HYPOTHESIS AND THEORY article

Front. Mol. Neurosci., 11 October 2024

Sec. Brain Disease Mechanisms

Volume 17 - 2024 | https://doi.org/10.3389/fnmol.2024.1455418

Inflammation and olfactory loss are associated with at least 139 medical conditions

  • 1. Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, United States

  • 2. Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA, United States

  • 3. Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States

  • 4. The Oxford Research Centre in the Humanities, University of Oxford, Oxford, United Kingdom

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Abstract

Olfactory loss accompanies at least 139 neurological, somatic, and congenital/hereditary conditions. This observation leads to the question of whether these associations are correlations or whether they are ever causal. Temporal precedence and prospective predictive power suggest that olfactory loss is causally implicated in many medical conditions. The causal relationship between olfaction with memory dysfunction deserves particular attention because this sensory system has the only direct projection to memory centers. Mechanisms that may underlie the connections between medical conditions and olfactory loss include inflammation as well as neuroanatomical and environmental factors, and all 139 of the medical conditions listed here are also associated with inflammation. Olfactory enrichment shows efficacy for both prevention and treatment, potentially mediated by decreasing inflammation.

1 Introduction

1.1 Observations linking olfactory loss and medical conditions: correlation, precedence, and prediction

1.1.1 Olfactory loss is associated with many medical conditions

First, a strikingly large number of medical conditions are accompanied by olfactory dysfunction (Tables 1–3). The remarkably long and diverse list of medical conditions that co-occur with olfactory loss raises the possibility that there is something deeper to these relationships.

Table 1

Medical condition Olfactory dysfunction Olfactory study size (N) Inflammation
Agnosia (olfactory) Kopala and Clark, 1990 77 Wang et al., 2010
Alcoholism Rupp et al., 2004 60 Leclercq et al., 2017
Alzheimer's disease Waldton, 1974 100 Xie et al., 2022
Amyotrophic lateral sclerosis Viguera et al., 2018 147 McCombe and Henderson, 2011
Anesthesia cognitive impairment Zhang C. et al., 2022 242 Subramaniyan and Terrando, 2019
Anorexia nervosa Roessner et al., 2005 32 Dalton et al., 2018
Anxiety Chen X. et al., 2021 107 Guo B. et al., 2023
Autism Kinnaird et al., 2020 80 Kern et al., 2016
Cerebral palsy Nakashima et al., 2019 14 Paton et al., 2022
Cervical dystonia Marek et al., 2018 198 Scorr et al., 2024
Childhood maltreatment Croy et al., 2010 22 Wong et al., 2022
Cluster headache Samanci et al., 2021 57 Hardebo, 1994
Corticobasal syndrome Luzzi et al., 2007 7 Alster et al., 2021
Creutzfeldt-Jakob disease Reuber et al., 2001 1 López González et al., 2016
Depression (unipolar) Eliyan et al., 2021 3,546 Kofod et al., 2022
Depression (bipolar) Kazour et al., 2020 176 Benedetti et al., 2020
Epilepsy Khurshid et al., 2019 912 Rana and Musto, 2018
Essential tremor Elhassanien et al., 2021 46 Muruzheva et al., 2022
Fibromyalgia Amital et al., 2014 45 Coskun Benlidayi, 2019
Frontotemporal dementia Luzzi et al., 2007 11 Bright et al., 2019
Glioblastoma Kebir et al., 2020 122 Zhang H. et al., 2022
Gulf war illness Chao, 2024 80 Michalovicz et al., 2020
Headache Gossrau et al., 2023 80 Biscetti et al., 2021
Heavy metal exposure Renzetti et al., 2024 130 He et al., 2024
Hepatic encephalopathy Zucco et al., 2006 24 Lu, 2023
Herpetic meningoencephalitis Landis et al., 2010 3 Li et al., 2023
Huntington's disease Fernandez-Ruiz et al., 2003 162 Valadão et al., 2020
Idiopathic intracranial hypertension Bershad et al., 2014 38 Sinclair et al., 2008
Impulsive violent offenders Challakere Ramaswamy et al., 2023 485 Hasan Balcioglu et al., 2022
Lewy body dementia Yoo et al., 2018 217 Amin et al., 2022
Loneliness Desiato et al., 2021 221 Van Bogart et al., 2022
Long COVID-19 Burges Watson et al., 2021 9,000 Aiyegbusi et al., 2021
ME/chronic fatigue syndrome Harris et al., 2017 11 Chaves-Filho et al., 2023
Memory loss with aging Doty et al., 1984 1,995 Sartori et al., 2012
Menopause Lee et al., 2019 3,863 Malutan et al., 2014
Migraine headaches Whiting et al., 2015 100 Kursun et al., 2021
Mild cognitive impairment Peters et al., 2003 100 Leonardo and Fregni, 2023
Motor neuron disease Hawkes et al., 1998 193 Komine and Yamanaka, 2015
Multiple sclerosis Atalar et al., 2018 55 Groppa et al., 2021
Multiple-system atrophy Abele et al., 2003 8 Rydbirk et al., 2022
Myasthenia gravis Leon-Sarmiento et al., 2012 27 Koneczny and Herbst, 2019
Myotonic dystrophy Masaoka et al., 2011 7 Azotla-Vilchis et al., 2021
Narcolepsy Buskova et al., 2010 66 Valizadeh et al., 2024
Neuromyelitis optica Schmidt et al., 2013 20 Kümpfel et al., 2024
Obsessive compulsive disorder Berlin et al., 2017 30 Marazziti et al., 2023
Parkinson's disease Haehner et al., 2009 50 Pajares et al., 2020
Posterior cortical atrophy Witoonpanich et al., 2013 15 Firth et al., 2019
Postoperative delirium Brown et al., 2015 165 Pang Y. et al., 2022
Postpartum depression Peng et al., 2021 39 Bränn et al., 2020
Posttraumatic stress disorder Vasterling et al., 2000 68 Hori and Kim, 2019
Prenatal alcohol syndrome Bower et al., 2013 16 Masehi-Lano et al., 2023
Progressive supranuclear palsy Shill et al., 2021 281 Alster et al., 2020
Psychopathy Bettison et al., 2013 381 Wang et al., 2017
Psychosis Kamath et al., 2024 195 Misiak et al., 2021
Pure autonomic failure Goldstein and Sewell, 2009 51 Brás et al., 2020
Radioactive iodine Suat et al., 2016 63 Stanciu et al., 2023
REM sleep behavior disorder Iranzo et al., 2021 140 Kim et al., 2019
Repetitive head impacts Alosco et al., 2017 123 McKee et al., 2014
Restless leg syndrome Adler et al., 1998 46 Jiménez-Jiménez et al., 2023
Schizophrenia Kopala et al., 1993 98 Müller, 2018
Semantic dementia Luzzi et al., 2007 20 Pascual et al., 2021
Sexual dysfunction Siegel et al., 2021 1,981 Yafi et al., 2016
Sociopathy Mahmut and Stevenson, 2012 79 Wang et al., 2017
Sodium channel Nav1.7 mutation Weiss et al., 2011 3 Cheng et al., 2021
Spinocerebellar ataxia type 7 Galvez et al., 2014 55 Goswami et al., 2022
Stroke Wehling et al., 2015 78 Lambertsen et al., 2019
Subarachnoid hemorrhagic surgery Bor et al., 2009 197 Hokari et al., 2020
Tinnitus Katayama et al., 2023 510 Kang et al., 2021
Tourette syndrome Kronenbuerger et al., 2018 56 Alshammery et al., 2022
Traumatic brain injury Frasnelli et al., 2016 63 Postolache et al., 2020
Vascular dementia Suh et al., 2020 1 Trares et al., 2022
Zika/Guillain-Barré syndrome Lazarini et al., 2022 38 Acosta-Ampudia et al., 2018

Neurological condition/disorder, the reference for accompanying olfactory dysfunction, study size of olfactory study, and reference for inflammation.

Table 2

Medical condition Olfactory dysfunction Olfactory study size (N) Inflammation
Adenoid hypertrophy Konstantinidis et al., 2005 65 Ye et al., 2022
Allergic rhinitis Apter et al., 1999 90 Klimek and Eggers, 1997
Anemia Dinc et al., 2016 100 Weiss et al., 2019
Arthritis Steinbach et al., 2011 101 Gwinnutt et al., 2022
Asthma Rhyou et al., 2021 68 Gillissen and Paparoupa, 2015
Autoimmune encephalitis Geran et al., 2019 64 Graus et al., 2016
Behcet disease Akyol et al., 2016 96 Nair and Moots, 2017
Blepharospasm Gamain et al., 2021 34 Lu et al., 2014
Cancer (head and neck) Spotten et al., 2016 40 Bonomi et al., 2014
Candida infection Fluitman et al., 2021 218 Dahlman et al., 2021
Cardiovascular disease Roh et al., 2021 20,016 Bafei et al., 2023
Celiac disease Berkiten et al., 2024 74 Barone et al., 2022
Chagas' disease Leon-Sarmiento et al., 2014 120 Nunes et al., 2023
COPD Thorstensen et al., 2022 183 Barnes, 2016
Cirrhosis Garrett-Laster et al., 1984 45 Dirchwolf and Ruf, 2015
Congestive heart failure Chamberlin et al., 2024 477 Cesari et al., 2003
Corticobasal syndrome Luzzi et al., 2007 40 Alster et al., 2021
COVID-19 Vaira et al., 2020 150 Radke et al., 2024
Crohn's disease Fischer et al., 2014 123 Petagna et al., 2020
Cushing syndrome Heger et al., 2021 60 Wurth et al., 2022
Diabetes Zhang et al., 2019 105 Lontchi-Yimagou et al., 2013
Erectile dysfunction Deng et al., 2020 102 Kaya-Sezginer and Gur, 2020
Frailty Van Regemorter et al., 2022 155 Soysal et al., 2016
Glaucoma Iannucci et al., 2024 NS Baudouin et al., 2021
Helicobacter pylori infection Üstün Bezgin et al., 2017 66 Guo X. et al., 2023
HIV/AIDS Zucco and Ingegneri, 2004 48 Deeks et al., 2013
Hypertension Datta et al., 2023 60 Patrick et al., 2021
Hypothyroidism McConnell et al., 1975 18 Kubiak et al., 2023
Idiopathic inflammatory myopathy Iaccarino et al., 2014 120 Lundberg et al., 2021
Inflammation Schubert et al., 2015 1,611 Schubert et al., 2015
Inflammatory bowel disease Sollai et al., 2021 199 Shi et al., 2006
Ischemic heart failure Akşit and Çil, 2020 80 Rao et al., 2021
Kidney disease Frasnelli et al., 2002 64 Rayego-Mateos et al., 2023
Laryngectomy Veyseller et al., 2012 30 Akizuki et al., 2022
Leptin imbalance East and Wilson, 2019 NS Likuni et al., 2008
Macular degeneration Kar et al., 2015 138 Tan et al., 2020
Malnutrition Gunzer, 2017 NS Muscaritoli et al., 2023
Obesity Velluzzi et al., 2022 80 Cox et al., 2015
Obstructive sleep disorder Kaya et al., 2020 26 Alberti et al., 2003
Paget's disease Wheeler et al., 1995 498 Numan et al., 2015
Periodontitis Schertel Cassiano et al., 2023 50 Cecoro et al., 2020
Polycystic ovary syndrome Koseoglu et al., 2016 55 Dabravolski et al., 2021
Premature menopause Lee et al., 2019 104 Bertone-Johnson et al., 2019
Psoriasis Zhong et al., 2023 10,918 Kommoss et al., 2023
Sarcopenia Harita et al., 2019 141 Dalle et al., 2017
Spondyloarthritis Yalcinkaya et al., 2019 50 Sieper and Poddubnyy, 2017
Systemic lupus erythematosus Schoenfeld et al., 2009 100 Frangou et al., 2019
Systemic sclerosis Amital et al., 2014 65 Volkmann et al., 2023
Testosterone deficiency Kirgezen et al., 2021 70 Mohamad et al., 2019
Ultra-processed diet Stevenson et al., 2020 222 Tristan Asensi et al., 2023
Vitamin B12 deficiency Derin et al., 2016 63 Al-Daghri et al., 2016
Vitamin D deficiency Bigman, 2020 2,216 Yin and Agrawal, 2014
Wegener's granulomatosis Laudien et al., 2009 76 Hajj-Ali et al., 2015

Somatic condition/disorder, the reference for accompanying olfactory dysfunction, study size of olfactory study, and reference for inflammation.

NS. not specified.

Table 3

Medical condition Olfactory dysfunction Olfactory study size (N) Inflammation
22q11 deletion syndrome Sobin et al., 2006 62 Dou et al., 2020
Angioedema (hereditary) Perricone et al., 2011 60 Maas and López-Lera, 2019
Bardet-Biedl syndrome Iannaccone et al., 2005 15 Melluso et al., 2023
Cystic fibrosis Miller et al., 2023 76 McElvaney et al., 2019
Down syndrome Cecchini et al., 2016 56 Huggard et al., 2020
Fragile X syndrome Juncos et al., 2012 83 Van Dijck et al., 2020
Friedreich ataxia Connelly et al., 2002 35 Apolloni et al., 2022
Gaucher disease McNeill et al., 2012 60 Francelle and Mazzulli, 2022
Neurofibromatosis type 1 Speth et al., 2023 26 Liao et al., 2018
Niemann-Pick Mishra et al., 2016 2 Han et al., 2023
Retinitis pigmentosa Charbel Issa et al., 2018 9 Zhao et al., 2022
Usher syndrome Ribeiro et al., 2016 130 Castiglione and Möller, 2022
Wilson's disease Chen L. et al., 2021 50 Wu et al., 2019
Wolfram syndrome Alfaro et al., 2020 40 Panfili et al., 2021

Congenital/hereditary disorder, the reference for accompanying olfactory dysfunction, study size of olfactory study, and reference for inflammation.

Many of the associations between olfactory loss and medical conditions are supported by a single study. However, there are several conditions that have been studied extensively and there is strong support that has been reviewed for the relationship between these conditions and olfactory dysfunction: COVID-19 (Las Casas Lima et al., 2022), Alzheimer's disease (McLaren and Kawaja, 2024), Parkinson's disease (Bagherieh et al., 2023), depression (Kohli et al., 2016), and rhinitis (Ahmed and Rowan, 2020).

1.1.2 Olfactory dysfunction occurs early in the development of some medical conditions

To show that olfactory loss increases the risk of developing symptoms of medical conditions, one would need to show that olfactory dysfunction arises before the medical condition. The relevant experiments are quite difficult to do because one must evaluate the olfactory ability of many individuals and then follow them for years to determine whether poor olfactory ability precedes the medical condition. Despite the challenge, several such studies have been conducted. Olfactory loss appears well before any other Parkinson's symptoms (Walker et al., 2021), and similarly, an early symptom of Alzheimer's disease is the loss of olfaction (Serby et al., 1991), with the first part of the brain to deteriorate in that disease being the olfactory pathway (Peters et al., 2003). Schizophrenia is associated with olfactory dysfunction and such dysfunction can be seen in youths who eventually develop schizophrenia (Kamath et al., 2012). Olfactory loss also precedes depression (Kamath et al., 2024), major cardiac events (Chamberlin et al., 2024), and multiple sclerosis (Constantinescu et al., 1994); olfactory dysfunction therefore appears to be a prodromal symptom of these conditions.

1.1.3 Olfactory dysfunction prospectively predicts cognitive loss and all-cause mortality

In men, significant correlations are found in measurements of olfactory thresholds and language index score, along with correlations with executive function. On the other hand, women had correlations for olfactory discrimination and olfactory identification with a visuospatial index score (Masala et al., 2024). In young adults, olfactory ability is correlated with cognitive performance as assessed by verbal fluency, word list learning, word list recall, and the Trail Making Tests, even when the outcomes were adjusted for age, sex, education, and depression symptoms (Yahiaoui-Doktor et al., 2019). Challakere Ramaswamy and Schofield (2022) reviewed 54 studies and found a variety of cognitive abilities that correlated with olfactory ability, including: impulsivity, processing speed, inhibitory control, verbal fluency, working memory, mental flexibility, decision-making, visuospatial processing, planning, and executive function.

If olfactory loss has a causal relationship with at least some medical conditions, one might expect that the loss of olfaction would predict the incidence of those conditions. Indeed, one can predict the probability that older adults will later develop mild cognitive impairment (MCI) based on their olfactory ability (Wheeler and Murphy, 2021). Furthermore, of those individuals who have MCI, one can predict which individuals will develop Alzheimer's disease, as well as which individuals will descend rapidly into their dementia, based on their olfactory ability (Wheeler and Murphy, 2021). Parkinson's patients have both a loss of olfactory function and a loss of executive function (Solla et al., 2023). There are now a number of large prospective cohort studies showing that olfactory ability is a strong predictive factor for all-cause mortality up to 17 years later (Wilson et al., 2011; Gopinath et al., 2012; Pinto et al., 2014; Devanand et al., 2015; Ekström et al., 2017; Schubert et al., 2017; Fuller-Thomson and Fuller-Thomson, 2019; Kamath and Leff, 2019; Liu et al., 2019; Choi et al., 2021; Pinto, 2021; Xiao et al., 2021; Pang N. Y. et al., 2022), with higher accuracy than predictions based on heart disease (Pinto et al., 2014).

1.2 Mechanisms linking olfactory loss and medical conditions: inflammation, neuroanatomy, environmental stressors

1.2.1 Mechanism for triggering olfactory system damage

There are several possibilities for the mechanism underlying the many associations between olfaction and disease. One possibility is that there is a common mechanism that affects both the olfactory system and various neurological and somatic targets. Another possibility is that the neurological and somatic conditions produce something that degrades the olfactory system. A third possibility is that the olfactory system produces something that puts the brain and the body at risk either for contracting diseases or for expressing the symptoms of those diseases. One common product of disease is inflammation, and there is a strong relationship between olfactory dysfunction and elevated inflammation. As can be seen in Tables 1–3, at least 139 conditions that are associated with olfactory loss are also associated with increased inflammatory responses. These conditions have been subdivided into three separate categories: neurological, somatic, and congenital/hereditary conditions (Tables 1–3, respectively). Although the conditions could have been further subdivided into many other more specific categories, and some of the conditions may fall under two different categories, for simplicity, each medical condition was included in only one of the three categories.

