Ask an Expert: Dr. Ahlskog Discusses the Nuts and Bolts of Parkinson’s Disease
Dr. J. Eric Ahlskog, PhD, MD, is a Professor of Neurology at the Mayo Medical School and has been Chair of the Mayo Section of Movement Disorders at the Mayo Clinic in Rochester, Minnesota. He is the author of The New Parkinson’s Disease Treatment Book and has over thirty years of experience treating people with Parkinson’s disease (PD). He is widely considered to be a leading expert on PD. In June 2016, Parkinson Society British Columbia (PSBC) invited him to speak at the Annual General Meeting, as well as present at community talks in Abbotsford and Victoria.
What are your thoughts on the theory that Parkinson’s disease has a long pre-clinical period?
Evidence supports a long pre-clinical period, especially based upon the work of Professor Heiko Braak, the German neuroanatomist who has developed a staging scheme for PD. He proposes that the motor symptoms of PD (e.g., tremor, slowness, stiffness, walking problems) reflect progression to middle stages of the PD process. Rapid eye movement (REM) sleep behavior disruption, loss of sense of smell, constipation or depression/anxiety tends to develop earlier in the Lewy disease process, often prior to the motor symptoms. For example, constipation or REM sleep disturbances may precede PD motor symptoms by 20 years or more. The disease itself progresses slowly and incompletely over a long period of time (Ahlskog, 2016).
What is the significance of dopamine and Lewy bodies in PD?
The brain is analogous to an enormous computer, controlling our actions, thoughts and emotions. Chemical messengers called neurotransmitters transmit signals from one brain cell (neuron) to the next. Dopamine is the substantia nigra neurotransmitter that transmits signals to the striatum. This brain circuit modulates movement, posture and influences mood (Neurotransmitters, n.d.). People with Parkinson’s have very low levels of brain dopamine. Years ago, it was discovered that replenishment of dopamine effectively treats Parkinson’s symptoms.
In 1913, Dr. Frederick Lewy reported unique changes in the brains of people with PD. Under the microscope, he found small deposits of a proteinaceous (protein) material in certain brain areas of deceased people who had PD. These deposits (“Lewy bodies”) are considered the microscopic marker of PD.
After many years living with PD, some people develop medicine-refractory motor symptoms, cognitive impairment and autonomic symptoms (e.g., urinary, low blood pressure). Notably, these are not caused by low dopamine levels and hence do not benefit from dopamine replacement measures. In other words, this reflects proliferation of the Lewy body neurodegenerative process to non-dopamine brain regions. This has implications for future research directed at finding the “cure” for PD; research directed at dopamine restoration will not provide the cure. Rather, we need to understand the mechanisms of this Lewy neurodegenerative process, which would be a crucial step toward the “cure” (Ahlskog, 2016).
Are there any drugs that slow the progression of Parkinson’s disease?
There is no proof of a neuroprotective effect from any drug. While there are no drugs that have been proven to slow the symptoms of Parkinson’s, there is a substantial volume of scientific literature that convincingly argues for exercise as a means of slowing the progression of Parkinson’s. Specifically, this relates to ongoing aerobic exercise (Ahlskog, 2016).
Why is exercise beneficial?
Studies on animals have documented that exercise enhances neuroplasticity. Neuroplasticity implies the generation of new neural connections or brain pathways. Animal studies have also documented exercise-related generation of neurotrophic factors in the brain; such factors are comparable to putting fertilizer on your lawn. Several studies involving humans have documented that midlife exercise significantly reduces the later risk of not only PD, but also dementia and mild cognitive impairment. There are a number of studies that have reported an association between fitness and long term cognitive function and integrity (Ahlskog, 2015, p. 121).
What type of exercise do you recommend?
Any type of regular aerobic exercise should be beneficial for people with Parkinson’s. This might include going for brisk walks, playing racquetball, tennis, using the gym, PWR! training – anything that makes you hot, sweaty and tired. The amount of exercise that captures the full benefit has not yet been established. I recommend an hour of aerobic exercise every other day, or one hour four times a week (Ahlskog, 2016).
When do you recommend an individual with Parkinson’s start managing their symptoms with medication?
A Parkinson’s diagnosis does not necessarily mean you should immediately start a medication. Since there are no drugs proven to slow disease progression, the only reason to take a medication is to manage symptoms. If the symptoms do not bother you, you may wait until they do. The goals of medical treatment are twofold:
- Optimize quality of life;
- Control the motor symptoms sufficiently to allow regular exercise (Ahlskog, 2015).
What drug(s) do you suggest to individuals who may want to manage their symptoms medically for the first time?
Carbidopa/levodopa is the gold standard medical treatment for Parkinson’s disease. Levodopa, the active component of carbidopa/levodopa is naturally produced by our bodies – it is from a class of natural substances called amino acids, and levodopa is the immediate precursor of dopamine. The other primary drugs used to treat PD also work through dopamine but are much less efficacious and some have substantially more side effects.
I recommend using the regular (immediate-release) formulation of carbidopa/levodopa instead of the sustained-release formulation, since this provides more consistent and predicable responses. It should be taken on an empty stomach, at least an hour or more before a meal or at least 2 hours after the end of a meal. I start patients on one 25/100 carbidopa/ levodopa tablet, three times a day. The most I prescribe is three of the 25/100 carbidopa/levodopa tablets each dose. In the initial few years, three doses daily are appropriate; however, later, more doses per day may be necessary.
Carbidopa/levodopa has a few important side effects. It can lower your standing blood pressure, translating into faintness when upright. If each levodopa dose is more than you need, involuntary movements may be provoked (dyskinesias), which resolve if each dose is lowered. Carbidopa/levodopa can also cause nausea but does not induce stomach ulcers (the nausea is mediated via the brain nausea centre).
Do dopamine agonists cause unusual side effects and, if so, why?
The two oral dopamine agonists used for Parkinson’s disease have a specific affinity for the D3 dopamine receptor class. These D3 receptors are predominantly found in the brain’s limbic system, which plays a role in the experience of reward. Chronic treatment with these dopamine agonists may provoke pathological behaviours, such as compulsive gambling, sexual indiscretions, excessive spending, etc.; these pathologic behaviours have been documented in about a quarter of PD patients taking therapeutic doses of pramipexole or ropinirole. These dopamine agonists may also trigger hallucinations, delusions, drowsiness or swelling (Ahlskog, 2016).
Dr. Ahlskog’s first and second editions of The Parkinson’s Disease Treatment Book: Partnering with Your Doctor to Get the Most from Your Medications (2005) and (2015) are available to members of PSBC, and can be borrowed from the Society’s library.
Sources
Ahlskog, J.E. (2015). The New Parkinson’s Disease Treatment Book (2nd edition). New York, NY: Oxford University Press.
Ahlskog, J.E. (2016). The Nuts and Bolts of Parkinson’s Disease Management [video].
Neurotransmitters. (n.d.) In The Brain from Top to Bottom. Retrieved from http://thebrain.mcgill.ca/flash/i/i_01/i_01_m/i_01_m_ana/i_01_m_ana.html
This content was published in the Fall 2016 edition of our quarterly magazine, Viewpoints. The content was accurate as of this publication date.