Anosmia can be an indicator of several neurodegenerative diseases. There are several diseases that can be associated with this symptom other than COVID-19.

By now, most of us are aware that loss of smell, known as anosmia, is one of the known symptoms of COVID-19. Losing the ability to smell can be significant, affecting the quality of life by dampening our sense of taste and appetite, and threatening our safety. Olfaction plays an important role in warning us of fires, natural gas, and even spoiled food.

But, if you’ve noticed changes to your sense of smell during the pandemic, don’t assume you necessarily have COVID-19. For one thing, around 12% of people over the age of 40 experience some disruption to their olfaction, and nearly 25% of men over 60 report an impaired sense of smell, according to Harvard Health. Beyond that, recent studies show that olfactory changes could be indicators of several non-COVID health diseases. Here’s a look at some of these conditions. 

Diseases associated with anosmia

As it relates to COVID-19, the reasons for anosmia remain unclear, but a study published in Science Advances sheds some light on the origin of this symptom. Researchers focused on the ACE2 receptor protein, which SARS-CoV-2 uses to enter human cells. They found that, while this gene isn’t expressed by olfactory sensory neurons, it is expressed in cells that provide metabolic and structural support to those neurons. The findings indicate that infection of non-neuronal cell types is responsible for anosmia, which is likely to explain why most patients experience a return of their sense of smell after they’ve recovered.

Anosmia may even serve as a marker of disease progression. A study published in Multiple Sclerosis and Related Disorders examined 55 multiple sclerosis (MS) patients and 20 healthy controls to clarify the relationship between smell identification ability and cognitive function in MS. They found that those whose sense of smell was most impaired also scored lower on cognitive tests, and concluded that “olfactory dysfunction might be considered as an indirect measure of MS severity”.

Although past research has shown that anosmia is linked with neurodegenerative disease, as well as increased mortality in general, the reasons for this remains unclear. It’s hypothesised that the loss of smell is an early biomarker of neurodegenerative disease; conversely, some experts believe certain conditions that affect olfaction increase the risk of diseases like Alzheimer's or Parkinson's, noted Harvard Health.

The aforementioned study published in Annals of Internal Medicine explored these associations. Researchers examined a cohort of 2,289 adults aged 71-82 years, over a 13-year follow-up period. During that time, 1,211 participants died, and researchers observed that those with poor olfaction had a 46% higher cumulative risk for death at year 10. The association was clearest in those who were otherwise healthy at baseline, which, the authors wrote, “highlights the fact that impaired olfaction is more than a marker of poor overall health”.

An unexplained association

Looking at cause-specific mortality, the study’s findings indicate that loss of sense of smell was strongly associated with mortality from dementia or Parkinson's disease, and modestly associated with death from cardiovascular disease.

While this came as no surprise to the researchers, understanding why older adults with poor olfaction are at higher risk for death proved tricky. Their findings showed that dementia, Parkinson's disease, and weight loss together explained roughly 30% of the higher long-term mortality associated with poor olfaction. The link between poor olfaction and malnutrition is likely due to the participants’ experiences of decreased appetite or poor food choices. The findings of the study are consistent with a growing body of evidence indicating that loss of smell is an early warning for several major neurodegenerative diseases, but they don’t explain why this is the case.

Factors associated with Anosmia

Additionally, the researchers were unable to get to the bottom of the majority of the deaths that appeared to be linked to anosmia. They pointed out that possible explanations like eating spoiled food, gas poisoning, or fires due to not being able to smell are rare, accounting for roughly three deaths per 100,000 persons. Which leaves the association between poor olfaction and higher mortality largely unexplained. “Future studies should investigate the connections between olfactory impairment and the health of older adults beyond the nervous system”, the authors wrote.

The researchers concluded that a loss of sense of smell among otherwise healthy older adults could be an early warning sign for adverse conditions which they may not be aware of. As such, it’s important to monitor patients with anosmia closely the condition may point to non-COVID neurodegenerative disease and be linked to increased risk of mortality.

And remember, there are other factors that can contribute to loss of smell, including smoking and certain medications, such as the statin-lowering drug atorvastatin, the blood pressure medication amlodipine, and the antibiotic erythromycin, noted Harvard Health.

This story is contributed by Alistair Gardiner and is a part of our Global Content Initiative, where we feature selected stories from our Global network which we believe would be most useful and informative to our doctor members.