1.2.2 Inflammation may be causing the olfactory dysfunction

Perhaps the olfactory system is particularly sensitive to inflammation that reaches it either from other parts of the brain or through the peripheral bloodstream. Alternatively, inflammation in the olfactory system may be triggered by agents that enter through the nose, such as air pollution (Ajmani et al., 2017) or unpleasant odors (Anja Juran et al., 2022). In addition, olfactory dysfunction associated with SARS-CoV-2 (COVID-19) infection is thought to be mediated in part via inflammation (Chang et al., 2024). The olfactory system may be uniquely sensitive to damage inflicted by other sources of inflammation (brain or body) that arise from various diseases because it is already sustaining high levels of inflammation from exposure to volatile agents from the air.

Poor ability to sniff contributes to the olfactory dysfunction of Parkinson's patients (Sobel et al., 2001). The ability to sniff predicted performance on olfactory tasks and increasing sniff vigor improved olfactory ability. The problems with sniffing may be due to increased inflammation that may prevent the respiratory system from compensating for the olfactory dysfunction (Huxtable et al., 2011).

Murphy et al. (2024) found that the efficacy of olfactory training for those individuals who had lost their olfactory ability after a COVID-19 infection was quite variable, with large differences in outcomes for different age groups. They surveyed more than 5,500 patients who had olfactory dysfunction following COVID-19 and compared the efficacy of various treatments including steroids and olfactory training. They found that nasal steroid use, given to reduce inflammation, was most effective for those 25–39 years old, with their effectiveness at about 25%, while oral steroid use was most effective for 18–24-year-olds, nearing 50%. Nasal steroids were most effective for treating hyposmia (poor olfactory ability), while oral steroids were most effective for phantosmia (imagined odors). Olfactory training was most effective for 18–24-year-olds, with effectiveness nearing 50%, while 40–60-year-olds had very poor effectiveness scores. Olfactory training was most effective for hyposmia.

Interestingly, several scents have been shown to have anti-inflammatory action in animal models, including: eucalyptol (Juergens et al., 2003), 1,8-cineol (Pries et al., 2023), lavender (Ueno-Iio et al., 2014), ginger (Aimbire et al., 2007), carvacrol (Alavinezhad et al., 2018), Shirazi thyme (Alavinezhad et al., 2017), farnesol (Ku and Lin, 2016), thymoquinone (El Gazzar et al., 2006, thymol (Gholijani et al., 2016), limonene (Hirota et al., 2012), citronellol (Pina et al., 2019), α-terpineol (Pina et al., 2019), Mentha piperita (Hudz et al., 2023), and mango (Rivera et al., 2011; see Ramsey et al., 2020 and Gandhi et al., 2020 for reviews).

The links between olfaction and inflammation seem also to be mediated by diet. Transgenic mice with high levels of the apolipoprotein E gene APOE4 (a risk factor for Alzheimer's disease) and given a diet with low docosahexaenoic acid (an omega-3 fatty acid) had olfactory loss and memory loss along with an increase in IBA-1, an inflammatory factor, in the olfactory bulb. The mice given a diet high in docosahexaenoic acid experienced no olfactory loss, cognitive loss, or elevated inflammation (González et al., 2023). Humans who have a diet low in monosaturated and polyunsaturated fats have an increased risk of both cognitive loss and olfactory loss (Vohra et al., 2023).

Although the list of conditions in which olfactory loss and inflammation co-occur is long, there do exist medical conditions that involve olfactory loss, without reports of inflammation. One example is Kallmann syndrome, in which olfactory bulb development is disordered. Individuals with this condition have olfactory loss as well as deterioration in various brain areas, but it is unclear whether the neurological differences arise from olfactory dysfunction or from the other aspects of the syndrome (Manara et al., 2014; Ottaviano et al., 2015). It certainly is possible that this condition involves an increase in inflammation, even though no one has reported it.

1.2.3 Olfactory loss results in damage to brain regions central to memory function

Given the predictive nature of olfactory loss for memory impairment in dementia, the question arises as to how olfactory loss could play a role in memory loss specifically. In fact, the olfactory system is anatomically unique among the senses, in that it has a “superhighway” that bypasses the thalamus and projects directly to regions of the brain involved in memory processing (Gottfried, 2006). Multiple studies now show that loss of olfaction is associated with deterioration of several brain regions (Bitter et al., 2010a,b; Eckert et al., 2024; Han et al., 2023; Kovalová et al., 2024; Peter et al., 2023; Seubert et al., 2020; Whitcroft et al., 2023; Yao et al., 2018), including the regions of the brain integral to memory acquisition and processing. While the deterioration of brain areas may be due to olfactory loss, it is also possible that the factor that produced the olfactory dysfunction also produced the damage in the other brain areas.

1.2.4 Environmental challenges compromise both olfaction and memory

Having identified inflammation as a possible global mediating factor in the links between olfactory loss and medical conditions and mortality, as well as neuroanatomical factors creating a tighter fit between olfactory loss and memory loss specifically, we can proceed to ask whether specific life experiences may activate such connections. There are indeed experiences that are known to cause both loss of olfactory ability and loss of memory, as well as the more diffuse impairments often referred to as “brain fog”. These include: smoking (Ajmani et al., 2017; Lewis et al., 2021), air pollution (Calderón-Garcidueñas and Ayala, 2022; Wang X. et al., 2021), a wide range of medications (Schiffman, 2018; Chavant et al., 2011), stress (Hoenen et al., 2017; Shields et al., 2017), childhood maltreatment (Maier et al., 2020; O'Shea et al., 2021), illiteracy (Dong et al., 2021; Arce Rentería et al., 2019), menopause (Lee et al., 2019; Maki, 2015), toxins (Upadhyay and Holbrook, 2004; Guan et al., 2022), alcoholism (Maurage et al., 2014; Pitel et al., 2014), respiratory infections (Potter et al., 2020; Matsui et al., 2003), nasal passage blockage (Mohamed et al., 2019; Arslan et al., 2018), head trauma (Lötsch et al., 2016; McInnes et al., 2017), highly processed food (Makhlouf et al., 2024; Gomes Gonçalves et al., 2023), and COVID-19 (Doty, 2022).

In one longitudinal study (Douaud et al., 2022), imaging was used to examine the effects of COVID-19 on the brain for individuals who had contracted a mild case of COVID-19 during the time between two brain scans. The second scan was completed approximately 141 days after testing positive for COVID-19, with an average time of 3 years between scans. Comparisons were made with brain scans from individuals who had not tested positive between scans. In the group who had contracted COVID-19, the researchers found significant damage in the regions of the brain involved in olfaction and memory, including the anterior cingulate cortex, orbitofrontal cortex, ventral striatum, amygdala, hippocampus, and parahippocampal gyrus, and the extent of olfactory loss predicted the extent of the brain damage (Campabadal et al., 2023). These individuals also continued to experience cognitive loss.

1.2.5 Olfactory dysfunction and cognitive loss

Compared to our ancestors, most humans in the affluent world experience a narrower range of evolutionarily relevant odors. In addition, people typically have experiences that damage their olfactory system: air pollution, stress, toxins, anatomical blockage, smoking, various medications, adverse childhood experiences, menopause, and even chronic sinusitis, all of which also trigger memory loss (Eimer and Vassar, 2013). As people age, the deterioration of their olfactory ability accompanies the deterioration of their cognitive ability (Leon and Woo, 2022; Doty et al., 1984), perhaps because olfactory loss results in a significant loss of both gray matter and white matter in the cognitive areas of human brains (Schaie et al., 2004; Bitter et al., 2010a,b).

1.2.5.1 Olfactory loss accompanies dementia

Olfactory dysfunction predicts cognitive dysfunction in humans (Schubert et al., 2008) and the loss of olfactory function precedes or parallels the initiation of a wide variety of cognitive disorders such as: AD, MCI, Parkinson's disease, Lewy body dementia, frontotemporal dementia, Creutzfeldt-Jakob disease, alcoholism, and schizophrenia (Wang Q. et al., 2021; Conti et al., 2013; Adams et al., 2018; Ponsen et al., 2004; Birte-Antina et al., 2018).

1.2.5.2 COVID-19 links olfactory loss and dementia

COVID-19 typically produces olfactory loss, and comparisons of MRI scans from individuals both pre-infection and post-infection have revealed neural deterioration that resembles a decade of aging in the cognitive brain regions that receive olfactory-system projections, along with damage to those areas involved in olfaction (Kollndorfer et al., 2015; Segura et al., 2013). Kay (2022) made the case that COVID-19 infections that produce olfactory loss may foster the cognitive loss that is seen in Alzheimer's disease. In fact, Wang et al. (2022) did a retrospective study of 6,245,282 older adults and showed that people with COVID-19 were at significantly increased risk for new diagnosis of Alzheimer's disease within 360 days after the initial COVID-19 diagnosis. Rahmati et al. (2023) went on to do a meta-analysis of twelve studies tracking over 33 million individuals who either had contracted COVID-19 or did not contract the virus. The pooled analyses showed a significant association between COVID-19 infection and subsequent increased risk for new-onset Alzheimer's disease. Given the remarkable number of physiological systems that were affected by the disease (Nasserie et al., 2021), there is no reason to believe that the olfactory loss was the sole factor in increasing the risk of Alzheimer's, but it may be that the loss of olfaction contributed to the degradation of regions in the brain integral to normal memory functioning, as mentioned previously (Kovalová et al., 2024).

1.3 Efficacy of olfactory enrichment

1.3.1 Olfactory enrichment improves symptoms of cognitive impairment

Shi et al. (2023) reviewed a number of studies examining the effects of exposure to essential oils and found a wide range of benefits to the brain and behavior. The benefits included normalizing neurotransmitter levels, decreasing inflammatory factors, decreasing oxidation, increasing neuroprotective factors, improving memory, decreasing neuronal loss, and suppressing beta amyloid levels.

1.3.2 Olfactory enrichment results in memory benefits for healthy adults

From a preventive perspective, about 20 studies have now been performed showing that increasing olfactory stimulation can improve memory (Vance et al., 2024).

For example, olfactory enrichment improves cognition in older adults. Birte-Antina et al. (2018) provided olfactory enrichment with 4 essential-oil odorants twice a day for 5 months, while controls solved daily Sudoku puzzles. The olfactory-enriched group had a significant improvement of olfactory function, improved verbal function, and decreased depression symptoms. Oleszkiewicz et al. (2022) exposed 68 older adults either to 9 odorants twice a day or to no new odorants for 3–6 months, and found the enriched olfactory experience produced improvements in cognitive abilities, dementia status, and olfactory function relative to controls. Specifically, the Montreal Cognitive Assessment revealed a significant improvement in the olfactory-enriched group relative to controls, and the AD8 Dementia Screening Interview showed that enriched participants had no increase in dementia symptoms over the trial period, while control participants had an increase in symptoms.

Increased complexity of olfactory enrichment also improves dementia symptoms. Cha et al. (2022) exposed 34 older adults with dementia to 40 odorants twice a day for 15 days. The control group consisting of 31 individuals with dementia received no such stimulation. There were no initial differences between groups, and all had a Mini-Mental Status Examination score of at least 10. The results were remarkable, as the olfactory-enriched group showed highly significant improvements in memory, olfactory identification, depression symptoms, attention, and language skills. Olfactory-enriched individuals improved their olfactory identification, while controls did not. The Verbal Fluency Test also showed significant improvements for the enriched group relative to the controls. Similarly, the Boston Naming Test revealed a significant improvement in the enriched subjects relative to controls. The Word-List Memory Test, the Word-List Recall Test, the Word List Recognition Test, and the Geriatric Depression Scale all improved in the enriched group relative to controls.

Lin and Li (2022) exposed older adults with mild-to-moderate dementia to 15 essential oils/essences twice a week for 30-min sessions over a 12-week randomized clinical trial. Participants in the olfactory enrichment group also were asked to relate each scent to a matching photo of the scent source. The olfactory enrichment group showed significant cognitive improvement on the Loewenstein Occupational Therapy Cognitive Assessment-Geriatric test. In addition, olfactory enrichment prevented the increase in plasma beta amyloid seen in the control group.

In an effort to minimize burden and increase compliance, we tested the idea that we could get enhanced neural and cognitive outcomes after even minimal olfactory enrichment at night (Woo et al., 2023). The limitations of the available diffusion devices at the time forced us to use this minimal level of olfactory enrichment. Therefore, we gave olfactory enrichment or control exposures to older adults (60–85 years old) for 2 h every night for 6 months, using a single odorant each night, rotating through seven scents a week (Woo et al., 2023). There were statistically significant differences between enriched and control older adults in their cognitive ability using the Rey Auditory Verbal Learning Test, with enriched individuals scoring 226% better than controls. We also found a statistically significant change in mean diffusivity in the uncinate fasciculus of the enriched group compared to controls.

1.4 Mechanisms of olfactory enrichment: inflammation, neuroanatomy, and cognitive reserve

1.4.1 Reduction of inflammation may be the mechanism by which olfactory enrichment improves neurological symptoms

A range of correlational and causal relationships connect inflammation with olfactory loss. Olfactory loss is associated with an increase in Interleukin-6 (IL-6), which increases both inflammation and the maturation of B cells (Henkin et al., 2013) and is also correlated with an increase in C-reactive protein, which increases in the presence of inflammation as indicated by IL-6 (Ekström et al., 2021). Chronic inflammation is associated with olfactory dysfunction (LaFever and Imamura, 2022). As noted earlier, a proinflammatory diet for older adults with low levels of polyunsaturated fatty acids and monosaturated fatty acids is associated with elevated inflammation, olfactory dysfunction, and cognitive decline (Vohra et al., 2023). Moreover, such a diet increases the risk of dementia (Simopoulos, 2002). The association between olfactory dysfunction and frailty varies with the level of inflammation, as measured by circulating levels of the pro-inflammatory cytokine IL-6 (Laudisio et al., 2019). Hahad et al. (2020) found that inflammation mediated the loss of cognition in those exposed to high levels of pollution.

Turning to causal links, unpleasant odors activate the inflammatory response by increasing tumor necrosis factor alpha (TNFα) and decreasing secretory immunoglobulin A (slgA) in saliva (Anja Juran et al., 2022). Imamura and Hasegawa-Ishii (2016) found that toxins can activate the immune response in the olfactory mucosa. Conversely, smelling pleasant odors suppresses immune activity, and more strikingly, even the act of imagining pleasant odors suppresses the immune response, specifically circulating interleukin-2 (IL-2; Matsunaga et al., 2013; Shibata et al., 1991). Casares et al. (2023) found that 6 months of exposure to menthol odor improved both the memory of young mice and the memory of mice that were modified to model Alzheimer's disease. This odor exposure also suppressed inflammation (IL-1β; Casares et al., 2023). Equally, pharmaceutical suppression of inflammation in those mice improved their memory (Casares et al., 2023).

The suppression of the inflammatory response may therefore underlie the finding that olfactory enrichment can improve memory (Cha et al., 2022; Woo et al., 2023). In addition, olfactory enrichment may improve symptoms of other neurological conditions through a similar mechanism.

1.4.2 Olfactory enrichment creates functional and structural changes in the brain

Increased olfactory stimulation, as experienced daily by master perfumers and sommeliers, who sample many odors each day for months and years, results in increased volume of brain regions that receive olfactory projections (Royet et al., 2013; Filiz et al., 2022). A longitudinal study showed that after a year and a half of olfactory training, sommeliers in training, who sampled dozens of odors every day for months to be able to identify those odors in fine wines, increased the thickness of their entorhinal cortex, a brain region critical for memory formation and consolidation (Filiz et al., 2022; Takehara-Nishiuchi, 2014). This structural change may well have functional benefits. Daily olfactory training for 6 weeks resulted in improved olfactory functioning as well as increased cortical thickness of olfactory processing regions of the brain (Al Aïn et al., 2019), and multiple scents presented daily improved cognition in both adults and older adults (Oleszkiewicz et al., 2021, 2022). Additionally, reversal of some medical issues, such as removing an anatomical blockade in the nasal passages, can result in improved cognition and attention, as measured using neuropsychological assessments and event-related auditory evoked potentials (P300; Arslan et al., 2018). In the memory study with healthy older adults described above (Woo et al., 2023), the enriched group that showed improvement in memory performance also had a statistically significant change in mean diffusivity in the uncinate fasciculus, a brain pathway involved with maintaining cognitive processes.

1.4.3 Electrical stimulation of the olfactory system

One mechanism by which olfactory enrichment may be working is by stimulating specific brain areas. Beta amyloid (Aβ) is elevated in Alzheimer's disease (Pignataro and Middei, 2017). In a rat model of Alzheimer's disease, electrical stimulation of the olfactory bulb reversed the accumulation of beta amyloid (Aβ) plaque formation in the prefrontal cortex, the entorhinal cortex, the dorsal hippocampus, and the ventral hippocampus. It also blocked the impairments in working memory in these rats (Salimi et al., 2024). In addition, electrical stimulation of the olfactory bulb also increased functional connectivity in the brain during a working memory task. It should be noted that transethmoid electrical stimulation of the human olfactory bulb induced olfactory perceptions (Holbrook et al., 2019). Olfactory enrichment may therefore act to stimulate the areas to which the olfactory input projects (Gottfried, 2006). Conversely, intrabulbar injections of Aβ in rats decreased olfactory function, a phenomenon that was more easily triggered in older rats (Alvarado-Martínez et al., 2013).

1.4.4 Making a distinction between contracting a disease vs. experiencing symptoms of a disease

It is important in a discussion regarding causality to consider whether something can differentially change the risk of contracting a disease or the risk of experiencing the symptoms of the disorder. This distinction may be important for our understanding of the relationships between olfaction, cognition, and disease. Typically, the symptoms of the disease accompany the disease itself, but there are exceptions. Some people who contracted the COVID-19 virus, for instance, did not show any symptoms of the disease (Rasmussen and Popescu, 2021). In the phenomenon called cognitive reserve, an individual can develop the neuropathology of Alzheimer's disease, indicating that they had contracted the disease, but show none of the symptoms of severe memory loss (Stern, 2012).

1.4.5 Olfactory ability and cognitive reserve

In mice, long-term olfactory enrichment improves olfactory ability, and it also improves learning and memory for tasks that do not involve odors (Terrier et al., 2024). This effect may represent a form of cognitive reserve in mice, here mediated by an increase in noradrenergic innervation and resulting in the remodeling of brain connectivity in older mice. These data suggest a causal association between olfactory enrichment and cognition. In humans, odor threshold correlates with a measure of cognitive reserve that involves education, while odor discrimination ability correlates with career experiences and leisure experiences. Women had significant correlations between odor threshold, discrimination and identification, and leisure experiences, while men had a significant association between odor threshold and educational experiences (Masala et al., 2023).

