Category: Parkinson’s

Dopamine replacement therapy, which is used to manage motor symptoms associated with Parkinson's disease, can, at times, adversely affect cognition. Dr. Oury Monchi, Ph. D. in neuronal modeling and Head of the Neurophysiological and Neuroimaging Research theme at the Centre de recherche de l'Institut universitaire de gériatrie de Montréal (IUGM), which is affiliated with the Université de Montréal, and Dr. Penny A. MacDonald, Neurologist and postdoctoral fellow in Dr. Monchi's laboratory, have identified the reasons why within the framework of a clinical study recently published in Brain: A Journal of Neurology.

"The aim of our study was to understand the effects of dopamine replacement therapy on various aspects of cognition in patients with Parkinson's disease. When it comes to this particular disease, the part of the brain most affected by dopamine depletion is the striatum which is divided into several structures. In Parkinson's disease, the dorsal striatum is more severely affected than the ventral striatum, which remains relatively unaffected, at least during the first phases of the disease. We observed that while dopamine replacement therapy enhances the functions of the dorsal striatum, it is at the expense of the ventral striatum which suffers a dopamine overdose, impairing its function," states Dr. Monchi.

Until now, the effect of dopamine replacement therapy on cognition in individuals with Parkinson's disease was controversial. The purpose of this study however, was to further investigate. This led to a series of laboratory tests and neuroimaging studies that allowed researchers to clearly define the distinct cognitive functions performed by the dorsal and ventral striatum, thereby shedding some light on the issue.

"The best treatment option for managing the motor symptoms of Parkinson's disease remains dopamine replacement therapy. In some patients however, it can have a negative effect on specific aspects of cognition. Our discovery will therefore enable us to explore different medication and non-medication based avenues that could help improve the overall health of those affected. Our findings may contribute to helping develop personalized medicine — an avenue that is currently commanding a great deal of attention," exclaims Dr. MacDonald.

Summary of the Research

Twenty two Parkinson's disease patients without dementia and twenty two healthy individuals were included in the first part of the study (behavioural), while thirteen healthy young adults participated in the second part of the study (neuroimaging). Each participant was asked to repeatedly choose numbers (288 times) such as selecting the higher of two numbers, for example. On some occasions, patients were given no reinforcement, while on other occasions, they were influenced by various cues that made it easier to answer (a function usually associated with the dorsal striatum), or more difficult to answer due to interference (associated with the ventral striatum). Parkinson's patients were tested on or off medication. Selection was validated with functional magnetic resonance imaging which was used to observe cerebral activity during the exercises. Results demonstrated that while dopamine replacement enhances results for conditions associated with interference (dorsal striatum), it reduces results for conditions associated with facilitation (ventral striatum).

Parkinson's disease

Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's disease. Onset usually begins between the ages of 45 and 70 years. For reasons that remain unknown, the cells that produce dopamine, a chemical that relays signals to the striatum, die. Since dopamine controls movement, the motor symptoms of Parkinson's disease gradually begin to appear. Motor symptoms manifest as tremor, rigidity and akinesia (inability to perform certain simple voluntary movements). Symptoms can also affect cognition and mood and may even lead to depression. According to Health Canada, it is estimated that 1 in 100 Canadians over age 60 are diagnosed with this condition. The direct and indirect costs associated with Parkinson's disease exceed $450 million a year.

The authors are grateful for the support provided by the IUGM Foundation and the Canadian Institutes of Health Research.

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Journal Reference:

1. P. A. MacDonald, A. A. MacDonald, K. N. Seergobin, R. Tamjeedi, H. Ganjavi, J.-S. Provost, O. Monchi. The effect of dopamine therapy on ventral and dorsal striatum-mediated cognition in Parkinson's disease: support from functional MRI. Brain, 2011; 134 (5): 1447 DOI: 10.1093/brain/awr075

Twice a month a jam session takes place on the third floor of Northwestern Memorial's Prentice Women's Hospital. A diverse group of men and women, ranging in age and ethnicity, gather in a circle with instruments in hand and sing together. This is no ordinary jam band; all its members have Parkinson's disease. They are participating in Creative Arts for Parkinson's, a music and drama therapy program offered through Northwestern's Parkinson's Disease and Movement Disorders Center.

