Category: Parkinson’s

We all know that living a stressful lifestyle can take its toll, making us age faster and making us more susceptible to the cold going around the office.

The same appears to be true of neurons in the brain. According to a new Northwestern Medicine study published Nov. 10 in the journal Nature, dopamine-releasing neurons in a region of the brain called the substantia nigra lead a lifestyle that requires lots of energy, creating stress that could lead to the neurons' premature death. Their death causes Parkinson's disease.

"Why this small group of neurons dies in Parkinson's disease is the core question we struggled with," says lead author D. James Surmeier, the Nathan Smith Davis Professor and chair of physiology at Northwestern University Feinberg School of Medicine. "Our research provides a potential answer by showing this small group of neurons uses a metabolically expensive strategy to do its job. This 'lifestyle' choice stresses the neurons' mitochondria and elevates the production of superoxide and free radicals — molecules closely linked to aging, cellular dysfunction and death."

The good news is preclinical research shows this stress can be controlled with a drug already approved for human use. By preventing calcium entry, the drug isradipine reduced the mitochondrial stress in dopamine-releasing neurons to the levels seen in neurons not affected by the disease.

Northwestern Medicine scientists currently are conducting a clinical trial to find out if isradipine can be used safely and is tolerated by patients with Parkinson's. Isradipine is already approved by the Food and Drug Administration for treatment of high blood pressure.

Parkinson's disease is the second most common neurodegenerative disease in the United States, second only to Alzheimer's disease. The average age of diagnosis is near 60. More than 1 million Americans currently have Parkinson's disease, and this number is rising as the population ages. The symptoms of Parkinson's disease include rigidity, slowness of movement and tremors. No treatment currently is known to prevent or slow the progression of Parkinson's disease.

Although most cases of Parkinson's disease have no known genetic link, Surmeier's study in mice showed that the mitochondrial stress in dopamine-releasing neurons was worsened in a genetic model of early-onset Parkinson's disease, suggesting a similar mechanism in rare familial forms of the disease and the more common forms.

Everyone loses dopamine-releasing neurons with age, Surmeier noted. "By lowering their metabolic stress level, we should be able to make dopamine-releasing neurons live longer and delay the onset of Parkinson's disease," he said. "For individuals diagnosed with Parkinson's disease, the hope is that this drug can slow disease progression, giving symptomatic therapies a broader window in which to work."

The study was supported by the National Institutes of Health, United States Department of Defense, Thomas Hartman Foundation For Parkinson's Research, Inc., The Picower Foundation and Dr. Ralph and Marian Falk Medical Research Trust.

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Journal Reference:

1. Jaime N. Guzman, Javier Sanchez-Padilla, David Wokosin, Jyothisri Kondapalli, Ema Ilijic, Paul T. Schumacker, D. James Surmeier. Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature, 10 November 2010 DOI: 10.1038/nature09536

A team of scientists from Japan and the University of California, San Diego School of Medicine have created a new mouse model that confirms that mutations of a protein called beta-synuclein promote neurodegeneration. The discovery creates a potential new target for developing treatments of diseases like Parkinson's and Alzheimer's.

The work is published in Nature Communications. Lead author is Makoto Hashimoto of the Division of Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience, with colleagues including Eliezer Masliah, MD, professor of neurosciences and pathology in the UC San Diego School of Medicine, Edward Rockenstein, a research associate in UCSD's Experimental Neuropath Laboratory and Albert R. LaSpada, MD, PhD, professor of cellular and molecular medicine, chief of the Division of Genetics in the Department of Pediatrics and associate director of the Institute for Genomic Medicine at UC San Diego.

In 2004, LaSpada discovered mutations in a family afflicted with a neurological disorder known as Dementia with Lewy Bodies. DLB is one of the most common types of progressive dementia, combining features of both Alzheimer's and Parkinson's diseases. Lewy bodies are abnormal aggregates of proteins. There are no known therapies to stop or slow the DLB's progression. There is no cure.

In the 2004 study, LaSpada and colleagues found that mutations of the naturally occurring B-synuclein protein in DLB patients "were strong strongly suggestive of being pathogenic." That is, the mutated protein caused or was a cause of the disease. But the findings were not definitive.

