Findings point to dopamine replacement therapy causing dysfunction in specific areas of the brain
People with Parkinson’s Disease are more likely to display abnormal social behaviour and make poor decisions in ambiguous circumstances if they are pathological gamblers, according to research in the January issue of the European Journal of Neurology.
A number of studies have already associated pathological gambling with Parkinson’s, suggesting that it is a frequent impulse control disorder associated mainly with dopamine replacement therapy.
Researchers from the Raul Carrea Institute for Neurological Research (FLENI) in Buenos Aires, Argentina, interviewed the immediate relatives of seven Parkinson’s patients who were pathological gamblers. They also interviewed the families of 13 patients – matched by age, sex, education and disease severity – who did not gamble.
They found that the gamblers were less co-operative with others, had difficulties making or keeping close relationships and often did what they wanted, without caring what other people thought.
The researchers also found that the patients in the pathological gambling group performed worse in the Iowa Gambling Task, which is used to assess decision-making abilities in ambiguous or risky situations.
“The object of this study was to assess decision-making processes in Parkinson’s Disease patients with and without pathological gambling by asking them and their relatives to take part in a series of tests” says Dr Ramon Leiguarda, an expert in cognitive neurology.
“We found that the patients in the pathological gambling group were more likely to make poor decisions and select disadvantageous alternatives more frequently than advantageous alternatives.”
The combination of poor decision-making and abnormal social behaviour has led the team to conclude that dopamine replacement therapy can induce dysfunction in the areas of the brain that control affective decision making – the ventromedial pre-frontal cortex and amygdala-ventral striatum system.
Six of the seven pathological gamblers who took part in the study were male. At the time of the study they had an average age of 61 and their average age at diagnosis was 52.
Six of the patients had no history of gambling before developing Parkinson’s Disease. One patient had played poker with friends for 30 years, but his gambling behaviour exacerbated after starting dopamine replacement therapy and now included roulette and horse racing.
The other six participants said that their preferred type of gambling was slot machines.
Four of the seven displayed other impulse control disorders – two were also compulsive shoppers and two displayed hypersexuality.
“We believe that the behaviour highlighted in our study, combined with previous research into the links between Parkinson’s Disease and pathological gambling, point to dopamine replacement therapy causing dysfunction in specific areas of the brain” says Dr Leiguarda.
“Further studies that assess Parkinson’s Disease patients recovering from pathological gambling are needed to better understand the physiopathology of this impulse control disorder.”
For more information go to www.parkinsonresearchfoundation.org
Wednesday, January 20, 2010
Monday, January 11, 2010
Small molecules 'protect cells in Parkinson's disease models'
Parkinson's disease could be fought with small molecules, new research suggests.
A number of structurally-similar small molecules appear to be able to protect cells from alpha-synuclein toxicity in several instances of Parkinson's disease, new research has concluded.
Susan Lundquist and her team at the Whitehead Institute used a form of brewers' yeast injected with several compounds and found that it was able to fight off Parkinson's disease-like cells.
Daniel Tardiff, a post-doctoral researcher with Ms Lindquist, said that theoretically speaking, if a compound is having a beneficial effect on yeast cells, in a worm and in primary neurons, it might "actually be a potential therapeutic avenue or drug".
He continued: "Though we started in yeast, one of those compounds could actually have some potential for human health in Parkinson's disease. That's always a lofty goal."
The upcoming World Parkinson Congress will be held in Glasgow from September 28th to October 1st 2010 and will provide an international forum for the latest medical practices, scientific discoveries and carers' initiatives related to Parkinson's disease.
For more information go to www.parkinsonresearchfoundation.org
A number of structurally-similar small molecules appear to be able to protect cells from alpha-synuclein toxicity in several instances of Parkinson's disease, new research has concluded.
Susan Lundquist and her team at the Whitehead Institute used a form of brewers' yeast injected with several compounds and found that it was able to fight off Parkinson's disease-like cells.
Daniel Tardiff, a post-doctoral researcher with Ms Lindquist, said that theoretically speaking, if a compound is having a beneficial effect on yeast cells, in a worm and in primary neurons, it might "actually be a potential therapeutic avenue or drug".
He continued: "Though we started in yeast, one of those compounds could actually have some potential for human health in Parkinson's disease. That's always a lofty goal."
The upcoming World Parkinson Congress will be held in Glasgow from September 28th to October 1st 2010 and will provide an international forum for the latest medical practices, scientific discoveries and carers' initiatives related to Parkinson's disease.
For more information go to www.parkinsonresearchfoundation.org
Monday, January 4, 2010
Despite Earlier Doubts, Feinstein Study Shows Fetal Transplants May Benefit Parkinson’s Patients Over Age 60
Fetal transplant surgery for Parkinson’s disease went on experimentally for more than a decade before it was put to the ultimate test in a double-blind, randomized study. It turned out that only patients under 60-years-old showed any benefit, but some also developed uncontrolled jerking movements that washed away hope for the technique. The findings were the death knell for the promising procedure.