Creative Arts for Parkinson's is lead by specially trained music and drama therapists from the Institute for Therapy through the Arts (ITA). The participants are asked to reach deep into their emotions and to push themselves physically to achieve the therapeutic benefits which address both the symptoms of the disease and its psychological burden.

On a recent Monday afternoon, the group took turns singing something that describes who they are while keeping the beat with percussion pieces. A small woman with a slight tremor sings in a loud, strong voice: "My disease made me stronger!" The group around her enthusiastically joins the chant, clapping their instruments, singing "My disease made me stronger! My disease made me stronger!"

"Patient care is much more than just medical; it's caring for the whole person," said Tanya Simuni, MD, a neurologist at Northwestern Memorial Hospital and director of the Parkinson 's Disease and Movement Disorders Center. Simuni is also an associate professor of neurology at Northwestern University Feinberg School of Medicine. "By providing music and drama therapy, we are hoping to help these patients find new means of fulfillment in their lives while also addressing some of the physical components of their illness."

Parkinson's disease is a neurodegenerative brain disorder that affects nearly 1.5 million Americans. Progressing slowly in most people, the disease involves a lack of dopamine in the brain which causes symptoms including tremor, slowness of movement, muscle stiffness and balance problems.

"Our goal is to find new approaches to help these patients address their illness," explained Diane Breslow, MSW, LCSW, coordinator and social worker for the center. "Very often with Parkinson's disease there is a fear of the future and the unknown; we want to give these patients a better way to live with their disease in the present."

Music and drama therapy addresses many of the physical and emotional components of Parkinson's disease. Benefits include improvement of physical coordination and functional movement, postural awareness, as well as speech and voice enrichment.

"In the music portion, the patients are learning the concept of rhythm which helps them improve their gait and movement," explained Breslow. "Reading scripts during the drama portion increases word recall and articulation, while the voice is exercised in both parts of the class."

Beyond the physical benefits of the therapy, Creative Arts also enhances mood and positive attitude. The patients use the opportunity to set personal goals and encourage one another to address specific challenges they face because of their illness. During one session, the group read through a scene from the Academy Award winning "King's Speech." One of the men in the group acknowledges the similarities between the main character's experience and his own. He tells the class that when first diagnosed, he would speak softer or take smaller steps in anticipation of the disease eventually limiting these abilities. After this revelation, he proposed a challenge to the group: "Let's make it a goal to use our loud voices and make sure we can be heard. We need our loud voices."

Moments like this are why Breslow loves her job. "I've seen firsthand how these techniques bring out feelings the patients might not otherwise have access to," said Breslow. "Music and drama are a beautiful way to access and deal with life experiences and Parkinson's disease. I learn more from these patients than I give."

Researchers at North Carolina State University have figured out how copper induces misfolding in the protein associated with Parkinson's disease, leading to creation of the fibrillar plaques which characterize the disease. This finding has implications for both the study of Parkinson's progression, as well as for future treatments.

The protein in question, alpha-synuclein, is the major component of fibrillar plaques found in Parkinson's patients. Researchers had already discovered that certain metals, including copper, could increase the rate of misfolding by binding with the protein, but were unsure of the mechanism by which this binding took place.

"We knew that the copper was interacting with a certain section of the protein, but we didn't have a model for what was happening on the atomic level," says Frisco Rose, Ph.D. candidate in physics and lead author of the paper describing the research. "Think of a huge swing set, with kids all swinging and holding hands — that's the protein. Copper is a kid who wants a swing. There are a number of ways that copper could grab a swing, or bind to the protein, and each of those ways would affect all of the other kids on the swing set differently. We wanted to find the specific binding process that leads to misfolding."

