Olfactory dysfunction in neurodegenerative diseases

Debanjan Dasgupta^1*Thomas Heinbockel²Swagata Ghatak³

• ¹Indian Institute of Technology Kanpur, Kanpur, India
• ²Howard University, Washington, D.C., United States
• ³National Institute of Science Education and Research (NISER), Bhubaneswar, Odisha, India

Neurodegenerative disorders are a major health concern in the aging world. Olfactory dysfunction (OD) is a condition characterized by altered olfactory perception. OD has been observed to be associated with many of such disorders like Parkinson's Disease (PD) and Alzheimer's Disease (AD). The OD is evident much earlier than the diagnosis of cognitive decline. Over the last few decades, a connection between OD and clinical symptoms of neurodegenerative diseases has been observed in studies [1]. According to one study, 90% of PD cases show OD in the early stages [2], while 80% of AD patients show a notable decrease in their ability to smell [3]. However, little is known about the mechanisms that can causally link the observed OD in different neurodegenerative disorders. The current research topic is a collection of research articles surrounding this central idea. Olfactory stimulation takes place either ortho-nasally such as during sniffing or retro-nasally such as when olfactory receptors get activated by odors coming from the mouth during food consumption [4]. The first route helps more in ambient odor perception while the latter route plays a role in flavour detection [5]. Retro-nasal olfactory stimulation should not be confused with taste which takes place in taste buds in the oral cavity. Depending on the symptoms, OD is classified into anosmia (total loss of the sense of smell), hyposmia (diminished capacity to detect odors), phantosmia (perception of odors without an actual source present), and parosmia (misinterpretation of odors) [6]. These can be grouped into qualitative (parosmia and phantosmia) and quantitative (anosmia and hyposmia) dysfunctions. These two types of OD can occur in isolation or in combination. A variety of conditions can cause ODs. Broadly, they can be classified into age-related, acquired or congenital ODs. Infections in the upper respiratory tract like that from COVID-19 can also cause OD. Other than this, most of the sinonasal inflammations cause a temporary OD during and post-infection. Neurodegenerative disorders are the next major cause for OD. Furthermore, ODs associated with neurodegenerative disorders are not temporary and rather deteriorate with progression of the disorder. Furthermore, OD in cognitively healthy people could indicate preclinical neurodegenerative disorders [1]. The current topic has a collection of review articles encircling the correlation of OD with neurodegenerative disorders [7,8], especially AD. Based on reports from the WHO, nearly 57 million people were suffering from dementia worldwide with an increase rate of ~18% annually. Out of this, more than 70% of the cases are due to AD. The early stage of AD is associated with subtle cognitive decline which is usually within the clinical limits of normalcy [9]. Reports from olfactory behavioural testing and fMRI-based approaches have demonstrated the strong link of OD with early stages of AD. Review articles from Elhabbari et al. [10], Liu et al. [11] and L Jeffs et al [12], summarize the connection in the topic. The review by Jeffs et al., includes a different dimension of circadian dysfunction associated with AD. Indeed, circadian rhythm dysfunction has been reported to be highly prevalent in AD patients [13]. However, dysfunction in both circadian rhythm and olfaction has been associated with different neurodegenerative disorders and normal ageing, a combinatorial approach suggested by Jeffs et al. [12], that might allow the detection of neurodegenerative disorders categorically. This might be because of the commonality of the association of the glymphatic system, a macroscopic waste clearance system in the central nervous system, with AD [14] as well as sleep [15]. Overall, this topic provides up-to-date information regarding the link between olfactory dysfunction and some of the major neurodegenerative disorders experienced by mankind. Furthermore, it is a timely attempt to raise the awareness of the neuroscience community to think towards strategies that can help in detection, delay and reversal of such devastating disorders.