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Frank-Ito DO. Olfaction and drug delivery to the human olfactory airspace: current challenges and recent advances. Expert Opin Drug Deliv 2025; 22:511-524. [PMID: 39955085 DOI: 10.1080/17425247.2025.2467784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 12/01/2024] [Accepted: 02/12/2025] [Indexed: 02/17/2025]
Abstract
INTRODUCTION Olfactory function, despite its critical role in human survival and quality of life, is often underappreciated. This could be associated with the fact that symptoms of olfactory dysfunction rarely occur in isolation as they are frequently concomitant with comorbidities. Furthermore, effective treatments for olfactory dysfunction largely remain elusive, and no standardized clinical practice for treating this dysfunction currently exist, thus complicating the initiation of appropriate therapeutic modalities. Intranasal administration of topical medication targeting the olfactory cleft represents a safe, noninvasive and potentially efficacious approach, but several challenges impede effective drug delivery. AREAS COVERED This review highlights the importance of human olfaction, assessment of olfactory function, underlying sources of olfactory dysfunction, and challenges involved in developing long-term and effective treatment modalities, particularly in the administration of topical medication to the olfactory cleft intranasally. Advancements in both device-related and administration-related modalities designed to enhance intranasal drug delivery are discussed. EXPERT OPINION Clinical management typically prioritizes comorbid conditions, relegating symptoms pertaining olfactory dysfunction to ancillary concerns. Device manufacturers for intranasal administration likewise underestimate the complexity and variabilities of the nasal cavity, and how these impact drug transport. Synergistic implementation of device and formulation strategies can potentially yield enhanced olfactory cleft drug delivery.
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Affiliation(s)
- Dennis Onyeka Frank-Ito
- Department of Head and Neck Surgery & Communication Sciences, Duke University Medical Center, Durham, North Carolina, USA
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, North Carolina, USA
- Computational Biology & Bioinformatics PhD Program, Duke University, Durham, North Carolina, USA
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Cameron EL, Follett SR, Rajcevich Schwer AS. How well can young adults and children discriminate between odors? PSYCHOLOGICAL RESEARCH 2024; 88:2360-2375. [PMID: 38896309 DOI: 10.1007/s00426-024-01981-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Accepted: 05/28/2024] [Indexed: 06/21/2024]
Abstract
It is widely believed that people can distinguish between many odors although there is limited empirical evidence. Odor discrimination tasks are employed much less often than other measures of olfaction, but, interestingly, performance is typically ~ 75% correct. This less-than-perfect performance is rarely highlighted, although it suggests that people may not be as good at discriminating odors as is commonly believed. Odor discrimination is understudied in children, and although available evidence suggests that it improves with age, children perform better when the task is simpler. In the present study, we explored odor discrimination in children and young adults with a relatively simple same-different task using common and uncommon odors. We found that children perform as well as young adults, but that overall performance was less than perfect and depended on the odors to be discriminated. We found evidence that ability to discriminate between odors improves as the difference in pleasantness of the odors increases. In a second experiment, we tested this directly by exploring whether odors that differ in pleasantness and edibility, two dimensions that appear to be important in olfactory perception, are easier to discriminate than odors that are the same on those dimensions. We found further evidence that odors that differ in pleasantness are easier to discriminate.
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Affiliation(s)
- E Leslie Cameron
- Department of Psychological Science, Carthage College, 2001 Alford Park Drive, Kenosha, WI, 53140, USA.
| | - Sierra R Follett
- Department of Psychological Science, Carthage College, 2001 Alford Park Drive, Kenosha, WI, 53140, USA
| | - Autumn S Rajcevich Schwer
- Department of Psychological Science, Carthage College, 2001 Alford Park Drive, Kenosha, WI, 53140, USA
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Li S, Wolter A, Kelly C, Smith B, Whitcroft K, Sherwood H, Longley B, Hummel T. A novel olfactory sorting task. Eur Arch Otorhinolaryngol 2024; 281:5823-5830. [PMID: 39001921 PMCID: PMC11512826 DOI: 10.1007/s00405-024-08811-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 06/24/2024] [Indexed: 07/15/2024]
Abstract
BACKGROUND This study aimed to develop a simple self-administered screening tool for odor memory, which allowed users to self-test their olfactory function repeatedly even at home. METHODS One hundred and ten participants were recruited (30 men, age = 50.1 ± 9.9 years; 80 women, age = 47.1 ± 11.5 years); half of them were heathy volunteers, the other half were patients with olfactory dysfunction. Fifty-one healthy participants volunteered for a retest within an interval of a maximum of 14 days. Olfactory function was assessed using the extended Sniffin' Sticks test (SST) comprising tests for odor threshold, identification, and discrimination. All participants received the Novel Olfactory Sorting Task (NOST) which is based on the sorting of 12 matching pairs of odors involving olfactory and cognitive functions. After that, all participants rated questions related to their test performance and the practicability of the test. RESULTS Consistent with the previous literature, significant effects of age were found. Results showed an acceptable test-retest reliability and a satisfactory validity of the NOST. The NOST score not only had positive correlations with SST, but also was capable of differentiating severe hyposmia/anosmia from normosmia by the score of 5.5 (sensitivity of 76.2%, specificity of 77.6%). CONCLUSION The present study showed the good reliability, validity, and possible clinical usefulness of the NOST. As a self-performed screening test, it can be comprehended and conducted easily, which may provide a quick and simple approach to obtaining a global estimation of olfactory and cognitive functions.
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Affiliation(s)
- Shubin Li
- Department of Otorhinolaryngology, Smell & Taste Clinic, Technische Universität Dresden, Dresden, Germany.
| | - Anne Wolter
- Department of Otorhinolaryngology, Smell & Taste Clinic, Technische Universität Dresden, Dresden, Germany
| | - Christine Kelly
- AbScent, 14 London Street, Andover, Hampshire, UK
- Centre for Olfactory Research and Applications, School of Advanced Study, University of London, London, UK
| | - Barry Smith
- Institute of Philosophy, School of Advanced Study, University of London, London, UK
- Centre for Olfactory Research and Applications, School of Advanced Study, University of London, London, UK
| | - Katie Whitcroft
- Department of Otorhinolaryngology, Smell & Taste Clinic, Technische Universität Dresden, Dresden, Germany
- Centre for Olfactory Research and Applications, School of Advanced Study, University of London, London, UK
| | - Harry Sherwood
- AbScent, 14 London Street, Andover, Hampshire, UK
- Centre for Olfactory Research and Applications, School of Advanced Study, University of London, London, UK
| | - Beth Longley
- Institute of Cognitive Neuroscience, UCL, London, UK
| | - Thomas Hummel
- Department of Otorhinolaryngology, Smell & Taste Clinic, Technische Universität Dresden, Dresden, Germany
- Centre for Olfactory Research and Applications, School of Advanced Study, University of London, London, UK
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Sabiniewicz A, Sorokowska A, Palmiero M, Nicotra M, Sorokowski P. Gender differences in the relationship between neuroticism and odor memory. Physiol Behav 2024; 276:114475. [PMID: 38278502 DOI: 10.1016/j.physbeh.2024.114475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 01/16/2024] [Accepted: 01/22/2024] [Indexed: 01/28/2024]
Abstract
Given the indications on the relationship between neuroticism and various olfactory functions as well as the emotionality of odor memory, it is surprising that no research so far has investigated whether neuroticism corresponds with odor memory performance. Thus, the purpose of our study was to address this question in the context of gender differences. Participants (73 men) completed the 60-items NEO Five Factor Inventory and participated in 32-items "Test for odor memory". In the separate analyses conducted for men and women, we demonstrated that women outperformed men regarding the number of correct odor recognitions in the odor memory test and had higher neuroticism level than men. Spearman correlation showed further that neuroticism was positively associated with D-prime (R = 0.3, p = .021) and the number of correct odor recognitions in women (R = 0.32, p = .014). This effect was, respectively, moderately (B10 = 5.2) and strongly confirmed using the Bayesian approach (B10 = 8). However, Bonferroni post-hoc correction for multiple comparisons further revealed that in case of neuroticism and the number of hits, as well as D-prime, alpha level was below significance, indicated by p = .006. The correlation between neuroticism level and odor memory performance was significantly higher in women compared to men (Z = 1.8, p = .038), while in case of neuroticism and D-prime, it was on a trend level (Z = 1.5, p = .074). Overall, the present results indicate that neuroticism might be linked to conscious odors' remembering for women, which can be explained by the warning role of odor memory and its connection to limbic structures, as well as by the higher level of neuroticism and odor memory performance in women compared to men.
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Affiliation(s)
- Agnieszka Sabiniewicz
- Institute of Psychology, University of Wrocław, Wrocław, Poland; Interdisciplinary Center "Smell & Taste", Department of Otorhinolaryngology, TU Dresden, Dresden, Germany.
| | - Agnieszka Sorokowska
- Institute of Psychology, University of Wrocław, Wrocław, Poland; Interdisciplinary Center "Smell & Taste", Department of Otorhinolaryngology, TU Dresden, Dresden, Germany
| | | | - Michele Nicotra
- Institute of Psychology, University of Wrocław, Wrocław, Poland
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Alotaibi M, Lessard-Beaudoin M, Busch K, Loudghi A, Gaudreau P, Graham RK. Olfactory Dysfunction Associated with Cognitive Decline in an Elderly Population. Exp Aging Res 2024; 50:1-16. [PMID: 36545820 DOI: 10.1080/0361073x.2022.2160597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND In many neurological disorders, including Alzheimer disease, early olfactory dysfunction is observed. OBJECTIVE In order to determine if deficits in olfactory memory are present in the elderly and if olfactory dysfunction correlates with cognitive impairment in the aging population, olfactory testing has been done on seniors from the NuAge cohort accepting to participate in the Olfactory Response Cognition and Aging (ORCA) secondary sub-study. The t-Mini Mental Statement Examination and the Telephone Interview for Cognitive Status tests were done to assess cognition levels. RESULTS Overall, 94% of the ORCA cohort displayed olfactory dysfunction. Deficits in olfactory memory were also present. A correlation was observed between olfactory function and cognitive test scores. Moreover, in women who smoked, there was an association between olfactory memory and cognitive scores. CONCLUSION Our results suggest that olfactory dysfunction may predict impending cognitive decline and highlights the need for olfactory training in seniors to improve olfaction and overall well-being.
