can be present in SCD. Subjective complaints may help when identifying individuals with brain changes that are associated with cognitive impairment. These findings may have important implications in targeting individuals that may benefit from cholinergic-target treatments at very early stages of neurodegenerative diseases.

Discriminating between sick and healthy faces based on early sickness cues: an exploratory analysis of sex differences.

Background and objectives: It has been argued that sex and disease-related traits should influence how observers respond to sensory sickness cues. In fact, there is evidence that humans can detect sensory cues related to infection in others, but lack of power from earlier studies prevents any firm conclusion regarding whether perception of sickness cues is associated with sex and disease-related personality traits. Here, we tested whether women (relative to men), individuals with poorer self-reported health, and who are more sensitive to disgust, vulnerable to disease, and concerned about their health, overestimate the presence of, and/or are better at detecting sickness cues. Methodology: In a large online study, 343 women and 340 men were instructed to identify the sick faces from a series of sick and healthy photographs of volunteers with an induced acute experimental inflammation. Participants also completed several disease-related questionnaires. Results: While both men and women could discriminate between sick and healthy individuals above chance level, exploratory analyses revealed that women outperformed men in accuracy and speed of discrimination. Furthermore, we demonstrated that higher disgust sensitivity to body odors is associated with a more liberal decision criterion for categorizing faces as sick. Conclusion: Our findings give strong support for the human ability to discriminate between sick and healthy individuals based on early facial cues of sickness and suggest that women are significantly, although only slightly, better at this task. If this finding is replicated, future studies should determine whether women's better performance is related to increased avoidance of sick individuals.

Semantic processing in children with Cochlear Implants: A review of current N400 studies and recommendations for future research.

Deaf and hard of hearing children with cochlear implants (CI) often display impaired spoken language skills. While a large number of studies investigated brain responses to sounds in this population, relatively few focused on semantic processing. Here we summarize and discuss findings in four studies of the N400, a cortical response that reflects semantic processing, in children with CI. A study with auditory target stimuli found N400 effects at delayed latencies at 12 months after implantation, but at 18 and 24 months after implantation effects had typical latencies. In studies with visual target stimuli N400 effects were larger than or similar to controls in children with CI, despite lower semantic abilities. We propose that in children with CI, the observed large N400 effect reflects a stronger reliance on top-down predictions, relative to bottom-up language processing. Recent behavioral studies of children and adults with CI suggest that top-down processing is a common compensatory strategy, but with distinct limitations such as being effortful. A majority of the studies have small sample sizes (N < 20), and only responses to image targets were studied repeatedly in similar paradigms. This precludes strong conclusions. We give suggestions for future research and ways to overcome the scarcity of participants, including extending research to children with conventional hearing aids, an understudied group.

Body odour disgust sensitivity is associated with xenophobia: evidence from nine countries across five continents.

Body odour disgust sensitivity (BODS) reflects a behavioural disposition to avoid pathogens, and it may also involve social attitudes. Among participants in the USA, high levels of BODS were associated with stronger xenophobia towards a fictitious refugee group. To test the generalizability of this finding, we analysed data from nine countries across five continents (N = 6836). Using structural equation modelling, we found support for our pre-registered hypotheses: higher BODS levels were associated with more xenophobic attitudes; this relationship was partially explained by perceived dissimilarities of the refugees' norms regarding hygiene and food preparation, and general attitudes toward immigration. Our results support a theoretical notion of how pathogen avoidance is associated with social attitudes: 'traditional norms' often involve behaviours that limit inter-group contact, social mobility and situations that might lead to pathogen exposure. Our results also indicate that the positive relationship between BODS and xenophobia is robust across cultures.

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.

Body odor disgust sensitivity (BODS) is related to extreme odor valence perception.