Rose and NC State colleagues Dr. Miroslav Hodak, research assistant professor of physics, and Dr. Jerzy Bernholc, Drexel Professor of Physics and Director of the Center for High Performance Simulation, developed a series of computer simulations designed to ferret out the most likely binding scenario.

According to Hodak, "We simulated the interactions of hundreds of thousands of atoms, which required multiple hundred thousand CPU-hour runs to study the onset of misfolding and the dynamics of the partially misfolded structures."

The number of calculations was so large that Hodak and Bernholc had to devise a new method to make it possible for a computer to process them. Only supercomputers like Jaguar, Oak Ridge National Laboratory's most powerful supercomputer — the most powerful in the United States, in fact — were up to the task. But the simulations finally revealed the binding configuration most likely to result in misfolding.

Their results appear in the June 14 edition of Nature Scientific Reports.

The researchers hope that their finding will advance our understanding of Parkinson's, one of the most common — and devastating — neurological diseases. "Understanding the molecular mechanism of Parkinson's disease should help researchers in developing drugs that treat the disease rather than merely alleviate symptoms," Bernholc says.

The research was funded by the Department of Energy and the National Science Foundation. The Department of Physics is part of NC State's College of Physical and Mathematical Sciences.

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Journal Reference:

1. Frisco Rose, Miroslav Hodak, Jerzy Bernholc. Mechanism of copper(II)-induced misfolding of Parkinson's disease protein. Scientific Reports, 2011; 1 DOI: 10.1038/srep00011

Few treatments for Parkinson's disease (PD) restore function for extended periods. In a new study published in the inaugural issue issue of the Journal of Parkinson's Disease, an international group of researchers reports that platelet-derived growth factor-BB (PDGF-BB) restored function in rodents and shows promise as a clinical candidate drug for treatment of PD.

Parkinson's disease is the second most common neurodegenerative disorder, affecting 1-2% of the population over the age of 65. It is characterized by loss of brain cells (neurons) from the mid-brain which use the neurotransmitter dopamine to help control voluntary movements. Investigators from NeuroNova AB, Stockholm, Sweden, the Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden, The Parkinson's Institute, Sunnyvale, CA, USA, and Motac Neuroscience Ltd, Manchester, UK, found that behavioral, tissue and biochemical changes in experimental models of Parkinson's disease in rodents could be counteracted by infusion of PDGF-BB. This could offer an alternative strategy to restore function in PD.

"In animal models of nigrostriatal injury, a two weeks treatment with platelet-derived growth factor-BB resulted in long-lasting restoration of striatal dopamine transporter binding sites and expression of nigral tyrosine hydroxylase," commented Anders Haegerstrand, MD, PhD, Chief Scientific Officer, NeuroNova AB, Stockholm, Sweden."It also normalized amphetamine-induced rotational behavior in 6-hydroxydopamine lesioned rats. Platelet-derived growth factor-BB promoted proliferation of neural progenitor cells in the subventricular zone. The effects on dopaminergic neurons and functional recovery could be blocked by co-infusion with a proliferation inhibitor, indicating a link between the proliferative and anti-parkinsonian effects. Based on the current data, we consider platelet-derived growth factor-BB a clinical candidate drug for treatment of Parkinson's disease."

The study demonstrated for the first time a functional relevance of a PDGF-induced cell proliferation in a model of CNS disease. In the rats studied, normalization of behavior after PDGF-BB treatment lasted for 10 weeks. PDGF-BB is already in clinical trial at NeuroNova.

