[1] Odor molecules can enter the peripheral pathway and reach the nasal cavity either through the nostrils when inhaling (olfaction) or through the throat when the tongue pushes air to the back of the nasal cavity while chewing or swallowing (retro-nasal olfaction).

[6] The main olfactory bulb transmits pulses to both mitral and tufted cells, which help determine odor concentration based on the time certain neuron clusters fire (called 'timing code').

These cells also note differences between highly similar odors and use that data to aid in later recognition.

The orbitofrontal cortex (OFC) is heavily correlated with the cingulate gyrus and septal area to act out positive/negative reinforcement.

In contrast, recent finding suggested the molecular aspects of olfactory dysfunction can be recognized as a hallmark of amyloidogenesis-related diseases and there may even be a causal link through the disruption of multivalent metal ion transport and storage.

Doctors must exclude other diseases that inhibit or eliminate 'the sense of smell' such as chronic colds or sinusitis before making the diagnosis that there is permanent damage to the olfactory system.

Prevalence of olfactory dysfunction in the general US population was assessed by questionnaire and examination in a national health survey in 2012–2014.

[31] Among over a thousand persons aged 40 years and older, 12.0% reported a problem with smell in the past 12 months and 12.4% had olfactory dysfunction on examination.

Prevalence rose from 4.2% at age 40–49 to 39.4% at 80 years and older and was higher in men than women, in blacks and Mexican Americans than in whites and in less than more educated.

Of concern for safety, 20% of persons aged 70 and older were unable to identify smoke and 31%, natural gas.

The olfactory system is a vital sense, and its dysfunction may lead to a reduced quality of life, an inability to determine hazardous odors, decreased pleasure in eating, and poor mental health.

[32] The common causes of olfactory dysfunction include advanced age, viral infections, exposure to toxic chemicals, head trauma, and neurodegenerative diseases.

[29] Age is the strongest reason for olfactory decline in healthy adults, having even greater impact than does cigarette smoking.

This increases greatly between people of ages 65 and 80 with about half experiencing significant problems smelling.

[33] The basis for age-related changes in smell function include closure of the cribriform plate,[29] and cumulative damage to the olfactory receptors from repeated viral and other insults throughout life.

Among these virus-related disorders are the common cold, hepatitis, influenza and influenza-like illness, as well as herpes.

[35] Chronic exposure to some airborne toxins such as herbicides, pesticides, solvents, and heavy metals (cadmium, chromium, nickel, and manganese), can alter the ability to smell.

These findings have led to the suggestion that olfactory testing may help in the diagnosis of several different neurodegenerative diseases.

[29] Linda B. Buck and Richard Axel won the 2004 Nobel Prize in Physiology or Medicine for their work on the olfactory system.