1.4.6 Olfactory enrichment may induce cognitive reserve in humans

Cognitive reserve in humans comes from leading a life filled with environmental enrichment, with a high level of education, a cognitively engaging career, and a high level of socializing (Stern, 2012). Conversely, illiterate individuals have the highest probability of developing Alzheimer's disease (Dong et al., 2021), and they have little of the enrichment that seems to protect those with cognitive reserve (Brucki, 2010). Perhaps the uniquely direct connections of the olfactory system to the regions of the brain that are critical for memory functioning allow the olfactory system to rapidly induce what may be called cognitive reserve in humans.

2 Discussion

There is reason to believe that the relationship between olfactory loss and medical conditions may be more than coincidental. First, there are many instances where both are present, with at least 139 medical conditions showing associations with olfactory dysfunction. Second, olfactory loss precedes the expression of the medical condition, raising the possibility that olfactory loss makes the brain or body vulnerable to expressing the symptoms of these medical conditions. Third, olfactory loss prospectively predicts both memory loss and all-cause mortality.

Inflammation could be a key mechanism underlying a causal relationship between olfaction and memory; neuroanatomical and environmental factors also play a role. While the causal arrow may go either way, it is possible that for some conditions, it is the olfactory loss that raises the risk of expressing the symptoms of those conditions.

If olfactory loss increases the risk of either developing these medical conditions or having the symptoms of the conditions, then it may be possible to prevent the onset of symptoms from these conditions. Studies show that olfactory enrichment improves memory performance in healthy adults and there are even greater improvements found for adults with dementia. These benefits may be mediated via reduction of inflammation.

A suggestive notion underlying many of these observations is that neuropathology is not always symptomatic, thanks to phenomena such as cognitive reserve. For instance, people with cognitive reserve have the neuropathology of Alzheimer's disease, but they don't have the memory-loss symptoms. The olfactory system may be involved in generating protective cognitive reserve especially for memory-related conditions. More widely, since pleasant scents can decrease harmful inflammation, it seems possible that olfactory enrichment may reduce the symptoms of other medical conditions.

Future directions for research in this area would include simultaneously studying both olfaction and inflammation in specific medical conditions, studying more conditions in individuals who have olfactory dysfunction, and studying these variables over time. It also would be interesting to block inflammation in specific medical conditions to determine the effects on olfaction.

Statements

Data availability statement

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

Author contributions

ML: Writing – original draft. ET: Conceptualization, Writing – review & editing. CW: Writing – review & editing.

Funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.

Acknowledgments

We thank Dr. Tom Lane for his insightful comments on the manuscript.

Conflict of interest

ML holds equity in Science Lab 3, which is developing Memory Air®, a system that automatically delivers olfactory enrichment. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

  • 1

    Abele M. Riet A. Hummel T. Klockgether T. Wüllner U. (2003). Olfactory dysfunction in cerebellar ataxia and multiple system atrophy. J. Neurol.250, 1453–1455. 10.1007/s00415-003-0248-4

  • 2

    Acosta-Ampudia Y. Monsalve D. M. Castillo-Medina L. F. Rodríguez Y. Pacheco Y. Halstead S. et al . (2018). Autoimmune neurological conditions associated with Zika virus infection. Front. Mol. Neurosci. 11:116. 10.3389/fnmol.2018.00116

  • 3

    Adams D. R. Kern D. W. Wroblewski K. E. McClintock M. K. Dale W. Pinto J. M. (2018). Olfactory dysfunction predicts subsequent dementia in older U.S. Adults. J. Am. Geriatr. Soc. 66, 140–144. 10.1111/jgs.15048

  • 4

    Adler C. H. Gwinn K. A. Newman S. (1998). Olfactory function in restless legs syndrome. Mov. Disord. 13, 563–565. 10.1002/mds.870130332

  • 5

    Ahmed O. G. Rowan N. R. (2020). Olfactory dysfunction and chronic rhinosinusitis. Immunol. Allergy Clin. North Am. 40, 223–232. 10.1016/j.iac.2019.12.013

  • 6

    Aimbire F. Penna S. C. Rodrigues M. Rodrigues K. C. Lopes-Martins R. A. Sertié J. A. (2007). Effect of hydroalcoholic extract of Zingiber officinalis rhizomes on LPS-induced rat airway hyperreactivity and lung inflammation. Prostagland. Leukot. Essent. Fatty Acids77, 129–138. 10.1016/j.plefa.2007.08.008

  • 7

    Aiyegbusi O. L. Hughes S. E. Turner G. Rivera S. C. McMullan C. Chandan J. S. et al . (2021). Symptoms, complications and management of long COVID: a review. J. R. Soc. Med. 114, 428–442. 10.1177/01410768211032850

  • 8

    Ajmani G. S. Suh H. H. Wroblewski K. E. Pinto J. M. (2017). Smoking and olfactory dysfunction: a systematic literature review and meta-analysis. Laryngoscope127, 1753–1761. 10.1002/lary.26558

  • 9

    Akizuki H. Wada T. Tabuchi K. (2022). Inflammation-based score (combination of platelet count and neutrophil-to-lymphocyte ratio) predicts pharyngocutaneous fistula after total laryngectomy. Laryngoscope132, 1582–1587. 10.1002/lary.29970

  • 10

    Akşit E. Çil Ö. Ç. (2020). Olfactory dysfunction in patients with ischemic heart failure. Acta Cardiol. Sin. 36, 133–139. 10.6515/ACS.202003_36(2).20190812B

  • 11

    Akyol L. Günbey E. Karlı R. Önem S. Özgen M. Sayarlioglu M. (2016). Evaluation of olfactory function in Behçet's disease. Eur. J. Rheumatol. 3, 153–156. 10.5152/eurjrheum.2016.017

  • 12

    Al Aïn S. Poupon D. Hétu S. Mercier N. Steffener J. Frasnelli J. (2019). Smell training improves olfactory function and alters brain structure. Neuroimage189, 45–54. 10.1016/j.neuroimage.2019.01.008

  • 13

    Alavinezhad A. Hedayati M. Boskabady M. H. (2017). The effect of Zataria multiflora and carvacrol on wheezing, FEV1 and plasma levels of nitrite in asthmatic patients. Avicenna J. Phytomed. 7, 531–541.

  • 14

    Alavinezhad A. Khazdair M. R. Boskabady M. H. (2018). Possible therapeutic effect of carvacrol on asthmatic patients: a randomized, double blind, placebo-controlled, Phase II clinical trial. Phytother. Res. 32, 151–159. 10.1002/ptr.5967

  • 15

    Alberti A. Sarchielli P. Gallinella E. Floridi A. Floridi A. Mazzotta et al . (2003). Plasma cytokine levels in patients with obstructive sleep apnea syndrome: a preliminary study. J. Sleep Res.12, 305–311. 10.1111/j.1365-2869.2003.00361.x

  • 16

    Al-Daghri N. M. Rahman S. Sabico S. Yakout S. Wani K. Al-Attas O. S. et al . (2016). Association of vitamin B12 with pro-inflammatory cytokines and biochemical markers related to cardiometabolic risk in Saudi subjects. Nutrients8:460. 10.3390/nu8090460

  • 17

    Alfaro R. Doty R. T. Narayanan A. Lugar H. Hershey T. Pepino M. Y. (2020). Taste and smell function in Wolfram syndrome. Orphanet J. Rare Dis. 15:57. 10.1186/s13023-020-1335-7

  • 18

    Alosco M. L. Jarnagin J. Tripodis Y. Platt M. Martin B. Chaisson C. E. et al . (2017). Olfactory function and associated clinical correlates in former National Football League players. J. Neurotrauma34, 772–780. 10.1089/neu.2016.4536

  • 19

    Alshammery S. Patel S. Jones H. F. Han V. X. Gloss B. S. Gold W. A. et al . (2022). Common targetable inflammatory pathways in brain transcriptome of autism spectrum disorders and Tourette syndrome. Front. Neurosci.16:999346. 10.3389/fnins.2022.999346

  • 20

    Alster P. Madetko N. Friedman A. (2021). Neutrophil-to-lymphocyte ratio (NLR) at boundaries of progressive supranuclear palsy syndrome (PSPS). and corticobasal syndrome (CBS). Neurol. Neurochir. Pol. 55, 97–101. 10.5603/PJNNS.a2020.0097

  • 21

    Alster P. Madetko N. Koziorowski D. Friedman A. (2020). microglial activation and inflammation as a factor in the pathogenesis of progressive supranuclear palsy (PSP). Front. Neurosci. 14:893. 10.3389/fnins.2020.00893

  • 22

    Alvarado-Martínez R. Salgado-Puga K. Peña-Ortega F. (2013). Amyloid beta inhibits olfactory bulb activity and the ability to smell. PLoS ONE8:e75745. 10.1371/journal.pone.0075745

  • 23

    Amin J. Erskine D. Donaghy P. C. Surendranathan A. Swann P. Kunicki A. P. et al . (2022). Inflammation in dementia with Lewy bodies. Neurobiol. Dis. 168:105698. 10.1016/j.nbd.2022.105698

  • 24

    Amital H. Agmon-Levin N. Shoenfeld N. Arnson Y. Amital D. Langevitz P. et al . (2014). Olfactory impairment in patients with the fibromyalgia syndrome and systemic sclerosis. Immunol. Res. 60, 201–207. 10.1007/s12026-014-8573-5

  • 25

    Anja Juran S. Tognetti A. Lundström J. N. Kumar L. Stevenson R. J. Lekander M. et al . (2022). Disgusting odors trigger the oral immune system. Evol. Med. Public Health11, 8–17. 10.1093/emph/eoac042

  • 26

    Apolloni S. Milani M. D'Ambrosi N. (2022). Neuroinflammation in Friedreich's ataxia. Int. J. Mol. Sci.23:6297. 10.3390/ijms23116297

  • 27

    Apter A. J. Gent J. F. Frank M. (1999). Fluctuating olfactory sensitivity and distorted odor perception in allergic rhinitis. Arch. Otolaryngol. Head Neck Surg.125, 1005–1010. 10.1001/archotol.125.9.1005

  • 28

    Arce Rentería M. Vonk J. M. J. Felix G. Avila J. F. Zahodne L. B. Dalchand E. et al . (2019). Illiteracy, dementia risk, and cognitive trajectories among older adults with low education. Neurology93, e2247–e2256. 10.1212/WNL.0000000000008587

  • 29

    Arslan F. Tasdemir S. Durmaz A. Tosun F. (2018). The effect of nasal polyposis related nasal obstruction on cognitive functions. Cogn. Neurodyn. 12, 385–390. 10.1007/s11571-018-9482-4

  • 30

    Atalar A. Ç. Erdal Y. Tekin B. Yildiz M. Akdogan Ö. Emre U. (2018). Olfactory dysfunction in multiple sclerosis. Mult. Scler. Relat. Disord. 21, 92–96. 10.1016/j.msard.2018.02.032

  • 31

    Azotla-Vilchis C. N. Sanchez-Celis D. Agonizantes-Juárez L. E. Suárez-Sánchez R. Hernández-Hernández J. M. Peña J. et al . (2021). Transcriptome analysis reveals altered inflammatory pathway in an inducible glial cell model of myotonic dystrophy type 1. Biomolecules11:159. 10.3390/biom11020159

  • 32

    Bafei S. E. C. Zhao X. Chen C. Sun J. Zhuang Q. Lu X. et al . (2023). Interactive effect of increased high sensitive C-reactive protein and dyslipidemia on cardiovascular diseases: a 12-year prospective cohort study. Lipids Health Dis. 22:113. 10.1186/s12944-023-01894-0

  • 33

    Bagherieh S. Arefian N. M. Ghajarzadeh M. Tafreshinejad A. Zali A. Mirmosayyeb O. et al . (2023). Olfactory dysfunction in patients with Parkinson's disease: a systematic review and meta-analysis. Curr. J. Neurol. 22, 249–254. 10.18502/cjn.v22i4.14530

  • 34

    Barnes P. J. (2016). Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J. Allergy Clin. Immunol.138, 16–27. 10.1016/j.jaci.2016.05.011

  • 35

    Barone M. V. Auricchio R Nanayakkara M. Greco L. Troncone R. Auricchio S. (2022). Pivotal role of inflammation in celiac disease. Int. J. Mol. Sci.23:7177. 10.3390/ijms23137177

  • 36

    Baudouin C. Kolko M. Melik-Parsadaniantz S. Messmer E. M. (2021). Inflammation in glaucoma: from the back to the front of the eye, and beyond. Prog. Retin. Eye Res. 83:100916. 10.1016/j.preteyeres.2020.100916

  • 37

    Benedetti F. Aggio V. Pratesi M. L. Greco G. Furlan R. (2020). Neuroinflammation in bipolar depression. Front. Psychiatry11:71. 10.3389/fpsyt.2020.00071

  • 38

    Berkiten G. Tutara B. G?¨kdenb Y. Sengiz S. Karaketir S. Sari?am S. S. et al . (2024). Does celiac disease affect smell sensation, mucociliary clearance and nasal smear?J. Ear Nose Throat Head Neck Surg.3, 23–29. 10.24179/kbbbbc.2023-99179

  • 39

    Berlin H. A. Stern E. R. Ng J. Zhang S. Rosenthal D. Turetzky R. et al . (2017). Altered olfactory processing and increased insula activity in patients with obsessive-compulsive disorder: an fMRI study. Psychiatry Res. Neuroimaging262, 15–24. 10.1016/j.pscychresns.2017.01.012

  • 40

    Bershad E. M. Urfy M. Z. Calvillo E. Tang R. Cajavilca C. Lee A. G. et al . (2014). Marked olfactory impairment in idiopathic intracranial hypertension. J. Neurol. Neurosurg. Psychiatr.85, 959–964. 10.1136/jnnp-2013-307232

  • 41

    Bertone-Johnson E. R. Manson J. E. Purdue-Smithe A. C. Hankinson S. E. Rosner B. A. Whitcomb B. W. (2019). A prospective study of inflammatory biomarker levels and risk of early menopause. Menopause26, 32–38. 10.1097/GME.0000000000001162

  • 42

    Bettison T. M. Mahmut M. K. Stevenson R. J. (2013). The relationship between psychopathy and olfactory tasks sensitive to orbitofrontal cortex function in a non-criminal student sample. Chemosens. Percept.6, 198–210. 10.1007/s12078-013-9157-9

  • 43

    Bigman G. (2020). Age-related smell and taste impairments and vitamin D associations in the U.S. Adults National Health and Nutrition Examination Survey. Nutrients12:984. 10.3390/nu12040984

  • 44

    Birte-Antina W. Ilona C. Antje H. Thomas H. (2018). Olfactory training with older people. Int. J. Geriatr. Psychiatry33, 212–220. 10.1002/gps.4725

  • 45

    Biscetti L. De Vanna G. Cresta E. Corbelli I. Gaetani L. Cupini L. et al . (2021). Headache and immunological/autoimmune disorders: a comprehensive review of available epidemiological evidence with insights on potential underlying mechanisms. J. Neuroinflamm.18:259. 10.1186/s12974-021-02229-5

  • 46

    Bitter T. Bruderle J. Gudziol H. Burmeister H. P. Gaser C. Guntinas-Lichius O. (2010a). Gray and white matter reduction in hyposmic subjects - a voxel-based morphometry study. Brain Res.1347, 42–47. 10.1016/j.brainres.2010.06.003

  • 47

    Bitter T. Gudziol H. Burmeister H. P. Mentzel H. J. Guntinas-Lichius O. Gaser C. (2010b). Anosmia leads to a loss of gray matter in cortical brain areas. Chem. Senses35, 407–415. 10.1093/chemse/bjq028

  • 48

    Bonomi M. Patsias A. Posner M. Sikora A. (2014). The role of inflammation in head and neck cancer. Adv. Exp. Med. Biol. 816, 107–127. 10.1007/978-3-0348-0837-8_5

  • 49

    Bor A. S. Niemansburg S. L. Wermer M. J. Rinkel G. J. (2009). Anosmia after coiling of ruptured aneurysms: prevalence, prognosis, and risk factors. Stroke40, 2226–2228. 10.1161/STROKEAHA.108.539445

  • 50

    Bower E. Szajer J. Mattson S. N. Riley E. P. Murphy C. (2013). Impaired odor identification in children with histories of heavy prenatal alcohol exposure. Alcohol47, 275–278. 10.1016/j.alcohol.2013.03.002

  • 51

    Bränn E. Fransson E. White R. A. Papadopoulos F. C. Edvinsson Å. Kamali-Moghaddam M. et al . (2020). Inflammatory markers in women with postpartum depressive symptoms. J. Neurosci. Res. 98, 1309–1321. 10.1002/jnr.24312

  • 52

    Brás I. C. Xylaki M. Outeiro T. F. (2020). Mechanisms of alpha-synuclein toxicity: an update and outlook. Prog. Brain Res. 252, 91–129. 10.1016/bs.pbr.2019.10.005

  • 53

    Bright F. Werry E. L. Dobson-Stone C. Piguet O. Ittner L. M. Halliday G. M. et al . (2019). Neuroinflammation in frontotemporal dementia. Nat. Rev. Neurol. 15, 540–555. 10.1038/s41582-019-0231-z

  • 54

    Brown C. H. 4th Morrissey C. Ono M. Yenokyan G. Selnes O. A. Walston J. et al . (2015). Impaired olfaction and risk of delirium or cognitive decline after cardiac surgery. J. Am. Geriatr. Soc. 63, 16–23. 10.1111/jgs.13198

  • 55

    Brucki S. M. D. (2010). Illiteracy and dementia. Dement. Neuropsychol. 4, 153–157. 10.1590/S1980-57642010DN40300002

  • 56

    Burges Watson D. L. Campbell M. Hopkins C. Smith B. Kelly C. Deary V. (2021). Altered smell and taste: anosmia, parosmia and the impact of long COVID-PLoS ONE 16:e0256998. 10.1371/journal.pone.0256998

  • 57

    Buskova J. Klaschka J. Sonka K. Nevsimalova S. (2010). Olfactory dysfunction in narcolepsy with and without cataplexy. Sleep Med. 11, 558–561. 10.1016/j.sleep.2010.01.009

  • 58

    Calderón-Garcidueñas L. Ayala A. (2022). Air pollution, ultrafine particles, and your brain: are combustion nanoparticle emissions and engineered nanoparticles causing preventable fatal neurodegenerative diseases and common neuropsychiatric outcomes?Environ. Sci. Tech. 56, 6847–6856. 10.1021/acs.est.1c04706

  • 59

    Campabadal A. Oltra J. Junqué C. Guillen N. Botí M. Á. Sala-Llonch R. et al . (2023). Structural brain changes in post-acute COVID-19 patients with persistent olfactory dysfunction. Ann. Clin. Transl. Neurol.10, 195–203. 10.1002/acn3.51710