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Affiliation(s)
- Majed Alotaibi
- King Abdullah International Medical Research Center, KSAU-HS, Riyadh, Saudi Arabia
- Department of Neuroscience, The University of Sheffield, Sheffiled, UK
- Research Centre on Aging CIUSSS de l'Estrie - CHUS, Sherbrooke, Quebec, Canada
| | - Melissa Lessard-Beaudoin
- Research Centre on Aging CIUSSS de l'Estrie - CHUS, Sherbrooke, Quebec, Canada
- Department of Pharmacology and Physiology, University of Sherbrooke, Sherbrooke, Canada
| | - Kate Busch
- Research Centre on Aging CIUSSS de l'Estrie - CHUS, Sherbrooke, Quebec, Canada
| | - Amal Loudghi
- Research Centre on Aging CIUSSS de l'Estrie - CHUS, Sherbrooke, Quebec, Canada
- Department of Pharmacology and Physiology, University of Sherbrooke, Sherbrooke, Canada
| | - Pierrette Gaudreau
- Department of Medicine, University of Montreal, Quebec, Canada
- Department of Biochemistry and Molecular Medicine, Centre Hospitalier de l'Université de Montréal Research Center, Montreal, Quebec, Canada
| | - Rona K Graham
- Research Centre on Aging CIUSSS de l'Estrie - CHUS, Sherbrooke, Quebec, Canada
- Department of Pharmacology and Physiology, University of Sherbrooke, Sherbrooke, Canada
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Camara G, Alotaibi M, Lessard-Beaudoin M, Busch K, Gendron L, Graham RK. Specific olfactory deficit patterns observed in seniors and associated with cognitive decline. Prog Neuropsychopharmacol Biol Psychiatry 2023; 126:110775. [PMID: 37120003 DOI: 10.1016/j.pnpbp.2023.110775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 04/20/2023] [Accepted: 04/21/2023] [Indexed: 05/01/2023]
Abstract
Olfactory dysfunction is a common symptom in neurodegenerative disorders and is regarded as a potential early predictor of impending cognitive decline. This study was undertaken in order to determine if olfactory dysfunction observed in the elderly is due to a general loss of smell or the inability to detect specific odours, and if misidentification of odours correlates with cognitive scores. Seniors for the Olfactory Response and Cognition in Aging (ORCA) sub-study were recruited from the Quebec Nutrition and Successful Aging (NuAge) cohort. The University of Pennsylvania smell identification test (UPSIT) was performed to measure olfactory function and the telephone Mini Mental State Examination (t-MMSE) and the French version of the Telephone Interview for Cognitive Status Modified (F-TICS-m) for cognitive status. The results demonstrate that seniors exhibit specific olfactory loss and had severe difficulty in particular in identifying lemon, pizza, fruit punch, cheddar cheese and lime. Furthermore, there was a significant difference in the ability to detect certain odours between the sexes. Results also showed that misidentification of certain scents was associated with cognitive scores, and when the sexes were assessed separately sex-specific misidentification of cognitive-associated odours was observed. The relationship between the cognitive scores and scent misidentification suggests that impending cognitive decline may be highlighted by the inability to smell specific odours. Our study provides additional support for the testing of olfactory function in the elderly and suggests that loss of smell for particular scents may become a useful diagnostic tool.
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Affiliation(s)
- Gemma Camara
- Research Centre on Aging CIUSSS de l'Estrie - CHUS, Canada; Dept of Pharmacology and Physiology, University of Sherbrooke, Sherbrooke, Canada
| | - Majed Alotaibi
- Medical Genomics Research Department, King Abdullah International Medical Research Center, United States of America; King Saud Bin Abdulaziz University for Health and Science, Riyadh, Kingdom of Saudi Arabia
| | - Melissa Lessard-Beaudoin
- Research Centre on Aging CIUSSS de l'Estrie - CHUS, Canada; Dept of Pharmacology and Physiology, University of Sherbrooke, Sherbrooke, Canada
| | - Kate Busch
- Research Centre on Aging CIUSSS de l'Estrie - CHUS, Canada
| | - Louis Gendron
- Dept of Pharmacology and Physiology, University of Sherbrooke, Sherbrooke, Canada
| | - Rona K Graham
- Research Centre on Aging CIUSSS de l'Estrie - CHUS, Canada; Dept of Pharmacology and Physiology, University of Sherbrooke, Sherbrooke, Canada.
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Li SB, Yan C, Hummel T, Zou LQ. Development and validation of the Olfactory Memory Test Battery (OMTB) based on odors with high- and low-verbalizability. J Neurosci Methods 2023; 388:109826. [PMID: 36822275 DOI: 10.1016/j.jneumeth.2023.109826] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 02/18/2023] [Accepted: 02/20/2023] [Indexed: 02/23/2023]
Abstract
BACKGROUND Odor memory is an important field of clinical research for its distinctive characteristics, which differ from those of other sensory systems. To date, several tests have been implemented for the assessment of odor memory. Despite a range of studies demonstrating the importance of verbal mediation in odor memory, few have distinguished odor memory performance in different odor verbalization levels. NEW METHOD We aimed to develop a standardized odor memory test toolbox with one group of odors that are easily verbally identified and the other group of odors that are difficult to identify. The test contained two odor categories (high- and low-verbalizability odors), each consisting of three subtests (short- and long-term memory and working memory). RESULTS Satisfactory test-retest reliability and solid validity of the odor recognition and working memory test were shown in both odor categories. Moreover, people scored significantly better with high- than low-verbalizability odors. A negative age effect on odor memory performance was also found. COMPARISON WITH EXISTING METHODS No previous odor memory test distinguished odor memory performance in different odor verbalization levels, while the Olfactory Memory Test Battery (OMTB) contains high- and low-verbalizability odors and each category has three subtests. CONCLUSIONS The present study indicated the OMTB is a comprehensive assessment of odor memory with good reliability and validity. All subtests can be used separately or in combination with each other according to the clinical and research needs.
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Affiliation(s)
- Shu-Bin Li
- Chemical Senses and Mental Health Lab, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China; Smell & Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Dresden, Germany
| | - Chao Yan
- Key Laboratory of Brain Functional Genomics (MOE&STCSM), Shanghai Changning-ECNU Mental Health Center, School of Psychology and Cognitive Science, East China Normal University, Shanghai, China
| | - Thomas Hummel
- Smell & Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Dresden, Germany
| | - Lai-Quan Zou
- Chemical Senses and Mental Health Lab, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.
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Cothren TO, Evonko CJ, MacQueen DA. Olfactory Dysfunction in Schizophrenia: Evaluating Olfactory Abilities Across Species. Curr Top Behav Neurosci 2023; 63:363-392. [PMID: 36059004 DOI: 10.1007/7854_2022_390] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
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.
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Affiliation(s)
- Taitum O Cothren
- Department of Psychology, University of North Carolina at Wilmington, Wilmington, NC, USA
| | - Christopher J Evonko
- Department of Psychology, University of North Carolina at Wilmington, Wilmington, NC, USA
| | - David A MacQueen
- Department of Psychology, University of North Carolina at Wilmington, Wilmington, NC, USA.
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Hunter SR, Hannum ME, Pellegrino R, O’Leary MA, Rawson NE, Reed DR, Dalton PH, Parma V. Proof-of-concept: SCENTinel 1.1 rapidly discriminates COVID-19 related olfactory disorders. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2022:2022.03.23.22272807. [PMID: 35350197 PMCID: PMC8963695 DOI: 10.1101/2022.03.23.22272807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
It is estimated that 20-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of four possible odors. Those who completed the test (N = 381) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder (anosmia or hyposmia, N = 135), qualitative olfactory disorder (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.
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Affiliation(s)
| | | | | | | | | | | | | | - Valentina Parma
- Monell Chemical Senses Center, Philadelphia, PA
- Department of Psychology, Temple University, Philadelphia, PA
- Correspondence: Valentina Parma, PhD, Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19143,
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Schlintl C, Schienle A. Reduced Olfactory Memory Performance Is Associated with Executive Function Deficits in Older Adults. Exp Aging Res 2022; 49:347-359. [PMID: 36100444 DOI: 10.1080/0361073x.2022.2122651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Previous research has identified an association between olfactory impairment (reduced odor sensitivity/ identification/ discrimination) and cognitive impairment in older adults. The present study focused on the relationship between olfactory memory performance and cognitive/affective functioning. METHOD Recognition performance for olfactory and visual stimuli (control condition) was tested through a matching task in older adults (n = 44; Mage = 76 years) and younger adults (n = 56; Mage = 24 years). Additionally, negative affect (anxiety, depression) and cognitive functioning were assessed via validated questionnaires and a neuropsychological test battery. RESULTS The older participants performed worse than the younger adults in the olfactory memory task. In older adults, difficulties in remembering odors were associated with reduced odor identification and executive functioning (reduced cognitive flexibility). Affective well-being was not related to olfactory memory performance. IMPLICATION Olfactory memory impairment in older adulthood might be a marker for cognitive decline in areas related to executive functions.
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Affiliation(s)
- Carina Schlintl
- Clinical Psychology, University of Graz, BioTechMed, Graz, Austria
| | - Anne Schienle
- Clinical Psychology, University of Graz, BioTechMed, Graz, Austria
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11
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Patel ZM, Holbrook EH, Turner JH, Adappa ND, Albers MW, Altundag A, Appenzeller S, Costanzo RM, Croy I, Davis GE, Dehgani-Mobaraki P, Doty RL, Duffy VB, Goldstein BJ, Gudis DA, Haehner A, Higgins TS, Hopkins C, Huart C, Hummel T, Jitaroon K, Kern RC, Khanwalkar AR, Kobayashi M, Kondo K, Lane AP, Lechner M, Leopold DA, Levy JM, Marmura MJ, Mclelland L, Miwa T, Moberg PJ, Mueller CA, Nigwekar SU, O'Brien EK, Paunescu TG, Pellegrino R, Philpott C, Pinto JM, Reiter ER, Roalf DR, Rowan NR, Schlosser RJ, Schwob J, Seiden AM, Smith TL, Soler ZM, Sowerby L, Tan BK, Thamboo A, Wrobel B, Yan CH. International consensus statement on allergy and rhinology: Olfaction. Int Forum Allergy Rhinol 2022; 12:327-680. [PMID: 35373533 DOI: 10.1002/alr.22929] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 01/01/2021] [Accepted: 11/19/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). METHODS Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence-based review, or evidence-based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus. RESULTS The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies. CONCLUSION This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further.
