Introduction

Ever wonder how we can recognise different smells? Our ability to smell is called olfaction. Any blocks in the pathways that mediate olfaction can lead to anosmia, which is a condition that causes a person to lose their sense of smell, either completely or partially. More specifically, it can be caused by influenza, hay fever, nasal deformities, cancer, and more. Chronic anosmia can also lead to behaviours that promote health-related issues. As olfaction allows an individual to detect and distinguish different smells and tastes, any olfactory abnormality can prevent a person from recognising harmful odours and environments, eventually leading to poor appetites and malnutrition. 

Anosmia can be temporary or permanent and can also be a result of damage or inflammation in the nasal pathway. Other similar conditions include - (a) Hyposmia, which is characterised by a reduced sensitivity to smell, and (b) Hyperosmia, which is when there is an abnormal increase in the perception of smell.

It is important to bear in mind that if the loss of smell persists in the absence of a health condition, seeking medical attention is of the utmost importance. Depending on the cause, anosmia may or may not be treated. Ultimately, a comprehensive diagnosis can establish the grounds for further medical interventions. 

The olfactory pathway and its components

Olfaction is one of our oldest and sharpest senses and comprises approximately 400 genes, accounting for 2.4% of the human genome.¹ It is a chemical sensory modality, which means that olfactory receptor neurons act as chemoreceptors that detect various odours. A key component of the olfactory system is the olfactory mucosa, which is a mucosal layer lining the nasal septum and nasal cavity. Once odour molecules come into contact with the olfactory mucosa, they bind to the olfactory chemoreceptor neurons, eventually resulting in action potentials.¹ The olfactory mucosa is thicker than the respiratory mucosa, which also lines the nasal cavity. It is composed of many different cells, such as the basal cells, olfactory neurons, and microvillar cells, and it is worth noting that each olfactory receptor can only detect one distinct odour molecule.¹ 

Additionally, the olfactory pathway extends to the brain, and its associated signals are primarily processed in the olfactory bulb. The neurons of the olfactory bulb form synapses with other olfactory receptor neurons and eventually extend their fibres to the primary olfactory cortex. The primary olfactory cortex is composed of other important regions of the brain, such as the amygdala, and can thus generate emotions and memories associated with specific smells.¹ On the other hand, the secondary olfactory cortex acts in coordination with the gustatory cortex (gustation meaning taste) and is mainly responsible for integrating the senses of vision, taste, olfaction, and touch to produce flavour.¹ 

Odour discrimination (the ability to differentiate smells) and odour perception (the ability to detect and recognize smells) are the key outcomes of these signalling centres and are achieved through the remapping of incoming olfactory signals with other associated sensory information.¹

Pathophysiology of anosmia

Olfactory dysfunction can be characterised as qualitative or quantitative.¹ Anosmia and hyposmia, as defined earlier, are said to be quantitative. Other conditions like phantosmia (perceiving an odour when an odour is absent) and parosmia (distorted sense of smell) are qualitative.

Anosmia may be multifactorial and can be a result of nasal blockages, infections like influenza, nasal deformities, head injury, and neurodegenerative disease. In some cases, anosmia is also thought to be a consequence of ciliopathies, which are disorders that arise due to alterations in the structure and function of cilia.² Non-functional cilia can disrupt odour detection and cause anosmia. Furthermore, the inflammation of olfactory receptor neurons can damage olfactory function and lead to rhinosinusitis and eventually, anosmia.² Anosmia can also be congenital (present from birth), and in some cases, is found to be associated with genetic syndromes.³ 

The lack of validated diagnostic tools can make the diagnosis of anosmia complicated and ambiguous. Certain tests used to detect odour thresholds may be used, wherein a patient may be asked to sniff odours of varying concentrations.³ Other methods may include a yes/no questionnaire or a “scratch-and-sniff” test.³ The scratch-and-sniff test is part of the University of Pennsylvania Smell Identification Test (UPSIT), which involves scratching an odorant strip and asking the patient to match the perceived smell with any one of the four given choices.^3,4 Other tests used to evaluate olfactory function may include the Sniffin’ Sticks’ test, the Brief Smell Identification Test (B-SIT), and more.⁴ Culturally-specific tests like the Barcelona Smell Test-24 (BAST24) and the Scandinavian Odour Identification Test (SOIT) have also been designed due to some odours not being universally recognised.⁴ Furthermore, sex differences in anosmia have been reported, with women exhibiting a better sense of olfaction, and hormonal changes seem to not affect this ability.³

