Editing Olfactory system (section)

==Clinical significance==
Loss of smell is known as [[anosmia]]. Anosmia can occur on both sides or a single side.

Olfactory problems can be divided into different types based on their malfunction. The olfactory dysfunction can be total ([[anosmia]]), incomplete (partial anosmia, [[hyposmia]], or microsmia), distorted ([[dysosmia]]), or can be characterized by spontaneous sensations like [[phantosmia]]. An inability to recognize odors despite a normally functioning olfactory system is termed olfactory [[agnosia]]. [[Hyperosmia]] is a rare condition typified by an abnormally heightened sense of smell. Like vision and hearing, the olfactory problems can be bilateral or unilateral meaning if a person has anosmia on the right side of the nose but not the left, it is a unilateral right anosmia. On the other hand, if it is on both sides of the nose it is called bilateral anosmia or total anosmia.<ref name="Doty2009">{{cite journal|last=Doty|first=Richard|title=The Olfactory System and Its Disorders|journal=Seminars in Neurology|date=12 February 2009|volume=29|issue=1|pages=074–081|doi=10.1055/s-0028-1124025|pmid=19214935|doi-access=free}}</ref>

Destruction to olfactory bulb, tract, and primary cortex ([[brodmann area 34]]) results in anosmia on the same side as the destruction. Also, irritative lesion of the [[uncus]] results in olfactory hallucinations.

Damage to the olfactory system can occur by [[traumatic brain injury]], [[cancer]], infection, inhalation of toxic fumes, or neurodegenerative diseases such as [[Parkinson's disease]] and [[Alzheimer's disease]]. These conditions can cause [[anosmia]]. 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.<ref name="Mahmoudi Suslick 2012">{{cite journal|last1=Mahmoudi| first1=Morteza| last2=Suslick|first2=Kenneth S.|title=Protein fibrillation and the olfactory system: speculations on their linkage|journal=Trends in Biotechnology|volume=30|issue=12|year=2012|pages=609–610| doi=10.1016/j.tibtech.2012.08.007| pmid=22998929}}</ref>  Doctors can detect damage to the olfactory system by presenting the patient with odors via a scratch and sniff card or by having the patient close their eyes and try to identify commonly available odors like coffee or peppermint candy.
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.<ref name="NH1">{{cite journal |last1=Hoffman |first1=Howard |last2=Rawal |first2=Shristi |last3=Li |first3=Chuan-Ming |last4=Duffy |first4=Valerie |title=New chemosensory component in the U.S. National Health and Nutrition Examination Survey (NHANES): first-year results for measured olfactory dysfunction |journal=Rev Endocr Metab Disord |date=June 2016 |volume=17 |issue=2 |pages=221–240 |doi=10.1007/s11154-016-9364-1 |pmid=27287364 |pmc=5033684 }}</ref> 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.

===Causes of olfactory dysfunction===

[[Image:1543,Vesalius'OlfactoryBulbs.jpg|150px|thumb|[[Vesalius]]' ''Fabrica'', 1543. [[Human]] [[Olfactory bulb]]s and Olfactory tracts outlined in red]]
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.<ref>{{Cite journal |last=Schafer |first=L |date=26 January 2021 |title=San Jose State University Library |journal=Cell and Tissue Research |language=en |volume=380 |issue=1 |pages=569–579 |doi=10.1007/s00441-020-03381-9|pmid=33496882 |pmc=7835667 }}</ref>

The common causes of olfactory dysfunction include advanced age, viral infections, exposure to toxic chemicals, head trauma, and neurodegenerative diseases.<ref name=Doty2009 /> 

====Age====

Age is the strongest reason for olfactory decline in healthy adults, having even greater impact than does cigarette smoking. Age-related changes in smell function often go unnoticed and smell ability is rarely tested clinically unlike hearing and vision. 2% of people under 65 years of age have chronic smelling problems. This increases greatly between people of ages 65 and 80 with about half experiencing significant problems smelling. Then for adults over 80, the numbers rise to almost 75%.<ref>{{cite journal|last=Doty|first=Richard L.|author2=Shaman, Paul |author3=Dann, Michael |title=Development of the university of pennsylvania smell identification test: A standardized microencapsulated test of olfactory function|journal=Physiology & Behavior|date=March 1984|volume=32|issue=3|pages=489–502|doi=10.1016/0031-9384(84)90269-5|pmid=6463130|s2cid=30923277}}</ref> The basis for age-related changes in smell function include closure of the cribriform plate,<ref name=Doty2009 /> and cumulative damage to the olfactory receptors from repeated viral and other insults throughout life.