  • 60

    Casares N. Alfaro M. Cuadrado-Tejedor M. Lasarte-Cia A. Navarro F. Vivas I. et al . (2023). Improvement of cognitive function in wild-type and Alzheimer's disease mouse models by the immunomodulatory properties of menthol inhalation or by depletion of T regulatory cells. Front. Immunol.14:1130044. 10.3389/fimmu.2023.1130044

  • 61

    Castiglione A. Möller C. (2022). Usher syndrome. Audiol. Res. 12, 42–65. 10.3390/audiolres12010005

  • 62

    Cecchini M. P. Viviani D. Sandri M. Hähner A. Hummel T. Zancanaro C. (2016). Olfaction in people with Down syndrome: a comprehensive assessment across four decades of age. PLoS ONE11:e0146486. 10.1371/journal.pone.0146486

  • 63

    Cecoro G. Annunziata M. Iuorio M. T. Nastri L. Guida L. (2020). Periodontitis, low-grade inflammation and systemic health: a scoping review. Medicina56:272. 10.3390/medicina56060272

  • 64

    Cesari M. Penninx B. W. Newman A. B. Kritchevsky S. B. Nicklas B. J. Sutton-Tyrrell K. et al . (2003). Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation108, 2317–2322. 10.1161/01.CIR.0000097109.90783.FC

  • 65

    Cha H. Kim S. Kim H. Kim G. Kwon K. Y. (2022). Effect of intensive olfactory training for cognitive function in patients with dementia. Geriatr. Gerontol. Int. 22, 5–11. 10.1111/ggi.14287

  • 66

    Challakere Ramaswamy V. M. Butler T. Ton B. Wilhelm K. Mitchell P. B. Knight L. et al . (2023). Neuropsychiatric correlates of olfactory identification and traumatic brain injury in a sample of impulsive violent offenders. Front. Psychol.14, 1254574. 10.3389/fpsyg.2023.1254574

  • 67

    Challakere Ramaswamy V. M. Schofield P. W. (2022). Olfaction and executive cognitive performance: a systematic review. Front. Psychol.13:871391. 10.3389/fpsyg.2022.871391

  • 68

    Chamberlin K. W. Yuan Y. Li C. Luo Z. Reeves M. Kucharska-Newton A. et al . (2024). Olfactory impairment and the risk of major adverse cardiovascular outcomes in older adults. J. Am. Heart Assoc. 13:e033320. 10.1161/JAHA.123.033320

  • 69

    Chang K. Zaikos T. Kilner-Pontone N. Ho C. Y. (2024). Mechanisms of COVID-19-associated olfactory dysfunction. Neuropath. Appl. Neurobiol. 50:e12960. 10.1111/nan.12960

  • 70

    Chao L. L. (2024). Olfactory and cognitive decrements in 1991 Gulf War veterans with gulf war illness/chronic multisymptom illness. Environ. Health23, 14–23. 10.1186/s12940-024-01058-2

  • 71

    Charbel Issa P. Reuter P. Kühlewein L. Birtel J. Gliem M. Tropitzsch A. et al . (2018). Olfactory dysfunction in patients with CNGB1-associated retinitis pigmentosa. JAMA Ophthalmol.136, 761–769. 10.1001/jamaophthalmol.2018.162

  • 72

    Chavant F. Favrelière S. Lafay-Chebassier C. Plazanet C. Pérault-Pochat M. C. (2011). Memory disorders associated with consumption of drugs: updating through a case/noncase study in the French PharmacoVigilance Database. Br. J. Clin. Pharmacol. 72, 898–904. 10.1111/j.1365-2125.2011.04009.x

  • 73

    Chaves-Filho A. M. Braniff O. Angelova A. Deng Y. Tremblay M. È. (2023). Chronic inflammation, neuroglial dysfunction, and plasmalogen deficiency as a new pathobiological hypothesis addressing the overlap between post-COVID-19 symptoms and myalgic encephalomyelitis/chronic fatigue syndrome. Brain Res. Bull.201:110702. 10.1016/j.brainresbull.2023.110702

  • 74

    Chen L. Wang X. Doty R. L. Cao S. Yang J. Sun F. et al . (2021). Olfactory impairment in Wilson's disease. Brain Behav. 11:e02022. 10.1002/brb3.2022

  • 75

    Chen X. Guo W. Yu L. Luo D. Xie L. Xu J. (2021). Association between anxious symptom severity and olfactory impairment in young adults with generalized anxiety disorder: a case-control study. Neuropsychiatr. Dis. Treat. 17, 2877–2883. 10.2147/NDT.S314857

  • 76

    Cheng X. Choi J. S. Waxman S. G. Dib-Hajj S. D. (2021). Sodium channels and beyond in peripheral nerve disease: modulation by cytokines and their effector protein kinases. Neurosci. Lett. 741:135446. 10.1016/j.neulet.2020.135446

  • 77

    Choi J. S. Jang S. S. Kim J. Hur K. Ference E. Wrobel B. (2021). Association between olfactory dysfunction and mortality in US adults. JAMA Otolaryngol. Head Neck Surg. 147, 49–55. 10.1001/jamaoto.2020.3502

  • 78

    Connelly T. Farmer J. M. Lynch D. R. Doty R. L. (2002). Olfactory dysfunction in degenerative ataxias. J. Neurol. Neurosurg. Psychiatr.74, 1435–1437. 10.1136/jnnp.74.10.1435

  • 79

    Constantinescu C. S. Raps E. C. Cohen J. A. West S. E. Doty R. L. (1994). Olfactory disturbances as the initial or most prominent symptom of multiple sclerosis. J. Neurol. Neurosurg. Psychiatr.57, 1011–1012. 10.1136/jnnp.57.8.1011

  • 80

    Conti M. Z. Vicini-Chilovi B. Riva M. Zanetti M. Liberini P. Padovani A. et al . (2013). Odor identification deficit predicts clinical conversion from mild cognitive impairment to dementia due to Alzheimer's disease. Arch. Clin. Neuropsychol. 28, 391–399. 10.1093/arclin/act032

  • 81

    Coskun Benlidayi I. (2019). Role of inflammation in the pathogenesis and treatment of fibromyalgia. Rheumatol. Int. 39, 781–791. 10.1007/s00296-019-04251-6

  • 82

    Cox A. J. West N. P. Cripps A. W. (2015). Obesity, inflammation, and the gut microbiota. Lancet Diabetes Endocrinol. 3, 207–215. 10.1016/S2213-8587(14)70134-2

  • 83

    Croy I. Schellong J. Gerber J. Joraschky P. Iannilli E. Hummel T. (2010). Women with a history of childhood maltreatment exhibit more activation in association areas following non-traumatic olfactory stimuli: a fMRI study. PLoS ONE5:e9362. 10.1371/journal.pone.0009362

  • 84

    Dabravolski S. A. Nikiforov N. G. Eid A. H. Nedosugova L. V. Starodubova A. V. Popkova T. V. et al . (2021). Mitochondrial dysfunction and chronic inflammation in polycystic ovary syndrome. Int. J. Mol. Sci.22:3923. 10.3390/ijms22083923

  • 85

    Dahlman A. Puthia M. Petrlova J. Schmidtchen A. Petruk G. (2021). Thrombin-derived c-terminal peptide reduces Candida-induced inflammation and infection in vitro and in vivo. Antimicrob. Agents Chemother. 65:e0103221. 10.1128/AAC.01032-21

  • 86

    Dalle S. Rossmeislova L. Koppo K. (2017). The role of inflammation in age-related sarcopenia. Front. Physiol. 8:1045. 10.3389/fphys.2017.01045

  • 87

    Dalton B. Campbell I. C. Chung R. Breen G. Schmidt U. Himmerich H. (2018). Inflammatory markers in anorexia nervosa: an exploratory study. Nutrients10:1573. 10.3390/nu10111573

  • 88

    Datta S. Jha K. Ganguly A. Kumar T. (2023). Olfactory dysfunction as a marker for essential hypertension in a drug-naive adult population: A hospital-based study. Cureus15:e41920. 10.7759/cureus.41920

  • 89

    Deeks S. G. Tracy R. Douek D. C. (2013). Systemic effects of inflammation on health during chronic HIV infection. Immunity39, 633–645. 10.1016/j.immuni.2013.10.001

  • 90

    Deng H. Y. Feng J. R. Zhou W. H. Kong W. F. Ma G. C. Hu T. F. et al . (2020). Olfactory sensitivity is related to erectile function in adult males. Front. Cell Devel. Biol.8:93. 10.3389/fcell.2020.00093

  • 91

    Derin S. Koseoglu S. Sahin C. Sahan M. (2016). Effect of vitamin B12 deficiency on olfactory function. Int. Forum Allergy Rhinol.6, 1051–1055. 10.1002/alr.21790

  • 92

    Desiato V. M. Soler Z. M. Nguyen S. A. Salvador C. Hill J. B. Lamira J. et al . (2021). Evaluating the relationship between olfactory function and loneliness in community-dwelling individuals: a cross-sectional study. Am. J. Rhinol. Allergy35, 334–340. 10.1177/1945892420958365

  • 93

    Devanand D. P. Lee S. Manly J. Andrews H. Schupf N. Masurkar A. et al . (2015). Olfactory identification deficits and increased mortality in the community. Ann. Neurol. 78, 401–411. 10.1002/ana.24447

  • 94

    Dinc M. E. Dalgic A. Ulusoy S. Dizdar D. Develioglu O. Topak M. (2016). Does iron deficiency anemia affect olfactory function?Acta Otolaryngol. 136, 754–757. 10.3109/00016489.2016.1146410

  • 95

    Dirchwolf M. Ruf A. E. (2015). Role of systemic inflammation in cirrhosis: from pathogenesis to prognosis. World J. Hepatol.7, 1974–1981. 10.4254/wjh.v7.i16.1974

  • 96

    Dong Y. Wang Y. Liu K. Liu R. Tang S. Zhang Q. et al . (2021). Olfactory impairment among rural-dwelling Chinese older adults: prevalence and associations with demographic, lifestyle, and clinical factors. Front. Aging Neurosci.13:621619. 10.3389/fnagi.2021.621619

  • 97

    Doty R. L. (2022). Olfactory dysfunction in COVID-19: pathology and long-term implications for brain health. Trends Mol. Med. 28, 781–794. 10.1016/j.molmed.2022.06.005

  • 98

    Doty R. L. Shaman P. Applebaum S. L. Giberson R. Siksorski L. Rosenberg L. (1984). Smell identification ability: changes with age. Science226, 1441–1443. 10.1126/science.6505700

  • 99

    Dou Y. Blaine Crowley T. Gallagher S. Bailey A. McGinn D. Zackai E. et al . (2020). Increased T-cell counts in patients with 22q11.2 deletion syndrome who have anxiety. Am. J. Med. Genet. A. 182, 1815–1818. 10.1002/ajmg.a.61588

  • 100

    Douaud G. Lee S. Alfaro-Almagro F. Arthofer C. Wang C. McCarthy P. et al . (2022). SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature604, 697–707. 10.1038/s41586-022-04569-5

  • 101

    East B. S. Wilson D. A. (2019). A hunger for odour: Leptin modulation of olfaction. Acta Physiol. 227:e13363. 10.1111/apha.13363

  • 102

    Eckert M. A. Benitez A. Soler Z. M. Dubno J. R. Schlosser R. J. (2024). Gray matter and episodic memory associations with olfaction in middle-aged to older adults. Int. Forum Allergy Rhinol. 14, 961–971. 10.1002/alr.23290

  • 103

    Eimer W. A. Vassar R. (2013). Neuron loss in the 5XFAD mouse model of Alzheimer's disease correlates with intraneuronal Aβ42 accumulation and Caspase-3 activation. Mol. Neurodegener. 8:2. 10.1186/1750-1326-8-2

  • 104

    Ekström I. Sjölund S. Nordin S. Nordin Adolfsson A. Adolfsson R. Nilsson L. G. et al . (2017). Smell loss predicts mortality risk regardless of dementia conversion. J. Am. Geriatr. Soc. 65, 1238–1243. 10.1111/jgs.14770

  • 105

    Ekström I. Vetrano D. L. Papenberg G. Laukka E. J. (2021). Serum C-reactive protein is negatively associated with olfactory identification ability in older adults. Iperception12:20416695211009928. 10.1177/20416695211009928

  • 106

    El Gazzar M. El Mezayen R. Nicolls M. R. Marecki J. C. Dreskin S. C. (2006).Downregulation of leukotriene biosynthesis by thymoquinone attenuates airway inflammation in a mouse model of allergic asthma. Biochim. Biophys. Acta1760, 1088–1095. 10.1016/j.bbagen.2006.03.006

  • 107

    Elhassanien M. E. M. Bahnasy W. S. El-Heneedy Y. A. E. Kishk A. M. Tomoum M. O. Ramadan K. M. et al . (2021). Olfactory dysfunction in essential tremor versus tremor dominant Parkinson disease. Clin. Neurol. Neurosurg. 200:106352. 10.1016/j.clineuro.2020.106352

  • 108

    Eliyan Y. Wroblewski K. E. McClintock M. K. Pinto J. M. (2021). Olfactory dysfunction predicts the development of depression in older US adults. Chem. Senses46:bjaa075. 10.1093/chemse/bjaa075

  • 109

    Fernandez-Ruiz J. Diaz R. Hall-Haro C. Vergara P. Fiorentini A. Nunez L. et al . (2003). Olfactory dysfunction in hereditary ataxia and basal ganglia disorders. Neuroreport14, 1339–1341. 10.1097/00001756-200307180-00011

  • 110

    Filiz G. Poupon D. Banks S. Fernandez P. Frasnelli J. (2022). Olfactory bulb volume and cortical thickness evolve during sommelier training. Hum. Brain Mapp. 43, 2621–2633. 10.1002/hbm.25809

  • 111

    Firth N. C. Primativo S. Marinescu R. V. Shakespeare T. J. Suarez-Gonzalez A. Lehmann M. et al . (2019). Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy. Brain142, 2082–2095. 10.1093/brain/awz136

  • 112

    Fischer M. Zopf Y. Elm C. Pechmann G. Hahn E. G. Schwab D. et al . (2014). Subjective and objective olfactory abnormalities in Crohn's disease. Chem. Senses39, 529–538. 10.1093/chemse/bju022

  • 113

    Fluitman K. S. van den Broek T. J. Nieuwdorp M. Visser M. IJzerman R. G. Keijser B. J. F. (2021). Associations of the oral microbiota and Candida with taste, smell, appetite and undernutrition in older adults. Sci. Rep.11:23254. 10.1038/s41598-021-02558-8

  • 114

    Francelle L. Mazzulli J. R. (2022). Neuroinflammation in Gaucher disease, neuronal ceroid lipofuscinosis, and commonalities with Parkinson's disease. Brain Res. 1780:147798. 10.1016/j.brainres.2022.147798

  • 115

    Frangou E. Vassilopoulos D. Boletis J. Boumpas D. T. (2019). An emerging role of neutrophils and NETosis in chronic inflammation and fibrosis in systemic lupus erythematosus (SLE) and ANCA-associated vasculitides (AAV): Implications for the pathogenesis and treatment. Autoimmun. Rev. 18, 751–760. 10.1016/j.autrev.2019.06.011

  • 116

    Frasnelli J. Laguë-Beauvais M. LeBlanc J. Alturki A. Y. Champoux M. C. Couturier C. et al . (2016). Olfactory function in acute traumatic brain injury. Clin. Neurol. Neurosurg. 140, 68–72. 10.1016/j.clineuro.2015.11.013

  • 117

    Frasnelli J. A. Temmel A. F. Quint C. Oberbauer R. Hummel T. (2002). Olfactory function in chronic renal failure. Am. J. Rhinol.16, 275–279.

  • 118

    Fuller-Thomson E. R. Fuller-Thomson E. G. (2019). Relationship between poor olfaction and mortality. Ann. Intern. Med. 171, 525–526. 10.7326/L19-0467

  • 119

    Galvez V. Diaz R. Hernandez-Castillo C. R. Campos-Romo A. Fernandez-Ruiz J. (2014). Olfactory performance in spinocerebellar ataxia type 7 patients. Parkinsonism Rel. Disord. 20, 499–502. 10.1016/j.parkreldis.2014.01.024

  • 120

    Gamain J. Herr T. Fleischmann R. Stenner A. Vollmer M. Willert C. et al . (2021). Smell and taste in idiopathic blepharospasm. J. Neural Transm. 128, 1215–1224. 10.1007/s00702-021-02366-4

  • 121

    Gandhi G. R. Leão G. C. S. Calisto V. K. D. S. Vasconcelos A. B. S. Almeida M. L. D. Quintans J. S. S. et al . (2020). Modulation of interleukin expression by medicinal plants and their secondary metabolites: A systematic review on anti-asthmatic and immunopharmacological mechanisms. Phytomedicine70:153. 10.1016/j.phymed.2020.153229

  • 122

    Garrett-Laster M. Russell R. M. Jacques P. F. (1984). Impairment of taste and olfaction in patients with cirrhosis: the role of vitamin A. Hum. Nutr. Clin.38, 203–214.