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Journal Reference:

1. Olof Zachrisson, Ming Zhao, Annica Andersson, Karin Dannaeus, Johan Häggblad, Ruben Isacson, Elisabet Nielsen, Cesare Patrone, Harriet Rönnholm, Lilian Wikstrom, Kristofer Delfani, Alison L. McCormack, Theo Palmer, Donato A. Di Monte, Michael P. Hill, Ann Marie Janson Lang, and Anders Haegerstrand. Restorative Effects of Platelet Derived Growth Factor-BB in Rodent Models of Parkinson's Disease. Journal of Parkinson's Disease, 2011; 1 (1) DOI: 10.3233/JPD-2011-0003

 An analysis of several studies shows that people with Parkinson's disease have a significantly higher risk of melanoma, the most dangerous type of skin cancer and the leading cause of death from skin diseases. The research is published in the June 7, 2011, print issue of Neurology®, the medical journal of the American Academy of Neurology.

Parkinson's disease is a brain disorder that causes tremors and difficulty with movement and walking. It affects about one million people in the United States.

"Past studies linking Parkinson's disease and melanoma have not been conclusive, so we wanted to explore a larger group of studies to see whether the link was consistent," said study author Honglei Chen, MD, PhD, with the National Institute of Environmental Health Sciences, a division of the National Institutes of Health in Research Triangle Park, N.C., and a member of the American Academy of Neurology.

The research examined 12 studies conducted from 1965 and 2010 that looked at the possible association between Parkinson's disease and melanoma. Most of the studies had fewer than 10 cases with both conditions.

The study found that men with Parkinson's disease were twice as likely as those without Parkinson's to have melanoma. Women with Parkinson's disease were one-and-a-half times as likely to be diagnosed with the dangerous form of skin cancer compared to women without Parkinson's. There was no clear link found between Parkinson's and non-melanoma skin cancer.

"Parkinson's disease patients in general have a lower risk for cancer, smoking-related cancers in particular, but they may have a higher risk for melanoma. One possible explanation for the link between Parkinson's and melanoma is that the two diseases may share some genetic or environmental risk factors," Chen said. "However, our understanding of this link is very preliminary."

The study was supported by the National Institute of Environmental Health Sciences.

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Journal Reference:

1. Rui Liu, Xiang Gao, Yi Lu, Honglei Chen. Meta-analysis of the relationship between Parkinson disease and melanoma. Neurology, 2011; 76: 2002-2009 DOI: 10.1212/WNL.0b013e31821e554e

 The stomach bacteria responsible for ulcers could also play a role in the development of Parkinson's disease according to research presented May 22 at the 111th General Meeting of the American Society for Microbiology.

"Infection of late middle-aged mice with a particular strain of the bacteria Helicobacter pylori results in development of Parkinson's disease symptoms after 3-5 months," says Traci Testerman of Louisiana State University Health Sciences Center, Shreveport, who presented the research. "Our findings suggest that H. pylori infection could play a signficant role in the development of Parkinson's disease in humans."

Physicians have noted a correlation between stomach ulcers and Parkinson's disease as far back as the 1960s, before it was even known that H. pylori was the cause of ulcers. More recently, a number of studies found that people with Parkinson's disease were more likely to be infected with the bacterium, and that Parkinson's patients who were treated and cured of infection showed slight improvement compared to controls that continued to deteriorate.

In Guam, a study of why some populations had a high risk of developing a Parkinson's-like disease discovered that a specific compound in cycad seeds eaten by these populations was neurotoxic. The compound, which resembles a cholesterol with an attached sugar group, is almost identical to a compound produced by H. pylori.

Testerman and her colleagues developed an animal model to more effectively understand the role of H. pylori and its modified cholesterol in Parkinson's disease. They infected young and aged mice with three different strains of the bacteria and monitored their locomotor activity and dopamine levels in the brain. Mice infected with one of the strains showed significant reductions in both.

"The results were far more dramatic in aged mice than in young mice, demonstrating that normal aging increases susceptibility to Parkinsonian changes in mice, as is seen in humans," says Testerman.

