Premotor Symptoms

The classic motor symptoms of Parkinson’s disease – bradykinesia, resting tremor and rigidity are still used as diagnostic markers in determining whether a patient’s clinical symptoms are consistent with a diagnosis of PD. But focus is now being placed onto a new groups of symptoms – pre-motor symptoms which can predate the classical signs by several years. This is supported by the fact that studies have shown that the process of dopamine loss has been going on for at least 5 years prior to the development of motor symptoms.. Many of the premotor symptoms are fairly nonspecific and relatively common in the general population. So not everyone who develops Parkinson’s displays these pre-motor symptoms and likewise not everyone who experiences these symptoms goes on to develop Parkinson’s.

What are considered to be pre-motor symptoms of Parkinson’s? The debate continues but the following are generally considered to be included in this group.

(1) Olfactory Dysfunction

Although difficulty smelling may seem like a rather trivial issue, it is actually one of importance. Approximately 60 – 100% of Parkinson’s patients who already have motor symptoms, have olfactory dysfunction. In fact there was a study that looked at the accuracy of testing the various motor and mon-motor symptoms for the diagnosis of PD and hyposmia was the most accurate predictive factor. From a pathology point of view the olfactory bulb (that part of the brain responsible for smell) is one of the earliest parts of the brain that has Lewy bodies in Parkinson’s patients. 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 4 years. All in all the evidence is compelling, one of the pre-motor symptoms of Parkinson’s is indeed olfactory dysfunction.

(2) Constipation

Constipation has long been associated with the motor symptoms of Parkinson’s, involves poor gut motility and in fact Lewy bodies have been found in the nerves that innervate the intestine. But it also seems that constipation may actually also be a pre-motor symptom of this disease, one study showing that if constipation is experienced midlife, then there was a four fold risk of developing Parkinson’s later in life.

(3) REM Sleep Behavior Disorder (RBD)

This is dream-enacting behaviors involving vocalizations and motor activities (grabbing, kicking, punching etc.) that are often violent and potentially injurious to the patient and / or bed partner. It is the most consistent pre-motor predictor of Parkinson’s. Studies have shown a significant correlation, one demonstrating that 45% of people with RBD developed Parkinson’s or Lewy body dementia at 11.5 years.

(4) Depression

Depression is a debatable symptom to include in this pre-motor group. The evidence is not strong when depressed patients are followed. However studies that look at the history of Parkinson’s patients often see an increase in the percentage of these individuals with depression compared to controls. What does this mean? It means that people with Parkinson’s are more likely to have a history of depression compared to the general population but most patients with depression don’t go on to develop Parkinson’s.

Why is it important to know about pre-motor symptoms? Well there are a number of reasons. First of all, recognizing these early manifestations of Parkinson’s increases our understanding of the course of the disease as well as the pathologic process that causes this condition. And although there are currently no disease-modifying or curative treatments, one can speculate that when these are developed they could be used to treat the disease at its earliest stages.