When somebody starts losing their sense of smell, it could be one of the first signs of Parkinson’s or Alzheimer’s disease, or another neurodegenerative disorder, researchers from Perelman School of Medicine at the University of Pennsylvania reported in PLoS One.

The common cold and upper respiratory tract infections are the main causes of loss of smell. Some studies have indicated that regular smokers’ sense of smell is weaker than non-smokers. Researchers in this study found a link between an impaired sense of smell and MG (myasthenia gravis).

Myasthenia gravis is a long-term autoimmune neuromuscular disease in which the patient experiences fluctuating levels of fatigue and muscle weakness. The muscles that weaken are those under the body’s voluntary control. MG is caused by a breakdown in the normal communication between nerves and muscles.

Senior author, Richard Doty, PhD, said:

“This study demonstrates, for the first time, that myasthenia gravis is associated with profound dysfunction of the olfactory system – dysfunction equivalent to that observed in Alzheimer’s disease and Parkinson’s disease. results are the strongest evidence to date that myasthenia gravis, once thought of as solely a disorder of the peripheral nervous system, involves the brain as well.”

Experts have always presumed that MG patients do not have any obvious brain pathology, because the symptoms are generally associated with the peripheral nervous system.

Any behavioral or physiological studies which found evidence of the central nervous system’s involvement in MG could not be replicated in further tests, the authors explained. For example, some studies had found that people with MG had deficits in verbal memory while others did not. Even so, researchers continue reporting CNS-related problems in patients with MG, including problems with eyesight and hearing. Moreover, EEG tests have revealed abnormalities in people with MG; MG-related antibodies have been found in their cerebrospinal fluid.

Doty and team used a smell test which assesses the underlying connection between sense of smell and other neurodegenerative conditions – they wanted to see in more detail what the CNS role might be in MG.

Doty was one of the first scientists to find a link between losing one’s sense of smell and Parkinson’s disease. “Our sense of smell is directly linked to numerous functions of the brain. Olfaction is a good model system for other, more complicated, brain circuits. Understanding our sense of smell, or lack thereof, offers broader insights into brain functions and diseases stemming from the brain.”

In this study, 27 patients with MG were individually matched to 27 healthy individuals (controls) – they were matched for age and sex. They also tested 11 patients with polymyositis – an autoimmune inflammatory muscle disease that starts off when white blood cells suddenly invade muscles, especially those closest to the torso. There is a lot of muscle pain, weakness and tenderness – muscle symptoms are similar to those in MG.

All the patients in the study were administered the UPSIT (University of Pennsylvania Smell Identification Test); it is a picture test said to be the equivalent to the UPSIT designed to control for other cognitive deficits not related to smell. They also checked each participant during the UPSIT and made sure they all could inhale properly.

The MG patients scored significantly lower in the UPSIT score than the controls, as well as those with polymyositis. Only 15% of the MG patients even knew they had a problem with their sense of smell.

Doty said:

“The marked difference in smell dysfunction between the MG patients and the controls cannot be explained by any other physical or cognitive differences. Although we are still exploring the physiological basis of this dysfunction in MG, it’s important to note that the extent of the diminished ability to identify odors found in this study is of the same magnitude as that observed a range of CNS-related diseases, including Alzheimer’s and Parkinson’s.”

The researchers suggest that further, larger studies should be carried out to determine CNS involvement in MG, and perhaps to use smell tests to better classify and monitor the progression of the disease.

They also advise doctors to discuss smell dysfunction with their MG patients. Patients should be alerted as to the potential dangers associated with smell dysfunction, such as not being able to sense natural gas leaks, fires, or rotten food.

Written by Christian Nordqvist