In order to determine whether the modified cholesterol or other substances could be responsible for Parkinson's disease development, they fed aged mice with H. pylori extracts. The mice did not become infected but developed the same symptoms as those infected with the bacteria, suggesting that the modified cholesterol or some other product contained within the bacteria contribute to disease development.

"Our mouse model demonstrates a direct effect of H. pylori infection on the development of Parkinson's disease. The observation that not all H. pylori strains are equally able to cause symptoms will allow us to investigate bacterial factors and/or immune response to H. pylori infection that increase the risk for Parkinson's disease," says Testerman.

 New data offer hints to why Parkinson's disease so selectively harms brain cells that produce the chemical dopamine, say researchers at Washington University School of Medicine in St. Louis.

Dopamine is involved in brain cell communications including the signals that control movement. As Parkinson's kills the dopamine-producing cells, patients begin to develop tremors, problems moving and other symptoms.

The new research shows that a drug known to damage dopamine-producing nerve cells and mimic Parkinson's disease does so by rapidly damaging cellular energy generators called mitochondria. This damage impairs the ability of mitochondria to circulate around the cell as they normally would. As a result, axons, the extended arms nerve cells use to send messages, wither; a few days later, the body or main portion of the cell also dies.

"Much of the research into Parkinson's disease treatments is focused on saving the bodies of these cells, but our results suggest that keeping axons healthy also is essential,"says Karen O'Malley, PhD, of Washington University School of Medicine in St. Louis. "When axons die back, dopamine is no longer delivered to the neurons that need it. The cell body also has fewer connections to other cells, and it needs those connections to survive."

The results were published May 11 in The Journal of Neuroscience.

Many processes and facilities for cellular maintenance are in the body of the nerve cell, and their products sometimes have to travel a significant distance to reach the axon's end.

"If you think, for example, about one of your peripheral nerves, the cell body is located in the spinal column, but some of the axons extend as far as your big toe," says O'Malley, professor of neurobiology. "That's like the cell body sits in an office in St. Louis and the end of the axon is in Chicago."

O'Malley compares the axon's system for transporting supplies to a railroad. Mitochondria are part of the railroad's cargo. They supply the energy that allows the axon to do its work.

For the study, O'Malley gave cultured mouse nerve cells a toxin called MPP+ that causes Parkinson's-like symptoms.

"MPP+ is a derivative of a synthetic form of heroin developed in California in the early 1980s," O'Malley says. "It came to scientists' attention when teenage abusers of the drug went to the hospital with Parkinson's disease symptoms."

O'Malley found that the toxin stopped the movement of mitochondria in the axon in 30 minutes. The railroad still functioned, shipping other cargo to the end of the axon. But most mitochondria either stopped moving or were headed for the cell body instead of the axon.

O'Malley suspected that this meant the mitochondria were damaged by the changes caused by the toxin and being shipped back to the cell body for repair. Additional tests supported this theory, showing that the mitochondria had lost their ability to maintain their membrane potential, a measure of mitochondrial fitness.

The specificity of this toxin for dopamine-producing cells is reinforced by the finding that other types of nerve cells did not have problems transporting mitochondria after toxin exposure. In a comparison between different nerve cell types, O'Malley found mitochondria in dopamine-producing nerve cells are smaller in size and travel three times slower. But she can't yet definitively say that these distinctions play a role in the problems caused by the toxin.

Scientists screened several compounds to see if they could block the toxin's effects. Only two antioxidants worked, glutathione and N-acetyl cysteine. The latter compound has already been shown to be effective in animal models of Parkinson's disease and is used as a treatment for other disorders in patients.

O'Malley is currently studying whether two genes linked to Parkinson's disease affect mitochondria damaged by the toxin.

"We're going to continue to look for specific differences in these cells that might help scientists develop better treatments," O'Malley says.