COVID-19 and anosmia

Multiple reports have discussed the effects of the SARS-CoV-2 viral infection on olfactory function. In many cases, patients with COVID-19 have displayed olfactory loss and damage to the olfactory epithelium.¹ Other findings report the downregulation of olfactory signalling components and atrophy of the olfactory bulb.¹

In general, patients with COVID-19 are also 27 times more susceptible to anosmia, although temporary.⁵ It is key to note that COVID-related anosmia can be different from anosmia that is acquired through other infections that damage the olfactory system, and this is because people with COVID-19 can develop anosmia without any nasal blockages and can recover their sense of smell faster.⁵ A meta-analysis indicated that around 95.7% of people with COVID-19 were able to regain their sense of smell within 3 months.¹

Neurodegeneration and anosmia

Olfactory dysfunction has been linked to neurodegenerative diseases like Alzheimer’s and Parkinson’s, and these symptoms often precede the motor and cognitive impairments that are observed in these disorders.^1,4 The olfactory system is thought to be more vulnerable to harmful protein misfolding and aggregation, as the olfactory bulb is one of the first areas to be affected in Parkinson’s disease pathology.^1,4 Approximately 90% of people with early-stage Parkinson’s report olfactory dysfunction, and these patients also had worse olfactory performance than those with other neurological conditions.^1,4 

In the case of Alzheimer’s disease, amyloid plaques and neurofibrillary tangles have been observed in the olfactory bulb.^1,4 The capacity to identify odours was diminished in patients with Alzheimer’s than in those without.¹ Structural deficits in the hippocampus have been linked to reduced odour recognition ability, and reductions in volume in the olfactory bulb and primary olfactory cortex have also been reported.⁴ In addition, postmortem studies have confirmed the direct association between the presence of amyloid plaques in the olfactory bulb and the severity of Alzheimer’s.⁴

Treatment and management

Treatment strategies for anosmia and other related olfactory abnormalities may depend entirely on the cause. A thorough check of one’s medical history can help confirm any underlying conditions that may contribute to the onset of anosmia. If an infection is the primary cause, an immediate line of treatment would be to battle the infection and reduce inflammation, if any, using corticosteroids. Interestingly, a study even identified the use of platelet-rich plasma to be beneficial in treating COVID-19-related anosmia.¹ Additionally, if the anosmia is a result of nasal polyps or nasal obstructions, surgical intervention may help restore one’s sense of smell.³ However, when it comes to congenital anosmia or age-related olfactory decline, there has not been much progress in terms of treatment.³ 

So far, the most successful line of treatment has been olfactory training. Of the few available options, olfactory training is recommended quite often and is based on the principle of reversing olfactory decline and restoring olfactory plasticity.¹ It has been effective in reestablishing cortical thickness in areas of the brain associated with olfactory signalling, as well as restoring healthy volumes of the olfactory bulb.¹

While olfactory training remains an important tool in the line of treatment, it is worth noting that the resolution of olfactory dysfunction can be temporary.³ More research is required to clearly understand the aetiology of these conditions to make a definite diagnosis that can be treated effectively. 

Summary

Anosmia is the loss of smell that can result from infections, nasal blockages, injuries, or neurological diseases like Alzheimer’s and Parkinson’s. It affects daily life by reducing appetite, enjoyment of food, and the ability to detect danger. COVID-19 also caused many temporary cases of anosmia, with most people recovering within months. Diagnosis involves smell tests, and treatment depends on the cause—such as treating infections, removing obstructions, or doing olfactory training. While recovery varies, olfactory training has shown the most promise in restoring smell and improving quality of life.