The newly published research describes the creation of a transgenic mouse model that expresses the B-synuclein mutation. The mice suffer from neurodegenerative disease, validating LaSpada's earlier work.

"Beta-synuclein is interesting because it is closely related to alpha-synuclein, a protein that can cause Parkinson's disease by being mutated or over-expressed," said LaSpada. "A-synuclein is viewed as central to Parkinson's disease pathogenesis. The question has been: could B-synuclein also promote neurodegeneration because it's similar in its sequence and expression pattern to A-synuclein? This study shows that the answer is yes."

These findings, said LaSpada, establish B-synuclein's links to Parkinson's disease and related disorders, making it a new and, now, proven target for potential therapies.

Co-authors of the study are Masaya Fujita, Shuei Sugama, Kazunari Sekiyama, Akio Sekigawa, Masaaki Nakai, Masaaki Waragai, Yoshiki Takamatsu and Jianshe Wei of the Division of Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience; Tohru Tsukui of the Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University; Takato Takenouchi of the Division of Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience and the Transgenic Animal Research Center, National Institute of Agrobiological Sciences in Japan; and Satoshi Inoue of Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University and Department of Anti-Aging, Graduate School of Medicine, University of Tokyo.

Funding for this study came in part from grants by Science Research, the Cell Innovation Project; Challenging Exploratory Research, the National Institute of Biomedical Innovation, the Takeda Foundation, the Novartis Foundation for Gerontological Research and the National Institutes of Health.

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Journal Reference:

1. Masayo Fujita, Shuei Sugama, Kazunari Sekiyama, Akio Sekigawa, Tohru Tsukui, Masaaki Nakai, Masaaki Waragai, Takato Takenouchi, Yoshiki Takamatsu, Jianshe Wei, Edward Rockenstein, Albert R. LaSpada, Eliezer Masliah, Satoshi Inoue, Makoto Hashimoto. A β-synuclein mutation linked to dementia produces neurodegeneration when expressed in mouse brain. Nature Communications, 2010; 1 (8): 110 DOI: 10.1038/ncomms1101

Daily sleeping and eating patterns are critical to human well-being and health. Now, a new study from Concordia University has demonstrated how the brain chemical dopamine regulates these cycles by altering the activity of the "clock-protein" PER2.

Published in the Journal of Neuroscience, these findings may have implications for individuals with Parkinson's Disease with disrupted 24-hour rhythms of activity and sleep.

"PER2 is a protein well-known for its role in the regulation of daily or circadian rhythms, this is why it is referred to as a clock protein," says senior author, Shimon Amir, a psychology professor at the Concordia Center for Studies in Behavioral Neurobiology. "Many molecules, such as stress hormones are known to have an impact on the activity of PER2. Until now, the role of dopamine in regulating circadian rhythms has been unclear. Our findings show that not only is PER2 influenced by dopamine but also that dopamine is necessary for its rhythmic expression in specific brain regions."

Dopamine and Parkinson's

Parkinson's disease is caused by the degeneration of specific nerve cells, which results in a decrease in dopamine levels in the brain. Dopamine is critical for normal movements and balance and its decreased level results in instability and involuntary movements, the telltale symptoms of Parkinson's.

The findings from this Concordia study may explain the disruptions of daily behavioral and physiological rhythms that are also frequently reported in Parkinson's.

Rise in dopamine followed by rise in PER2

Amir and his colleagues studied the role of dopamine in rats. Their first steps were to show that PER2 is present in a specific brain area that normally receive dopamine, namely the dorsal striatum, and that it fluctuates daily in this area.

In this same region of the brain the research group demonstrated that a rise of dopamine preceded the rise in PER2 and that removing dopamine from the brain or blocking one of its receptors resulted in decreased PER2, which, in turn, could be reversed by the administration of a drug that mimics the action of dopamine on this receptor.

"Our findings are consistent with the idea that the rhythm of expression of PER2 depends on the daily activation by dopamine," says first author Suzanne Hood, a doctoral student at Concordia.

This study was funded by the Canadian Institutes of Health Research and the Fonds de la Recherche en Santé du Québec.