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Journal Reference:

1. J. S. Kim-Han, J. A. Antenor-Dorsey, K. L. O'Malley. The Parkinsonian Mimetic, MPP , Specifically Impairs Mitochondrial Transport in Dopamine Axons. Journal of Neuroscience, 2011; 31 (19): 7212 DOI: 10.1523/JNEUROSCI.0711-11.2011

— In Parkinson's disease, the human body generates antibodies to combat the amyloid-producing protein alpha synuclein early in the course of the disease. A simple blood test that measures these antibodies can facilitate early diagnosis of the disorder, writes Ludmilla Morozova-Roche and her associates at Umeå University in Sweden in the latest issue of the journal PLoS One.

The need for diagnostic biomarkers for degenerative disorders affecting the nervous system, such as Parkinson's and Alzheimer's, is great and acute. Early diagnosis of such diseases would enable treatment at a stage when they are most responsive to intervention, during the period when the greatest number of nerve cells are being damaged or dying. Research is underway around the world to develop substances that can affect the course of the disease.

What many neurodegenerative diseases have in common is that they are caused by proteins that lump together into so-called amyloid. Ludmilla Morozova-Roche's research team has found endogenous antibodies against the most important amyloid-producing protein in Parkinson's disease, antibodies that could function as a diagnostic marker for the disease. Monitoring the levels of endogenous antibodies in patients' blood serum is simple and requires nothing more than a blood sample. This can become a method in clinical practice.

Ludmilla Morozova-Roche's research is conducted in collaboration with Lars Forsgren, professor of neurology at Umeå University and chief physician at Norrlands University Hospital in Umeå, who is directing the research program on early diagnostics and monitoring of Parkinson's patients. The findings indicate that autoimmunity may play a protective role in Parkinson's disease. Immune reactions to the disease's most significant amyloid-producing protein alpha synuclein may be of value in developing treatment strategies such as vaccination with amyloid antigens and antibodies, especially in the early stages of the disorder.

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Journal Reference:

1. Kiran Yanamandra, Marina A. Gruden, Vida Casaite, Rolandas Meskys, Lars Forsgren, Ludmilla A. Morozova-Roche. α-Synuclein Reactive Antibodies as Diagnostic Biomarkers in Blood Sera of Parkinson's Disease Patients. PLoS ONE, 2011; 6 (4): e18513 DOI: 10.1371/journal.pone.0018513

 Results of the first randomized, placebo-controlled long-term clinical trial show the investigational drug safinamide may reduce dyskinesia or involuntary movements in mid-to-late stage Parkinson's disease. The findings will be presented as late-breaking research at the 63rd Annual Meeting of the American Academy of Neurology, April 9-16, 2011, in Honolulu.

"Our findings over a two-year treatment period suggest that taking safinamide in addition to levodopa and other dopaminergic treatments could help patients who continue to experience tremors and involuntary movement problems," said study author Ravi Anand, MD, a consultant with Newron Pharmaceuticals in Bresso, Italy. "These results are an important step forward in understanding how safinamide impacts patients with severe Parkinson's disease. Symptoms of Parkinson`s disease, motor fluctuations and dyskinesia can greatly affect a person's daily living and quality of life."

For the two-year study, 669 patients with mid-to-late stage Parkinson's disease who were already taking levodopa and other dopaminergic treatments were given 50 or 100 milligrams of safinamide per day or a placebo pill. Scientists tested participant's movement ability using the United Parkinson's disease rating scale that measures activities such as tremor, speech, behavior, mood and daily activities including swallowing, dressing and walking. A specific tool measuring severity of dyskinesia (DRS) was used in addition as primary efficacy endpoint.

At the start of the study, patients who took the 50 milligram dose of safinamide had an average score of 3.9 compared to a score of 3.4 for those taking a placebo pill. Patients who took the 100 milligram dose had an average score of 3.7.

After two years, researchers discovered in a post-hoc analysis that safinamide at 100 milligrams a day on top of taking levodopa reduced dyskinesia, or movement problems, by 24 percent in the one-third of participants who had scored a four or higher on the dyskinesia rating scale at the beginning of the study compared to those taking a placebo. There were no significant differences for people who took the 50 milligram dose.

