According to the Parkinson's Disease Foundation, approximately 1 million people have Parkinson's disease in the United States. Addressing Parkinson’s disease symptoms, genetics, treatment options and more from NorthShore neurologist—Ashvini Premkumar, MD—discuss and raise awareness about this common and often disabling neurological disorder.

By Ashvini Premkumar, MD

Is it possible to detect PD before symptoms begin?

There is no established method of detecting Parkinson’s disease before symptoms begin. Because patients with Parkinson’s disease may lose their sense of smell decades before the onset of their movement disorder, some investigators have explored the use of smell testing as a method of detecting Parkinson’s disease in at-risk subjects (e.g., persons who carry a rare gene mutation known to cause Parkinson’s disease). Persons can lose their sense of smell for many unrelated reasons though (e.g., following an upper respiratory infection, head trauma, or if they smoke). Loss of smell can precede other brain degenerations such as Alzheimer’s disease, so smell testing lacks the specificity needed for a predictive test.

A more promising approach is brain imaging using a radiopharmaceutical called DATSCAN. This is a compound that is injected into a vein and that binds to the endings of dopamine nerve cells in the brain. In Parkinson’s disease, dopamine nerve cells degenerate; hence, there is less binding of DATSCAN. The uptake and binding of DATSCAN can be measured using a single-photon emission computerized tomogram or “SPECT” camera.  We are currently conducting a study at NorthShore to determine if persons with mild to moderate traumatic brain injury, who are at an 11-fold increased risk for Parkinson’s disease, have lower DATSCAN binding than persons without a history of brain injury. This study would demonstrate that it’s possible to detect Parkinson’s disease in at-risk subjects before symptoms begin. 

DATSCAN could prove useful as a method to develop asymptomatic Parkinson’s disease in at-risk subjects who could then be prescribed treatments or lifestyle changes that might delay or possibly even prevent the onset of Parkinson’s disease symptoms.  My research associate Dr. Ying Wu is also exploring the use of automated MRI brain measurements in the same brain injury population to see whether MRI may prove effective in detecting preclinical Parkinson’s disease changes in at-risk subjects.

Are PD symptoms or outcomes different between men and women? Between races?

My research collaborators and I have conducted several studies of gender differences in Parkinson’s disease. At every age men are 1.5 times more likely to develop Parkinson’s disease than women. We observed no convincing difference in survival for men and women with Parkinson’s disease. While there was no difference in motor outcomes, we observed that the risk for dementia was greater in men than in women with Parkinson’s disease. It's possible that estrogen protects against dementia in women.

My collaborators and I observed no important differences in the rates of Parkinson’s disease worldwide, and I’m not aware of any convincing data to suggest that symptoms of Parkinson’s disease or its outcomes differ according to race or ethnicity.

What are some of the later complications of Parkinson’s disease?

Typically we associate Parkinson’s disease with movement disorders. As the disease progresses, patients may develop balance difficulties that result in falls. As a result, patients become increasingly dependent on assistance in walking. For example, they may need a cane or a walker or someone to walk with them. As the movement disorder progresses more, patients may be entirely unable to stand or walk even with assistance.

Parkinson’s disease is not just a movement disorder though. About one in three patients develop a significant decline in memory and mental faculties, or what we call dementia.  Both falls and dementia are dreaded late complications of Parkinson’s disease because they are resistant to medical or surgical treatments and because they carry an increased risk for nursing home placement and even death. Predicting falls and dementia as late complications of Parkinson’s disease is a research priority of the Department of Neurology at NorthShore and a current focus of my research.

Is there a way to slow or halt the progression of PD?

There is no proven method of slowing or halting the progression of Parkinson's disease. Treatments that have been studied and that failed to provide evidence of neuroprotection are: selegiline, vitamins E and C, pramipexole, ropinerole, and COQ10. There is some statistical evidence that carbidopa/levodopa therapy may slow motor progression in Parkinson's disease, but the benefits are trivial.