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Journal Reference:

1. Suzanne Hood, Pamela Cassidy, Marie-Pierre Cossette, Yuval Weigl, Michael Verwey, Barry Robinson, Jane Stewart, and Shimon Amir. Endogenous Dopamine Regulates the Rhythm of Expression of the Clock Protein PER2 in the Rat Dorsal Striatum via Daily Activation of D2 Dopamine Receptors. Journal of Neuroscience, 2010; DOI: 10.1523/JNEUROSCI.2128-10.2010

An international collaboration led by academics at the University of Sheffield has shed new light into Parkinson's disease. The research could help with the development of cures or treatments in the future.

The collaboration, which was led by Professor Peter Redgrave from the University's Department of Psychology, suggests that many of the problems suffered by patients with Parkinson's disease — difficulties in initiating actions, slow laboured movements and tremors — can be understood in terms of damage to control circuits in the brain responsible for habits.

The analysis, which is published online and will appear in the November issue of Nature Reviews Neuroscience, has involved combining the experience of an international team of clinical experts to explain why, paradoxically, removal of part of the brain can help sufferers of Parkinson's disease regain smooth initiation of movements.

An important processing unit in the brain (the basal ganglia) is part of two behavioural control circuits — habitual control, which directs our fast, stimulus-driven automatic, largely unconscious movements; and voluntary goal-directed control, which is driven by a conscious appreciation of the action's outcome. This means goal-directed movements are typically slower, require effort, and can only be done one at a time. Different regions of the basal ganglia are involved in goal-directed and habitual control. An important proposal in the Nature Reviews Neuroscience article is that Parkinson's disease is linked to a preferential loss of the neurotransmitter dopamine from the regions involved in habitual control.

Many of the symptoms of Parkinson's disease can therefore be understood in terms of a catastrophic loss of habits, which means patients have to rely on the goal-directed control system for everything they do. This idea can explain why their movements are slow, effortful and easily interrupted. For example, when approaching a narrow door or object, a patient with Parkinson's disease can suddenly freeze and find it difficult to start again. Under serial goal-directed control, (i.e. you can only think about doing one thing at a time), when the patient stops thinking about walking and starts to think about going through the door or avoiding the object, they stop walking.

The proposed analysis offers a further important insight into the symptoms of Parkinson's disease. At the level of the basal ganglia, the goal-directed and habitual control circuits are physically separated, but down-stream, they converge on shared motor systems (that is, we can do the same action either under goal-directed or habitual control). Numerous experiments show that the loss of dopamine from the basal ganglia increases inhibitory output from the habitual control circuits. Therefore, for a patient with Parkinson's disease to express goal-directed behaviour, they have to overcome the distorting inhibitory signals from the malfunctioning habitual control system. This provides a further reason for why patients find it so difficult to initiate and maintain actions and why their behaviour is so effortful and slow.

These ideas also offer a potential resolution of a continuing paradox in Parkinson's disease research — why destruction of the parts of the basal ganglia responsible for habits can have such a beneficial effect on Parkinson's disease. Professor Redgrave and his team propose that removal of the distorting inhibitory output from habitual control circuits could make it easier for goal-directed behaviour to be expressed.

It is hoped this new interpretation of Parkinson's disease will help in the discovery of new cures and treatment in the future for the 120,000 people in the UK suffering with the disease. Firstly, by directing attention to what makes the habitual basal ganglia particularly vulnerable, and secondly to parts of the brain where goal-directed behaviour is being disrupted by dysfunctional signals from the circuits responsible for habits.

Neuroscientist Professor Peter Redgrave from the University of Sheffield's Department of Psychology, said: "We hope our analysis provides a better understanding of the link between normal and abnormal functioning in the basal ganglia. This is important because the better your understanding of normal function, the better the questions you can ask about its failings, which hopefully, will direct you towards more effective treatments."

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Journal Reference:

1. Peter Redgrave, Manuel Rodriguez, Yoland Smith, Maria C. Rodriguez-Oroz, Stephane Lehericy, Hagai Bergman, Yves Agid, Mahlon R. DeLong, Jose A. Obeso. Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease. Nature Reviews Neuroscience, 2010; DOI: 10.1038/nrn2915

Alzheimer’s disease is not the only type of dementia. Two particular forms are dementia with Lewy bodies and Parkinson’s disease dementia. In both forms, the diagnosis is of vital importance because the treatment for these dementias differs from that for Alzheimer’s dementia, as Brit Mollenhauer and co-authors explain in the dementia theme issue of Deutsches Ärzteblatt International.