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Affiliation(s)
- Zara M Patel
- Otolaryngology, Stanford University School of Medicine, Stanford, California, USA
| | - Eric H Holbrook
- Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA
| | - Justin H Turner
- Otolaryngology, Vanderbilt School of Medicine, Nashville, Tennessee, USA
| | - Nithin D Adappa
- Otolaryngology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Mark W Albers
- Neurology, Harvard Medical School, Boston, Massachusetts, USA
| | - Aytug Altundag
- Otolaryngology, Biruni University School of Medicine, İstanbul, Turkey
| | - Simone Appenzeller
- Rheumatology, School of Medical Sciences, University of Campinas, São Paulo, Brazil
| | - Richard M Costanzo
- Physiology and Biophysics and Otolaryngology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Ilona Croy
- Psychology and Psychosomatic Medicine, TU Dresden, Dresden, Germany
| | - Greg E Davis
- Otolaryngology, Proliance Surgeons, Seattle and Puyallup, Washington, USA
| | - Puya Dehgani-Mobaraki
- Associazione Naso Sano, Umbria Regional Registry of Volunteer Activities, Corciano, Italy
| | - Richard L Doty
- Smell and Taste Center, Otolaryngology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Valerie B Duffy
- Allied Health Sciences, University of Connecticut, Storrs, Connecticut, USA
| | | | - David A Gudis
- Otolaryngology, Columbia University Irving Medical Center, New York, USA
| | - Antje Haehner
- Smell and Taste, Otolaryngology, TU Dresden, Dresden, Germany
| | - Thomas S Higgins
- Otolaryngology, University of Louisville School of Medicine, Louisville, Kentucky, USA
| | - Claire Hopkins
- Otolaryngology, Guy's and St. Thomas' Hospitals, London Bridge Hospital, London, UK
| | - Caroline Huart
- Otorhinolaryngology, Cliniques universitaires Saint-Luc, Institute of Neuroscience, Université catholgique de Louvain, Brussels, Belgium
| | - Thomas Hummel
- Smell and Taste, Otolaryngology, TU Dresden, Dresden, Germany
| | | | - Robert C Kern
- Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Ashoke R Khanwalkar
- Otolaryngology, Stanford University School of Medicine, Stanford, California, USA
| | - Masayoshi Kobayashi
- Otorhinolaryngology-Head and Neck Surgery, Mie University Graduate School of Medicine, Mie, Japan
| | - Kenji Kondo
- Otolaryngology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Andrew P Lane
- Otolaryngology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Matt Lechner
- Otolaryngology, Barts Health and University College London, London, UK
| | - Donald A Leopold
- Otolaryngology, University of Vermont Medical Center, Burlington, Vermont, USA
| | - Joshua M Levy
- Otolaryngology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Michael J Marmura
- Neurology Thomas Jefferson University School of Medicine, Philadelphia, Pennsylvania, USA
| | - Lisha Mclelland
- Otolaryngology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Takaki Miwa
- Otolaryngology, Kanazawa Medical University, Ishikawa, Japan
| | - Paul J Moberg
- Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
| | | | - Sagar U Nigwekar
- Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Erin K O'Brien
- Otolaryngology, Mayo Clinic Rochester, Rochester, Minnesota, USA
| | - Teodor G Paunescu
- Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | | | - Carl Philpott
- Otolaryngology, University of East Anglia, Norwich, UK
| | - Jayant M Pinto
- Otolaryngology, University of Chicago, Chicago, Illinois, USA
| | - Evan R Reiter
- Otolaryngology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - David R Roalf
- Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
| | - Nicholas R Rowan
- Otolaryngology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Rodney J Schlosser
- Otolaryngology, Medical University of South Carolina, Mt Pleasant, South Carolina, USA
| | - James Schwob
- Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Allen M Seiden
- Otolaryngology, University of Cincinnati School of Medicine, Cincinnati, Ohio, USA
| | - Timothy L Smith
- Otolaryngology, Oregon Health and Sciences University, Portland, Oregon, USA
| | - Zachary M Soler
- Otolaryngology, Medical University of South Carolina, Mt Pleasant, South Carolina, USA
| | - Leigh Sowerby
- Otolaryngology, University of Western Ontario, London, Ontario, Canada
| | - Bruce K Tan
- Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Andrew Thamboo
- Otolaryngology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Bozena Wrobel
- Otolaryngology, Keck School of Medicine, USC, Los Angeles, California, USA
| | - Carol H Yan
- Otolaryngology, School of Medicine, UCSD, La Jolla, California, USA
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12
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Patel RA, Torabi SJ, Kasle DA, Manes RP. Five-item odorant test as an indicator of COVID-19 infection in a general population. Am J Otolaryngol 2022; 43:103376. [PMID: 35151176 PMCID: PMC8800163 DOI: 10.1016/j.amjoto.2022.103376] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 01/24/2022] [Indexed: 11/13/2022]
Abstract
Purpose To analyze the utility of a 5-item odorant test (U-Smell-It™) in determining COVID-19 status in COVID-19 polymerase chain reaction (PCR)-positive and -negative participants. Methods Symptoms, COVID-19 status, and 5-item odorant test results were collected from general population COVID-19 testing in Louisiana (n = 1042), and routine COVID-19 screening of healthcare workers in a nursing home in Florida (n = 278) (ClinicalTrials.gov Identifier: NCT04431908). Results In the general population COVID-19 testing site, a cutoff point of ≤2 (0, 1, or 2 correct answers out of 5) achieved sensitivity of 40.0% (95% CI: 26.4%–54.8%) and specificity of 89.2% (95% CI: 87.1%–91.1%) in detecting COVID-19 infection. Within this population, analysis of individuals with no self-reported loss of smell/taste and runny/stuffy nose resulted in sensitivity of 38.1% (95% CI: 18.1%–61.6%) and specificity of 92.3% (95% CI: 89.1%–93.4%), while analysis of individuals with self-reported loss of smell/taste and/or runny/stuffy nose resulted in sensitivity of 41.4% (95% CI: 23.5%–61.1%) and specificity of 82.4% (95% CI: 77.7%–86.5%). Conclusions The quick turnaround time, low cost, reduced resource requirement, and ease of administering odorant tests provide many advantages as an indicator sign to help flag a molecular diagnostic COVID-19 test with relatively high specificity. Our results suggest that this odorant testing for olfactory dysfunction may be a viable option in pre-screening COVID-19 infection. This tool has the potential to allow for continued monitoring and surveillance, while helping mitigate surges of COVID-19 variants. Further investigation is warranted to observe the extent to which odorant testing might be applied in a serial testing scenario.
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13
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Honnens de Lichtenberg Broge E, Wendin K, Hyldig G, Bredie WLP. Development of an olfactory test method for measuring perception of everyday food odors among older adults. J SENS STUD 2021. [DOI: 10.1111/joss.12706] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Eva Honnens de Lichtenberg Broge
- Department of Food Science, Section for Food Design and Consumer Behaviour, Future Consumer Lab University of Copenhagen Frederiksberg Denmark
| | - Karin Wendin
- Department of Food Science, Section for Food Design and Consumer Behaviour, Future Consumer Lab University of Copenhagen Frederiksberg Denmark
- Department of Food and Meal Science Kristianstad University Kristianstad Sweden
| | - Grethe Hyldig
- Division of Food Technology, National Food Institute Technical University of Denmark Lyngby Denmark
| | - Wender L. P. Bredie
- Department of Food Science, Section for Food Design and Consumer Behaviour, Future Consumer Lab University of Copenhagen Frederiksberg Denmark
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14
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Mitrano DA, Houle SE, Pearce P, Quintanilla RM, Lockhart BK, Genovese BC, Schendzielos RA, Croushore EE, Dymond EM, Bogenpohl JW, Grau HJ, Webb LS. Olfactory dysfunction in the 3xTg-AD model of Alzheimer's disease. IBRO Neurosci Rep 2021; 10:51-61. [PMID: 33842910 PMCID: PMC8019944 DOI: 10.1016/j.ibneur.2020.12.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Accepted: 12/13/2020] [Indexed: 12/01/2022] Open
Abstract
Alzheimer's disease (AD) is an incurable neurodegenerative disease in which the risk of development increases with age. People with AD are plagued with deficits in their cognition, memory, and basic social skills. Many of these deficits are believed to be caused by the formation of amyloid-β plaques and neurofibrillary tangles in regions of the brain associated with memory, such as the hippocampus. However, one of the early, preclinical symptoms of AD is the loss of olfactory detection and discrimination. To determine if a mouse model of AD expresses the same olfactory dysfunction seen in human AD, 3xTg-AD mice were given a buried food test and, unlike previous studies, compared to their background and parental strains. Results showed that over 52 weeks, the 3xTg-AD mice took significantly longer to find the buried food than the control strains. The olfactory bulbs of the 3xTg-AD mice were removed, sliced, and stained using Congo red for histological analysis. Amyloid deposits were observed predominantly in the granule layer of the olfactory bulb beginning at 13 weeks of age in 3xTg-AD mice, but not in the control strains of mice. Further examination of the buried food test data revealed that 3xTg-AD females had a significantly longer latency to detect the buried food than males beginning at 26 weeks of age. Overall, this study provides further validation of the 3xTg-AD mouse model of AD and supports the idea that simple olfactory testing could be part of the diagnostic process for human AD.
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Affiliation(s)
- Darlene A. Mitrano
- Department of Molecular Biology & Chemistry, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
- Program in Neuroscience, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
| | - Sam E. Houle
- Program in Neuroscience, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
| | - Patrick Pearce
- Program in Neuroscience, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
| | - Ricardo M. Quintanilla
- Department of Molecular Biology & Chemistry, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
| | - Blakely K. Lockhart
- Program in Neuroscience, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
| | - Benjamin C. Genovese
- Department of Molecular Biology & Chemistry, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
| | - Rachel A. Schendzielos
- Department of Molecular Biology & Chemistry, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
| | - Emma E. Croushore
- Department of Molecular Biology & Chemistry, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
| | - Ethan M. Dymond
- Department of Molecular Biology & Chemistry, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
| | - James W. Bogenpohl
- Department of Molecular Biology & Chemistry, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
- Program in Neuroscience, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
| | - Harold J. Grau
- Department of Molecular Biology & Chemistry, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
- Program in Neuroscience, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
| | - Lisa Smith Webb
- Department of Molecular Biology & Chemistry, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
- Program in Neuroscience, Christopher Newport University, 1 Avenue of the Arts, Newport News, VA 23606, USA
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15
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Olofsson JK. Olfaction and Aging: A Review of the Current State of Research and Future Directions. Iperception 2021; 12:20416695211020331. [PMID: 34249327 PMCID: PMC8239976 DOI: 10.1177/20416695211020331] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 04/21/2021] [Indexed: 11/16/2022] Open
Abstract
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.
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Affiliation(s)
- Jonas K. Olofsson
- Gösta Ekman Laboratory, Stockholm University, Stockholm, Sweden; Department of Psychology, Stockholm University, Stockholm, Sweden
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16
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Tzeng WY, Figarella K, Garaschuk O. Olfactory impairment in men and mice related to aging and amyloid-induced pathology. Pflugers Arch 2021; 473:805-821. [PMID: 33608800 PMCID: PMC7895745 DOI: 10.1007/s00424-021-02527-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 01/07/2021] [Accepted: 01/28/2021] [Indexed: 12/31/2022]
Abstract
Olfaction, or the sense of smell, is one of the most ancient senses in men and mice, important for a large variety of innate and acquired behaviors. Clinical data reveal an early impairment of olfaction during normal aging and in the course of neurodegenerative diseases, but the underlying cellular/molecular mechanisms remain obscure. In the current review, we compare different aspects of the aging- and Alzheimer's disease related impairment of olfaction in men and mice, aiming at the identification of common morbidities and biomarkers, which can be analyzed in detail in the appropriate mouse models. We also identify common, often interdependent (patho)physiological pathways, including but not limited to extracellular amyloid depositions, neuroinflammation, ɛ4 allele of the apolipoprotein E, CNS insulin resistance, and the impairment of adult neurogenesis, to be targeted by basic and clinical research.
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Affiliation(s)
- Wen-Yu Tzeng
- Institute of Physiology, Department of Neurophysiology, Eberhard Karls University of Tübingen, Keplerstr. 15, 72074, Tübingen, Germany
| | - Katherine Figarella
- Institute of Physiology, Department of Neurophysiology, Eberhard Karls University of Tübingen, Keplerstr. 15, 72074, Tübingen, Germany
| | - Olga Garaschuk
- Institute of Physiology, Department of Neurophysiology, Eberhard Karls University of Tübingen, Keplerstr. 15, 72074, Tübingen, Germany.
