Studies reveal severe diabetes worsens Parkinson's symptoms

A pair of studies from the Perelman School of Medicine at the University of Pennsylvania demonstrate a correlation between diabetes severity and parkinsonism, or parkinsonian tremors; and examine the caregiving differences between men and women with PD.

26 april 2015--The findings will be presented this week at the American Academy of Neurology's 67th Annual Meeting in Washington, D.C.

Diabetes Severity is Associated with Worse Parkinsonism

The study enrolled 1,100 subjects over the age of 55 without Parkinson's disease or dementia from the existing Philadelphia Healthy Bran Aging cohort at the University of Pennsylvania. At baseline testing, 34 percent of subjects were found to have diabetes. A Hemoglobin A1c glucose test was performed and a diabetes severity score created that combined the presence of retinopathy, neuropathy, nephropathy and insulin dependence.

Subjects were then assessed for parkinsonian signs and cognitive impairment. The median hemoglobin A1c was 6.6 (less than 6.5 is ideal in most cases) and the median parkinsonism score was 8.3 (anything above zero is abnormal).

Higher parkinsonian scores were associated with greater diabetes severity, older age, African-American race and a past history of arthritis. Further analysis showed diabetes severity remained significantly associated with higher parkinsonian sign scores.

"Our study was based on emerging evidence that the presence of diabetes may increase the risk of both Parkinson's disease and specific motor features in parkinsonism," said Nabila Dahodwala, MD, an assistant professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania and director of the National Parkinson Foundation Center of Excellence at the Parkinson's Disease and Movement Disorders Center at Pennsylvania Hospital.

"We hypothesize that the high burden of cardiovascular risk from diabetes contributes to brain injury, which can impact cognition and parkinsonism," explains Dahodwala. Further studies are needed to show causality between diabetes and parksonism. These could indicate that aggressive management of diabetes could provide additional motor benefit.

This work was funded by the Parkinson Council, NIA K23 AG034236 and P30 AG031043 and Penn Minority Aging Research for Community Health (MARCH).

Sex Differences in Parkinson's Disease Caregiving

Researchers looked at caregiving patterns among PD patients to determine if there are sex differences in caregiver accompaniment to visits, paid caregiving and caregiving strain and found that women with PD have fewer informal caregiving resources and are more likely to use formal, paid caregiving.

"Parkinson's patients rely on formal and informal caregiver support as the disease worsens," Dahodwala said. Previous research has shown that there is a higher incidence of Parkinson's disease among men, but little is known about caregiving patterns by sex.

Dahodwala and her team collected information on each of 4,718 men and 2,788 women in the National Parkinson Foundation Parkinson's Outcomes Project's medication, disease duration as well as caregiver presence and the caregiver type, time to first paid caregiver and more.

Their analysis showed that compared with women, men were significantly more likely to have a regular care partner (88 versus 80 percent), but less likely to have a paid caregiver at baseline than women (2.2 versus 4.9 percent). In addition, women were found to have lower odds of caregiver accompaniment at baseline visit, but faster time to first paid caregiver. Caregiver strain was found to be higher among caregivers of male subjects.

"We hope that this study spurs some of the key stakeholders in PD to develop policies that ensure adequate support for women with the disease. Our analysis shows there is a real need for it," Dahodwala said.

More information: "Diabetes severity is associated with worse Parkinsonism." (P4.148). www.neurology.org/content/84/1… plement/P4.148.short

"Sex Differences in Parkinson's Disease Caregiving." (S48.003). www.neurology.org/content/84/1… /S48.003.short?rss=1

Provided by University of Pennsylvania School of Medicine

Turning back the clock on Parkinson's

David Higgins was diagnosed with Parkinson's disease years after his initial symptoms appeared. Credit: Ryan Parks/UC San Diego Health Sciences

18 april 2015--Like many young people, David Higgins was initially in denial about the possibility of having a serious, lifelong disease.