In more than 75% of patients, the memory impairments are due to Alzheimer’s disease. In Lewy body dementia, which is accompanied by cognitive and/or further psychiatric symptoms, and in Parkinson’s disease dementia, these develop only after the motor symptoms of the disorder have fully developed.

Gerhard Eschweiler and co-authors in their article introduce biomarkers that raise the probability of identifying Alzheimer’s disease at the stage of mild cognitive impairment and up to five years before full-blown dementia to 80%.

Richard Mahlberg in an introductory editorial emphasizes that the attempts to find an exact differential diagnosis are not merely academic exercises, but that new developments of diagnosis-specific, differentiated interventions for the future depend crucially on a correct initial diagnosis.

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Journal Reference:

1. Lewy Body and Parkinsonian Dementia Common, but Often Misdiagnosed Conditions. Brit Mollenhauer, Hans Förstl, Günther Deuschl, Alexander Storch, Wolfgang Oertel, Claudia Trenkwalder. Dtsch Arztebl Int, 2010; 107[39]: 684-91 [link]

Since the late 1990s, deep brain stimulation (DBS) has proven to be a lifeline for some patients suffering from Parkinson's disease, a cruel neurological disorder that can cause lack of control over movement, poor balance and coordination, and rigidity, among other symptoms.

The procedure is used only for patients whose symptoms cannot be adequately controlled with medications. A neurosurgeon uses magnetic resonance imaging or computed tomography to identify the exact target within the brain where abnormal electrical nerve signals generate the disease's tremors and other symptoms, and a neurostimulator is then surgically implanted to deliver electrical stimulation to that area to block the signals.

The goal, ultimately, is to improve the patient's quality of life.

Yet despite its effectiveness, there has been no consensus on several aspects of the use DBS, including which patients make the best candidates, where the optimal location for the placement of electrodes is, and the role that still exists for surgical removal of the damaged areas of the brain.

To address these concerns, a more than 50 DBS experts — including world-renowned neurologists, clinicians and surgeons — pooled their experience with the procedure and reached a consensus. The goal of this "meeting of the minds" was to better inform Parkinson's patients and their families about the potential of DBS treatment and to better inform the medical community in suggesting the procedure.

The results of their April 2009 meeting are presented in the current online edition of the journal Archives of Neurology.

"We know that very little accessible information is out there to help a Parkinson's patient make an informed decision as to whether he or she would be a good candidate for deep brain stimulation," said Jeff Bronstein, a UCLA professor of neurology and lead author of the report.

Surgical trials take a long time, he said, and what information is available on DBS appears in academic journals, is focused and limited, and is usually written by one group reflecting their biases.

Bronstein, who directs the UCLA Movement Disorder Program and is a member of the UCLA Brain Research Institute, said the results of the group's meeting will help clarify some of the issues about DBS treatment. Among their findings:

• The best candidates for DBS are those who can't tolerate the side effects of medications, who don't suffer from significant active cognitive or psychiatric problems, and who do suffer from tremors and/or motor fluctuations.
• DBS surgery is best performed by an experienced team and neurosurgeon with expertise in stereotactic neurosurgery — microsurgery deep within the brain that is based on a three-dimensional coordinate system using advanced neuroimaging.
• DBS, when used in the two most commonly treated areas of the brain — the subthalamic nuclei and the globus pallidus pars interna — is effective in addressing the motor symptoms of Parkinson's, but treatment in the subthalamic nuclei may cause increased depression and other symptoms in some patients.
• Surgical removal of the area of the brain causing Parkinson's disease is still an effective alternative and should be considered in patients.
• Surgical complication rates vary widely, with infection being the most commonly reported complication of DBS.

The study was supported primarily by the Parkinson Alliance, the Davis Phinney Foundation, National Parkinson's Disease Foundation, and the Lee Silverman Voice Treatment Foundation.