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17
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Wenzel ES, Cameron EL, Møller P, Köster EP. Novelty Detection in Memory for Common and Uncommon Odors over Short Delays. Chem Senses 2021; 46:6174308. [PMID: 33725719 DOI: 10.1093/chemse/bjab013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Odor memory is commonly believed to be very strong and long-lasting. The present study examined factors that impact odor recognition memory over short delay intervals (immediately or 30 s after target presentation) with emphasis on memory task (forced-choice vs "monadic"/single stimulus yes/no), odor category, and target/foil relationship. We explored trial-by-trial confidence as well as the effect of target familiarity, pleasantness, and intensity ratings, and odor nameability on memory for odors. Overall odor recognition memory in terms of proportion correct and sensitivity measures did not decline significantly during the 30-s delay interval in either task. However, hit rates were lower at 30 s and correct rejection rates for common odors remained consistently high. Recognition memory was better on trials in which the odor pairs were highly dissimilar, as well as on trials in which the target was an uncommon odor, particularly if it could be named. Familiarity, pleasantness, and intensity had no systematic effect on recognition memory. Whereas the results provide evidence of a fading memory trace, indicated by the decreased hit rates after a 30-s delay, the constant rates of correct rejections and high confidence ratings on those trials, even after delay, suggests that novelty detection (i.e., recognition that an odor is not one that has been encountered previously in that context) may play an important role in the memory for odors over short delays. Whether there is a separate short-term odor memory store is also addressed.
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Affiliation(s)
| | - E Leslie Cameron
- Department of Psychological Science, Carthage College, Kenosha, WI, USA
| | - Per Møller
- Department of Food Science, University of Copenhagen, Copenhagen, Denmark
| | - Egon P Köster
- Helmholtz Institute, University of Utrecht, Utrecht, the Netherlands
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18
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Odorant-induced brain activation as a function of normal aging and Alzheimer's disease: A preliminary study. Behav Brain Res 2021; 402:113078. [PMID: 33359846 DOI: 10.1016/j.bbr.2020.113078] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 12/10/2020] [Accepted: 12/14/2020] [Indexed: 11/23/2022]
Abstract
Olfactory dysfunction consistently occurs in patients with Alzheimer's disease (AD), beyond the mild and gradual decline in olfactory ability found in normal aging. This dysfunction begins early in the disease course, typically before clinical diagnosis, and progresses with disease severity. While odor identification and detection deficits clearly differentiate AD from controls, there remains uncertainty as to whether these are determined by olfactory threshold. The purpose of the current preliminary fMRI study was to examine the neural correlates of olfactory processing in healthy young and old adults and compare them with AD patients. We also explored the interplay between age and disease-related psychophysical olfactory declines and odorant-induced brain activation. Results indicated AD patients had decreased odor detection task-related signal in all regions of the primary olfactory cortex, with activity in the entorhinal cortex best differentiating the groups. Moderated-mediation analyses on neuro-psychophysical relationships found that increased brain activation in the entorhinal cortex moderated the negative effect of disease-related threshold changes on olfactory detection. Therefore, even in the face of higher (worse) olfactory thresholds, older adults and AD patients compensated for this effect with increased brain activation in a primary olfactory brain region. This was the case for odor detection but not odor identification. fMRI activation induced by an olfactory detection task may eventually be useful in improving early discovery of AD and may, eventually, facilitate early treatment interventions in subjects at risk for AD.
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19
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Parma V, Hannum ME, O’Leary M, Pellegrino R, Rawson NE, Reed DR, Dalton PH. SCENTinel 1.0: Development of a Rapid Test to Screen for Smell Loss. Chem Senses 2021; 46:bjab012. [PMID: 33773496 PMCID: PMC8083606 DOI: 10.1093/chemse/bjab012] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Commercially available smell tests are primarily used in research or in-depth clinical evaluations and are too costly and time-consuming for population surveillance in health emergencies like COVID-19. To address this need, we developed the SCENTinel 1.0 test, which rapidly evaluates 3 olfactory functions: detection, intensity, and identification. We tested whether self-administering the SCENTinel 1.0 test discriminates between individuals with self-reported smell loss and those with average smell ability (normosmic individuals) and provides performance comparable to the validated and standardized NIH Toolbox Odor Identification Test in normosmic individuals. Using Bayesian linear models and prognostic classification algorithms, we compared the SCENTinel 1.0 performance of a group of self-reported anosmic individuals (N = 111, 47 ± 13 years old, F = 71%) and normosmic individuals (N = 154, 47 ± 14 years old, F = 74%) as well as individuals reporting other smell disorders (such as hyposmia or parosmia; N = 42, 55 ± 10 years old, F = 67%). Ninety-four percent of normosmic individuals met our SCENTinel 1.0 accuracy criteria compared with only 10% of anosmic individuals and 64% of individuals with other smell disorders. Overall performance on SCENTinel 1.0 predicted belonging to the normosmic group better than identification or detection alone (vs. anosmic: AUC = 0.95, specificity = 0.94). Odor intensity provided the best single-feature predictor to classify normosmic individuals. Among normosmic individuals, 92% met the accuracy criteria at both SCENTinel 1.0 and the NIH Toolbox Odor Identification Test. SCENTinel 1.0 is a practical test able to discriminate individuals with smell loss and will likely be useful in many clinical situations, including COVID-19 symptom screening.
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Affiliation(s)
- Valentina Parma
- Department of Psychology, Temple University, 1701 N 13th Street, Philadelphia, PA, USA
- Monell Chemical Senses Center, 3500 Market Street, 19104, Philadelphia, PA, USA
| | - Mackenzie E Hannum
- Monell Chemical Senses Center, 3500 Market Street, 19104, Philadelphia, PA, USA
| | - Maureen O’Leary
- Monell Chemical Senses Center, 3500 Market Street, 19104, Philadelphia, PA, USA
| | - Robert Pellegrino
- Monell Chemical Senses Center, 3500 Market Street, 19104, Philadelphia, PA, USA
| | - Nancy E Rawson
- Monell Chemical Senses Center, 3500 Market Street, 19104, Philadelphia, PA, USA
| | - Danielle R Reed
- Monell Chemical Senses Center, 3500 Market Street, 19104, Philadelphia, PA, USA
| | - Pamela H Dalton
- Monell Chemical Senses Center, 3500 Market Street, 19104, Philadelphia, PA, USA
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20
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SCENTinel 1.0 : development of a rapid test to screen for smell loss. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2020. [PMID: 33330892 DOI: 10.1101/2020.12.10.20244301] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Background Commercially available smell tests are primarily used in research or in-depth clinical evaluations, but are too costly and lengthy for population surveillance in health emergencies like COVID-19. We developed the SCENTinel 1 . 0 test which rapidly evaluates three olfactory functions (detection, intensity, and identification). We tested whether self-administering the SCENTinel 1 . 0 test discriminates between individuals with smell loss or average smell ability (normosmics), and provides comparable performance as the validated and standardized NIH Toolbox ® Odor Identification Test in normosmics. Methods Using Bayesian linear models and prognostic classification algorithms, we compared the SCENTinel 1 . 0 performance of a group of self-reported anosmics (N=111, 47±13yo, F=71%,) and normosmics (N=154, 47±14yo, F=74%), as well as individuals reporting other smell disorders (e.g., hyposmia, parosmia; N=42, 55±10yo, F=67%). Results Ninety-four percent of normosmics met our SCENTinel 1 . 0 accuracy criteria, while only 10% of anosmics and 64% of individuals with other smell disorders did. Overall performance on SCENTinel 1 . 0 predicted belonging to the normosmic group better than identification or detection alone (vs. anosmic: AUC=0.95, Sensitivity=0.72, Specificity=0.94). Odor intensity provided the best single-feature predictor to classify normosmics. Among normosmics, 92% met the accuracy criteria at both SCENTinel 1 . 0 and the NIH Toolbox ® Odor Identification Test. Conclusions SCENTinel 1 . 0 is a practical test able to discriminate individuals with smell loss and is likely to be useful in many clinical situations, including COVID-19 symptom screening.
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21
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Spanish Validation for Olfactory Function Testing Using the Sniffin' Sticks Olfactory Test: Threshold, Discrimination, and Identification. Brain Sci 2020; 10:brainsci10120943. [PMID: 33297359 PMCID: PMC7762307 DOI: 10.3390/brainsci10120943] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/04/2020] [Accepted: 12/04/2020] [Indexed: 12/14/2022] Open
Abstract
The assessment of olfactory function is becoming increasingly relevant, especially in cases of cognitive decline (i.e., neurodegenerative diseases), where olfactory alterations may be relevant as potential early biomarkers. The Sniffin' Sticks Olfactory Test, developed in Germany and validated in several countries, is an objective measure of olfactory performance. This study aims to validate this test in a Spanish sample. This study included 209 healthy normosmic volunteers (154 females and 55 males) aged between 20 to 79 years (mean age = 50.11 ± 15.18 years) as the normative sample. From this group, 22 participants were retested in order to obtain test-retest reliability evidence. Odor familiarity for descriptors in the olfactory identification test was also studied on an independent healthy sample (n = 69), and required cultural modifications were applied. Results indicate that men and women, as well as smokers and non-smokers, performed equally in every test. However, significant differences were found between age groups in every score. The general trend is that olfactory function progressively decreases as a function of age, the elderly group (+60 years) being the one with the lowest scores. In conclusion, this normative data, in addition to the test's cultural modifications, allows the Sniffin' Sticks Olfactory Test to be administered on a Spanish population.
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22
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Jalali MM, Faghih Habibi A, Ghorbani Samin M. Predictors of Olfactory Impairment among Northern Iranian Population. IRANIAN JOURNAL OF OTORHINOLARYNGOLOGY 2020; 32:271-279. [PMID: 33014903 PMCID: PMC7515626 DOI: 10.22038/ijorl.2019.40358.2325] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Introduction The performance in most smell identification tests is subjected to cultural variations. This study aimed to evaluate age, gender, and smoking-related effects on the test performance in the North of Iran. Materials and Methods The olfactory function of 1470 eligible subjects was assessed in this study. Moreover, this study evaluated the influence of age, gender, and education on the test scores. Results According to the results, females obtained higher mean test scores, compared to males (18.4 vs. 17.6). In general, the elderly obtained lower scores, and about 30% of the subjects who were ≥65 years of age had severe hyposmia or anosmia. Furthermore, the olfactory impairment frequency in smoker subjects was significantly more than non-smokers (P<0.001). Test scores were generally higher in subjects with higher education levels. Logistic regression analysis revealed that the total number of cigarette doses in smokers and age had a significant association with olfactory dysfunction (P value <0.001 and 0.004, respectively). Cronbach's α of Iran-SIT was obtained at 0.78 which was more than an acceptable value of 0.7. Conclusion The findings of this study revealed that a low score in the Iran-SIT correlated with smoking, older age, low education level, and gender (male).
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Affiliation(s)
- Mir Mohammad Jalali
- Otorhinolaryngology Research Center, Department of Otolaryngology and Head and Neck Surgery, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Ali Faghih Habibi
- Otorhinolaryngology Research Center, Department of Otolaryngology and Head and Neck Surgery, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
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Sorokowska A, Sabiniewicz A, Larsson M. TOM-32-An extended test for the assessment of olfactory memory. J Neurosci Methods 2020; 344:108873. [PMID: 32710924 DOI: 10.1016/j.jneumeth.2020.108873] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 07/08/2020] [Accepted: 07/20/2020] [Indexed: 11/15/2022]
Abstract
BACKGROUND Olfactory memory testing is a promising way to explore different aspects of smell-related abilities in healthy subjects as well as to diagnose various diseases associated with disorders of this type of memory. Despite the obvious value of olfactory memory assessments, few available methods enable its diagnosis. NEW METHOD The aim of our study was to create a standardized research tool designed for olfactory memory studies: an extended, 32-item version of an available "Test for Odor Memory". RESULTS The study involving 222 subjects revealed satisfactory psychometric qualities of TOM-32, and - as hypothesized - subjects with depression scored significantly lower than healthy participants. We additionally showed that TOM-32 scores was associated with sex, age and olfactory awareness. Women performed significantly better than men, young people tended to have lower false alarm rate than older subjects and olfactory awareness was positively associated with olfactory memory. COMPARISON WITH EXISTING METHOD(S) TOM-32 could expand the possibilities of testing olfactory memory. It may offer additional information about cognitive and sensory abilities relative to existing research tools, and the large number of included test items may facilitate repeated and longitudinal testing. Wide range of applied odors increases the possibility to detect subtle differences between, as well as changes within, individuals. CONCLUSIONS We present an extensive olfactory memory test with satisfactory psychometric qualities - a test that is comprehensive enough to show significant inter- and intra-individual differences, but time-efficient enough to be comfortable in daily research and clinical usage.