There were no significant differences in the primary efficacy measure (movement control, i.e., dyskinesia) scores in the overall population. Side effects were comparable among the three treatment groups.

The study was supported by Newron/Merck Serono S.A.-Geneva.

University of Utah School of Medicine researchers have found compelling evidence that Parkinson's disease is associated with an increased risk of prostate cancer and melanoma, and that this increased cancer risk also extends to close and distant relatives of individuals with Parkinson's disease. Although a link between Parkinson's disease and melanoma has been suspected before, this is the first time that an increased risk of prostate cancer has been reported in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurologic condition that leads to tremors and difficulty with walking, movement, and coordination. Most studies demonstrate that individuals with PD have an overall decreased rate of cancer, with the notable exception of melanoma, the most serious form of skin cancer. Previous research has suggested a possible genetic link between PD and melanoma, but these studies have been limited to first-degree relatives who often share a similar environment, making it difficult to distinguish between genetic and environmental risk factors.

"Neurodegenerative disorders such as Parkinson's disease may share common disease-causing mechanisms with some cancers," says Stefan-M. Pulst, MD, professor and chair of the department of neurology, at the University of Utah, and co-author on this study. "Using the Utah Population Database, we were able to explore the association of PD with different types of cancer by studying cancer risk in individuals with PD, as well as their close and distant relatives."

The Utah Population Database (UPDB) includes birth, death, and family relationship data for over 2.2 million individuals, including genealogy data from the original Utah pioneers. Some of the records in this computerized database extend back over 15 generations, making the UPDB a useful resource for studying genetic risk. The UPDB is also linked with the Utah Cancer Registry and Utah death certificates dating back to 1904.

"In Utah, we have the unique opportunity to evaluate the relationship between PD and certain cancers using a population-based approach that eliminates many of the typical types of bias associated with epidemiological studies," says Lisa Cannon-Albright, PhD, University of Utah professor of internal medicine and division chief of genetic epidemiology, and co-author of this study. "Rather than relying on patient interviews for family medical history, we were able to use the UPDB, along with statewide registries of cancer and death, to look for links between PD and cancer."

The study team, including Seth A. Kareus, MD, University of Utah chief resident of neurology and Karla P. Figueroa, MS., screened the UPDB to identify nearly 3000 individuals with at least three generations of genealogical data who had PD listed as their cause of death. The researchers discovered that the risk of prostate cancer and melanoma within this PD population was significantly higher than expected. They also observed an increased risk for prostate cancer and melanoma among first-, second-, and third-degree relatives of these individuals with PD, although the excess risk for melanoma in third-degree relatives did not reach statistical significance.

In order to validate the observed association between PD-related death and these two cancers, the researchers also identified individuals who were diagnosed with either melanoma or prostate cancer to evaluate their risk for death with PD. They found that these individuals, as well as all their relatives, had a significantly increased risk for death with PD.

"In our study, we not only identified an increased risk for prostate cancer and melanoma among individuals with PD and their relatives, but also established a reciprocal risk for PD among individuals with these two cancers and their relatives," says Pulst. "Collectively, these data strongly support a genetic association between PD and both prostate cancer and melanoma."

Interesting, Pulst and his colleagues noted that, while a decreased risk for lung cancer was observed among individuals with PD, this decrease in risk did not extend to any of their relatives. This finding suggests that environmental, rather than genetic, factors might be responsible for this association.

"Our findings point to the existence of underlying pathophysiologic changes that are common to PD, prostate cancer, and melanoma," says Cannon-Albright. "Exploring the precise genetic links among these diseases could improve our understanding of PD and influence strategies for prostate and skin cancer screening."

These findings will be presented at the American Academy of Neurology (AAN) 2011 Annual Meeting in Honolulu, HI.