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Journal Reference:

1. J. M. Bronstein, M. Tagliati, R. L. Alterman, A. M. Lozano, J. Volkmann, A. Stefani, F. B. Horak, M. S. Okun, K. D. Foote, P. Krack, R. Pahwa, J. M. Henderson, M. I. Hariz, R. A. Bakay, A. Rezai, W. J. Marks, E. Moro, J. L. Vitek, F. M. Weaver, R. E. Gross, M. R. DeLong. Deep Brain Stimulation for Parkinson Disease: An Expert Consensus and Review of Key Issues. Archives of Neurology, 2010; DOI: 10.1001/archneurol.2010.260

 In a study that sheds new light on the causes of Parkinson's disease, researchers report that brain cells in Parkinson's patients abandon their energy-producing machinery, the mitochondria. A shutdown in fuel can have devastating effects on brain cells, which consume roughly 20 percent of the body's energy despite making up only 2 percent of body weight.

The findings indicate that boosting the mitochondria with FDA approved drugs early on may prevent or delay the onset of Parkinson's. The study will be published in the one-year anniversary issue of the journal Science Translational Medicine, on Oct. 6, 2010. Science Translational Medicine is published by AAAS, the nonprofit science society.

Affecting roughly 5 million people worldwide, Parkinson's disease is a relentless condition that starts killing dopamine neurons in the brain many years before the onset of hallmark symptoms like tremors, muscle rigidity and slow movements. Thus, much-needed drugs to slow or halt the disease would have the greatest benefit for patients if they are given early on, before too many dopamine neurons die.

Clemens Scherzer from Brigham and Women's Hospital and Harvard Medical School, along with an international team of researchers, now show that a root cause of Parkinson's disease may lie in 10 gene sets related to energy production that spur neurons in the brain to "divorce" their mitochondria and related energy-producing pathways.

These gene sets are controlled by a master regulator–the PGC-1alpha gene. Moreover, abnormal expression of these genes likely occurs during the initial stages of Parkinson's disease, long before the onset of symptoms, the study shows. Targeting PGC-1alpha may thus be an effective way to slow down or halt the earliest stages of Parkinson's, staving off permanent damage and neuronal loss.

"The most exciting result from our study for me is the discovery of PGC-1alpha as a new therapeutic target for early intervention in Parkinson's disease. PGC-1alpha is a master switch that activates hundreds of mitochondrial genes, including many of those needed to maintain and repair the power plants in the mitochondria," Scherzer said.

FDA-approved medications that activate that PGC-1alpha are already available for widespread diseases like diabetes. These medications may jumpstart the development of new Parkinson's drugs; instead of having to start from scratch, pharmaceutical companies may be able to dust off their drug libraries and find look-alike drugs capable of targeting PGC-1alpha in the brain.

"As we wrap up our first year of publishing the journal, the new study from Zheng et al. exemplifies the goal of Science Translational Medicine, applying knowledge and technology from different fields-such as neuroscience, genomics and bioinformatics-to achieve new discoveries," said Editor Katrina Kelner.

Previous studies have linked defects in mitochondrial activity to Parkinson's disease, but they generally have not provided such a comprehensive, specific set of genes as Scherzer and colleagues now report. The researchers analyzed a part of the brain called the substantia nigra in 185 tissue samples from deceased Parkinson's patients.

The substantia nigra (Latin for "black substance") contains dopamine-producing neurons. Scherzer and colleagues used a laser beam to precisely cut out the dopamine neurons that are abnormal in Parkinson's. Next, the team looked at gene activity in these dopamine neurons and identified gene sets–groups of genes involved in one biological process–that are associated with Parkinson's disease. At the end of this tour-de-force analysis, 10 gene sets linked to Parkinson's emerged. All of these gene sets had a common thread — the master regulator gene PGC-1alpha.

The 10 gene sets encode proteins responsible for cellular processes related to mitochondrial function and energy production. Suppressing these genes is likely to severely damage components required for brain energy metabolism. One of these components is the electron transport chain; a set of reactions controlled by mitochondria that generates the energy cells need to function. Other studies have hinted that one of the five complexes making up the electron transport chain malfunctions in Parkinson's. Yet, Scherzer and colleagues found that not just one, but virtually all of the components needed by mitochondria to build the electron transport chain are deficient.