  • 123

    Geran R. Uecker F. C. Prüss H. Haeusler K. G. Paul F. Ruprecht K. et al . (2019). Olfactory and gustatory dysfunction in patients with autoimmune encephalitis. Front. Neurol. 10:480. 10.3389/fneur.2019.00480

  • 124

    Gholijani N. Gharagozloo M. Farjadian S. Amirghofran Z. (2016). Modulatory effects of thymol and carvacrol on inflammatory transcription factors in lipopolysaccharide-treated macrophages. J. Immunotoxicol. 13, 157–164. 10.3109/1547691X.2015.1029145

  • 125

    Gillissen A. Paparoupa M. (2015). Inflammation and infections in asthma. Clin. Respir. J. 9, 257–269. 10.1111/crj.12135

  • 126

    Goldstein D. S. Sewell L. (2009). Olfactory dysfunction in pure autonomic failure: implications for the pathogenesis of Lewy body diseases. Parkinson. Relat. Disord. 1, 516–520. 10.1016/j.parkreldis.2008.12.009

  • 127

    Gomes Gonçalves N. Vidal Ferreira N. Khandpur N. Martinez Steele E. Bertazzi Levy R. Andrade Lotufo P. et al . (2023). Association between consumption of ultraprocessed foods and cognitive decline. JAMA Neurol.80, 142–150. 10.1001/jamaneurol.2022.4397

  • 128

    González L. M. Bourissai A. Lessard-Beaudoin M. Lebel R. Tremblay L. Lepage M. et al . (2023). Amelioration of cognitive and olfactory system deficits in APOE4 transgenic mice with DHA treatment. Mol. Neurobiol. 60, 5624–5641. 10.1007/s12035-023-03401-z

  • 129

    Gopinath B. Sue C. M. Kifley A. Mitchell P. (2012). The association between olfactory impairment and total mortality in older adults. J. Gerontol. A Biol. Sci. Med. Sci. 67, 204–209. 10.1093/gerona/glr165

  • 130

    Gossrau G. Zaranek L. Klimova A. Sabatowski R. Koch T. Richter M. et al . (2023). Olfactory training reduces pain sensitivity in children and adolescents with primary headaches. Front. Pain Res.4:1091984. 10.3389/fpain.2023.1091984

  • 131

    Goswami R. Bello A. I. Bean J. Costanzo K. M. Omer B. Cornelio-Parra D. et al . (2022). The molecular basis of spinocerebellar ataxia type 7. Front. Neurosci. 16:818757. 10.3389/fnins.2022.818757

  • 132

    Gottfried J. A. (2006). Smell: central nervous processing. Adv. Otorhinolaryngol. 63, 44–69. 10.1159/000093750

  • 133

    Graus F. Titulaer M. J. Balu R. Benseler S. Bien C. G. Cellucci T. et al . (2016). A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 15, 391–404. 10.1016/S1474-4422(15)00401-9

  • 134

    Groppa S. Gonzalez-Escamilla G. Eshaghi A. Meuth S. G. Ciccarelli O. (2021). Linking immune-mediated damage to neurodegeneration in multiple sclerosis: could network-based MRI help?Brain Commun. 3:fcab237. 10.1093/braincomms/fcab237

  • 135

    Guan R. Wang T. Dong X. Du K. Li J. Zhao F. et al . (2022). Effects of co-exposure to lead and manganese on learning and memory deficits. J. Environ. Sci. 121, 65–76. 10.1016/j.jes.2021.09.012

  • 136

    Gunzer W. (2017). Changes of olfactory performance during the process of aging-psychophysical testing and its relevance in the fight against malnutrition. J. Nutr. Health Aging21, 1010–1015. 10.1007/s12603-017-0873-8

  • 137

    Guo B. Zhang M. Hao W. Wang Y. Zhang T. Liu C. (2023). Neuroinflammation mechanisms of neuromodulation therapies for anxiety and depression. Transl. Psychiatry13:5. 10.1038/s41398-022-02297-y

  • 138

    Guo X. Tang P. Zhang X. Li R. (2023). Causal associations of circulating Helicobacter pylori antibodies with stroke and the mediating role of inflammation. Inflamm. Res. 72,1193–1202. 10.1007/s00011-023-01740-0

  • 139

    Gwinnutt J. M. Norton S. Hyrich K. L. Lunt M. Combe B. Rincheval N. et al . (2022). Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis. Rheumatology61, 4687–4701. 10.1093/rheumatology/keac137

  • 140

    Haehner A. Hummel T. Reichmann H. (2009). Olfactory dysfunction as a diagnostic marker for Parkinson's disease. Expert Rev. Neurother. 9, 1773–1779. 10.1586/ern.09.115

  • 141

    Hahad O. Lelieveld J. Birklein F. Lieb K. Daiber A. Münzel T. (2020). Ambient air pollution increases the risk of cerebrovascular and neuropsychiatric disorders through induction of inflammation and oxidative stress. Int. J. Mol. Sci. 21:4306. 10.3390/ijms21124306

  • 142

    Hajj-Ali R. A. Major J. Langford C. Hoffman G. S. Clark T. Zhang L. et al . (2015). The interface of inflammation and subclinical atherosclerosis in granulomatosis with polyangiitis (Wegener's): a preliminary study. Transl. Res. 166, 366–374. 10.1016/j.trsl.2015.04.001

  • 143

    Han S. Wang Q. Song Y. Pang M. Ren C. Wang J. et al . (2023). Lithium ameliorates Niemann-Pick C1 disease phenotypes by impeding STING/SREBP2 activation. iScience26:106613. 10.1016/j.isci.2023.106613

  • 144

    Hardebo J. E. (1994). How cluster headache is explained as an intracavernous inflammatory process lesioning sympathetic fibers. Headache34, 125–131. 10.1111/j.1526-4610.1994.hed3403125.x

  • 145

    Harita M. Miwa T. Shiga H. Yamada K. Sugiyama E. Okabe Y. et al . (2019). Association of olfactory impairment with indexes of sarcopenia and frailty in community-dwelling older adults. Geriatr. Gerontol. Int.19, 384–391. 10.1111/ggi.13621

  • 146

    Harris S. Gilbert M. Beasant L. Linney C. Broughton J. Crawley E. (2017). A qualitative investigation of eating difficulties in adolescents with chronic fatigue syndrome/myalgic encephalomyelitis. Clin. Child Psychol. Psychiatry22, 128–139. 10.1177/1359104516646813

  • 147

    Hasan Balcioglu Y. Kirlioglu Balcioglu S. S. Oncu F. Turkcan A. Coskun Yorulmaz A. (2022). Impulsive and aggressive traits and increased peripheral inflammatory status as psychobiological substrates of homicide behavior in schizophrenia. Euro. J. Psychiatry36, 207–214. 10.1016/j.ejpsy.2022.01.004

  • 148

    Hawkes C. H. Shephard B. C. Geddes J. F. Body G. D. Martin J. E. (1998). Olfactory disorder in motor neuron disease. Exp. Neurol. 150, 248–253. 10.1006/exnr.1997.6773

  • 149

    He Y. S. Cao F. Musonye H. A. Xu Y. Q. Gao Z. X. Ge M. et al . (2024). Serum albumin mediates the associations between heavy metals and two novel systemic inflammation indexes among U.S. adults. Ecotoxicol. Environ. Safety270:115863. 10.1016/j.ecoenv.2023.115863

  • 150

    Heger E. Rubinstein G. Braun L. T. Zopp S. Honegger J. Seidensticker M. et al . (2021). Chemosensory dysfunction in Cushing's syndrome. Endocrine73, 674–681. 10.1007/s12020-021-02707-z

  • 151

    Henkin R. I. Schmidt L. Velicu I. (2013). Interleukin 6 in hyposmia. JAMA Otolaryngol. Head Neck Surg. 139, 728–734. 10.1001/jamaoto.2013.3392

  • 152

    Hirota R. Nakamura H. Bhatti S. A. Ngatu N. R. Muzembo B. A. Dumavibhat N. et al . (2012). Limonene inhalation reduces allergic airway inflammation in Dermatophagoides farinae-treated mice. Inhal. Toxicol. 24, 373–381. 10.3109/08958378.2012.675528

  • 153

    Hoenen M. Wolf O. T. Pause B. M. (2017). The impact of stress on odor perception. Perception46, 366–376. 10.1177/0301006616688707

  • 154

    Hokari M. Uchida K. Shimbo D. Gekka M. Asaoka K. Itamoto K. (2020). Acute systematic inflammatory response syndrome and serum biomarkers predict outcomes after subarachnoid hemorrhage. J. Clin. Neurosci. 78, 108–113. 10.1016/j.jocn.2020.05.055

  • 155

    Holbrook E. H. Puram S. V. See R. B. Tripp A. G. Nair D. G. (2019). Induction of smell through transethmoid electrical stimulation of the olfactory bulb. Int. Forum Allergy Rhinol. 9, 158–164. 10.1002/alr.22237

  • 156

    Hori H. Kim Y. (2019). Inflammation and post-traumatic stress disorder. Psychiatry Clin. Neurosci. 73, 143–153. 10.1111/pcn.12820

  • 157

    Hudz N. Kobylinska L. Pokajewicz K. Horčinová Sedláčkov,á V. Fedin R. Voloshyn M. et al . (2023). Mentha piperita: essential oil and extracts, their biological activities, and perspectives on the development of new medicinal and cosmetic products. Molecules28:7444. 10.3390/molecules28217444

  • 158

    Huggard D. Kelly L. Ryan E. McGrane F. Lagan N. Roche E. et al . (2020). Increased systemic inflammation in children with Down syndrome. Cytokine127:154938. 10.1016/j.cyto.2019.154938

  • 159

    Huxtable A. G. Vinit S. Windelborn J. A. Crader S. M. Guenther C. H. Watters J. J. et al . (2011). Systemic inflammation impairs respiratory chemoreflexes and plasticity. Respir. Physiol. Neurobiol. 178, 482–489. 10.1016/j.resp.2011.06.017

  • 160

    Iaccarino L. Shoenfeld N. Rampudda M. Zen M. Gatto M. Ghirardello A. et al . (2014). The olfactory function is impaired in patients with idiopathic inflammatory myopathies. Immunol. Res.60, 247–252. 10.1007/s12026-014-8581-5

  • 161

    Iannaccone A. Mykytyn K. Persico A. M. Searby C. C. Baldi A. Jablonski M. M. et al . (2005). Clinical evidence of decreased olfaction in Bardet-Biedl syndrome caused by a deletion in the BBS4 gene. Am. J. Med. Genet. A.132, 343–346. 10.1002/ajmg.a.30512

  • 162

    Iannucci V. Bruscolini A. Iannella G. Visioli G. Alisi L. Salducci M. et al . (2024). Olfactory dysfunction and glaucoma. Biomedicines12:1002. 10.3390/biomedicines12051002

  • 163

    Imamura F. Hasegawa-Ishii S. (2016). Environmental toxicants-induced immune responses in the olfactory mucosa. Front. Immunol. 7:475. 10.3389/fimmu.2016.00475

  • 164

    Iranzo A. Marrero-González P. Serradell M. Gaig C. Santamaria J. Vilaseca I. (2021). Significance of hyposmia in isolated REM sleep behavior disorder. J. Neurol. 268, 963–966. 10.1007/s00415-020-10229-3

  • 165

    Jiménez-Jiménez F. J. Alonso-Navarro H. García-Martín E. Agúndez J. A. G. (2023). Inflammatory factors and restless legs syndrome: a systematic review and meta-analysis. Sleep Med. Rev. 68:101744. 10.1016/j.smrv.2022.101744

  • 166

    Juergens U. R. Dethlefsen U. Steinkamp G. Gillissen A. Repges R. Vetter H. (2003). Anti-inflammatory activity of 1.8-cineol (eucalyptol) in bronchial asthma: a double-blind placebo-controlled trial. Respir. Med. 97, 250–256. 10.1053/rmed.2003.1432

  • 167

    Juncos J. L. Lazarus J. T. Rohr J. Allen E. G. Shubeck L. Hamilton D. et al . (2012). Olfactory dysfunction in fragile X tremor ataxia syndrome. Mov. Disord. 27, 1556–1559. 10.1002/mds.25043

  • 168

    Kamath V. Jiang K. Manning K. J. Mackin R. S. Walker K. A. Powell D. et al . (2024). Olfactory dysfunction and depression trajectories in community-dwelling older adults. J. Gerontol. A. Biol. Sci. Med. Sci.79:glad139. 10.1093/gerona/glad139

  • 169

    Kamath V. Leff B. (2019). Mortality risk in older adults: what the nose knows. Ann. Intern. Med. 170, 722–723. 10.7326/M19-1013

  • 170

    Kamath V. Moberg P. J. Calkins M. E. Borgmann-Winter K. Conroy C. G. Gur R. E. et al . (2012). An odor-specific threshold deficit implicates abnormal cAMP signaling in youths at clinical risk for psychosis. Schizophr. Res. 138, 280–284. 10.1016/j.schres.2012.03.029

  • 171

    Kang D. W. Kim S. S. Park D. C. Kim S. H. Yeo S. G. (2021). Objective and measurable biomarkers in chronic subjective tinnitus. Int. J. Mol. Sci. 22:6619. 10.3390/ijms22126619

  • 172

    Kar T. Yildirim Y. Altundag A. Sonmez M. Kaya A. Colakoglu K. et al . (2015). The relationship between age-related macular degeneration and olfactory function. J. Neuro-degener. Dis.15, 219–224. 10.1159/000381216

  • 173

    Katayama N. Yoshida T. Nakashima T. Ito Y. Teranishi M. Iwase T. et al . (2023). Relationship between tinnitus and olfactory dysfunction: audiovisual, olfactory, and medical examinations. Front. Pub. Health11:1124404. 10.3389/fpubh.2023.1124404

  • 174

    Kay L. M. (2022). COVID-19 and olfactory dysfunction: a looming wave of dementia?J. Neurophysiol.128, 436–444. 10.1152/jn.00255.2022

  • 175

    Kaya K. S. Akpinar M. Turk B. Seyhun N. Cankaya M. Coskun B. U. (2020). Olfactory function in patients with obstructive sleep apnea using positive airway pressure. Ear, Nose Throat J.99, 239–244. 10.1177/0145561319878949

  • 176

    Kaya-Sezginer E. Gur S. (2020). The inflammation network in the pathogenesis of erectile dysfunction: attractive potential therapeutic targets. Curr. Pharm. Des. 26, 3955–3972. 10.2174/1381612826666200424161018

  • 177

    Kazour F. Richa S. Char C. A. Atanasova B. El-Hage W. (2020). Olfactory memory in depression: state and trait differences between bipolar and unipolar disorders. Brain Sci.10:189. 10.3390/brainsci10030189

  • 178

    Kebir S. Hattingen E. Niessen M. Rauschenbach L. Fimmers R. Hummel T. et al . (2020). Olfactory function as an independent prognostic factor in glioblastoma. Neurology94, e529–e537. 10.1212/WNL.0000000000008744

  • 179

    Kern J. K. Geier D. A. Sykes L. K. Geier M. R. (2016). Relevance of neuroinflammation and encephalitis in autism. Front. Cell. Neurosci. 9:519. 10.3389/fncel.2015.00519

  • 180

    Khurshid K. Crow A. J. D. Rupert P. E. Minniti N. L. Carswell M. A. Mechanic-Hamilton D. J. et al . (2019). A quantitative meta-analysis of olfactory dysfunction in epilepsy. Neuropsychol. Rev. 29, 328–337. 10.1007/s11065-019-09406-7

  • 181

    Kim R. Jun J. S. Kim H. J. Jung K. Y. Shin Y. W. Yang T. W. et al . (2019). Peripheral blood inflammatory cytokines in idiopathic REM sleep behavior disorder. Mov. Disord. 34, 1739–1744. 10.1002/mds.27841

  • 182

    Kinnaird E. Stewart C. Tchanturia K. (2020). The relationship of autistic traits to taste and olfactory processing in anorexia nervosa. Mol. Autism11:25. 10.1186/s13229-020-00331-8

  • 183

    Kirgezen T. Yücetaş U. Server E. A. Övünç O. Yigit Ö. (2021). Possible effects of low testosterone levels on olfactory function in males. Braz. J. Otorhinolaryngol. 87, 702–710. 10.1016/j.bjorl.2020.03.001

  • 184

    Klimek L. Eggers G. (1997). Olfactory dysfunction in allergic rhinitis is related to nasal eosinophilic inflammation. J. Allergy Clin. Immunol. 100, 158–164. 10.1016/s0091-6749(97)70218-5

  • 185

    Kofod J. Elfving B. Nielsen E. H. Mors O. Köhler-Forsberg O. (2022). Depression and inflammation: correlation between changes in inflammatory markers with antidepressant response and long-term prognosis. Eur. Neuropsychopharmacol. 54, 116–125. 10.1016/j.euroneuro.2021.09.006

  • 186

    Kohli P. Soler Z. M. Nguyen S. A. Muus J. S. Schlosser R. J. (2016). The association between olfaction and depression: a systematic review. Chem. Senses41, 479–486. 10.1093/chemse/bjw061

  • 187

    Kollndorfer K. Jakab A. Mueller C. A. Trattnig S. Schöpf V. (2015). Effects of chronic peripheral olfactory loss on functional brain networks. Neuroscience310, 589–599. 10.1016/j.neuroscience.2015.09.045

  • 188

    Komine O. Yamanaka K. (2015). Neuroinflammation in motor neuron disease. Nagoya J. Med. Sci. 77, 537–549.