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Affiliation(s)
- Agnieszka Sorokowska
- Smell and Taste Research Lab, Institute of Psychology, University of Wroclaw, Pl. Dawida 1, 50-527 Wroclaw, Poland.
| | - Agnieszka Sabiniewicz
- Smell and Taste Research Lab, Institute of Psychology, University of Wroclaw, Pl. Dawida 1, 50-527 Wroclaw, Poland.
| | - Maria Larsson
- Gösta Ekman Laboratory, Department of Psychology, Stockholm University, Frescati Hagväg 9A, 106 91 Stockholm, Sweden.
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Laroche M, Lessard-Beaudoin M, Garcia-Miralles M, Kreidy C, Peachey E, Leavitt BR, Pouladi MA, Graham RK. Early deficits in olfaction are associated with structural and molecular alterations in the olfactory system of a Huntington disease mouse model. Hum Mol Genet 2020; 29:2134-2147. [PMID: 32436947 DOI: 10.1093/hmg/ddaa099] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 04/25/2020] [Accepted: 05/12/2020] [Indexed: 12/22/2022] Open
Abstract
Olfactory dysfunction and altered neurogenesis are observed in several neurodegenerative disorders including Huntington disease (HD). These deficits occur early and correlate with a decline in global cognitive performance, depression and structural abnormalities of the olfactory system including the olfactory epithelium, bulb and cortices. However, the role of olfactory system dysfunction in the pathogenesis of HD remains poorly understood and the mechanisms underlying this dysfunction are unknown. We show that deficits in odour identification, discrimination and memory occur in HD individuals. Assessment of the olfactory system in an HD murine model demonstrates structural abnormalities in the olfactory bulb (OB) and piriform cortex, the primary cortical recipient of OB projections. Furthermore, a decrease in piriform neuronal counts and altered expression levels of neuronal nuclei and tyrosine hydroxylase in the OB are observed in the YAC128 HD model. Similar to the human HD condition, olfactory dysfunction is an early phenotype in the YAC128 mice and concurrent with caspase activation in the murine HD OB. These data provide a link between the structural olfactory brain region atrophy and olfactory dysfunction in HD and suggest that cell proliferation and cell death pathways are compromised and may contribute to the olfactory deficits in HD.
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Affiliation(s)
- M Laroche
- Research Center on Aging, CIUSSS-IUGS de l'Estrie-CHUS, FMSS, Department of Pharmacology and Physiology, University of Sherbrooke, Quebec J1K 2R1, Canada
| | - M Lessard-Beaudoin
- Research Center on Aging, CIUSSS-IUGS de l'Estrie-CHUS, FMSS, Department of Pharmacology and Physiology, University of Sherbrooke, Quebec J1K 2R1, Canada
| | - M Garcia-Miralles
- Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (ASTAR), Singapore 138632
| | - C Kreidy
- Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (ASTAR), Singapore 138632
| | - E Peachey
- Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver V6T 1Z4, Canada
| | - B R Leavitt
- Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver V6T 1Z4, Canada
| | - M A Pouladi
- Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (ASTAR), Singapore 138632.,Departments of Medicine and Physiology, National University of Singapore, Singapore 119077
| | - R K Graham
- Research Center on Aging, CIUSSS-IUGS de l'Estrie-CHUS, FMSS, Department of Pharmacology and Physiology, University of Sherbrooke, Quebec J1K 2R1, Canada
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Joseph T, Auger SD, Peress L, Rack D, Cuzick J, Giovannoni G, Lees A, Schrag AE, Noyce AJ. Screening performance of abbreviated versions of the UPSIT smell test. J Neurol 2019; 266:1897-1906. [PMID: 31053960 PMCID: PMC6647236 DOI: 10.1007/s00415-019-09340-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 04/17/2019] [Accepted: 04/23/2019] [Indexed: 01/17/2023]
Abstract
BACKGROUND Hyposmia can develop with age and in neurodegenerative conditions, including Parkinson's disease (PD). The University of Pennsylvania Smell Identification Test (UPSIT) is a 40-item smell test widely used for assessing hyposmia. However, in a number of situations, such as identifying hyposmic individuals in large populations, shorter tests are preferable. METHODS We assessed the ability of shorter UPSIT subsets to detect hyposmia in 891 healthy participants from the PREDICT-PD study. Shorter subsets included Versions A and B of the 4-item Pocket Smell Test (PST) and 12-item Brief Smell Identification Test (BSIT). Using a data-driven approach, we evaluated screening performances of 23,231,378 combinations of 1-7 smell items from the full UPSIT to derive "winning" subsets, and validated findings separately in another 191 healthy individuals. We then compared discriminatory UPSIT smells between PREDICT-PD participants and 40 PD patients, and assessed the performance of "winning" subsets containing discriminatory smells in PD patients. RESULTS PST Versions A and B achieved sensitivity/specificity of 76.8%/64.9% and 86.6%/45.9%, respectively, while BSIT Versions A and B achieved 83.1%/79.5% and 96.5%/51.8%. From the data-driven analysis, 2 "winning" 7-item subsets surpassed the screening performance of 12-item BSITs (validation sensitivity/specificity of 88.2%/85.4% and 100%/53.5%), while a "winning" 4-item subset had higher sensitivity than PST-A, -B, and even BSIT-A (validation sensitivity 91.2%). Interestingly, several discriminatory smells featured within "winning" subsets, and demonstrated high-screening performances for identifying hyposmic PD patients. CONCLUSION Using abbreviated smell tests could provide a cost-effective means of large-scale hyposmia screening, allowing more targeted UPSIT administration in general and PD-related settings.
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Affiliation(s)
| | - Stephen D Auger
- Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK
| | - Luisa Peress
- Barts and The London School of Medicine and Dentistry, London, UK
| | - Daniel Rack
- Barts and The London School of Medicine and Dentistry, London, UK
| | - Jack Cuzick
- Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK
| | - Gavin Giovannoni
- Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK
- Blizard Institute, Barts and the London Queen Mary University of London, London, UK
| | - Andrew Lees
- Reta Lila Weston Institute, Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, UK
| | - Anette E Schrag
- Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, UK
| | - Alastair J Noyce
- Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
- Reta Lila Weston Institute, Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, UK.
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Martinec Nováková L, Havlíček J. Time, Age, Gender, and Test Practice Effects on Children’s Olfactory Performance: a Two-Year Longitudinal Study. CHEMOSENS PERCEPT 2019. [DOI: 10.1007/s12078-019-09260-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Morquecho-Campos P, Larsson M, Boesveldt S, Olofsson JK. Achieving Olfactory Expertise: Training for Transfer in Odor Identification. Chem Senses 2019; 44:197-203. [DOI: 10.1093/chemse/bjz007] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Paulina Morquecho-Campos
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, The Netherlands
| | - Maria Larsson
- Gösta Ekman Laboratory, Department of Psychology, Stockholm University, Stockholm, Sweden
| | - Sanne Boesveldt
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, The Netherlands
| | - Jonas K Olofsson
- Gösta Ekman Laboratory, Department of Psychology, Stockholm University, Stockholm, Sweden
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Maharjan A, Peng M, Cakmak YO. Non-invasive High Frequency Median Nerve Stimulation Effectively Suppresses Olfactory Intensity Perception in Healthy Males. Front Hum Neurosci 2019; 12:533. [PMID: 30719001 PMCID: PMC6348262 DOI: 10.3389/fnhum.2018.00533] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2018] [Accepted: 12/17/2018] [Indexed: 01/27/2023] Open
Abstract
Median nerve stimulation (MNS) had been performed in the existing literature to alleviate symptoms of nausea and vomiting. The observed facilitative effects are thought to be mediated by the vagal pathways, particularly the vagus nerve (VN) brainstem nuclei of the dorsal motor nucleus of vagus and nucleus tractus solitarius (DMV-NTS). Sense of smell is one of the major sensory modalities for inducing vomiting and nausea as a primary defense against potentially harmful intake of material. This study aimed to test effects of non-invasive, high and low frequency MNS on human olfactory functioning, with supplementary exploration of the orbitofrontal cortex (OFC) using near-infrared spectroscopy (NIRS). Twenty healthy, male, adults performed supra-threshold odor intensity tests (labeled magnitude scale, LMS) for four food-related odorant samples (presented in three different concentrations) before and after receiving high-, low frequency MNS and placebo (no stimulation), while cortical activities in the OFC was monitored by the NIRS. Data of the NIRS and LMS test of separate stimulation parameters were statistically analyzed using mixed-model analysis of variance (ANOVA). Only the high frequency MNS showed effects for suppressing the intensity perception of the moderate concentration of Amyl Acetate (p:0.042) and strong concentration of Isovaleric Acid (p:0.004) and 1-Octen-3-ol (p:0.006). These behavioral changes were coupled with significant changes in the NIRS recordings of the left (p:0.000) and right (p:0.003) hemispheric orbitofrontal cortices. This is the first study that applied non-invasive, high frequency MNS to suppress the supra-threshold odor ratings of specific concentrations of odors. The vagal networks are potential relays of MNS to influence OFC. Results from the current article implore further research into non-invasive, high frequency MNS in the investigation of its modulatory effects on olfactory function, given its potential to be used for ameliorating nausea and malnutrition associated with various health conditions.
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Affiliation(s)
- Ashim Maharjan
- Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
| | - Mei Peng
- Department of Food Science, University of Otago, Dunedin, New Zealand
| | - Yusuf O Cakmak
- Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.,Brain Health Research Centre, Division of Sciences, University of Otago, Dunedin, New Zealand.,Medical Technologies Centre of Research Excellence, Auckland, New Zealand
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Abstract
The senses of smell and taste are largely underappreciated by laypersons and medical professionals alike. Unlike vision, hearing, balance, and touch, they are rarely evaluated quantitatively in the clinic, even though hundreds of thousands of persons seek medical help annually for disorders of these senses. Chemosensory disorders impact quality of life, including the flavor of foods and beverages, and compromise the ability to detect such environmental hazards as fires, leaking natural gas, and spoiled foodstuffs. Moreover, olfactory dysfunction can be a harbinger for Alzheimer's and other neurodegenerative diseases, and is known to triple the likelihood of mortality in older persons over the course of 4 or 5 years. Without accurate testing, one cannot establish the veracity of a patient's complaint, the probability of malingering, the impact of treatments, and whether the degree of dysfunction is normal relative to a patient's age and sex. This chapter provides basic information as to how to measure both the senses of smell and taste, as well as normative data for several clinical smell and taste tests.