Why would the brain, being so highly energy dependent, abandon its entire energy-producing apparatus? That seems to be the core mystery of Parkinson's disease. Some think that mitochondrial activity may be affected by a combination of genes and the environment.

"I believe that environmental chemicals, risk genes, and aging–each having a small effect when taken separately–in combination may lead to the pervasive electron transport chain deficit we found in common Parkinson's disease and to which dopamine neurons might be intrinsically more susceptible," said senior author Clemens Scherzer, Assistant Professor of Neurology at Harvard Medical School.

Science Translational Medicine launched October 7 2009, as new journal in the Science family of journals intended to help speed basic research advances into clinics and hospitals. Serving scientists from academia and industry, as well as doctors, regulators and policy-makers, the journal aims to help researchers more efficiently access and apply new findings from many different fields.

This study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Aging (NIA), the Maximillian E. & Marion O. Hoffman Foundation, the RJG Foundation and the Michael J. Fox Foundation.

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Journal Reference:

1. B. Zheng, Z. Liao, J. J. Locascio, K. A. Lesniak, S. S. Roderick, M. L. Watt, A. C. Eklund, Y. Zhang-James, P. D. Kim, M. A. Hauser, E. Grunblatt, L. B. Moran, S. A. Mandel, P. Riederer, R. M. Miller, H. J. Federoff, U. Wullner, S. Papapetropoulos, M. B. Youdim, I. Cantuti-Castelvetri, A. B. Young, J. M. Vance, R. L. Davis, J. C. Hedreen, C. H. Adler, T. G. Beach, M. B. Graeber, F. A. Middleton, J.-C. Rochet, C. R. Scherzer. PGC-1α, A Potential Therapeutic Target for Early Intervention in Parkinson's Disease. Science Translational Medicine, 2010; 2 (52): 52ra73 DOI: 10.1126/scitranslmed.3001059

New research shows how old people are when they first develop Parkinson's disease is one of many clues in how long they'll survive with the disease. The research is published in the October 5, 2010, print issue of Neurology®, the medical journal of the American Academy of Neurology.

The 12-year study included 230 people with Parkinson's disease, of whom 211 died by the end of the research. "Remarkably, time to death for these people took anywhere from two to 37 years from diagnosis so it's important we try to identify those risk factors that lead to an early death so we can find ways to increase a person's life expectancy," said Elin Bjelland Forsaa, MD, with Stavanger University Hospital in Norway and a member of the American Academy of Neurology.

The average time from the appearance of movement problems to death was 16 years. The average age at death was 81.

The study found that the risk of earlier death was increased about 1.4 times for every 10-year increase in age when symptoms began. People with psychotic symptoms, such as delusions and hallucinations, were also 1.5 times more likely to die sooner compared to those without these symptoms.

The odds of dying earlier were nearly two times higher for people who had symptoms of dementia in the study compared to those without memory problems. In addition, men were 1.6 times more likely to die earlier from the disease compared to women. Participants who scored worst on movement tests also had a higher risk of earlier death compared to those with the highest scores.

"Our findings suggest that treatments to prevent or delay the progression of movement problems, psychosis and dementia in people with Parkinson's disease could help people live longer," said Forsaa.

The study also found that taking antipsychotic drugs or drugs for Parkinson's disease had no negative effect on survival.

It is estimated that about one million people in the United States have Parkinson's disease.

Walking and talking at the same time can put people with Parkinson's disease at risk for injurious falls.

A new Florida State University study found that older adults with Parkinson's disease altered their gait — stride length, step velocity and the time they spent stabilizing on two feet — when asked to perform increasingly difficult verbal tasks while walking. But the real surprise was that even older adults without a neurological impairment demonstrated similar difficulties walking and talking.

A disruption in gait could place Parkinson's patients and the elderly at an increased risk of falls, according to the Florida State researchers.

Francis Eppes Professor of Communication Science and Disorders Leonard L. LaPointe and co-authors Julie A.G. Stierwalt, associate professor in the School of Communication Science and Disorders, and Charles G. Maitland, professor of neurology in the College of Medicine, outlined their findings in "Talking while walking: Cognitive loading and injurious falls in Parkinson's disease." The study will be published in the October issue of the International Journal of Speech-Language Pathology.