Odors are important disease cues, and disgust sensitivity to body odors reflects individual differences in disease avoidance. The body odor disgust sensitivity (BODS) scale provides a rapid and valid assessment of individual differences. Nevertheless, little is known about how individual differences in BODS might correlate with overall odor perception or how it is related to other differences in emotional reactivity (e.g., affect intensity). We investigated how BODS relates to perceptual ratings of pleasant and unpleasant odors. We aggregated data from 4 experiments (total N = 190) that were conducted in our laboratory, and where valence and intensity ratings were collected. Unpleasant odors were body-like (e.g., sweat-like valeric acid), which may provide disease cues. The pleasant odors were, in contrast, often found in soap and cleaning products (e.g., lilac, lemon). Across experiments, we show that individuals with higher BODS levels perceived smells as more highly valenced overall: unpleasant smells were rated as more unpleasant, and pleasant smells were rated as more pleasant. These results suggest that body odor disgust sensitivity is associated with a broader pattern of affect intensity which causes stronger emotional responses to both negative and positive odors. In contrast, BODS levels were not associated with odor intensity perception. Furthermore, disgust sensitivity to odors coming from external sources (e.g., someone else's sweat) was the best predictor of odor valence ratings. The effects were modest in size. The results validate the BODS scale as it is explicitly associated with experimental ratings of odor valence.

A parosmia severity index based on word-classification predicts olfactory abilities and impairment.

Parosmia is an olfactory disorder that involves distortions of specific odors that may co-occur with anosmia, loss of smell of other odors. Little is known about which odors frequently trigger parosmia, and measures of parosmia severity are lacking. Here, we present an approach to understand and diagnose parosmia that is based on semantic properties (e.g., valence) of words describing odor sources ("fish", "coffee", etc.). Using a data-driven method based on natural language data, we identified 38 odor descriptors. Descriptors were evenly dispersed across an olfactory-semantic space, which was based on key odor dimensions. Parosmia patients (n = 48) classified the corresponding odors in terms of whether they trigger parosmic or anosmic sensations. We investigated whether these classifications are related to semantic properties of the descriptors. Parosmic sensations were most often reported for words describing unpleasant odors of inedibles that are highly associated to olfaction (e.g., "excrement"). Based on PCA modeling, we derived the Parosmia Severity Index-a measure of parosmia severity that can be determined solely from our non-olfactory behavioral task. This index predicts olfactory-perceptual abilities, self-reported olfactory impairment, and depression. We thus provide a novel approach for investigating parosmia and establishing its severity that does not require odor exposure. Our work may enhance our understanding of how parosmia changes over time and how it is expressed differently across individuals.

Subjective Impairments in Olfaction and Cognition Predict Dissociated Behavioral Outcomes.

BACKGROUND: Self-rated subjective cognitive decline (SCD) and subjective olfactory impairment (SOI) are associated with objective cognitive decline and dementia. However, their relationship and co-occurrence is unknown. We aimed to (a) describe the occurrence of SOI, SCD and their overlap in the general population; (b) compare SOI and SCD in terms of longitudinal associations with corresponding objective olfactory and cognitive measures; and (c) describe how SOI and SCD may lead to distinct sensory and cognitive outcomes. METHODS: Cognitively unimpaired individuals from the third wave of the Swedish population-based Betula study (n = 784, aged 35-90 years; 51% females) were split into self-rated SOI, SCD, overlapping SCD + SOI, and controls. Between-subject and within-subject repeated-measures MANCOVA were used to compare the groups regarding odor identification, cognition, age, sex, and education. Spearman correlation was used to assess the different patterns of association between olfaction and cognition across groups. RESULTS: SOI was present in 21.1%, whereas SCD was present in 9.9% of participants. According to a chi-square analysis, the SCD + SOI overlap (2.7%) is on a level that could be expected if the phenomena were independent. Odor identification in SOI showed decline at the 10-year follow-up (n = 284) and was positively associated with cognition. The SOI and SCD groups showed distinct cognitive-olfactory profiles at follow-up. CONCLUSIONS: SOI occur independently of SCD in the population, and these risk factors are associated with different cognitive and olfactory outcomes. The biological causes underlying SOI and SCD, as well as the risk for future cognitive impairment, need further investigation.

The Semantic Organization of the English Odor Vocabulary.