  • 189

    Kommoss K. S. Enk A. Heikenwälder M. Waisman A. Karbach S. Wild J. (2023). Cardiovascular comorbidity in psoriasis - psoriatic inflammation is more than just skin deep. J. Dtsch. Dermatol. Ges. 21, 718–725. 10.1111/ddg.15071

  • 190

    Koneczny I. Herbst R. (2019). Myasthenia gravis: Pathogenic effects of autoantibodies on neuromuscular architecture. Cells8:671. 10.3390/cells8070671

  • 191

    Konstantinidis I. Triaridis S. Triaridis A. Petropoulos I. Karagiannidis K. Kontzoglou G. (2005). How do children with adenoid hypertrophy smell and taste? Clinical assessment of olfactory function pre- and post-adenoidectomy. Int. J. Pediatr. Otorhinolaryngol. 69, 1343–1349. 10.1016/j.ijporl.2005.03.022

  • 192

    Kopala L. Clark C. (1990). Implications of olfactory agnosia for understanding sex differences in schizophrenia. Schizophr. Bull. 16, 255–261. 10.1093/schbul/16.2.255

  • 193

    Kopala L. C. Clark C. Hurwitz T. (1993). Olfactory deficits in neuroleptic naive patients with schizophrenia. Schizophr. Res. 8, 245–250. 10.1016/0920-9964(93)90022-B

  • 194

    Koseoglu S. B. Koseoglu S. Deveer R. Derin S. Kececioglu M. Sahan M. (2016). Impaired olfactory function in patients with polycystic ovary syndrome. Kaohsiung J. Med. Sci.32, 313–316. 10.1016/j.kjms.2016.04.015

  • 195

    Kovalová M. Gottfriedová N. Mrázková E. Janout V. Janoutová J. (2024). Cognitive impairment, neurodegenerative disorders, and olfactory impairment: a literature review. Polish Otolaryngol. 78, 1–17. 10.5604/01.3001.0053.6158

  • 196

    Kronenbuerger M. Belenghi P. Ilgner J. Freiherr J. Hummel T. Neuner I. (2018). Olfactory functioning in adults with Tourette syndrome. PLoS ONE13:e0197598. 10.1371/journal.pone.0197598

  • 197

    Ku C. M. Lin J. Y. (2016). Farnesol, a sesquiterpene alcohol in essential oils, ameliorates serum allergic antibody titres and lipid profiles in ovalbumin-challenged mice. Allergol Immunopathol.44, 149–159. 10.1016/j.aller.2015.05.009

  • 198

    Kubiak K. Szmidt M. K. Kaluza J. Zylka A. Sicinska E. (2023). Do dietary supplements affect inflammation, oxidative stress, and antioxidant status in adults with hypothyroidism or Hashimoto's disease? A systematic review of controlled trials. Antioxidants12:1798. 10.3390/antiox12101798

  • 199

    Kümpfel T. Giglhuber K. Aktas O. Ayzenberg I. Bellmann-Strobl J. Häußler V. et al . (2024). Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD). - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management. J. Neurol. 271, 141–176. 10.1007/s00415-023-11910-z

  • 200

    Kursun O. Yemisci M. van den Maagdenberg A. M. J. M. Karatas H. (2021). Migraine and neuroinflammation: the inflammasome perspective. J. Headache Pain22:55. 10.1186/s10194-021-01271-1

  • 201

    LaFever B. J. Imamura F. (2022). Effects of nasal inflammation on the olfactory bulb. J. Neuroinflamm. 19:294. 10.1186/s12974-022-02657-x

  • 202

    Lambertsen K. L. Finsen B. Clausen B. H. (2019). Post-stroke inflammation-target or tool for therapy?Acta Neuropathol. 137, 693–714. 10.1007/s00401-018-1930-z

  • 203

    Landis B. N. Vodicka J. Hummel T. (2010). Olfactory dysfunction following herpetic meningoencephalitis. J. Neurol.257, 439–443. 10.1007/s00415-009-5344-7

  • 204

    Las Casas Lima M. H. Cavalcante A. L. B. Leão S. C. (2022). Pathophysiological relationship between COVID-19 and olfactory dysfunction: a systematic review. Braz. J. Otorhinolaryngol. 88, 794–802. 10.1016/j.bjorl.2021.04.001

  • 205

    Laudien M. Lamprecht P. Hedderich J. Holle J. Ambrosch P. (2009). Olfactory dysfunction in Wegener's granulomatosis. Rhinology47, 254–259. 10.4193/Rhin08.159

  • 206

    Laudisio A. Navarini L. Margiotta D. P. E. Fontana D. O. Chiarella I. Spitaleri D. et al . (2019). The association of olfactory dysfunction, frailty, and mortality is mediated by inflammation: results from the InCHIANTI Study. J. Immunol. Res. 2019:3128231. 10.1155/2019/3128231

  • 207

    Lazarini F. Lannuzel A. Cabi,é A. Michel V. Madec Y. Chaumont H. et al . (2022). Olfactory outcomes in Zika virus-associated Guillain-Barré syndrome. Eur. J. Neurol. 29, 2823–2831. 10.1111/ene.15444

  • 208

    Leclercq S. de Timary P. Delzenne N. M. Stärkel P. (2017). The link between inflammation, bugs, the intestine and the brain in alcohol dependence. Transl. Psychiatry7:e1048. 10.1038/tp.2017.15

  • 209

    Lee K. Choi I. H. Lee S. H. Kim T. H. (2019). Association between subjective olfactory dysfunction and female hormone-related factors in South Korea. Sci. Rep.9:20007. 10.1038/s41598-019-56565-x

  • 210

    Leon M. Woo C. C. (2022). Olfactory loss is a predisposing factor for depression, while olfactory enrichment is an effective treatment for depression. Front. Neurosci. 16:1013363. 10.3389/fnins.2022.1013363

  • 211

    Leonardo S. Fregni F. (2023). Association of inflammation and cognition in the elderly: a systematic review and meta-analysis. Front. Aging Neurosci. 15:1069439. 10.3389/fnagi.2023.1069439

  • 212

    Leon-Sarmiento F. E. Bayona E. A. Bayona-Prieto J. Osman A. Doty R. L. (2012). Profound olfactory dysfunction in myasthenia gravis. PLoS ONE7:e45544. 10.1371/journal.pone.0045544

  • 213

    Leon-Sarmiento F. E. Bayona E. A. Rizzo-Sierra C. V. Garavito A. Campos M. F. Doty R. (2014). Olfactory dysfunction in Chagas' disease. Neurology 82 (Suppl. 10), P3–027. 10.1212/WNL.82.10_supplement.P3.027

  • 214

    Lewis C. R. Talboom J. S. De Both M. D. Schmidt A. M. Naymik M. A. Håberg A. K. et al . (2021). Smoking is associated with impaired verbal learning and memory performance in women more than men. Sci. Rep. 11:10248. 10.1038/s41598-021-88923-z

  • 215

    Li F. Wang Y. Zheng K. (2023). Microglial mitophagy integrates the microbiota-gut-brain axis to restrain neuroinflammation during neurotropic herpesvirus infection. Autophagy19, 734–736. 10.1080/15548627.2022.2102309

  • 216

    Liao C. P. Booker R. C. Brosseau J. P. Chen Z. Mo J. Tchegnon E. et al . (2018). Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis. J. Clin. Invest.128, 2848–2861. 10.1172/JCI99424

  • 217

    Likuni N. Lam Q. L. Lu L. Matarese G. La Cava A. (2008). Leptin and inflammation. Curr. Immunol. Rev.4, 70–79. 10.2174/157339508784325046

  • 218

    Lin L.-J. Li K.-Y. (2022). Comparing the effects of olfactory-based sensory 223. stimulation and board game training on cognition, emotion, and blood biomarkers among individuals with dementia: a pilot randomized controlled trial. Front. Psychol.13:1003325. 10.3389/fpsyg.2022.1003325

  • 219

    Liu B. Luo Z. Chen H. (2019). Relationship between poor olfaction and mortality. Ann. Intern. Med. 171:526. 10.7326/L19-0468

  • 220

    Lontchi-Yimagou E. Sobngwi E. Matsha T. E. Kengne A. P. (2013). Diabetes mellitus and inflammation. Curr. Diab. Rep. 13, 435–444. 10.1007/s11892-013-0375-y

  • 221

    López González I. Garcia-Esparcia P. Llorens F. Ferrer I. (2016). Genetic and transcriptomic profiles of inflammation in neurodegenerative diseases: Alzheimer, Parkinson, Creutzfeldt-Jakob and tauopathies. Int. J. Mol. Sci. 17:206. 10.3390/ijms17020206

  • 222

    Lötsch J. Ultsch A. Eckhardt M. Huart C. Rombaux P. Hummel T. (2016). Brain lesion-pattern analysis in patients with olfactory dysfunctions following head trauma. Neuroimage Clin. 11, 99–105. 10.1016/j.nicl.2016.01.011

  • 223

    Lu K. (2023). Cellular pathogenesis of hepatic encephalopathy: an update. Biomolecules13:396. 10.3390/biom13020396

  • 224

    Lu R. Huang R. Li K. Zhang X. Yang H. Quan Y. et al . (2014). The influence of benign essential blepharospasm on dry eye disease and ocular inflammation. Am. J. Ophthalmol. 157, 591–597. 10.1016/j.ajo.2013.11.014

  • 225

    Lundberg I. E. Fujimoto M. Vencovsky J. Aggarwal R. Holmqvist M. Christopher-Stine L. et al . (2021). Idiopathic inflammatory myopathies. Nature Rev. Dis. Prim.7:86. 10.1038/s41572-021-00321-x

  • 226

    Luzzi S. Snowden J. S. Neary D. Coccia M. Provinciali L. Lambon Ralph M. A. (2007). Distinct patterns of olfactory impairment in Alzheimer's disease, semantic dementia, frontotemporal dementia, and corticobasal degeneration. Neuropsychologia45, 1823–1831. 10.1016/j.neuropsychologia.2006.12.008

  • 227

    Maas C. López-Lera A. (2019). Hereditary angioedema: Insights into inflammation and allergy. Mol. Immunol.112, 378–386. 10.1016/j.molimm.2019.06.017

  • 228

    Mahmut M. K. Stevenson R. J. (2012). Olfactory abilities and psychopathy: Higher psychopathy scores are associated with poorer odor discrimination and identification. Chemosens. Percept.5, 300–307. 10.1007/s12078-012-9135-7

  • 229

    Maier A. Heinen-Ludwig L. Güntürkün O. Hurlemann R. Scheele D. (2020). Childhood maltreatment alters the neural processing of chemosensory stress signals. Front. Psychiatry11:783. 10.3389/fpsyt.2020.00783

  • 230

    Makhlouf M. Souza D. G. Kurian S. Bellaver B. Ellis H. Kuboki A. et al . (2024). Short-term consumption of highly processed diets varying in macronutrient content impair the sense of smell and brain metabolism in mice. Mol. Metab. 79:101837. 10.1016/j.molmet.2023.101837

  • 231

    Maki P. M. (2015). Verbal memory and menopause. Maturitas82, 288–290. 10.1016/j.maturitas.2015.07.023

  • 232

    Malutan A. M. Dan M. Nicolae C. Carmen M. (2014). Proinflammatory and anti-inflammatory cytokine changes related to menopause. Menopause Rev. 13, 162–168. 10.5114/pm.2014.43818

  • 233

    Manara R. Salvalaggio A. Favaro A. Palumbo V. Citton V. Elefante A. et al . (2014). Brain changes in Kallmann syndrome. Am. J. Neuroradiol. 35, 1700–1706. 10.3174/ajnr.A3946

  • 234

    Marazziti D. Palermo S. Arone A. Massa L. Parra E. Simoncini M. et al . (2023). Obsessive-compulsive disorder, PANDAS, and Tourette syndrome: immuno-inflammatory disorders. Adv. Exp. Med. Biol. 1411, 275–300. 10.1007/978-981-19-7376-5_13

  • 235

    Marek M. Linnepe S. Klein C. Hummel T. Paus S. (2018). High prevalence of olfactory dysfunction in cervical dystonia. Parkinsonism Relat. Disord. 53, 33–36. 10.1016/j.parkreldis.2018.04.028

  • 236

    Masala C. Loy F. Pinna I. Manis N. A. Ercoli T. Solla P. (2024). Olfactory function as a potential predictor of cognitive impairment in men and women. Biology13:503. 10.3390/biology13070503

  • 237

    Masala C. Solla P. Loy F. (2023). Gender-related differences in the correlation between odor threshold, discrimination, identification, and cognitive reserve index in healthy subjects. Biology12:586. 10.3390/biology12040586

  • 238

    Masaoka Y. Kawamura M. Takeda A. Kobayakawa M. Kuroda T. Kasai H. et al . (2011). Impairment of odor recognition and odor-induced emotions in type 1 myotonic dystrophy. Neurosci. Lett. 503, 163–166. 10.1016/j.neulet.2011.08.006

  • 239

    Masehi-Lano J. J. Deyssenroth M. Jacobson S. W. Jacobson J. L. Molteno C. D. Dodge N. C. et al . (2023). Alterations in placental inflammation-related gene expression partially mediate the effects of prenatal alcohol consumption on maternal iron homeostasis. Nutrients15:4105. 10.3390/nu15194105

  • 240

    Matsui T. Arai H. Nakajo M. Maruyama M. Ebihara S. Sasaki H. et al . (2003). Role of chronic sinusitis in cognitive functioning in the elderly. J. Am. Geriatr. Soc. 51, 1818–1819. 10.1046/j.1532-5415.2003.51572_5.x

  • 241

    Matsunaga M. Bai Y. Yamakawa K. Toyama A. Kashiwagi M. Fukuda K. et al . (2013). Brain-immune interaction accompanying odor-evoked autobiographic memory. PLoS ONE8:e72523. 10.1371/journal.pone.0072523

  • 242

    Maurage P. Rombaux P. de Timary P. (2014). Olfaction in alcohol-dependence: a neglected yet promising research field. Front. Psychol. 4:1007. 10.3389/fpsyg.2013.01007

  • 243

    McCombe P. A. Henderson R. D. (2011). The role of immune and inflammatory mechanisms in ALS. Curr. Mol. Med. 11, 246–254. 10.2174/156652411795243450

  • 244

    McConnell R. J. Menendez C. E. Smith F. R. Henkin R. I. Rivlin R. S. (1975). Defects of taste and smell in patients with hypothyroidism. Am. J. Med.59, 354–364. 10.1016/0002-9343(75)90394-0

  • 245

    McElvaney O. J. Wade P. Murphy M. Reeves E. P. McElvaney N. G. (2019). Targeting airway inflammation in cystic fibrosis. Expert Rev. Respir. Med. 13, 1041–1055. 10.1080/17476348.2019.1666715

  • 246

    McInnes K. Friesen C. L. MacKenzie D. E. Westwood D. A. Boe S. G. (2017). Mild traumatic brain injury (mTBI) and chronic cognitive impairment: a scoping review. PLoS ONE12:e0174847. 10.1371/journal.pone.0174847

  • 247

    McKee A. C. Daneshvar D. H. Alvarez V. E. Stein T. D. (2014). The neuropathology of sport. Acta Neuropathol. 127, 29–51. 10.1007/s00401-013-1230-6

  • 248

    McLaren A. M. R. Kawaja M. D. (2024). Olfactory dysfunction and Alzheimer's disease: a review. J. Alzheimers Dis. 99, 811–827. 10.3233/JAD-231377

  • 249

    McNeill A. Duran R. Proukakis C. Bras J. Hughes D. Mehta A. et al . (2012). Hyposmia and cognitive impairment in Gaucher disease patients and carriers. Mov. Disord. 27, 526–532. 10.1002/mds.24945

  • 250

    Melluso A. Secondulfo F. Capolongo G. Capasso G. Zacchia M. (2023). Bardet-Biedl syndrome: current perspectives and clinical outlook. Ther. Clin. Risk Manag. 19, 115–132. 10.2147/TCRM.S338653

  • 251

    Michalovicz L. T. Kelly K. A. Sullivan K. O'Callaghan J. P. (2020). Acetylcholinesterase inhibitor exposures as an initiating factor in the development of Gulf War Illness, a chronic neuroimmune disorder in deployed veterans. Neuropharmacology171:108073. 10.1016/j.neuropharm.2020.108073

  • 252

    Miller J. E. Liu C. M. Zemanick E. T. Woods J. C. Goss C. H. Taylor-Cousar J. L. et al . (2023). Olfactory loss in people with cystic fibrosis: community perceptions and impact. J. Cys. Fibros. 10.1016/j.jcf.2023.11.006. [Epub ahead of print].

  • 253

    Mishra S. Karan K. Nag D. Sengupta P. (2016). Adult onset Niemann–Pick type C disease: two different presentations. Neurol. India64, 1044–1047. 10.4103/0028-3886.190242

  • 254

    Misiak B. Bartoli F. Carr,à G. Stańczykiewicz B. Gładka A. Frydecka D. et al . (2021). Immune-inflammatory markers and psychosis risk: a systematic review and meta-analysis. Psychoneuroendocrinology127:105200. 10.1016/j.psyneuen.2021.105200

  • 255

    Mohamad N. V. Wong S. K. Wan Hasan W. N. Jolly J. J. Nur-Farhana M. F. Ima-Nirwana S. et al . (2019). The relationship between circulating testosterone and inflammatory cytokines in men. Aging Male22, 129–140. 10.1080/13685538.2018.1482487

  • 256

    Mohamed S. Emmanuel N. Foden N. (2019). Nasal obstruction: a common presentation in primary care. Br. J. Gen. Pract. 69, 628–629. 10.3399/bjgp19X707057

  • 257

    Müller N. (2018). Inflammation in schizophrenia: pathogenetic aspects and therapeutic considerations. Schizophr. Bull. 44, 973–982. 10.1093/schbul/sby024

  • 258

    Murphy C. Dalton P. Boateng K. Hunter S. Silberman P. Trachtman J. et al . (2024). Integrating the patient's voice into the research agenda for treatment of chemosensory disorders. Chem. Senses49:bjae020. 10.1093/chemse/bjae020

  • 259

    Muruzheva Z. M. Ivleva I. S. Traktirov D. S. Zubov A. S. Karpenko M. N. (2022). The relationship between serum interleukin-1β, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α levels and clinical features in essential tremor. Int. J. Neurosci. 132, 1143–1149. 10.1080/00207454.2020.1865952

  • 260

    Muscaritoli M. Imbimbo G. Jager-Wittenaar H. Cederholm T. Rothenberg E. di Girolamo F. G. et al . (2023). Disease-related malnutrition with inflammation and cachexia. Clin. Nutr.42, 1475–1479. 10.1016/j.clnu.2023.05.013

  • 261

    Nair J. R. Moots R. J. (2017). Behçet's disease. Clin. Med.17, 71–77. 10.7861/clinmedicine.17-1-71

  • 262

    Nakashima T. Katayama N. Sugiura S. Teranishi M. Suzuki H. Hirabayashi M. et al . (2019). Olfactory function in persons with cerebral palsy. J. Policy Pract. Intellect. Disabil. 16, 217–222. 10.1111/jppi.12284

  • 263

    Nasserie T. Hittle M. Goodman S. N. (2021). Assessment of the frequency and variety of persistent symptoms among patients with COVID-19: a systematic review. JAMA Netw. Open4:e2111417. 10.1001/jamanetworkopen.2021.11417

  • 264

    Numan M. S. Amiable N. Brown J. P. Michou L. (2015). Paget's disease of bone: an osteoimmunological disorder?Drug Des. Devel. Ther. 9, 4695–4707. 10.2147/DDDT.S88845

  • 265

    Nunes J. P. S. Roda V. M. P. Andrieux P. Kalil J. Chevillard C. Cunha-Neto E. (2023). Inflammation and mitochondria in the pathogenesis of chronic Chagas disease cardiomyopathy. Exp. Biol. Med. 248, 2062–2071. 10.1177/15353702231220658

  • 266

    Oleszkiewicz A. Abriat A. Doelz G. Azema E. Hummel T. (2021). Beyond olfaction: Beneficial effects of olfactory training extend to aging-related cognitive decline. Behav. Neurosci.135, 732–740. 10.1037/bne0000478

  • 267

    Oleszkiewicz A. Bottesi L. Pieniak M. Fujita S. Krasteva N. Nelles G. et al . (2022). Olfactory training with aromastics: olfactory and cognitive effects. Head Neck Surg.279, 225–232. 10.1007/s00405-021-06810-9

  • 268

    O'Shea B. Q. Demakakos P. Cadar D. Kobayashi L. C. (2021). Adverse childhood experiences and rate of memory decline from mid to later life: evidence from the English longitudinal study of ageing. Am. J. Epidemiol. 190, 1294–1305. 10.1093/aje/kwab019

  • 269

    Ottaviano G. Cantone E. D'Errico A. Salvalaggio A. Citton V. Scarpa B. et al . (2015). Sniffin' Sticks and olfactory system imaging in patients with Kallmann syndrome. Int. Forum Allergy Rhinol. 5, 855–861. 10.1002/alr.21550