"My friends would say, 'You walk funny," and I'd say, 'I have a stiff back,'' recalled Higgins, now 57. "Parkinson's was the last thing on my mind," he said, or on the mind of his doctor at the time, who had him tested for cardiovascular disease, brain cancer and stroke.

"There was a lot of rationalizing and denial on my part," said Higgins even though his mother, maternal grandmother and an uncle all died of Parkinson's disease, a group of progressive motor system disorders that affect as many as 1 million Americans.

Eventually, after several years, Higgins' worsening condition was impossible to ignore. "I went out for a run one day and it felt like I was moving through mud. I knew I had to do something."

That something was a life-changing consultation with Dr. Irene Litvan, the Tasch Endowed Professor in Parkinson's Disease Research and director of the Movement Disorder Center at UC San Diego Health System.

"Dr. Litvan diagnosed me in 2.5 seconds," Higgins said. "At the exact precise moment she said 'You have Parkinson's,' there was relief. Adversity is less troubling than ambiguity."

That moment occurred on Dec. 5, 2011.

Higgins was Litvan's first patient on her first day of clinical work at UC San Diego.

Center for Excellence

Since then, under her leadership, the Movement Disorder Center has grown and blossomed. In February, the center's outstanding track record in comprehensive patient care, research and education was formally recognized by other leaders in the field through its designation as a Center for Excellence by the National Parkinson Foundation.

There are only 25 Centers of Excellence for Parkinson's in the United States; 16 internationally.

Peter Schmidt, vice president of research and professional programs at the Parkinson Foundation, characterized the designation as reflecting a shared vision "for the integrated research and care enterprise, where patient-focused clinicians deliver the latest care and newest therapies."

"Their clinic benefits from research into novel approaches that advance our knowledge and their research agenda reflects the priorities of patients and families," he said.

Higgins puts it this way: "I know good people attract good people. The Center of Excellence will bring in smarter and better researchers to whom I will have access. I know I will have immediate, early access to any innovations that come about, and I have Dr. Litvan to filter out which new treatments are most substantiated and relevant to me. It means I get the best care possible."

Target: early diagnosis

Parkinson's disease—the disease that actor Michael J. Fox has—is a chronic, progressive neurological disorder, characterized by tell-tale tremors, stiffness and other declines in motor control. Loss of motor function is caused by degeneration of neurons that produce the chemical messenger dopamine. Classic Parkinson's disease symptoms usually begin when 50 to 80 percent of these dopamine neurons have died.

The Holy Grail of many progressive, currently incurable, diseases—including Parkinson's—is to be able to diagnose the disease in its earliest stages and halt its progression before damage has been done. Among the more intriguing discoveries made about Parkinson's in recent years is that some of its earliest signs may be unrelated to declines in motor skills. Loss of smell, constipation, depression and dream-enacting behaviors, for example, often precede more identifiable Parkinson's symptoms.

"The definition of Parkinson's disease is presently being refined," said Litvan, who is a member of the International Parkinson and Movement Disorder Task Force working on this re-definition. "One of the advantages of being treated at a Center of Excellence such as ours is that the professionals who evaluate patients also participate in research and are up-to-date on the latest diagnostic methods, technology and treatment options for Parkinson's disease and related disorders.

New developments

UC San Diego is one of only a few centers in the nation conducting research on a PET scan that detects deposits of a protein called tau that aggregates in the brain of patients with a related Parkinsonian disorder called progressive supranuclear palsy (PSP). "The PET scan may allow us to make an accurate diagnosis of this disorder in vivo," Litvan said. "This could help us properly manage the person's condition and identify people who would be most likely to benefit from investigational therapies."

There is also a growing interest in identifying biomarkers in blood that could inexpensively and non-invasively diagnose different neurodegenerative disorders at their most incipient stages.

Another promising development is evidence suggesting that Parkinson's may spread from one neuron to its neighbors by aggregations of a protein called alpha-synuclein. If this is the case, capturing and removing the aggregations before they affect neighboring cells might slow or halt the progression of the disease. "I am very excited about this area of research," Litvan said.

