The olfactory system serves multiple functions in humans. Through direct connection with the limbic system and cerebral cortex, smells intertwine with experiencing emotions and memories. Olfaction also serves a role in shaping behaviors and communication between animals.[16] Odorants within the environment provide fundamental information for survival. Several species rely on olfaction to identify nutritional resources, mates, toxins, predators, and impending danger.[17]

The process of olfaction involves the conversion of a chemical stimulus, an odorant, into an electrical signal sent to the brain for interpretation. This mechanism begins after olfactory sensory neurons depolarize in response to the binding of an odorant molecule to G-protein coupled receptors (GPCR). The dissociated G protein activates an intracellular cascade via adenylyl cyclase producing a molecule of cyclic adenosine monophosphate (cAMP) that binds and opens ion channels within the neuron’s plasma membrane. Subsequently, an influx of positive sodium and calcium ions and an efflux of negative chloride ions occurs. Neuronal depolarization continues until the threshold potential occurs, firing a resulting action potential. The action potential travels down the olfactory nerves through the cribriform plate towards glomeruli in the olfactory bulb. The glomeruli then project to specific areas within the brain where higher-level processing, modulation, and interpretation occur.[18]

Testing the olfactory nerve is an essential component when conducting a comprehensive cranial nerve examination. The examiner can instruct the patient to occlude one nare while holding a discretely scented object (coffee grounds, orange peels, or tobacco are common choices) and asking the patient to identify the smell. Note, using an alcohol swab should be avoided because the nociceptive intranasal odorants may also stimulate the chemoreceptors of the trigeminal nerve (cranial nerve five) and bypass or interfere with the olfactory system.[19]

The pathophysiology of olfactory disorders can be better understood by first identifying the type of dysfunction present. Anosmia exists on a spectrum ranging from a complete lack of smell to a diminished ability or hyposmia (partial anosmia). Furthermore, a disturbance in olfaction may present as the inability to distinguish odorants apart from one another, known as olfactory agnosia. Distortions or pathologic alterations in perception can occur, collectively referred to as dysosmias. Interestingly, spontaneous experience of smell in the absence of an odorant stimulus can occur. Such chemosensory hallucinations are designated phantosmias. Reports exist of the presence of phantosmias as high as 55% in transient epileptic amnesia.[20] Clinically, it is essential to distinguish the laterality (unilateral or bilateral) anytime an abnormality in olfaction is encountered to investigate the underlying cause further.[21]

Alterations in the ability to smell can be the result of disease processes, environmental exposure, or simply a product of normal aging. In adults under 65 years of age, the estimated prevalence of olfactory dysfunction is approximately 2%. However, this number increases drastically to 75% in populations over 80 years old.[22] These changes are likely multifactorial, caused in part by the ossification of the cribriform plate and a reduction in the size of its foramina.[23] Additionally, the cumulative damage to olfactory receptors encountered throughout one’s lifetime appears to play a role in the age-related olfactory decline.[3]

A benign decline in olfactory sensation is commonly encountered in aging populations and may appear transiently in the setting of intranasal inflammation or obstruction. However, when clinicians encounter abnormalities such as anosmia or hyposmia in a clinical setting, it is crucial to investigate the underlying etiology further. This process begins by taking a focused patient history and conducting a thorough neurologic examination, including evaluation of cranial nerve one. 

A wide variety of diseases impact the olfactory function. Upper respiratory viral infections are the most common cause of both permanent anosmia and hyposmia.[24] Neurotropic viruses can cause permanent damage to the neural tissue of the olfactory system. In the setting of sinusitis, inflamed nasal mucosa and increased mucus production may result in nasal obstruction and commonly causes transient and incomplete anosmia.[25] This condition is one of the common causes of transient anosmia, frequently seen in all age groups.

Recently, studies have identified anosmia as a vital early sign of neurodegenerative disorders such as Parkinson and Alzheimer disease.[26][27] So it is crucial to check the olfactory function in the evaluation of the neurodegenerative diseases. Facial trauma, especially fractures involving injury to the cribriform plate, can also precipitate a loss of smell.[28] During the facial trauma, there are sometimes a fracture of the cribriform plate and the release of the CSF fluid. So, we have to do thorough work up in these cases to avoid potential infection to the brain and meninges.

Similarly, meningiomas of the olfactory groove and other intracranial masses can be secondary causes of olfaction loss.[29] Scientific evidence also supports a strong association between olfactory dysfunction and schizophrenia.[30] Current investigations of olfactory stimuli inciting migraine headaches and hyperemesis gravidarum in pregnancy suggest a common mechanism involving allelic variations in dopaminergic receptors.[31] Anecdotally, women have reported hyperosmia during pregnancy, but the scientific understanding of this phenomenon remains limited.[32]

Roughly 5 to 7% of patients with head injuries also reported a decrease in the olfactory sense. Some patients with diabetes also have dysfunction of the olfactory nerve. Olfactory hallucinations also occur in hippocampal lesions or psychosis. Patients describe olfactory hallucinations as unpleasant and strange odors.