====Viral infections====

The most common cause of permanent hyposmia and anosmia are upper respiratory infections. Such dysfunctions show no change over time and can sometimes reflect damage not only to the [[olfactory epithelium]], but also to the central olfactory structures as a result of viral invasions into the brain. Among these virus-related disorders are the [[common cold]], [[hepatitis]], [[influenza]] and [[influenza-like illness]], as well as [[Herpes simplex|herpes]]. Notably, [[COVID-19]] is associated with olfactory disturbance.<ref name="Parma2020">{{cite journal | vauthors = Parma V | title = More than smell–COVID-19 is associated with severe impairment of smell, taste, and chemesthesis | journal = Chemical Senses| volume =  bjaa041 | date = June 2020 | issue = 7 | pages = 609–622 | doi =10.1093/chemse/bjaa041| pmid = 32564071 | pmc = 7337664 | doi-access = free }}</ref> Most viral infections are unrecognizable because they are so mild or entirely [[asymptomatic]].<ref name=Doty2009 /> There are no known cures for olfactory loss due to viral infections, however olfactory training is a highly recommended option, as well as oral steroids for a short period of time when discussed with a medical professional.<ref>{{Cite journal |last1=Hura |first1=Nanki |last2=Xie |first2=Deborah X. |last3=Choby |first3=Garret W. |last4=Schlosser |first4=Rodney J. |last5=Orlov |first5=Cinthia P. |last6=Seal |first6=Stella M. |last7=Rowan |first7=Nicholas R. |date=June 6, 2020 |title=Treatment of post-viral olfactory dysfunction: an evidence-based review with recommendations |journal=International Forum of Allergy & Rhinology |language=en |volume=10 |issue=9 |pages=1065–1086 |doi=10.1002/alr.22624 |issn=2042-6976 |pmc=7361320 |pmid=32567798}}</ref>

====Exposure to toxic chemicals====
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.<ref>{{cite journal |last=Doty |first=RL |author2=Hastings, L. |title=Neurotoxic exposure and olfactory impairment |journal=Clin Occupat Environ Med |year=2001 |volume=1 |pages=547–575}}</ref> These agents not only damage the olfactory epithelium, but they are likely to enter the brain via the olfactory mucosa.<ref>{{cite journal |last1=Tjalve |first1=H. |last2=Henriksson |first2=J. |last3=Tallkvist |first3=J. |last4=Larsson |first4=B. S. |last5=Lindquist |first5=N. G. |title=Uptake of manganese and cadmium from the nasal mucosa into the central nervous system via olfactory pathways in rats |journal=Pharmacology & Toxicology |year=1996 |volume=79 |issue=6 |pages=347–356 |doi=10.1111/j.1600-0773.1996.tb00021.x|pmid=9000264 }}</ref>

====Head trauma====
Trauma-related olfactory dysfunction depends on the severity of the trauma and whether strong acceleration/deceleration of the head occurred. Occipital and side impact causes more damage to the olfactory system than frontal impact.<ref>{{cite journal |last1=Doty |first1=R. L. |last2=Yousem |first2=D. M. |last3=Pham |first3=L. T. |last4=Kreshak |first4=A. A. |last5=Geckle |first5=R. |last6=Lee |first6=W. W. |title=Olfactory dysfunction in patients with head trauma |journal=Arch Neurol |year=1997 |volume=54 |issue=9 |pages=1131–1140 |doi=10.1001/archneur.1997.00550210061014 |pmid=9311357}}</ref> However, recent evidence from individuals with traumatic brain injury suggests that smell loss can occur with changes in brain function outside of olfactory cortex.<ref>{{cite journal |last1=Pellegrino |first1=Robert |title=Post-traumatic olfactory loss and brain response beyond olfactory cortex |journal=Scientific Reports |date=17 February 2021 |volume=11 |issue=1 |page=4043 |doi=10.1038/s41598-021-83621-2 |pmid=33597627 |pmc=7889874 |bibcode=2021NatSR..11.4043P |doi-access=free }}</ref>