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Affiliation(s)
- Richard L Doty
- Smell and Taste Center and Department of Otorhinolaryngology: Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
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30
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Besser G, Jobs L, Liu DT, Mueller CA, Renner B. The Sniffin' Sticks Odor Discrimination Memory Test: A Rapid, Easy-to-Use, Reusable Procedure for Testing Olfactory Memory. Ann Otol Rhinol Laryngol 2018; 128:227-232. [PMID: 30522337 DOI: 10.1177/0003489418818189] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Neurodegenerative diseases can alter odor memory in addition to inducing quantitative impairment, and olfactory memory can be tested using the validated olfactory memory test with encapsulated odors (Odor Discrimination Memory Test [ODMT]). The aim of this study was to investigate the new Sniffin' Sticks ODMT (SSODMT), which is comparable with the ODMT. METHODS The SSODMT was administered to 48 subjects (30 women, 18 men; mean age, 34.6 ± 16.3 years). Olfactory function was assessed using the 16-item Sniffin' Sticks Identification Test. The ODMT was administered to a subgroup of 10 subjects to assess the comparability of the SSODMT and the ODMT. Test-retest reliability was studied in another 20 subjects (10 women, 10 men; mean age, 32.9 ± 16.4 years). RESULTS The mean SSODMT score was 10.7 ± 1.8 (range, 5-12). SSODMT test scores were significantly correlated with Sniffin' Sticks Identification Test scores (r67 = 0.66, P < .001) and were significantly negatively correlated with subject age (r48 = -0.70, P < .001). SSODMT and ODMT scores were highly and significantly correlated, indicating that the test results were comparable (r10 = 0.75, P < .05). Test-retest analysis revealed a significant correlation (r20 = 0.68, P < .001). CONCLUSIONS These results demonstrate the usefulness of the new SSODMT and its comparability with the ODMT. The SSODMT is an easy, rapid, and low-cost tool that is suitable for routine use in evaluating odor memory.
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Affiliation(s)
- Gerold Besser
- Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, Vienna, Austria
| | - Leandra Jobs
- Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, Vienna, Austria
| | - David Tianxiang Liu
- Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, Vienna, Austria
| | - Christian A Mueller
- Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, Vienna, Austria
| | - Bertold Renner
- Institute of Experimental and Clinical Pharmacology and Toxicology, Erlangen, Erlangen, Germany
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Doty RL, Tourbier I, Neff JK, Silas J, Turetsky B, Moberg P, Kim T, Pluta J, French J, Sharan AD, Sperling MJ, Mirza N, Risser A, Baltuch G, Detre JA. Influences of temporal lobe epilepsy and temporal lobe resection on olfaction. J Neurol 2018; 265:1654-1665. [PMID: 29767353 PMCID: PMC6239967 DOI: 10.1007/s00415-018-8891-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Revised: 04/26/2018] [Accepted: 04/27/2018] [Indexed: 10/16/2022]
Abstract
Although temporal lobe epilepsy (TLE) and resection (TLR) impact olfactory eloquent brain structures, their influences on olfaction remain enigmatic. We sought to more definitively assess the influences of TLE and TLR on olfaction using three well-validated olfactory tests and measuring the tests' associations with the volume of numerous temporal lobe brain structures. The University of Pennsylvania Smell Identification Test and an odor detection threshold test were administered to 71 TLE patients and 71 age- and sex-matched controls; 69 TLE patients and controls received an odor discrimination/memory test. Fifty-seven patients and 57 controls were tested on odor identification and threshold before and after TLR; 27 patients and 27 controls were similarly tested for odor detection/discrimination. Scores were compared using analysis of variance and correlated with pre- and post-operative volumes of the target brain structures. TLE was associated with bilateral deficits in all test measures. TLR further decreased function on the side ipsilateral to resection. The hippocampus and other structures were smaller on the focus side of the TLE subjects. Although post-operative volumetric decreases were evident in most measured brain structures, modest contralateral volumetric increases were observed in some cases. No meaningful correlations were evident pre- or post-operatively between the olfactory test scores and the structural volumes. In conclusion, we demonstrate that smell dysfunction is clearly a key element of both TLE and TLR, impacting odor identification, detection, and discrimination/memory. Whether our novel finding of significant post-operative increases in the volume of brain structures contralateral to the resection side reflects plasticity and compensatory processes requires further study.
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Affiliation(s)
- Richard L Doty
- Smell and Taste Center, Perelman School of Medicine, Hospital of the University of Pennsylvania, 5 Ravdin Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104-4283, USA.
- Department of Otorhinolaryngology, Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
| | - Isabelle Tourbier
- Smell and Taste Center, Perelman School of Medicine, Hospital of the University of Pennsylvania, 5 Ravdin Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104-4283, USA
- Department of Otorhinolaryngology, Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Jessica K Neff
- Smell and Taste Center, Perelman School of Medicine, Hospital of the University of Pennsylvania, 5 Ravdin Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104-4283, USA
- Department of Otorhinolaryngology, Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Jonathan Silas
- Smell and Taste Center, Perelman School of Medicine, Hospital of the University of Pennsylvania, 5 Ravdin Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104-4283, USA
- Department of Psychology, Middlesex University, London, UK
| | - Bruce Turetsky
- Smell and Taste Center, Perelman School of Medicine, Hospital of the University of Pennsylvania, 5 Ravdin Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104-4283, USA
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Paul Moberg
- Smell and Taste Center, Perelman School of Medicine, Hospital of the University of Pennsylvania, 5 Ravdin Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104-4283, USA
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Taehoon Kim
- Smell and Taste Center, Perelman School of Medicine, Hospital of the University of Pennsylvania, 5 Ravdin Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104-4283, USA
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - John Pluta
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Jaqueline French
- Department of Neurology, New York University Langone Medical Center, New York, NY, 10016, USA
| | - Ashwini D Sharan
- Department of Neurosurgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Michael J Sperling
- Department of Neurology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Natasha Mirza
- Smell and Taste Center, Perelman School of Medicine, Hospital of the University of Pennsylvania, 5 Ravdin Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104-4283, USA
- Department of Otorhinolaryngology, Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Anthony Risser
- Smell and Taste Center, Perelman School of Medicine, Hospital of the University of Pennsylvania, 5 Ravdin Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104-4283, USA
| | - Gordon Baltuch
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - John A Detre
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Doty RL. Measurement of chemosensory function. World J Otorhinolaryngol Head Neck Surg 2018; 4:11-28. [PMID: 30035257 PMCID: PMC6051764 DOI: 10.1016/j.wjorl.2018.03.001] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Accepted: 03/01/2018] [Indexed: 12/02/2022] Open
Abstract
Although hundreds of thousands of patients seek medical help annually for disorders of taste and smell, relatively few medical practitioners quantitatively test their patients' chemosensory function, taking their complaints at face value. This is clearly not the approach paid to patients complaining of visual, hearing, or balance problems. Accurate chemosensory testing is essential to establish the nature, degree, and veracity of a patient's complaint, as well as to aid in counseling and in monitoring the effectiveness of treatment strategies and decisions. In many cases, patients perseverate on chemosensory loss that objective assessment demonstrates has resolved. In other cases, patients are malingering. Olfactory testing is critical for not only establishing the validity and degree of the chemosensory dysfunction, but for helping patients place their dysfunction into perspective relative to the function of their peer group. It is well established, for example, that olfactory dysfunction is the rule, rather than the exception, in members of the older population. Moreover, it is now apparent that such dysfunction can be an early sign of neurodegenerative diseases such as Alzheimer's and Parkinson's. Importantly, older anosmics are three times more likely to die over the course of an ensuring five-year period than their normosmic peers, a situation that may be averted in some cases by appropriate nutritional and safety counseling. This review provides the clinician, as well as the academic and industrial researcher, with an overview of the available means for accurately assessing smell and taste function, including up-to-date information and normative data for advances in this field.
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Affiliation(s)
- Richard L Doty
- Smell & Taste Center, University of Pennsylvania, Philadelphia, PA 19104, USA.,Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Abstract
PURPOSE OF REVIEW The sense of smell is today one of the focuses of interest in aging and neurodegenerative disease research. In several neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease, the olfactory dysfunction is one of the initial symptoms appearing years before motor symptoms and cognitive decline, being considered a clinical marker of these diseases' early stages and a marker of disease progression and cognitive decline. Overall and under the umbrella of precision medicine, attention to olfactory function may help to improve chances of success for neuroprotective and disease-modifying therapeutic strategies. RECENT FINDINGS The use of olfaction, as clinical marker for neurodegenerative diseases is helpful in the characterization of prodromal stages of these diseases, early diagnostic strategies, differential diagnosis, and potentially prediction of treatment success. Understanding the mechanisms underlying olfactory dysfunction is central to determine its association with neurodegenerative disorders. Several anatomical systems and environmental factors may underlie or contribute to olfactory loss associated with neurological diseases, although the direct biological link to each disorder remains unclear and, thus, requires further investigation. In this review, we describe the neurobiology of olfaction, and the most common olfactory function measurements in neurodegenerative diseases. We also highlight the evidence for the presence of olfactory dysfunction in several neurodegenerative diseases, its value as a clinical marker for early stages of the diseases when combined with other clinical, biological, and neuroimage markers, and its role as a useful symptom for the differential diagnosis and follow-up of disease. The neuropathological correlations and the changes in neurotransmitter systems related with olfactory dysfunction in the neurodegenerative diseases are also described.
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Abstract
Background Despite the importance of the sense of smell for establishing the flavor of foods and beverages, as well as protecting against environmental dangers, this primary sensory system is commonly ignored by the rhinologist. Methods In this article basic issues related to practical measurement of olfactory function in the clinic are described and examples of the application of the two most common paradigms for such measurement—odor identification and detection–are presented. A listing is made of the 27 olfactory tests currently used clinically, along with their strengths and weaknesses. A brief review of common nasosinus-related disorders for which quantitative olfactory testing has been performed is provided. Results Although many psychophysical tests are available for quantifying olfactory loss, it is apparent that a number are limited in terms of practicality, sensitivity, and reliability. In general, sensitivity and reliability are positively correlated with test length. Given the strengths of the more reliable forced-choice pyschophysical tests and the limitations of electrophysiological tests, the common distinction between “subjective” and “objective” tests is misleading and should not be used. Complete recovery of olfactory function, as measured quantitatively, rarely follows surgical or medical interventions in patients with rhinosinusitis. Conclusion Given the availability of practical clinical olfactory tests, the modern rhinologist can easily quantify cranial nerve (CN) I function. The application of such tests has led to a new understanding of the effects of nasal disease on olfactory function. Except in cases of total or near-total nasal obstruction, olfactory and airway patency measures usually are unrelated, in accord with the concept that rhinosinusitis primarily influences olfactory function by apoptotic pathological changes within the olfactory neuroepithelium.
