Earliest Pre-Motor Signs of Parkinson's Disease

Doctors use the classic motor symptoms of Parkinson’s disease—slowness of movement (bradykinesia), resting tremor and rigidity—to determine whether a patient’s symptoms are consistent with a diagnosis of Parkinson's.

However, some researchers are now focusing on a new group of symptoms: so-called "pre-motor symptoms" that can predate the three classic signs of Parkinson's by several years.

Studies have shown that the process of dopamine loss has been going on for at least five years prior to the development of motor symptoms in Parkinson's disease, so it would be possible to have very early symptoms related to the disease.

Of course, many of these pre-motor symptoms are not very specific and are relatively common in people who don't go on to have Parkinson's. Therefore, not everyone who develops Parkinson’s displays these pre-motor symptoms, and not everyone who experiences these symptoms goes on to develop Parkinson’s.

The main pre-motor symptoms that researchers have identified include:

• Olfactory dysfunction (difficulty smelling)
• Constipation
• Rapid-eye movement (REM) sleep behavior disorder
• Depression

A review of research published in 2017 stated that people with these symptoms rarely go to a neurologist for diagnosis. By the time they do see a neurologist, they've already lost more than 50% of the brain cells in a region called the substantia nigra. This points to the dire need for recognition of these early symptoms by the medical community as a whole.

Although difficulty smelling (also called hyposmia) may seem like a rather trivial issue, it is actually pretty important. It's found in about 90% of early-stage cases of Parkinson's.

In fact, one early study found this symptom was the most accurate predictive factor that a person would develop Parkinson's. A huge clinical trial showed that individuals with low olfactory functioning had a 5.2-fold increase in developing Parkinson’s and that impaired smell can precede motor symptoms by at least four years.

More recent research has supported this finding, with some researchers calling it a potential biomarker of the disease.

Constipation has long been associated with the motor symptoms of Parkinson’s and it can have a tremendous impact on the daily lives of people with the disease. Studies show:

• It's one of the most common non-motor symptoms, found in as many as 80% of cases
• It may precede motor symptoms in up to 61.4% of cases by up to 20 years
• It's a significant risk factor, about quadrupling the risk of developing Parkinson's, depending on the severity

People who have this disorder play out their dreams while asleep by vocalizing, grabbing, kicking and punching. Their dream activities are often violent and can injure either the patient or the patient's bed partner.

This disorder is among the most consistent pre-motor predictors of Parkinson’s. In a 2017 review, researchers found that between 35% and 91.9% of people diagnosed with RBD eventually developed either Parkinson’s, Lewy body dementia, or a similar neurodegenerative disease.

Research shows that depression is linked to Parkinson's, possibly due to decreased activity between certain regions of the brain, and that it's common enough before the onset of motor symptoms to be considered a risk factor.

However, while it may be a significant early indicator, most patients with depression don’t go on to develop Parkinson’s.

Why is it important to know about pre-motor symptoms of Parkinson's disease?

• Recognizing these early manifestations of Parkinson’s increases our understanding of the course of the disease, as well as the process that causes it. That can lead to better treatments, prevention, and, possibly, a cure.
• Earlier diagnosis can lead to earlier treatment, which means better outcomes.
• While no treatments will cure Parkinson's right now, should a cure be developed, it could be used to stop the disease at its earliest stages—before the motor symptoms begin.