====Neurodegenerative diseases====

Neurologists have observed that olfactory dysfunction is a cardinal feature of several neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Most of these patients are unaware of an olfactory deficit until after testing where 85% to 90% of early-stage patients showed decreased activity in central odor processing structures.<ref>{{cite journal|author2-link=Martin Rossor|last=Quinn|first=N P|author2=Rossor, M N |author3=Marsden, C D |title=Olfactory threshold in Parkinson's disease.|journal=Journal of Neurology, Neurosurgery & Psychiatry|date=1 January 1987|volume=50|issue=1|pages=88–89|doi=10.1136/jnnp.50.1.88|pmc=1033256|pmid=3819760}}</ref>

Other neurodegenerative diseases that affect olfactory dysfunction include Huntington's disease, multi-infarct dementia, amyotrophic lateral sclerosis, and schizophrenia. These diseases have more moderate effects on the olfactory system than Alzheimer's or Parkinson's diseases.<ref>{{cite journal|last=Doty|first=Richard L.|author2=Bromley, Steven M. |author3=Stern, Matthew B. |title=Olfactory Testing as an Aid in the Diagnosis of Parkinson's Disease: Development of Optimal Discrimination Criteria|journal=Neurodegeneration|date=March 1995|volume=4|issue=1|pages=93–97|doi=10.1006/neur.1995.0011|pmid=7600189|doi-access=free}}</ref> Furthermore, progressive supranuclear palsy and parkinsonism are associated with only minor olfactory problems. These findings have led to the suggestion that olfactory testing may help in the diagnosis of several different neurodegenerative diseases.<ref>{{cite journal|last=Doty|first=R. L.|author2=Golbe, L. I. |author3=McKeown, D. A. |author4=Stern, M. B. |author5=Lehrach, C. M. |author6= Crawford, D. |title=Olfactory testing differentiates between progressive supranuclear palsy and idiopathic Parkinson's disease|journal=Neurology|date=1 May 1993|volume=43|issue=5|pages=962–965|doi=10.1212/WNL.43.5.962|pmid=8492953|s2cid=41865918}}</ref>

Neurodegenerative diseases with well-established genetic determinants are also associated with olfactory dysfunction. Such dysfunction, for example, is found in patients with familial Parkinson's disease and those with Down syndrome.<ref>{{cite journal|last=CHEN|first=M|author2=LANDER, T |author3=MURPHY, C |title=Nasal health in Down syndrome: A cross-sectional study|journal=Otolaryngology–Head and Neck Surgery|date=May 2006|volume=134|issue=5|pages=741–745|doi=10.1016/j.otohns.2005.12.035|pmid=16647527|s2cid=21198608}}</ref> Further studies have concluded that the olfactory loss may be associated with intellectual disability, rather than any Alzheimer's disease-like pathology.<ref>{{cite journal|last=McKeown|first=D A|author2=Doty, R L |author3=Perl, D P |author4=Frye, R E |author5=Simms, I |author6= Mester, A |title=Olfactory function in young adolescents with Down's syndrome.|journal=Journal of Neurology, Neurosurgery & Psychiatry|date=1 October 1996|volume=61|issue=4|pages=412–414|doi=10.1136/jnnp.61.4.412|pmc=486586 |pmid=8890783}}</ref>

Huntington's disease is also associated with problems in odor identification, detection, discrimination, and memory. The problem is prevalent once the phenotypic elements of the disorder appear, although it is unknown how far in advance the olfactory loss precedes the phenotypic expression.<ref name=Doty2009 />