Is a loss of smell an early sign of Parkinson’s?

Barrie Smith was 29 when his sense of smell suddenly disappeared almost overnight. “I kept smelling something like electrical burning, which was really weird,” he remembers. “And then within about two weeks, I couldn’t smell a thing.”

Smith assumed it was only a temporary problem. But his ability to smell never returned, and over the following 15 years, a constellation of new ailments kept emerging, from bouts of insomnia, to digestive issues, high blood pressure, and an episode of depression.

Doctors put most of these problems down to the stress of his job as a child protection officer. The smell loss was attributed to his passion for scuba diving, as pressure changes can sometimes damage the cells in the upper nose.

Then at the age of 47, Smith developed a tremor in his right hand. “I was with a neurologist who ran a few tests, looked at my medical history, and said, ‘You’ve got young-onset Parkinson’s. You’ve had it a long time. In fact it looks like you’ve had it 18 years’.”

Over the past year, anosmia – the symptom of smell loss – has been thrust into the spotlight because of the number of Covid-19 patients developing temporary or permanent smell impairments, a consequence of the inflammation the virus triggers in the upper nose. As a result, scientific interest in this neglected health problem has soared, which could have benefits for other health conditions, such as Parkinson’s. “One of the chief concerns for years was the fact that so little is known about the condition,” says Chrissi Kelly, founder of the UK charity AbScent, which supports people who have lost the ability to smell. “Covid has changed all that.”

Somewhere between 75 and 95 per cent of Parkinson’s patients experience smell loss, with studies showing that on average it predates the onset of motor symptoms such as stiffness or tremor, by at least four years. It’s thought that the process of Parkinson’s – the abnormal clumps of proteins that form in the brain, affecting dopamine production – may start in the olfactory bulb, the region controlling smell.

Of course, not everyone who loses their sense of smell will go on to develop Parkinson’s. Anosmia can happen as a result of ageing, the common cold, or allergies, for example. However, neurologists are interested in whether subtle shifts in odour sensitivity can be used to pinpoint the first signs that something is amiss.

It could have major implications for the treatment of the disease. At the moment, while Parkinson’s drugs such as levodopa can temporarily help manage the symptoms, they have little effect on the underlying disease. Neurologists think this is because patients are so often diagnosed too late, once substantial damage has already occurred to the central nervous system.

Alastair Noyce, a researcher in preventative neurology at Queen Mary University of London, has identified six smells that Parkinson’s patients struggle to detect. He is running a project called Predict-PD which is following 10,000 people over several years to see whether this smell test can be used to predict who goes on to develop Parkinson’s. A similar initiative, called the Parkinson’s Progression Markers Initiative, is taking place in the US.

“At the moment, by the time you get a diagnosis of Parkinson’s, you’ve already lost 50 to 60 per cent of the cells in that part of the brain,” says Noyce. “We want to get to people earlier, before there’s been such marked cell loss.”

Meanwhile, separate research has shown another way in which smell could be used to help earlier diagnosis of Parkinson’s. Scientists at the University of Manchester have been studying changes in sebum, the oily substance that protects the skin, in Parkinson’s patients to develop a skin test, which may be available in the next three years.

The research began after the team were contacted by Joy Milne, a retired nurse from Perth, who noticed that her husband Les began to smell differently some 14 years before he was diagnosed with Parkinson’s at the age of 45. Milne was convinced that the initial smell change she had noticed all those years ago may have been a warning sign. She later took part in tests in which she correctly detected Parkinson’s with 100 per cent accuracy in a group of 12 people, six of whom had it.

“Since Joy approached us, I’ve had many, many conversations with people, often wives or daughters who have said that their partner or father’s smell changed, and then they developed Parkinson’s,” says Perdita Barran, a chemist at Manchester. It has been known since the 1920s that Parkinson’s patients tend to produce large quantities of sebum.

Barran and others have identified a series of chemicals in sebum which are produced in unusually high concentrations in Parkinson’s patients, which likely cause the tell-tale odour that Milne and others have noticed.

In a recent study, they even showed that the levels of these compounds may even be capable of predicting the precise stage of the disease process that a patient is in. “Our aim within the next one to three years is to get this into the diagnostic pathway for Parkinson’s,” says Barran. “A lot of younger patients often get repeatedly misdiagnosed so if there is a medical test that can tell either a GP or a neurologist that this person does or doesn’t have Parkinson’s, that would be a great benefit.”

For patients like Smith, there is a sense of regret that no one recognised the signs sooner. He believes that had he known in his 30s that he was going to develop the disease, it would have been easier to deal with the emotional impact. “When I was eventually diagnosed, it came as a big shock because everybody labours under the illusion that it’s only elderly people who get Parkinson’s,” he says. “If it had been diagnosed sooner, at least [I may have been] more prepared.”