Litvan is also involved in a phase 3, double-blind placebo-controlled study of a calcium channel blocker use to treat high blood pressure. In animal studies, the drug, called isradapine, blocks specific calcium channels that increase before dopamine-producing neurons die. "We hope what is observed in animals will also occur in humans," she said.

Since 2011, Higgins has gone on medications and embraced a physical therapy regime at the Movement Disorder Center that has virtually erased any outward signs of illness. He has also become a full-time patient advocate for Parkinson's and was recently in Washington, D.C. lobbying officials to appropriate more funding for Parkinson's disease research.

"People see me and they ask why I am here," he said. "They can't tell I have Parkinson's. I am here because I believe that institutions like UC San Diego and science in general are our hope for new therapies and cures."

Provided by University of California - San Diego

New study links depression in newly diagnosed Parkinson's disease patients to reduced striatal dopamine synthesis

According to the Parkinson's Disease Foundation, up to 60% of individuals with Parkinson's disease (PD) exhibit mild to moderate depression, which is often underdiagnosed. It is unclear whether depression results from having a debilitating disease or reflects a parallel abnormal change in the brain caused by PD pathophysiology.

10 oct 2013--One hypothesis is that depression in PD may reflect impaired striatal dopamine function, but previous investigations have produced contradictory results. By scanning the brains of newly diagnosed patients not yet taking PD medications, Finnish investigators have shown that the level of depression is inversely related to the ability to synthesize dopamine in the striatum and the effect is seen only in the left striatum. Their results are published in the latest issue of the Journal of Parkinson's Disease.

Depression in Parkinson's patients can reduce quality of life and impede daily activities, and those with depressive symptoms tend to begin medications for motor symptoms earlier than those who are not depressed. Treating depression can improve both quality of life and movement, and medications such as dopamine agonists have antidepressant effects in PD patients.

In the current report, investigators used 18fluorodopa PET scans to look at two different groups of PD patients. One group consisted of 15 de novo patients, meaning that the patients were newly diagnosed with PD and that they had never been treated with PD medications such as levodopa. The average PD disease duration for this group was less than 5 years. Two of these patients were diagnosed with clinical depression.

In the unmedicated PD group, the authors found significant negative correlations between symptoms of depression (as measured by the Beck Depression Inventory (BDI)) and dopamine synthesis capacity (as measured by FDOPA uptake) in the left striatum (putamen p=0.002, caudate p=0.042). No significant correlations were observed in the right striatum. Neither the severity nor side of motor symptoms affected the findings.

Different results were found in a group of 20 patients with moderate disease severity who were already being treated with PD medications. The average duration of disease for these patients was 5.6 years and 90% were using levodopa, 90% a dopamine agonist, and 60% a MAO-B inhibitor. Ten percent were also on an antidepressant. In this group, no significant correlations were found between BDI scores and regional FDOPA uptake in the caudate or putamen.

"Previous studies looking at depression and striatal dopamine synthesis capacity using 18Ffluorodopa PET scanning yielded inconsistent results, most likely reflecting marked heterogeneity in patients' disease severity and medication history," says lead investigator Juho Joutsa, MD, of the Division of Clinical Neurosciences at Turku University Hospital and University of Turku in Finland. "The results should be interpreted to indicate a link between mood and dopamine, which can be observed in early-stage unmedicated patients, but the relationship may also be present, but masked, in more advanced patients."

The study was the first using 18fluorodopa PET scanning technology to show that depression was associated with reduced dopamine synthesis capacity only on the left side. However, Dr. Joutsa comments that studies using dopamine transporter ligands have also reported a similar lateralization of effect.

PD is the second most common neurodegenerative disorder in the United States, affecting approximately one million Americans and five million people worldwide. Its prevalence is projected to double by 2030. The most obvious symptoms are movement-related, such as involuntary shaking and muscle stiffness. Non-motor symptoms, such as worsening depression, anxiety, and sleep disturbances, can appear prior to the onset of motor symptoms.