"These results suggest that it might be prudent for health care professionals and caregivers to alter expectations and monitor cognitive-linguistic demands placed on these individuals while they are walking, particularly during increased risk situations such as descending stairs, in low-light conditions or avoiding obstructions," LaPointe said.

In other words, don't ask an elderly person or someone with Parkinson's to give directions or provide a thoughtful response to a complicated question while walking.

"One of the most common dual tasks performed is talking while walking," the researchers wrote. "In isolation, neither talking nor walking would be considered difficult to perform, yet when coupled, the relative ease of each task may change."

Twenty-five individuals with Parkinson's disease — six women and 19 men — participated in the study. The mean age of participants was 67.4 years. Thirteen people who matched in age and education but without a reported history of neurological impairment made up the control group.

The researchers used the GAITRite Portable Walkway System, a 14-foot mat containing 13,824 sensors that measures, interprets and records gait data as participants walk on it. After establishing a baseline, the participants were asked to walk while completing a "low load" task, counting by ones; a "mid load" task, serial subtraction of threes; and a "high load" task, continuation of an alpha numeric sequence, such as D-7, E-8, F-9, etc.

While there were no significant differences between the two groups in stride length and step velocity, members if the control group significantly increased the time they spent stabilizing on two feet from the low load to high load tasks. The researchers theorized that the control group used the "double support time" as a compensatory strategy to gain greater control of gait and balance. The Parkinson's group did not use this strategy and therefore placed themselves at greater risk for falls, they said.

Among older adults, falls are the leading cause of injury deaths, according to the Center for Disease Prevention and Control. They are also the most common cause of non-fatal-injuries and hospital admissions for trauma.

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Journal Reference:

1. Leonard L. LaPointe, Julie A. G. Stierwalt, Charles G. Maitland. Talking while walking: Cognitive loading and injurious falls in Parkinson's disease. International Journal of Speech-Language Pathology, 2010; 12 (5): 455 DOI: 10.3109/17549507.2010.486446

 A protein linked to Parkinson's disease may cause neurodegeneration by inhibiting autophagy — the process in which cells digest some of their contents — according to a study in the September 20 issue of the Journal of Cell Biology.

Autophagy serves to clear a variety of toxic waste from cells, including misfolded proteins and defective mitochondria. These two types of cellular trash accumulate in neurons from Parkinson's patients, suggesting that autophagy could be impaired in these cells. A commonly amassed protein in Parkinson's disease is alpha-synuclein, whose gene is often mutated or overexpressed in familial forms of the illness. David Rubinsztein and researchers from the University of Cambridge in England found that excess alpha-synuclein inhibits autophagy by blocking formation of the autophagosome — the double-membraned vesicle that engulfs cytoplasmic garbage and delivers it to lysosomes for destruction.

Previous research revealed that alpha-synuclein inhibits Rab1a, a small GTPase that controls secretory transport from the Endoplasmic Reticulum to the Golgi. Rubinsztein and colleagues now provide new insight into the role Rab1a plays in autophagy, and why blocking it has such dire consequences. The team found that lack of Rab1a impaired autophagosome formation, whereas an abundance of the GTPase reversed the inhibitory effects of alpha-synuclein on autophagy. Rab1a and alpha-synuclein act specifically at an early stage of autophagosome formation: an abundance of alpha-synuclein or lack of Rab1a disrupted an early acting part of the autophagy machinery called Atg9 and blocked the formation of autophagosome precursors known as omegasomes.

Alpha-synuclein's blockade of autophagy could enhance the gradual accumulation of toxic proteins and dysfunctional mitochondria, sensitizing neurons to cell death.

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Journal Reference:

1. A. R. Winslow, C.-W. Chen, S. Corrochano, A. Acevedo-Arozena, D. E. Gordon, A. A. Peden, M. Lichtenberg, F. M. Menzies, B. Ravikumar, S. Imarisio, S. Brown, C. J. O'Kane, D. C. Rubinsztein.  -Synuclein impairs macroautophagy: implications for Parkinson's disease. The Journal of Cell Biology, 2010; 190 (6): 1023 DOI: 10.1083/jcb.201003122