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Affiliation(s)
- Richard L Doty
- Smell and Taste Center, Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
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Wrobel BB, Bien AG, Holbrook EH, Meyer GE, Bratney NA, Meza J, Leopold DA. Decreased Nasal Mucosal Sensitivity in Older Subjects. ACTA ACUST UNITED AC 2018; 20:364-8. [PMID: 16871945 DOI: 10.2500/ajr.2006.20.2862] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Background The sensitivity of the human nasal cavity mucosa to touch is not well understood. The site of receptors and mode of action responsible for the sensation of the nasal airflow is a topic of controversy. Previous studies have suggested that the skin-lined nasal vestibule is more sensitive to airflow than the mucosa of the nasal cavity. A possible decline in nasal sensitivity to airflow in older subjects has not been studied. Methods The threshold of the mucosal sensitivity to jets of air was assessed in 76 subjects with healthy nasal cavities. A total of 141 nostrils were tested, 67 in younger patients and 74 in older patients. Results Statistically significant (p < 0.001) increases in thresholds were found for all points tested for older patients compared with the younger patients. In general, the more sensitive locations were in the nasal vestibule. The nasal cavity mucosa in the inferior meatus was slightly more sensitive than the middle meatus. Conclusion We have measured the threshold to touch (air jet sensitivity) in nine places in each of 141 nasal cavities and determined that the variability and sensitivity of these measurements among people varies by age and the distance from the nostril. Older subjects were found to have a higher threshold for the sensation of air flow, and the nasal vestibule was found to be more sensitive than the rest of the nasal cavity mucosa with the inferior meatus slightly more sensitive then the middle meatus.
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Affiliation(s)
- Bozena B Wrobel
- Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, California, USA
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Sorokowska A, Karwowski M. No Sensory Compensation for Olfactory Memory: Differences between Blind and Sighted People. Front Psychol 2017; 8:2127. [PMID: 29276494 PMCID: PMC5727095 DOI: 10.3389/fpsyg.2017.02127] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Accepted: 11/21/2017] [Indexed: 11/13/2022] Open
Abstract
Blindness can be a driving force behind a variety of changes in sensory systems. When vision is missing, other modalities and higher cognitive functions can become hyper-developed through a mechanism called sensory compensation. Overall, previous studies suggest that olfactory memory in blind people can be better than that of the sighted individuals. Better performance of blind individuals in other-sensory modalities was hypothesized to be a result of, among others, intense perceptual training. At the same time, if the superiority of blind people in olfactory abilities indeed results from training, their scores should not decrease with age to such an extent as among the sighted people. Here, this hypothesis was tested in a large sample of 94 blind individuals. Olfactory memory was assessed using the Test for Olfactory Memory, comprising episodic odor recognition (discriminating previously presented odors from new odors) and two forms of semantic memory (cued and free identification of odors). Regarding episodic olfactory memory, we observed an age-related decline in correct hits in blind participants, but an age-related increase in false alarms in sighted participants. Further, age moderated the between-group differences for correct hits, but the direction of the observed effect was contrary to our expectations. The difference between blind and sighted individuals younger than 40 years old was non-significant, but older sighted individuals outperformed their blind counterparts. In conclusion, we found no positive effect of visual impairment on olfactory memory. We suggest that daily perceptual training is not enough to increase olfactory memory function in blind people.
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Affiliation(s)
- Agnieszka Sorokowska
- Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universität Dresden, Dresden, Germany.,Institute of Psychology, University of Wrocław, Wrocław, Poland
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Zhang B, Huo X, Xu L, Cheng Z, Cong X, Lu X, Xu X. Elevated lead levels from e-waste exposure are linked to decreased olfactory memory in children. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2017; 231:1112-1121. [PMID: 28802781 DOI: 10.1016/j.envpol.2017.07.015] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Revised: 06/20/2017] [Accepted: 07/06/2017] [Indexed: 02/05/2023]
Abstract
Lead (Pb) is a developmental neurotoxicant and can cause abnormal development of the nervous system in children. Hence, the aim of this study was to investigate the effect of Pb exposure on child olfactory memory by correlating the blood Pb levels of children in Guiyu with olfactory memory tests. We recruited 61 preschool children, 4- to 7-years of age, from Guiyu and 57 children from Haojiang. The mean blood Pb level of Guiyu children was 9.40 μg/dL, significantly higher than the 5.04 μg/dL mean blood Pb level of Haojiang children. In addition, approximately 23% of Guiyu children had blood Pb levels exceeding 10.00 μg/dL. The correlation analysis showed that blood Pb levels in children highly correlated with e-waste contact (rs = 0.393). Moreover, the mean concentration of serum BDNF in Guiyu children (35.91 ng/ml) was higher than for Haojiang (28.10 ng/ml) and was positively correlated with blood Pb levels. Both item and source olfactory memory tests at 15 min, 5 h and 24 h after odor exposure showed that scores were lower in Guiyu children indicative of reduced olfactory memory in Guiyu children. Olfactory memory tests scores negatively correlated with blood Pb and serum BDNF levels, but were positively associated with parental education levels. At the same time, scores of both tests on children in the high blood Pb level group (blood Pb levels > 5.00 μg/dL) were lower than those in the low blood Pb level group (blood Pb levels ≤ 5.00 μg/dL), implying that Pb exposure decreases olfactory memory in children. Our findings suggest that Pb exposure in e-waste recycling and dismantling areas could result in an increase in serum BDNF level and a decrease in child olfactory memory, in addition, BDNF might be involved in olfactory memory impairment.
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Affiliation(s)
- Bo Zhang
- Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Xia Huo
- School of Environment, Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, Guangdong, 510632, China
| | - Long Xu
- Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Zhiheng Cheng
- Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Xiaowei Cong
- Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Xueling Lu
- Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Xijin Xu
- Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, Guangdong, China.
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Hirsch A, Roussos A, Freels S. Validation of olfactory threshold testing methods. EAR, NOSE & THROAT JOURNAL 2017; 96:E4-E6. [PMID: 28346647 DOI: 10.1177/014556131709600317] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
In patients with chemosensory complaints, a head-to-head comparison of unilateral olfaction threshold testing with the Phenyl Ethyl Alcohol Smell Threshold Test (PEA) and the OLFACT-RL Odor Threshold Test (OLFACT-RL) was undertaken. The charts of 23 consecutive patients presenting with chemosensory complaints seen at the Smell and Taste Treatment and Research Foundation were reviewed and information extracted per Institutional Review Board guidelines. All patients had undergone olfactory testing with the PEA test and the OLFACT-RL test in accordance with their published administration manuals. Using Spearman correlation coefficients to measure the statistical correlation between tests, we found evidence of a correlation between PEA and OLFACT-RL values on the left side only, overall (r = 0.49, p = 0.0184); in those who had hyposmia and did not have anosmia (r = 0.42, p = 0.0668); in those who did not have burning mouth syndrome (r = 0.46, p = 0.0304); and in those who did not have dysosmia (r = 0.47, p = 0.0553). There is no evidence of a correlation on the right side. The correlation for the left nostril suggests that these tests may be interchangeable. However, lack of correlation with the right nostril requires further investigation.
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Affiliation(s)
- Alan Hirsch
- Smell and Taste Treatment and Research Foundation, 223 E. Erie St., Ste. 712, Chicago, IL 60611, USA.
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Martinec Nováková L, Vojtušová Mrzílková R, Kernerová A. Gender differences in influences of temperament on olfactory reactivity and awareness. Sci Rep 2017; 7:8920. [PMID: 28827577 PMCID: PMC5566423 DOI: 10.1038/s41598-017-09231-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 07/19/2017] [Indexed: 11/09/2022] Open
Abstract
Children's olfactory performance is associated with temperament but whether there is a link with olfactory reactivity and awareness is not known. In adults negative affectivity is linked to reactivity to environmental odours but it is not clear whether these associations extend to children. We aimed to investigate the effect of temperamental factors on olfactory reactivity and awareness. In so doing, we controlled for the effect of parenting styles on temperamental assessment and of verbal fluency on children's olfactory reactivity and awareness. We hypothesised that children with a high degree of negative affectivity would show greater olfactory reactivity and awareness. 129 children (62 boys, mean age 6.83 ± 0.40 years) were interviewed about their olfactory reactivity and awareness in everyday life using the established Children's Olfactory Behavior in Everyday Life questionnaire (COBEL). Parents assessed their child's temperament using the 94-item short form of the Children's Behavior Questionnaire. We found that the relationship between negative affectivity and total COBEL scores varied between the genders: there was a positive, medium to large effect in boys and a negative, small one in girls. Future studies could include behavioural observations of temperament and olfactory reactivity and awareness.
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Affiliation(s)
- Lenka Martinec Nováková
- Department of Anthropology, Faculty of Humanities, Charles University, U Kříže 8, Prague 5 - Jinonice, 15800, Czech Republic. .,National Institute of Mental Health, Topolová 748, 25067, Klecany, Czech Republic.
| | - Radka Vojtušová Mrzílková
- Department of Anthropology, Faculty of Humanities, Charles University, U Kříže 8, Prague 5 - Jinonice, 15800, Czech Republic
| | - Anna Kernerová
- Department of Anthropology, Faculty of Humanities, Charles University, U Kříže 8, Prague 5 - Jinonice, 15800, Czech Republic.,National Institute of Mental Health, Topolová 748, 25067, Klecany, Czech Republic
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Olfactory disturbances in ageing with and without dementia: towards new diagnostic tools. The Journal of Laryngology & Otology 2017; 131:572-579. [PMID: 28424103 DOI: 10.1017/s0022215117000858] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND Olfactory disorders increase with age and often affect elderly people who have pre-dementia or dementia. Despite the frequent occurrence of olfactory changes at the early stages of neurodegenerative disorders such as Alzheimer's disease, olfactory disorders are rarely assessed in daily clinical practice, mainly due to a lack of standardised assessment tools. The aims of this review were to (1) summarise the existing literature on olfactory disorders in ageing populations and patients with neurodegenerative disorders; (2) present the strengths and weaknesses of current olfactory disorder assessment tools; and (3) discuss the benefits of developing specific olfactory tests for neurodegenerative diseases. METHODS A systematic review was performed of literature published between 2000 and 2015 addressing olfactory disorders in elderly people with or without Alzheimer's disease or other related disorders to identify the main tools currently used for olfactory disorder assessment. RESULTS Olfactory disorder assessment is a promising method for improving both the early and differential diagnosis of Alzheimer's disease. However, the current lack of consensus on which tests should be used does not permit the consistent integration of olfactory disorder assessment into clinical settings. CONCLUSION Otolaryngologists are encouraged to use olfactory tests in older adults to help predict the development of neurodegenerative diseases. Olfactory tests should be specifically adapted to assess olfactory disorders in Alzheimer's disease patients.
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Gunzer W. Changes of Olfactory Performance during the Process of Aging - Psychophysical Testing and Its Relevance in the Fight against Malnutrition. J Nutr Health Aging 2017; 21:1010-1015. [PMID: 29083442 DOI: 10.1007/s12603-017-0873-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVES Olfactory performance plays a vital role in several aspects of everyday life. A decrease in olfactory function leading to reduced appetite and inadequate food intake could contribute to higher risk of malnutrition and has a significant impact on quality of life. Early detection of olfactory impairment may help to maintain normal, or - through early training - to improve olfactory function and could thus contribute to the prevention of malnutrition. This review summarizes recent findings on the association between decreased olfactory performance in older adults, its implication for overall health and discusses issues regarding the assessment of olfactory performance in older people. METHODS A non-systematic literature search using databases (PubMed, ScienceDirect, Google Scholar) was conducted up to March 2016 to review recent findings on the topics of olfactory impairment, age, malnutrition and issues in psychophysical testing. RESULTS Although the association of olfactory impairment and malnutrition is widely accepted strong evidence is scarce. This could be because existing psychophysiological olfactory performance tests are not suitable and inefficient for older adults or people with cognitive impairment due to their required time and concentration. Since prevalence of olfactory impairment remains poorly documented in European regions and varies from 13.9% to >60% depending on age and due to considerable methodological diversity in studies there is need to develop rapid and efficient screening tools which are suitable for this target group. CONCLUSION Due to numerous causes and health consequences of olfactory impairment in older people, early detection of olfactory malfunction by rapid, inexpensive but valid tests, which could be used by geriatricians and other healthcare professionals, might be useful in patient counselling by identifying individuals at nutritional risk.