But scientists involved with brain imaging studies of the fetal transplant recipients did not put away their study tools. In fact, they kept bringing the Parkinson’s patients back into the laboratory to take snapshots of their brains over time. And what they have now found, and reported in the latest issue of The Journal of Nuclear Medicine (JNM), is that people over age 60 began to show improvements more than a year after fetal dopamine cells were infused into the brain region damaged by Parkinson’s.
“This was totally surprising,” said David Eidelberg, MD, director of the Center for Neurosciences at The Feinstein Institute for Medical Research in Manhasset, NY. “The use of fetal transplantation for Parkinson’s encountered a good deal of skepticism after five patients in the study (all under age 60) developed dyskinesias.”
Dr. Eidelberg said that the Parkinson’s community basically forgot about the research and turned their attention to other promising techniques.
There were 33 patients, 13 of whom were over age 60 when the cells were infused into their brains. It was a double-blinded study so that 19 patients received the fetal cells and 14 others had a sham surgery and were offered the fetal cell transplant a year later. But by that time, the word had come out about the devastating side effect (the dyskinesias) and some older people opted out of the second surgery.
The Feinstein researchers have now looked at the brains of the transplanted patients two years and four years after the initial infusion of fetal cells. And they learned a few things: Beyond the first five people who developed dyskinesia, none of the other 15 younger people in the study showed signs of the troubling side effect. In about 25 percent of the cases, clinical improvement was noted and the transplanted cells were still working to make the dopamine up to four years later.
They also discovered that the older people gradually got better after the first year and that their improvements continued over the long term. “The older the brain, the harder it is to integrate the graft,” said Dr. Eidelberg. “But the PET scans told us that the graft was viable. And it took awhile before the cells worked to improve symptoms.”
The Feinstein group has identified two different brain networks hard hit in the disease. One is obvious: the motor regions that, when damaged, lead to tremors, rigidity and difficulty initiating movement. The other piece relates to cognition and mood, and there are discrete brain regions that worsen over time. In this study, researchers found that people did better overall on motor functions if they entered the study with their putamen intact – putamen is an area of the brain that governs cognition and mood. Dopamine is the key brain chemical in both these networks and it is critical for motor planning. When dementia sets in, people may have improvements in the motor network, but it isn’t observable because their cognitive network is abnormal and their ability to make plans to move is impaired.
The good news, said Dr. Eidelberg, is that the grafts stayed where they were and delivered dopamine to the tissue. The finding is critical as the field moves to transplant other types of cells, including embryonic stem cells or their ultimate product.
For more information go to www.parkinsonresearchfoundation.org
But scientists involved with brain imaging studies of the fetal transplant recipients did not put away their study tools. In fact, they kept bringing the Parkinson’s patients back into the laboratory to take snapshots of their brains over time. And what they have now found, and reported in the latest issue of The Journal of Nuclear Medicine (JNM), is that people over age 60 began to show improvements more than a year after fetal dopamine cells were infused into the brain region damaged by Parkinson’s.
“This was totally surprising,” said David Eidelberg, MD, director of the Center for Neurosciences at The Feinstein Institute for Medical Research in Manhasset, NY. “The use of fetal transplantation for Parkinson’s encountered a good deal of skepticism after five patients in the study (all under age 60) developed dyskinesias.”
Dr. Eidelberg said that the Parkinson’s community basically forgot about the research and turned their attention to other promising techniques.
There were 33 patients, 13 of whom were over age 60 when the cells were infused into their brains. It was a double-blinded study so that 19 patients received the fetal cells and 14 others had a sham surgery and were offered the fetal cell transplant a year later. But by that time, the word had come out about the devastating side effect (the dyskinesias) and some older people opted out of the second surgery.
The Feinstein researchers have now looked at the brains of the transplanted patients two years and four years after the initial infusion of fetal cells. And they learned a few things: Beyond the first five people who developed dyskinesia, none of the other 15 younger people in the study showed signs of the troubling side effect. In about 25 percent of the cases, clinical improvement was noted and the transplanted cells were still working to make the dopamine up to four years later.
They also discovered that the older people gradually got better after the first year and that their improvements continued over the long term. “The older the brain, the harder it is to integrate the graft,” said Dr. Eidelberg. “But the PET scans told us that the graft was viable. And it took awhile before the cells worked to improve symptoms.”
The Feinstein group has identified two different brain networks hard hit in the disease. One is obvious: the motor regions that, when damaged, lead to tremors, rigidity and difficulty initiating movement. The other piece relates to cognition and mood, and there are discrete brain regions that worsen over time. In this study, researchers found that people did better overall on motor functions if they entered the study with their putamen intact – putamen is an area of the brain that governs cognition and mood. Dopamine is the key brain chemical in both these networks and it is critical for motor planning. When dementia sets in, people may have improvements in the motor network, but it isn’t observable because their cognitive network is abnormal and their ability to make plans to move is impaired.
The good news, said Dr. Eidelberg, is that the grafts stayed where they were and delivered dopamine to the tissue. The finding is critical as the field moves to transplant other types of cells, including embryonic stem cells or their ultimate product.
For more information go to www.parkinsonresearchfoundation.org
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