The vocabulary for describing odors in English natural language is not well understood, as prior studies of odor descriptions have often relied on preselected descriptors and odor ratings. Here, we present a data-driven approach that automatically identifies English odor descriptors based on their degree of olfactory association, and derive their semantic organization from their distributions in natural texts, using a distributional-semantic language model. We identify 243 descriptors that are much more strongly associated with olfaction than English words in general. We then derive the semantic organization of these olfactory descriptors, and find that it is captured by four clusters that we name Offensive, Malodorous, Fragrant, and Edible. The semantic space derived from our model primarily differentiates descriptors in terms of pleasantness and edibility along which our four clusters are positioned, and is similar to a space derived from perceptual data. The semantic organization of odor vocabulary can thus be mapped using natural language data (e.g., online text), without the limitations of odor-perceptual data and preselected descriptors. Our method may thus facilitate research on olfaction, a sensory system known to often elude verbal description.

Perceptual odor qualities predict successful odor identification in old age.

Odor identification is a common assessment of olfaction, and it is affected in a large number of diseases. Identification abilities decline with age, but little is known about whether there are perceptual odor features that can be used to predict identification. Here, we analyzed data from a large, population-based sample of 2,479 adults, aged 60 years or above, from the Swedish National study on Aging and Care in Kungsholmen. Participants performed both free and cued odor identification tests. In a separate experiment, we assessed perceived pleasantness, familiarity, intensity, and edibility of all odors in the first sample, and examined how odor identification performance is associated with these variables. The analysis showed that high-intensity odors are easier to identify than low-intensity odors overall, but also that they are more susceptible to the negative repercussions of old age. This result indicates that sensory decline is a major aspect of age-dependent odor identification impairment, and suggests a framework where identification likelihood is proportional to the perceived intensity of the odor. Additional analyses further showed that high-performing individuals can discriminate target odors from distractors along the pleasantness and edibility dimensions and that unpleasant and inedible odors show smaller age-related differences in identification. Altogether, these results may guide further development and optimization of brief and efficient odor identification tests as well as influence the design of odorous products targeted toward older consumers.

Cerebrovascular damage in subjective cognitive decline: A systematic review and meta-analysis.

BACKGROUND: Subjective cognitive decline (SCD) has been postulated as an early marker of Alzheimer's Disease (AD) but it can also be associated to other non-AD pathologies such as Vascular Dementia (VaD). Nevertheless, there is scarce data about SCD as a potential harbinger of cerebrovascular pathology. Thus, we conducted a systematic review and meta-analysis on the association between SCD and cerebrovascular damage measured by neuroimaging markers. METHOD: This study was performed following the PRISMA guidelines. The search was conducted in 3 databases (PubMed, Scopus and Web of Science) from origin to December 8th, 2021. Primary studies including cognitively unimpaired adults with SCD and neuroimaging markers of cerebrovascular damage (i.e., white matter signal abnormalities, WMSA) were selected. Qualitative synthesis and meta-analysis of studies with a case-control design was performed. RESULTS: Of 241 articles identified, 21 research articles were selected. Eight case-control studies were included for the meta-analysis. A significant overall effect-size was observed for the mean WMSA burden in SCD relative to controls, where the WMSA burden was higher in SCD. CONCLUSION: Our findings show the potential usefulness of SCD as a harbinger of cerebrovascular disease in cognitively healthy individuals. Further research is needed in order to elucidate the role of SCD as a preclinical marker of vascular cognitive impairment.

Hippocampal subfield volumes and olfactory performance: Emerging longitudinal associations over a 5-year interval.

Olfaction, the sense of smell, provides important behavioral functions in many species. The hippocampus (HC) is critical for identifying odors, and hippocampal volume is associated with odor identification ability. Impaired odor identification is often reported in old age and might provide an early marker of cognitive decline and dementia. Here, we explored cross-sectional (n = 225) and longitudinal (n = 118) associations between odor identification ability and hippocampal subfield volumes in a sample of middle-aged and older persons (25-80 years). In older participants, longitudinally decreasing volumes of the hippocampal tail, subiculum, CA4 and the dentate gyrus correlated with changes in odor identification. None of these correlations were observed in younger participants, but there was a significant correlation between longitudinal volume reduction in the tail subfield of the hippocampus and odor identification change across all participants. There were no significant cross-sectional associations between hippocampal subfields and odor identification. These exploratory results provide new information regarding precisely where and when declining HC subfield volumes might be associated with odor identification.

Olfactory distortions in the general population.