  • 270

    Pajares M. I. Rojo A. Manda G. Boscá L. Cuadrado A. (2020). Inflammation in Parkinson's disease: mechanisms and therapeutic implications. Cells9:1687. 10.3390/cells9071687

  • 271

    Panfili E. Mondanelli G. Orabona C. Belladonna M. L. Gargaro M. Fallarino F. et al . (2021). Novel mutations in the WFS1 gene are associated with Wolfram syndrome and systemic inflammation. Hum. Mol. Genet. 30, 265–276. 10.1093/hmg/ddab040

  • 272

    Pang N. Y. Song H. J. J. Tan B. K. J. Tan J. X. Chen A. S. R. See A. et al . (2022). Association of olfactory impairment with all-cause mortality: a systematic review and meta-analysis. JAMA Otolaryngol. Head Neck Surg. 148, 436–445. 10.1001/jamaoto.2022.0263

  • 273

    Pang Y. Li Y. Zhang Y. Wang H. Lang J. Han L. et al . (2022). Effects of inflammation and oxidative stress on postoperative delirium in cardiac surgery. Front. Cardiovasc. Med. 9:1049600. 10.3389/fcvm.2022.1049600

  • 274

    Pascual B. Funk Q. Zanotti-Fregonara P. Cykowski M. D. Veronese M. Rockers E. et al . (2021). Neuroinflammation is highest in areas of disease progression in semantic dementia. Brain144, 1565–1575. 10.1093/brain/awab057

  • 275

    Paton M. C. B. Finch-Edmondson M. Dale R. C. Fahey M. C. Nold-Petry C. A. Nold M. F. et al . (2022). Persistent inflammation in cerebral palsy: pathogenic mediator or comorbidity? A scoping review. J. Clin. Med. 11:7368. 10.3390/jcm11247368

  • 276

    Patrick D. M. Van Beusecum J. P. Kirabo A. (2021). The role of inflammation in hypertension: novel concepts. Curr. Opin. Physiol. 19, 92–98. 10.1016/j.cophys.2020.09.016

  • 277

    Peng M. Potterton H. Chu J. T. W. Glue P. (2021). Olfactory shifts linked to postpartum depression. Sci. Rep.11:14947. 10.1038/s41598-021-94556-z

  • 278

    Perricone C. Agmon-Levin N. Shoenfeld N. de Carolis C. Guarino M. D. Gigliucci G. et al . (2011). Evidence of impaired sense of smell in hereditary angioedema. Allergy66, 149–154. 10.1111/j.1398-9995.2010.02453.x

  • 279

    Petagna L. Antonelli A. Ganini C. Bellato V. Campanelli M. Divizia A. et al . (2020). Pathophysiology of Crohn's disease inflammation and recurrence. Biol. Direct. 15:23. 10.1186/s13062-020-00280-5

  • 280

    Peter M. G. Darki F. Thunell E. Mårtensson G. Postma E. M. Boesveldt S. et al . (2023). Lifelong olfactory deprivation-dependent cortical reorganization restricted to orbitofrontal cortex. Hum. Brain Mapp.44, 6459–6470. 10.1002/hbm.26522

  • 281

    Peters J. M. Hummel T. Kratzsch T. Lötsch J. Skarke C. Frölich L. (2003). Olfactory function in mild cognitive impairment and Alzheimer's disease: an investigation using psychophysical and electrophysiological techniques. Am. J. Psychiatry160, 1995–2002. 10.1176/appi.ajp.160.11.1995

  • 282

    Pignataro A. Middei S. (2017). Trans-synaptic spread of amyloid-β in Alzheimer's disease: paths to β-amyloidosis. Neural Plast.2017:5281829. 10.1155/2017/5281829

  • 283

    Pina L. T. S. Ferro J. N. S. Rabelo T. K. Oliveira M. A. Scotti L. Scotti M. T. et al . (2019). Alcoholic monoterpenes found in essential oil of aromatic spices reduce allergic inflammation by the modulation of inflammatory cytokines. Nat. Prod. Res. 33, 1773–1777. 10.1080/14786419.2018.1434634

  • 284

    Pinto J. M. (2021). The specter of olfactory impairment: lessons about mortality in older US adults. JAMA Otolaryngol. Head Neck Surg. 147, 56–57. 10.1001/jamaoto.2020.3745

  • 285

    Pinto J. M. Wroblewski K. E. Kern D. W. Schumm L. P. McClintock M. K. (2014). Olfactory dysfunction predicts 5-year mortality in older adults. PLoS ONE9:e107541. 10.1371/journal.pone.0107541

  • 286

    Pitel A. L. Eustache F. Beaunieux H. (2014). Component processes of memory in alcoholism: pattern of compromise and neural substrates. Handb. Clin. Neurol. 125, 211–225. 10.1016/B978-0-444-62619-6.00013-6

  • 287

    Ponsen M. M. Stoffers D. Booij J. van Eck-Smit B. L. Wolters E. C. Berendse H. W. (2004). Idiopathic hyposmia as a preclinical sign of Parkinson's disease. Ann. Neurol. 56, 173–181. 10.1002/ana.20160

  • 288

    Postolache T. T. Wadhawan A. Can A. Lowry C. A. Woodbury M. Makkar H. et al . (2020). Inflammation in traumatic brain injury. J. Alzheimers. Dis. 74, 1–28. 10.3233/JAD-191150

  • 289

    Potter M. R. Chen J. H. Lobban N. S. Doty R. L. (2020). Olfactory dysfunction from acute upper respiratory infections: relationship to season of onset. Int. Forum Allergy Rhinol. 10, 706–712. 10.1002/alr.22551

  • 290

    Pries R. Jeschke S. Leichtle A. Bruchhage K. L. (2023). Modes of Action of 1,8-Cineol in Infections and Inflammation. Metabolites13:751. 10.3390/metabo13060751

  • 291

    Radke J. Meinhardt J. Aschman T. Chua R. L. Farztdinov V. Lukassen S. et al . (2024). Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19. Nature Neurosci.27, 409–420. 10.1038/s41593-024-01573-y

  • 292

    Rahmati M. Yon D. K. Lee S. W. Soysal P. Koyanagi A. Jacob L. et al . (2023). New-onset neurodegenerative diseases as long-term sequelae of SARS-CoV-2 infection: a systematic review and meta-analysis. J. Med. Virol. 95, e28909. 10.1002/jmv.28909

  • 293

    Ramsey J. T. Shropshire B. C. Nagy T.R. Chambers K. D. Li Y. Korach K. S . Essential oils and health. Yale J. Biol. Med. (2020) 93:291.

  • 294

    Rana A. Musto A. E. (2018). The role of inflammation in the development of epilepsy. J. Neuroinflamm. 15:144. 10.1186/s12974-018-1192-7

  • 295

    Rao M. Wang X. Guo G. Wang L. Chen S. Yin P. et al . (2021). Resolving the intertwining of inflammation and fibrosis in human heart failure at single-cell level. Basic Res. Cardiol. 116:55. 10.1007/s00395-021-00897-1

  • 296

    Rasmussen A. L. Popescu S. V. (2021). SARS-CoV-2 transmission without symptoms. Science371, 1206–1207. 10.1126/science.abf9569

  • 297

    Rayego-Mateos S. Rodrigues-Diez R. R. Fernandez-Fernandez B. Mora-Fernández C. Marchant V. Donate-Correa J. et al . (2023). Targeting inflammation to treat diabetic kidney disease: the road to 2Kidney Int. 103, 282–296. 10.1016/j.kint.2022.10.030

  • 298

    Renzetti S. van Thriel C. Lucchini R. G. Smith D. R. Peli M. Borgese L. et al . (2024). A multi-environmental source approach to explore associations between metals exposure and olfactory identification among school-age children residing in northern Italy. J. Expos. Sci. Environ. Epidemiol.34, 699–708. 10.1038/s41370-024-00687-6

  • 299

    Reuber M. Al-Din A. S. Baborie A. Chakrabarty A. (2001). New variant Creutzfeldt-Jakob disease presenting with loss of taste and smell. J. Neurol. Neurosurg. Psychiatr.71, 412–413. 10.1136/jnnp.71.3.412

  • 300

    Rhyou H. I. Bae W. Y. Nam Y. H. (2021). Association between olfactory function and asthma in adults. J. Asthma Allergy14, 309–316. 10.2147/JAA.S299796

  • 301

    Ribeiro J. C. Oliveiros B. Pereira P. António N. Hummel T. Paiva A. et al . (2016). Accelerated age-related olfactory decline among type 1 Usher patients. Sci. Rep. 6:28309. 10.1038/srep28309

  • 302

    Rivera D. G. Hernández I. Merino N. Luque Y. Álvarez A. Martín Y. et al . (2011). Mangifera indica L. extract (Vimang) and mangiferin reduce the airway inflammation and Th2 cytokines in murine model of allergic asthma. J. Pharm. Pharmacol. 63, 1336–1345. 10.1111/j.2042-7158.2011.01328.x

  • 303

    Roessner V. Bleich S. Banaschewski T. Rothenberger A. (2005). Olfactory deficits in anorexia nervosa. Eur. Arch. Psychiatry Clin. Neurosci. 255, 6–9. 10.1007/s00406-004-0525-y

  • 304

    Roh D. Lee D. H. Kim S. W. Kim S. W. Kim B. G. Kim D. H. et al . (2021). The association between olfactory dysfunction and cardiovascular disease and its risk factors in middle-aged and older adults. Sci. Rep.11:1248. 10.1038/s41598-020-80943-5

  • 305

    Royet J. P. Plailly J. Saive A. L. Veyrac A. Delon-Martin C. (2013). The impact of expertise in olfaction. Front. Psychol. 4:928. 10.3389/fpsyg.2013.00928

  • 306

    Rupp C. I. Fleischhacker W. W. Hausmann A. Mair D. Hinterhuber H. Kurz M. (2004). Olfactory functioning in patients with alcohol dependence: Impairments in odor judgements. Alcohol39, 514–519. 10.1093/alcalc/agh100

  • 307

    Rydbirk R. Østergaard O. Folke J. Hempel C. DellaValle B. Andresen T. L. et al . (2022). Brain proteome profiling implicates the complement and coagulation cascade in multiple system atrophy brain pathology. Cell. Mol. Life Sci. 79:336. 10.1007/s00018-022-04378-z

  • 308

    Salimi M. Nazari M. Shahsavar P. Dehghan S. Javan M. Mirnajafi-Zadeh J. et al . (2024). Olfactory bulb stimulation mitigates Alzheimer-like disease progression. bioRxiv.10.1101/2024.03.03.583116

  • 309

    Samanci B. Sahin E. Sen C. Samanci Y. Sezgin M. Emekli S. et al . (2021). Olfactory dysfunction in patients with cluster headache. Eur. Arch. Otorhinolaryngol. 278, 4361–4365. 10.1007/s00405-021-06738-0

  • 310

    Sartori A. C. Vance D. E. Slater L. Z. Crowe M. (2012). The impact of inflammation on cognitive function in older adults: Implications for healthcare practice and research. J. Neurosci. Nurs. 44, 206–217. 10.1097/JNN.0b013e3182527690

  • 311

    Schaie K. W. Willis S. L. Caskie G. I. (2004). The Seattle longitudinal study: relationship between personality and cognition. Neuropsychol. Dev. Cogn. B Aging Neuropsychol. Cogn. 11, 304–324. 10.1080/13825580490511134

  • 312

    Schertel Cassiano L. Ribeiro A. P. Peres M. A. Lopez R. Fjaeldstad A. Marchini L. et al . (2023). Self-reported periodontitis association with impaired smell and taste: a multicenter survey. Oral Dis. 30, 1516–1524. 10.1111/odi.14601

  • 313

    Schiffman S. S. (2018). Influence of medications on taste and smell. World J. Otorhinolaryngol. Head Neck Surg. 4, 84–91. 10.1016/j.wjorl.2018.02.005

  • 314

    Schmidt F. Göktas O. Jarius S. Wildemann B. Ruprecht K. Paul F. et al . (2013). Olfactory dysfunction in patients with neuromyelitis optica. Mult. Scler. Int.2013, 654501. 10.1155/2013/654501

  • 315

    Schoenfeld N. Agmon-Levin N. Flitman-Katzevman I. Paran D. Katz B. S. Kivity S. et al . (2009). The sense of smell in systemic lupus erythematosus. Arthritis Rheum. 60, 1484–1487. 10.1002/art.24491

  • 316

    Schubert C. R. Carmichael L. L. Murphy C. Klein B. E. Klein R. Cruickshanks K. J. (2008). Olfaction and the 5-year incidence of cognitive impairment in an epidemiological study of older adults. J. Am. Geriatr. Soc. 56, 1517–1521. 10.1111/j.1532-5415.2008.01826.x

  • 317

    Schubert C. R. Cruickshanks K. J. Fischer M. E. Klein B. E. Klein R. Pinto A. A. (2015). Inflammatory and vascular markers and olfactory impairment in older adults. Age Ageing44, 878–882. 10.1093/ageing/afv075

  • 318

    Schubert C. R. Fischer M. E. Pinto A. A. Klein B. E. K. Klein R. Tweed T. S. et al . (2017). Sensory impairments and risk of mortality in older adults. J. Gerontol. A Biol. Sci. Med. Sci. 72, 710–715. 10.1093/gerona/glw036

  • 319

    Scorr L. M. Kilic-Berkmen G. Sutcliffe D. J. Dinasarapu A. R. McKay J. L. Bagchi P. et al . (2024). Exploration of potential immune mechanisms in cervical dystonia. Parkinsonism Relat. Disord. 122:106036. 10.1016/j.parkreldis.2024.106036

  • 320

    Segura B. Baggio H. C. Solana E. Palacios E. M. Vendrell P. Bargalló N. et al . (2013). Neuroanatomical correlates of olfactory loss in normal aged subjects. Behav. Brain Res. 246, 148–153. 10.1016/j.bbr.2013.02.025

  • 321

    Serby M. Larson P. Kalkstein D. (1991). The nature and course of olfactory deficits in Alzheimer's disease. Am. J. Psychiatry148, 357–360. 10.1176/ajp.148.3.357

  • 322

    Seubert J. Kalpouzos G. Larsson M. Hummel T. Bäckman L. Laukka E. J. (2020). Temporolimbic cortical volume is associated with semantic odor memory performance in aging. Neuroimage211:116600. 10.1016/j.neuroimage.2020.116600

  • 323

    Shi A. Long Y. Ma Y. et al . (2023). Natural essential oils derived from herbal medicines: a promising therapy strategy for treating cognitive impairment. Front. Aging Neurosci. 15:1104269. 10.3389/fnagi.2023.1104269

  • 324

    Shi D. Das J. Das G. (2006). Inflammatory bowel disease requires the interplay between innate and adaptive immune signals. Cell Res.16, 70–74. 10.1038/sj.cr.7310009

  • 325

    Shibata H. Fujiwara R. Iwamoto M. Matsuoka H. Yokoyama M. M. (1991). Immunological and behavioral effects of fragrance in mice. Int. J. Neurosci. 57, 151–159. 10.3109/00207459109150355

  • 326

    Shields G. S. Doty D. Shields R. H. Gower G. Slavich G. M. Yonelinas A. P. (2017). Recent life stress exposure is associated with poorer long-term memory, working memory, and self-reported memory. Stress20, 598–607. 10.1080/10253890.2017.1380620

  • 327

    Shill H. A. Zhang N. Driver-Dunckley E. Mehta S. Adler C. H. Beach T. G. (2021). Olfaction in neuropathologically defined progressive supranuclear palsy. Mov. Disord. 36, 1700–1704. 10.1002/mds.28568

  • 328

    Siegel J. K. Kung S. Y. Wroblewski K. E. Kern D. W. McClintock M. K. Pinto J. M. (2021). Olfaction is associated with sexual motivation and satisfaction in older men and women. J. Sex. Med.18, 295–302. 10.1016/j.jsxm.2020.12.002

  • 329

    Sieper J. Poddubnyy D. (2017). Axial spondyloarthritis. Lancet390, 73–84. 10.1016/S0140-6736(16)31591-4

  • 330

    Simopoulos A. P. (2002). Omega-3 fatty acids in inflammation and autoimmune diseases. J. Am. Coll. Nutr. 21, 495–505. 10.1080/07315724.2002.10719248

  • 331

    Sinclair A. J. Ball A. K. Burdon M. A. Clarke C. E. Stewart P. M. Curnow S. J. et al . (2008). Exploring the pathogenesis of IIH: an inflammatory perspective. J. Neuroimmunol. 201–202, 212–220. 10.1016/j.jneuroim.2008.06.029

  • 332

    Sobel N. Thomason M. E. Stappen I. Tanner C. M. Tetrud J. W. Bower J. M. et al . (2001). An impairment in sniffing contributes to the olfactory impairment in Parkinson's disease. Proc. Natl. Acad. Sci. U. S. A.98, 4154–4159. 10.1073/pnas.071061598

  • 333

    Sobin C. Kiley-Brabeck K. Dale K. Monk S. H. Khuri J. Karayiorgou M. (2006). Olfactory disorder in children with 22q11 deletion syndrome. Pediatrics118, e697–e703. 10.1542/peds.2005-3114

  • 334

    Solla P. Masala C. Ercoli T. Frau C. Bagella C. Pinna I. et al . (2023). Olfactory impairment correlates with executive functions disorders and other specific cognitive dysfunctions in Parkinson's disease. Biology12:112. 10.3390/biology12010112

  • 335

    Sollai G. Melis M. Mastinu M. Paduano D. Chicco F. Magri S. et al . (2021). Olfactory function in patients with inflammatory bowel disease (IBD) is associated with their body mass index and polymorphism in the odor binding-protein (OBPIIa) gene. Nutrients13:703. 10.3390/nu13020703

  • 336

    Soysal P. Stubbs B. Lucato P. Luchini C. Solmi M. Peluso R. et al . (2016). Inflammation and frailty in the elderly: a systematic review and meta-analysis. Ageing Res. Rev. 31, 1–8. 10.1016/j.arr.2016.08.006

  • 337

    Speth U. S. König D. Burg S. Gosau M. Friedrich R. E. (2023). Evaluation of the sense of taste and smell in patients with neurofibromatosis type 1. J. Stomatol. Oral Maxillofac. Surg.124:101271. 10.1016/j.jormas.2022.08.014

  • 338

    Spotten L. Corish C. Lorton C. Dhuibhir P. U. O'Donoghue N. O'Connor B. et al . (2016). Subjective taste and smell changes in treatment-naive people with solid tumours. Support. Care Cancer24, 3201–3208. 10.1007/s00520-016-3133-2