Azilect is being promoted as a neuroprotective agent, but it’s dubious because the beneficial effects were observed at smaller and not higher doses. The drug is also very expensive and prone to multiple drug-diet and drug-drug interactions. At best, the benefits are nominal. A recent medical advisory panel to the FDA voted 17 to 0 that Azilect should not be approved as a neuroprotective therapy in Parkinson's disease.

Inosine dietary supplementation, to increase blood uric acid levels, may be neuroprotective; however, it may also increase the risk for heart disease, stroke or dementia. There is some evidence that vitamin D deficiency is a risk factor for Parkinson's disease; however, there are no clinical trials to suggest that vitamin D therapy slows the progression of Parkinson's disease. Similarly, observational studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs) or cholesterol-lowering medications (statins) are associated with a reduced risk for Parkinson’s disease, but clinical trials evidence of neuroprotection is lacking. There are some early clinical trials of the calcium channel blocker isradipine, which may have neuroprotective effects in animal models of Parkinson's disease. Though the animal models of Parkinson's disease are not always informative, and some calcium channel blockers can actually cause reversible parkinsonism.

One big hope on the near horizon is therapies targeting the alpha-synuclein protein in Parkinson's disease, including a vaccine that is in early phase clinical trials.  However, while genetic studies have indicated that alpha-synuclein is neurotoxic prior to the onset of Parkinson’s disease symptoms, my research team recently provided genetic evidence that alpha-synuclein may be neuroprotective late in the disease process. So it’s unclear if therapies targeting alpha-synuclein in Parkinson’s disease will be effective and safe. 

Recent studies have suggested that exercise might slow the progression of Parkinson’s disease. Apart from exercise, I have no recommendations regarding neuroprotection at this time.

Once dementia starts is there anything that can be done to reduce the loss of memory?

There are certain “cognitive-enhancing” medications that may be useful in improving cognitive symptoms and slowing the progression of dementia in patients with Parkinson’s disease. These include a class of drugs entitled cholinesterase inhibitors (rivastigmine, galantamine, donepezil). The Exelon patch, in particular, was specifically studied in Parkinson’s patients and obtained FDA approval for treatment of Parkinson’s related dementia. Memantine, an NMDA receptor antagonist, has been FDA approved for the treatment of Alzheimer’s dementia; however, in clinical practice, it has also been found to be helpful in certain patients with Parkinson’s disease-related dementia. In addition, nonpharmacological interventions including exercise, social stimulation, and cognitive rehabilitation can be helpful in the treatment of dementia in Parkinson’s disease.

Apart from genes, are there any environmental risk factors for PD? 

My research team was funded by the National Institute for Environmental Health Sciences for more than ten years to study both genetic and environmental risk factors for Parkinson’s disease. We found that pesticide exposure, both occupational and gardening-related, was associated with a two-fold increased risk for Parkinson’s disease. In particular, exposure to herbicides carried an increased risk. Of the herbicides recalled by our study subjects, the one most significantly associated with Parkinson’s disease was 2,4-Dichlorophenoxyacetic acid, a major component of Agent Orange. There have been reports that Vietnam War veterans are at an increased risk for Parkinson’s disease. Pesticides may contribute to an increased risk for Parkinson’s disease by causing the alpha-synuclein protein to misfold and form toxic accumulations within vulnerable nerve cell regions.

My research team also observed that head trauma may be a risk factor for Parkinson’s disease. A closed head injury that produced loss of consciousness or that required hospitalization was associated with an 11-fold increased risk for Parkinson’s disease.  Head trauma may contribute to an increased risk for Parkinson’s disease by causing an acute spike in alpha-synuclein levels.

While my research team observed no evidence for an interaction of pesticide exposures and alpha-synuclein gene variants, a research team from California recently reported an interaction of head trauma and alpha-synuclein gene variants in Parkinson’s disease. Currently, my research team at NorthShore is conducting a brain imaging study of mild traumatic brain injury to determine if there are Parkinson’s disease-like abnormalities in the brain scans of persons exposed to head trauma, even in the absence of symptoms of Parkinson’s disease. We will also consider the interaction of traumatic brain injury and alpha-synuclein gene variations in that study.