Parosmia, distorted smell sensations, is a common consequence of respiratory virus infections. The phenomenon is not well understood in terms of its impact and long-term outcomes. We examined self-reported experiences of parosmia in a population-based sample from the Betula study that was conducted in Umeå in northern Sweden (baseline data collected in 1998-2000). We used a baseline sample of 2168 individuals aged 35-90 years and with no cognitive impairment at baseline. We investigated the prevalence of parosmia experiences and, using regression analyses, its relationship to other olfactory and cognitive variables and quality of life. Benefitting from the longitudinal study design, we also assessed the persistence of parosmia over 5 and 10 years prospectively. Parosmia experiences were prevalent in 4.8% of the population and it often co-occurred with phantosmia ("olfactory hallucinations"), but was not associated with lower self-rated overall quality of life or poor performance on olfactory or cognitive tests. For some individuals, parosmia was retained 5 years (17.0%) or even 10 years later (10.3%). Thus, parosmia experiences are commonly reported in the population, and can be persistent for some individuals, but might be mostly benign in nature. Our work complements research on clinical-level parosmia, which is typically more severe, and recent parosmia reports during the COVID-19 pandemic, where long-term outcomes are still unknown.

Olfaction and Aging: A Review of the Current State of Research and Future Directions.

Olfaction, the sense of smell, is characterized by a notable age-dependency such that aging individuals are more likely to have poor olfactory abilities. These impairments are considered to be mostly irreversible and as having potentially profound effects on quality of life and food behavior, as well as constituting warning signs of mortality, cognitive dysfunction, and dementia. Here, we review the current state of research on aging and olfaction, focusing on five topics which we regard to be of particular relevance for the field: nutrition and health, cognition and dementia, mortality, environment and genetics, and training-based enhancement. Under each of these headlines, we provide a state-of-the-art overview and discuss gaps in our knowledge which might be filled by further research. Understanding how olfactory abilities are diminished in aging, and how they may be alleviated or recovered, involves a set of challenging tasks for researchers in the years to come.

Joint trajectories of episodic memory and odor identification in older adults: patterns and predictors.

Emerging evidence suggests that olfactory function is closely linked to memory function. The aims of this study were to assess whether olfactory and episodic memory functions follow similar age-related decline trajectories, to identify different patterns of decline, as well as predictors of the patterns. 1023 participants from the Memory and Aging Project were followed for up to 8 years with annual episodic memory and odor identification assessments. Trajectories were modelled using growth mixture models. Multivariate logistic regression was used to identify pattern predictors. Three patterns of joint trajectories were identified; Class 1- stable average performance in both functions (n=690, 67.4%); Class 2- stable average episodic memory and declining odor identification (n=231, 22.6%); and Class 3- decline in both functions (n= 102, 10.0%). Class predictors included age, sex, APOE ε4 status, cognitive activity level and BMI. Participants in Class 3 were most likely to develop dementia. Episodic memory and olfactory function show similar trajectories in aging. Such classification can contribute to a better understanding of the factors related to cognitive decline and dementia.

A Method for Computerized Olfactory Assessment and Training Outside of Laboratory or Clinical Settings.

There are currently few ways to reliably and objectively assess olfaction outside of the research laboratory or clinic. The COVID-19 pandemic has highlighted the need for remote olfactory assessment; in particular, smell training at home is a promising method for olfactory rehabilitation, but further methodological advances might enhance its effectiveness and range of use. Here, we present Exerscent, a portable, low-cost olfactory display designed primarily for uses outside of the laboratory and that can be operated with a personal computer. Exerscent includes Radio Frequency Identification (RFID) tags that are attached to odor stimuli and read with a MFRC522 module RFID reader/antenna that encodes the odor in order to provide adaptive challenges for the user (e.g., an odor identification task). Hardware parts are commercially available or 3D printed. Instructions and code for building the Exerscent are freely available online (https://osf.io/kwftm/). As a proof of concept, we present a case study in which a participant trained daily to identify 54 odors, improving from 81% to 96% accuracy over 16 consecutive days. In addition, results from a laboratory experiment with 11 volunteers indicated a very high level of perceived usability and engagement. Exerscent may be used for olfactory skills development (e.g., perfumery, enology), and rehabilitation purposes (e.g., postviral olfactory loss), but it also allows for other forms of technological interactions such as olfactory-based recreational interactions.