More than Dopamine

Although James Parkinson first wrote a passage describing the movement disorder which we now know as Parkinson’s Disease in 1817, it wasn’t until the mid 1950s that dopamine deficiency was suggested to be the cause. Since that time, it is most commonly thought that people without enough dopamine in particular areas of the brain develop the characteristic symptoms of this illness – resting tremor, bradykinesia (slow movement) and rigidity. And much of the efforts in the research community have been directed towards replacing or preserving dopamine in the hopes of alleviating the constellation of symptoms that were described almost two centuries ago.

Dopamine is one of many neurotransmitters or chemical messengers produced by neurons (nerve cells) in the brain and are responsible for communication between our brains and our bodies. This chemical messenger in particular, is important for our bodies to move in a normal, smooth and coordinated manner. In Parkinson’s, the neurons that are responsible for producing dopamine die off in an area called the substantia nigra and without enough of it, movement becomes erratic – a tremor appears, muscles become stiff and slow. Naturally the development of dopamine replacement became and is still considered to be the standard of treatment for motor symptoms, a successful management option, improving functioning and effectively reducing disability.

But as we’ve learned to control the hallmark motor symptoms to some extent, it has become clear that there’s much more to this disease and that there are features that are not only debilitating but for the most part, undertreated.

These are known as non-dopaminergic symptoms; those features that result from problems with other messengers and other areas of the nervous system. And because they are not a result of low dopamine levels, they don’t necessarily respond to typical Parkinson’s medications. These symptoms are wide-ranging and variable. Pain, incontinence, sleep disturbance, depression, anxiety, cognitive impairment and dementia are but a few examples of the non-dopaminergic manifestations of Parkinson’s. A number of these symptoms such as loss of smell, constipation and sleep disorder actually develop before the motor symptoms even appear.

Like most cases in Parkinson’s, there is a huge variation in what symptoms people develop and when. Studies do however seem to indicate the majority of Parkinson’s patients will exhibit some of these features at some point during the course of their disease. And quality of life studies in Parkinson’s Disease have shown that nondopaminergic symptoms are more closely associated with disability and deterioration in quality of life than even motor symptoms.

So why is this new understanding of Parkinson’s Disease important? First and foremost given the degree to which these symptoms can affect a person’s quality of life, knowing about all the potential issues that are part of Parkinson’s beyond the motor symptoms, is invaluable for patients. For a long time many of these issues were not recognized. Now patients are becoming educated that this disease is much more than a movement disorder and that allows patients to have more of their problems addressed which improves their overall care.

For the research and medical community, recognition of the complexity of factors that contribute to this disease opens up new approaches and novel areas to study. Until recently, much of the research focused on the dopamine system but increased recognition of non-dopaminergic symptoms and their impact on the quality of life of patients, attention is now being directed towards developing therapies to address these issues. Overall better understanding of this complex disease will lead to better patient care, the development of more effective treatments and ultimately that elusive cure.