  • 339

    Stanciu A. E. Hurduc A. Stanciu M. M. Gherghe M. Gheorghe D. C. Prunoiu V. M. et al . (2023). Portrait of the inflammatory response to radioiodine therapy in female patients with differentiated thyroid cancer with/without type 2 diabetes mellitus. Cancers15:3793. 10.3390/cancers15153793

  • 340

    Steinbach S. Proft F. Schulze-Koops H. Hundt W. Heinrich P. Schulz S. et al . (2011). Gustatory and olfactory function in rheumatoid arthritis. Scand. J. Rheum.40, 169–177. 10.3109/03009742.2010.517547

  • 341

    Stern Y. (2012). Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurol. 11, 1006–1012. 10.1016/S1474-4422(12)70191-6

  • 342

    Stevenson R. J. Mahmut M. K. Horstmann A. Hummel T. (2020). The aetiology of olfactory dysfunction and its relationship to diet quality. Brain Sci.10:769. 10.3390/brainsci10110769

  • 343

    Suat B. Deniz Tuna E. Ozgur Y. Muhammet Y. Tevfik Fikret C. (2016). The effects of radioactive iodine therapy on olfactory function. Am. J. Rhinol. Allergy30, 206–210. 10.2500/ajra.2016.30.4384

  • 344

    Subramaniyan S. Terrando N. (2019). Neuroinflammation and perioperative neurocognitive disorders. Anesth. Analg. 128, 781–788. 10.1213/ANE.0000000000004053

  • 345

    Suh K. D. Kim S. M. Han D. H. Min H. J. Kim K. S. (2020). Olfactory function test for early diagnosis of vascular dementia. Korean J. Fam. Med. 41, 202–204. 10.4082/kjfm.18.0202

  • 346

    Takehara-Nishiuchi K. (2014). Entorhinal cortex and consolidated memory. Neurosci. Res. 84, 27–33. 10.1016/j.neures.2014.02.012

  • 347

    Tan W. Zou J. Yoshida S. Jiang B. Zhou Y. (2020). The role of inflammation in age-related macular degeneration. Int. J. Biol. Sci. 16, 2989–3001. 10.7150/ijbs.49890

  • 348

    Terrier C. Greco-Vuilloud J. Cavelius M. Thevenet M. Mandairon N. Didier A. et al . (2024). Long-term olfactory enrichment promotes non-olfactory cognition, noradrenergic plasticity and remodeling of brain functional connectivity in older mice. Neurobiol. Aging136, 133–156. 10.1016/j.neurobiolaging.2024.01.011

  • 349

    Thorstensen W. M. Oie M. R. Dahlslett S. B. Sue-Chu M. Steinsvag S. K. Helvik A. S. (2022). Olfaction in COPD. Rhinology60, 47–55. 10.4193/Rhin21.037

  • 350

    Trares K. Bhardwaj M. Perna L. Stocker H. Petrera A. Hauck S. M. et al . (2022). Association of the inflammation-related proteome with dementia development at older age: results from a large, prospective, population-based cohort study. Alzheimers. Res. Ther. 14:128. 10.1186/s13195-022-01063-y

  • 351

    Tristan Asensi M. Napoletano A. Sofi F. Dinu M. (2023). Low-grade inflammation and ultra-processed foods consumption: a review. Nutrients15:1546. 10.3390/nu15061546

  • 352

    Ueno-Iio T. Shibakura M. Yokota K. Aoe M. Hyoda T. Shinohata R. et al . (2014). Lavender essential oil inhalation suppresses allergic airway inflammation and mucous cell hyperplasia in a murine model of asthma. Life Sci.108, 109–115. 10.1016/j.lfs.2014.05.018

  • 353

    Upadhyay U. D. Holbrook E. H. (2004). Olfactory loss as a result of toxic exposure. Otolaryngol. Clin. North Am. 37, 1185–1207. 10.1016/j.otc.2004.05.003

  • 354

    Üstün Bezgin S. Çakabay T. Irak K. Koçyigit M. Serin Keskinege B. Cevizci R. et al . (2017). Association of Helicobacter pylori infection with olfactory function using smell identification screening test. Eur. Arch. Otorhinolaryngol.274, 3403–3405. 10.1007/s00405-017-4656-y

  • 355

    Vaira L. A. Hopkins C. Petrocelli M. Lechien J. R. Chiesa-Estomba C. M. Salzano G. et al . (2020). Smell and taste recovery in coronavirus disease 2019 patients: a 60-day objective and prospective study. J. Laryngol. Otol. 134, 703–709. 10.1017/S0022215120001826

  • 356

    Valadão P. A. C. Santos K. B. S. Ferreira Vieira T. H. Macedo E Cordeiro T. Teixeira A. L. Guatimosim C. et al . (2020). Inflammation in Huntington's disease: a few new twists on an old tale. J. Neuroimmunol. 348:577380. 10.1016/j.jneuroim.2020.577380

  • 357

    Valizadeh P. Momtazmanesh S. Plazzi G. Rezaei N. (2024). Connecting the dots: an updated review of the role of autoimmunity in narcolepsy and emerging immunotherapeutic approaches. Sleep Med. 113, 378–396. 10.1016/j.sleep.2023.12.005

  • 358

    Van Bogart K. Engeland C. G. Sliwinski M. J. Harrington K. D. Knight E. L. Zhaoyang R. et al . (2022). The association between loneliness and inflammation: findings from an older adult sample. Front. Behav. Neurosci. 15:801746. 10.3389/fnbeh.2021.801746

  • 359

    Van Dijck A. Barbosa S. Bermudez-Martin P. Khalfallah O. Gilet C. Martinuzzi E. et al . (2020). Reduced serum levels of pro-inflammatory chemokines in fragile X syndrome. BMC Neurol. 20:138. 10.1186/s12883-020-01715-2

  • 360

    Van Regemorter V. Dollase J. Coulie R. Stouffs A. Dieu A. de Saint-Hubert M. et al . (2022). Olfactory dysfunction predicts frailty and poor postoperative outcome in older patients scheduled for elective non-cardiac surgery. J. Nutr. Health Aging.26, 981–986. 10.1007/s12603-022-1851-3

  • 361

    Vance D. E. Del Bene V. A. Kamath V. Frank J. S. Billings R. Cho D. Y. et al . (2024). Does olfactory training improve brain function and cognition? A systematic review. Neuropsychol. Rev.34, 155–191. 10.1007/s11065-022-09573-0

  • 362

    Vasterling J. J. Brailey K. Sutker P. B. (2000). Olfactory identification in combat-related posttraumatic stress disorder. J. Trauma. Stress13, 241–253. 10.1023/A:1007754611030

  • 363

    Velluzzi F. Deledda A. Onida M. Loviselli A. Crnjar R. Sollai G. (2022). Relationship between olfactory function and BMI in normal weight healthy subjects and patients with overweight or obesity. Nutrients14:1262. 10.3390/nu14061262

  • 364

    Veyseller B. Ozucer B. Aksoy F. Yildirim Y. S. Gürbüz D. Balikçi H. H. et al . (2012). Reduced olfactory bulb volume and diminished olfactory function in total laryngectomy patients: a prospective longitudinal study. Am. J. Rhinol. Allergy26, 191–193. 10.2500/ajra.2012.26.3768

  • 365

    Viguera C. Wang J. Mosmiller E. Cerezo A. Maragakis N. J. (2018). Olfactory dysfunction in amyotrophic lateral sclerosis. Ann. Clin. Transl. Neurol. 5, 976–981. 10.1002/acn3.594

  • 366

    Vohra V. Assi S. Kamath V. Soler Z. M. Rowan N. R. (2023). Potential role for diet in mediating the association of olfactory dysfunction and cognitive decline: a nationally representative study. Nutrients15:3890. 10.3390/nu15183890

  • 367

    Volkmann E. R. Andréasson K. Smith V. (2023). Systemic sclerosis. Lancet401, 304–318. 10.1016/S0140-6736(22)01692-0

  • 368

    Waldton S. (1974). Clinical observations of impaired cranial nerve function in senile dementia. Acta Psychiatr. Scand. 50, 539–547. 10.1111/j.16000447.1974.tb09714.x

  • 369

    Walker I. M. Fullard M. E. Morley J. F. Duda J. E. (2021). Olfaction as an early marker of Parkinson's disease and Alzheimer's disease. Handb. Clin. Neurol. 182, 317–329. 10.1016/B978-0-12-819973-2.00030-7

  • 370

    Wang H. J. Zakhari S. Jung M. K. (2010). Alcohol, inflammation, and gut-liver-brain interactions in tissue damage and disease development. World J. Gastroenterol. 16, 1304–1313. 10.3748/wjg.v16.i11.1304

  • 371

    Wang L. Davis P. B. Volkow N. D. Berger N. A. Kaelber D. C. Xu R. (2022). Association of COVID-19 with new-onset Alzheimer's disease. J. Alzheimers Dis. 89, 411–414. 10.3233/JAD-220717

  • 372

    Wang Q. Chen B. Zhong X. Zhou H. Zhang M. Mai N. et al . (2021). Olfactory dysfunction is already present with subjective cognitive decline and deepens with disease severity in the Alzheimer's disease spectrum. J. Alzheimers Dis. 79, 585–595. 10.3233/JAD-201168

  • 373

    Wang T. Y. Lee S. Y. Hu M. C. Chen S. L. Chang Y. H. Chu C. H. et al . (2017). More inflammation but less brain-derived neurotrophic factor in antisocial personality disorder. Psychoneuroendocrinology85, 42–48. 10.1016/j.psyneuen.2017.08.006

  • 374

    Wang X. Younan D. Petkus A. J. Beavers D. P. Espeland M. A. Chui H. C. et al . (2021). Ambient air pollution and long-term trajectories of episodic memory decline among older women in the WHIMS-ECHO Cohort. Environ. Health Perspect. 129:97009. 10.1289/EHP7668

  • 375

    Wehling E. Naess H. Wollschlaeger D. Hofstad H. Bramerson A. Bende M. et al . (2015). Olfactory dysfunction in chronic stroke patients. BMC Neurol. 15:199. 10.1186/s12883-015-0463-5

  • 376

    Weiss G. Ganz T. Goodnough L. T. (2019). Anemia of inflammation. Blood133, 40–50. 10.1182/blood-2018-06-856500

  • 377

    Weiss J. Pyrski M. Jacobi E. Bufe B. Willnecker V. Schick B. et al . (2011). Loss-of-function mutations in sodium channel Nav1.7 cause anosmia. Nature472, 186–190. 10.1038/nature09975

  • 378

    Wheeler P. L. Murphy C. (2021). Olfactory measures as predictors of conversion to mild cognitive impairment and Alzheimer's disease. Brain Sci.11, 1391. 10.3390/brainsci11111391

  • 379

    Wheeler T. T. Alberts M. A. Dolan T. A. McGorray S. P. (1995). Dental, visual, auditory and olfactory complications in Paget's disease of bone. J. Am. Geriatr. Soc. 43, 1384–1391. 10.1111/j.1532-5415.1995.tb06618.x

  • 380

    Whitcroft K. L. Mancini L. Yousry T. Hummel T. Andrews P. J. (2023). Functional septorhinoplasty alters brain structure and function: Neuroanatomical correlates of olfactory dysfunction. Front. Allergy4, 1079945. 10.3389/falgy.2023.1079945

  • 381

    Whiting A. C. Marmura M. J. Hegarty S. E. Keith S. W. (2015). Olfactory acuity in chronic migraine: A cross-sectional study. Headache55, 71–75. 10.1111/head.12462

  • 382

    Wilson R. S. Yu L. Bennett D. A. (2011). Odor identification and mortality in old age. Chem. Senses36, 63–67. 10.1093/chemse/bjq098

  • 383

    Witoonpanich P. Cash D. M. Shakespeare T. J. Yong K. X. Nicholas J. M. Omar R. et al . (2013). Olfactory impairment in posterior cortical atrophy. J. Neurol. Neurosurg. Psychiatr.84, 588–590. 10.1136/jnnp-2012-304497

  • 384

    Wong K. E. Wade T. J. Moore J. Marcellus A. Molnar D. S. O'Leary D. D. et al . (2022). Examining the relationships between adverse childhood experiences (ACEs), cortisol, and inflammation among young adults. Brain Behav. Immun. Health25, 100516. 10.1016/j.bbih.2022.100516

  • 385

    Woo C. C. Miranda B. Sathishkumar M. Dehkordi-Vakil F. Yassa M. A. Leon M. (2023). Overnight olfactory enrichment using an odorant diffuser improves memory and modifies the uncinate fasciculus in older adults. Front. Neurosci. 17, 1200448. 10.3389/fnins.2023.1200448

  • 386

    Wu P. Dong J. Cheng N. Yang R. Han Y. Han Y. (2019). Inflammatory cytokines expression in Wilson's disease. Neurol. Sci. 40, 1059–1066. 10.1007/s10072-018-3680-z

  • 387

    Wurth R. Rescigno M. Flippo C. Stratakis C. A. Tatsi C. (2022). Inflammatory biomarkers in the evaluation of pediatric endogenous Cushing syndrome. Eur. J. Endocrinol.186, 503–510. 10.1530/EJE-21-1199

  • 388

    Xiao Z. Zhao Q. Liang X. Wu W. Cao Y. Ding D. (2021). Poor odor identification predicts mortality risk in older adults without neurodegenerative diseases: The Shanghai Aging Study. J. Am. Med. Dir. Assoc. 22, 2218-2219.e1. 10.1016/j.jamda.2021.05.026

  • 389

    Xie J. Van Hoecke L. Vandenbroucke R. E. (2022). The impact of systemic inflammation on Alzheimer's disease pathology. Front. Immunol. 12, 796867. 10.3389/fimmu.2021.796867

  • 390

    Yafi F. A. Jenkins L. Albersen M. Corona G. Isidori A. M. Goldfarb S. et al . (2016). Erectile dysfunction. Nature Rev. Dis. Primers2, 16003. 10.1038/nrdp.2016.3

  • 391

    Yahiaoui-Doktor M. Luck T. Riedel-Heller S. G. Loeffler M. Wirkner K. Engel C. (2019). Olfactory function is associated with cognitive performance: results from the population-based LIFE-Adult-Study. Alzheimers. Res. Ther. 11, 43. 10.1186/s13195-019-0494-z

  • 392

    Yalcinkaya E. Basaran M. M. Erdem H. Kocyigit M. Altundag A. Hummel T. (2019). Olfactory dysfunction in spondyloarthritis. Eur. Arch. Oto-rhino-laryngol.276, 1241–1245. 10.1007/s00405-019-05364-1

  • 393

    Yao L. Yi X. Pinto J. M. Yuan X. Guo Y. Liu Y. et al . (2018). Olfactory cortex and olfactory bulb volume alterations in patients with post-infectious olfactory loss. Brain Imag. Behav. 12, 1355–1362. 10.1007/s11682-017-9807-7

  • 394

    Ye C. Guo X. Wu J. Wang M. Ding H. Ren X. (2022). Mediated macrophage activation and polarization can promote adenoid epithelial inflammation in adenoid hypertrophy. J. Inflamm. Res. 15, 6843–6855. 10.2147/JIR.S390210

  • 395

    Yin K. Agrawal D. K. (2014). Vitamin D and inflammatory diseases. J. Inflamm. Res.7, 69–87. 10.2147/JIR.S63898

  • 396

    Yoo H. S. Jeon S. Chung S. J. Yun M. Lee P. H. Sohn Y. H. et al . (2018). Olfactory dysfunction in Alzheimer's disease- and Lewy body-related cognitive impairment. Alzheimers. Dement. 14, 1243–1252. 10.1016/j.jalz.2018.05.010

  • 397

    Zhang C. Han Y. Liu X. Tan H. Dong Y. Zhang Y. et al . (2022). Odor enrichment attenuates the anesthesia/surgery-induced cognitive impairment. Ann. Surg. 277, e1387–e1396. 10.1097/SLA.0000000000005599

  • 398

    Zhang H. Wang Y. Zhao Y. Liu T. Wang Z. Zhang N. et al . (2022). PTX3 mediates the infiltration, migration, and inflammation-resolving-polarization of macrophages in glioblastoma. CNS Neurosci. Therap.28, 1748–1766. 10.1111/cns.13913

  • 399

    Zhang Z. Zhang B. Wang X. Zhang X. Yang Q. X. Qing Z. et al . (2019). Olfactory dysfunction mediates adiposity in cognitive impairment of type 2 diabetes: Insights from clinical and functional neuroimaging studies. Diabetes Care42, 1274–1283. 10.2337/dc18-2584

  • 400

    Zhao L. Hou C. Yan N. (2022). Neuroinflammation in retinitis pigmentosa: therapies targeting the innate immune system. Front. Immunol.13:1059947. 10.3389/fimmu.2022.1059947

  • 401

    Zhong P. X. Chen Y. H. Li I. H. Wen Y. L. Kao H. H. Chiang K. W. et al . (2023). Increased risk of olfactory and taste dysfunction in the United States psoriasis population. Eur. Arch. Otorhinolaryngol. 280, 695–702. 10.1007/s00405-022-07530-4

  • 402

    Zucco G. M. Amodio P. Gatta A. (2006). Olfactory deficits in patients affected by minimal hepatic encephalopathy: a pilot study. Chem. Senses31, 273–278. 10.1093/chemse/bjj029

  • 403

    Zucco G. M. Ingegneri G. (2004). Olfactory deficits in HIV-infected patients with and without AIDS dementia complex. Physiol. Behav. 80, 669–674. 10.1016/j.physbeh.2003.12.001

Summary

Keywords

olfaction, inflammation, medical conditions, causation, correlation, olfactory dysfunction, olfactory enrichment

Citation

Leon M, Troscianko ET and Woo CC (2024) Inflammation and olfactory loss are associated with at least 139 medical conditions. Front. Mol. Neurosci. 17:1455418. doi: 10.3389/fnmol.2024.1455418

Received

27 June 2024

Accepted

16 September 2024

Published

11 October 2024

Volume

17 - 2024

Edited by

Jolanta Dorszewska, Poznan University of Medical Sciences, Poland

Reviewed by

Donald A. Wilson, New York University, United States

Brigit High, National Institutes of Health (NIH), United States

Carla Masala, University of Cagliari, Italy

Leslie M. Kay, The University of Chicago, United States

Updates

Copyright

© 2024 Leon, Troscianko and Woo.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Michael Leon

†Present address: Emily T. Troscianko, Department of English, University of California, Santa Barbara, Santa Barbara, CA, United States

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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