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Affiliation(s)
- W Gunzer
- W. Gunzer, FH JOANNEUM University of Applied Sciences, Department of Health Studies, Insitute of Dietetics and Nutrition, Graz, Austria,
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Kollndorfer K, Reichert J, Braunsteiner J, Schöpf V. Assessment of Olfactory Memory in Olfactory Dysfunction. Perception 2016; 46:516-529. [PMID: 28325138 DOI: 10.1177/0301006616683201] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
To assess all clinically relevant components of olfactory perception, examinations for olfactory sensitivity, discrimination, and identification are performed. Besides the standard perceptual test battery, episodic olfactory memory might offer additional information about olfactory abilities relative to these standard clinical tests. As both olfactory deficits and memory deficits are early symptoms in neurodegenerative disorders, olfactory memory may be of particular interest. However, to date little is known about episodic olfactory memory performance in patients with decreased olfactory function. This study includes the investigation of olfactory memory performance in 14 hyposmic patients (8 female, mean age 52.6 years) completing two episodic odor memory tests (Sniffin' Test of Odor Memory and Odor Memory Test). To control for a general impairment in memory function, a verbal and a figural memory test were carried out. A regression model with multiple predictors was calculated for both odor memory tests separately. Odor identification was identified as the only significant predictor for both odor memory tasks. From our results, we conclude that currently available olfactory memory tests are highly influenced by odor identification abilities, implying the need for the development and validation of additional tests in this field which could serve as additional olfactory perception variables for clinical assessment.
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Affiliation(s)
- Kathrin Kollndorfer
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Austria
| | - Johanna Reichert
- Institute of Psychology, University of Graz, Austria; BioTechMed, Graz, Austria
| | - Josephine Braunsteiner
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Austria
| | - Veronika Schöpf
- Institute of Psychology, University of Graz, Austria; BioTechMed, Graz, Austria
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Ward AM, Calamia M, Thiemann E, Dunlap J, Tranel D. Association between olfaction and higher cortical functions in Alzheimer's disease, mild cognitive impairment, and healthy older adults. J Clin Exp Neuropsychol 2016; 39:646-658. [PMID: 27868477 DOI: 10.1080/13803395.2016.1253667] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Neural regions important for smell are proximal and closely connected to cortical areas that have been strongly implicated in higher order functions of value-based decision making and emotional memory. The integrity of these neural regions are affected in aging and neurodegenerative conditions. Two specific predictions follow from these neuroanatomical arrangements-namely, that olfaction would be associated with value-based decision making and with emotional memory. METHOD To test these predictions, we measured these different capacities in participants with presumed varying degrees of integrity of the relevant brain structures: specifically, 13 patients with Alzheimer's disease, 8 patients with mild cognitive impairment, and 20 healthy older adults. The participants completed detailed tests of olfaction, value-based decision making, emotional memory, and general cognitive ability. RESULTS Olfactory functioning was significantly associated with emotional and nonemotional memory. The association was especially strong and consistent for memory recall with olfaction, explaining as much as 10% additional variance over and above general cognition. Olfactory functioning was not strongly or consistently associated with decision making over and above general cognition. CONCLUSION Olfaction is a strong predictor of memory recall. These findings may contribute to a better understanding of olfaction and specific cognitive domains known to be affected by aging and implicated in neurodegenerative disease.
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Affiliation(s)
- Amanda M Ward
- a Department of Psychological and Brain Sciences , University of Iowa , Iowa City , IA , USA
| | - Matthew Calamia
- b Department of Psychology , Louisiana State University , Baton Rouge , LA , USA
| | - Erin Thiemann
- a Department of Psychological and Brain Sciences , University of Iowa , Iowa City , IA , USA
| | - Jamie Dunlap
- a Department of Psychological and Brain Sciences , University of Iowa , Iowa City , IA , USA
| | - Daniel Tranel
- a Department of Psychological and Brain Sciences , University of Iowa , Iowa City , IA , USA.,c Department of Neurology , University of Iowa Carver College of Medicine , Iowa City , IA , USA
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Olfactory Deficits Predict Cognitive Improvement on Donepezil in Patients With Depression and Cognitive Impairment: A Randomized Controlled Pilot Study. Alzheimer Dis Assoc Disord 2016; 30:67-9. [PMID: 26398910 DOI: 10.1097/wad.0000000000000107] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Doty RL, De Fonte TP. Relationship of Phenylthiocarbamide (PTC) Taster Status to Olfactory and Gustatory Function in Patients with Chemosensory Disturbances. Chem Senses 2016; 41:685-96. [PMID: 27402661 DOI: 10.1093/chemse/bjw070] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Poor sensitivity to the bitter taste of phenylthiocarbamide (PTC) and related substances has been associated with a number of diseases. We determined, in patients with chemosensory dysfunction from multiple etiologies, whether PTC "tasters" (n = 511) exhibit less smell and taste dysfunction than their non-PTC-tasting counterparts (n = 432) on a comprehensive battery of olfactory and gustatory tests. The proportion of tasters (54%) in our study population was much lower than that calculated from 11 North American population studies (76.5%; P < 0.0001). This taster/nontaster ratio was maintained across a range of etiologic categories. More women (60.7%) than men (45.5%) were PTC tasters (P < 0.0001). Although PTC tasting status was unrelated to scores on the olfactory tests (which included tests of odor identification, detection threshold, and odor memory/discrimination), tasters significantly outperformed nontasters on suprathreshold identification and intensity taste tests employing both bitter (caffeine) and nonbitter (sucrose, citric acid, sodium chloride) tasting stimuli. Regardless of PTC taster status, women outperformed men on the taste tests. Our findings suggest the possibility that the T2R38 gene may protect against significant olfactory dysfunction, but once such dysfunction becomes manifest at a level where professional help is sought, such protection is not evident. However, other hypotheses for this phenomenon are possible. This study demonstrates that patients with chemosensory disturbances who are PTC tasters outperform their non-PTC taster counterparts in both identifying and perceiving the intensity of a range of suprathreshold tastants, including ones that do not taste bitter.
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Affiliation(s)
- Richard L Doty
- Smell and Taste Center, Department of Otorhinolaryngology: Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, 5 Ravdin Pavilion, 3400 Spruce Street, Philadelphia, PA 19104, USA and
| | - Tatiana Prosini De Fonte
- Pediatric Dentistry, Faculty of Dentistry, University of Pernambuco, Recife, Camaragibe, PE 54753-020, Brazil
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Odours reduce the magnitude of object substitution masking for matching visual targets in females. Atten Percept Psychophys 2016; 78:1702-11. [PMID: 27306640 DOI: 10.3758/s13414-016-1157-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Recent evidence suggests that olfactory stimuli can influence early stages of visual processing, but there has been little focus on whether such olfactory-visual interactions convey an advantage in visual object identification. Moreover, despite evidence that some aspects of olfactory perception are superior in females than males, no study to date has examined whether olfactory influences on vision are gender-dependent. We asked whether inhalation of familiar odorants can modulate participants' ability to identify briefly flashed images of matching visual objects under conditions of object substitution masking (OSM). Across two experiments, we had male and female participants (N = 36 in each group) identify masked visual images of odour-related objects (e.g., orange, rose, mint) amongst nonodour-related distracters (e.g., box, watch). In each trial, participants inhaled a single odour that either matched or mismatched the masked, odour-related target. Target detection performance was analysed using a signal detection (d') approach. In females, but not males, matching odours significantly reduced OSM relative to mismatching odours, suggesting that familiar odours can enhance the salience of briefly presented visual objects. We conclude that olfactory cues exert a subtle influence on visual processes by transiently enhancing the salience of matching object representations. The results add to a growing body of literature that points towards consistent gender differences in olfactory perception.
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DelGaudio JM, Panella NJ. Presbynasalis. Int Forum Allergy Rhinol 2016; 6:1083-1087. [DOI: 10.1002/alr.21787] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 03/10/2016] [Accepted: 03/15/2016] [Indexed: 11/07/2022]
Affiliation(s)
- John M. DelGaudio
- Division of Rhinology and Sinus Surgery; Emory University; Atlanta GA
- Department of Otolaryngology-Head and Neck Surgery; Emory University; Atlanta GA
| | - Nicholas J. Panella
- Department of Otolaryngology-Head and Neck Surgery; Emory University; Atlanta GA
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Mazzatenta A, Cellerino A, Origlia N, Barloscio D, Sartucci F, Giulio CD, Domenici L. Olfactory phenotypic expression unveils human aging. Oncotarget 2016; 7:19193-200. [PMID: 27027240 PMCID: PMC4991375 DOI: 10.18632/oncotarget.8393] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 03/18/2016] [Indexed: 02/07/2023] Open
Abstract
The mechanism of the natural aging of olfaction and its declinein the absence of any overt disease conditions remains unclear. Here, we investigated this mechanism through measurement of one of the parameters of olfactory function, the absolute threshold, in a healthy population from childhood to old age. The absolute olfactory threshold data were collected from an Italian observational study with 622 participants aged 5-105 years. A subjective testing procedure of constant stimuli was used, which was also compared to the 'staircase' method, with the calculation of the reliability. The n-butanol stimulus was used as an ascending series of nine molar concentrations that were monitored using an electronic nose. The data were analyzed using nonparametric statistics because of the multimodal distribution. We show that the age-related variations in the absolute olfactory threshold are not continuous; instead, there are multiple olfactory phenotypes. Three distinct age-related phenotypes were defined, termed as 'juvenile', 'mature' and 'elder'. The frequency of these three phenotypes depends on age. Our data suggest that the sense of smell does not decrease linearly with aging. Our findings provide the basis for further understanding of olfactory loss as an anticipatory sign of aging and neurodegenerative processes.
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Affiliation(s)
- Andrea Mazzatenta
- Department of Neuroscience, Imaging and Clinical Science, ‘G. d'AnnunziO' University of Chieti-Pescara, Chieti, Italy
| | | | | | - Davide Barloscio
- Neuroscience Institute, CNR-Pisa, Pisa, Italy
- Department di Medicina Clinica e Sperimentale, Sezione di Neurologia, e Dai di Neuroscienze, Pisa, Italy
| | - Ferdinando Sartucci
- Department di Medicina Clinica e Sperimentale, Sezione di Neurologia, e Dai di Neuroscienze, Pisa, Italy
| | - Camillo Di Giulio
- Department of Neuroscience, Imaging and Clinical Science, ‘G. d'AnnunziO' University of Chieti-Pescara, Chieti, Italy
| | - Luciano Domenici
- Neuroscience Institute, CNR-Pisa, Pisa, Italy
- Department of Applied Clinical Science and Biotechnology (DISCAB), School of Medicine, l'Aquila University, L'Aquila, Italy
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Effects of chronic peripheral olfactory loss on functional brain networks. Neuroscience 2015; 310:589-99. [DOI: 10.1016/j.neuroscience.2015.09.045] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 09/16/2015] [Accepted: 09/18/2015] [Indexed: 01/18/2023]
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