More information: Joutsa, J. et al. Reduced Striatal Dopamine Synthesis Capacity is Associated with Symptoms of Depression in Patients with de novo Unmedicated Parkinson's Disease, Journal of Parkinson's Disease, Volume 3/Issue 3. DOI: 10.3233/JPD-130205

Provided by IOS Press

Low-Contrast Visibility May Be Issue for Parkinson's Drivers

Study suggests patients may be at increased risk for unsafe driving during fog or twilight

09 oct 2009-- Drivers with Parkinson's disease may be more prone to poor vehicle control and crashes while driving in low-contrast visibility conditions due to issues with perception, cognition and motor dysfunction, according to a study in the Oct. 6 issue of Neurology.

Ergun Y. Uc, M.D., of the University of Iowa in Iowa City, and colleagues analyzed data from 67 currently active drivers with mild to moderate Parkinson's disease and 51 controls. Participants drove using a driving simulator under clear conditions and then mildly foggy conditions. During the study, participants reached an intersection where another vehicle posed a crash risk under low-contrast visibility.

The researchers found that drivers with Parkinson's disease had a higher standard deviation of lateral position and lane violation counts than unaffected controls under low-contrast visibility. These measurements increased more in drivers with Parkinson's disease upon the transition from clear to foggy conditions. More drivers with Parkinson's disease crashed at the foggy intersection (76.1 versus 37.3 percent), as their time to first reaction in response to the incursion was longer.

"Our results suggest that a large proportion of drivers with Parkinson's disease may be at further risk for unsafe driving during fog or twilight because of visual, cognitive, and motor impairments," the authors conclude.

Abstract
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Parkinson's Patients More Prone to Vitamin D Deficiency

16 oct 2008-- Parkinson's disease patients are more likely than healthy people or Alzheimer's patients to have vitamin D deficiency, say researchers from the Emory University School of Medicine in Atlanta.
They compared vitamin D levels in 100 Parkinson's patients, 97 Alzheimer's patients, and 99 healthy people matched for age and other factors.
"Significantly more patients with Parkinson's disease [55 percent] had insufficient vitamin D than did controls [36 percent] or patients with Alzheimer's disease [41 percent]," the researchers wrote.
The average vitamin D concentration among Parkinson's patients was 31.9 nanograms per milliliter, compared with 34.8 nanograms among Alzheimer's patients, and 37 nanograms among healthy people.
The study was published in the October issue of the Archives of Neurology.
"These findings support the previously suggested need for further studies to assess what contribution a low 25 (OH)D [a measure of blood vitamin D levels] concentration adds to the risk of developing Parkinson's disease [vs. other neurodegenerative disorders] and to determine whether correction of vitamin D insufficiency and deficiency will improve motor or non-motor symptoms in Parkinson's disease," the study authors concluded.
"Finally, the finding of a high incidence of vitamin D deficiency in the Parkinson's disease and other cohorts highlights the importance of routinely checking the level of 25(OH)D, particularly in elderly patients, since deficiency is strongly associated with a higher incidence of osteoporosis, falls and hip fractures and has been associated with a higher incidence of several forms of cancer and autoimmune disorders," the researchers added.
More information
We Move has more about Parkinson's disease.

Treatment for Parkinson's examined

10 sept 2008--The PhD defended by Juan Carlos Gómez-Esteban at the University of the Basque Country analysed the results of the clinical research undertaken at the Movement Disorders Unit at Cruces Hospital since 1998. It involved a study of the most efficacious surgical operations undertaken and pharmaceutical drugs used to treat these disorders as well genetic studies carried out to date.
The field of movement disorders is one of the most complex branches of neurology. The volume of knowledge acquired is so large that it has needed a number of neurologists to sub-specialise in the matter and multidisciplinary units have been created to tackle problems such as the diagnosis of Parkinson's Disease and of atypical Parkinsonisms, the choice of the most suitable surgical therapies and pharmaceutical drugs or the carrying out of genetic studies. Thus is 1998 the Movement Disorders Unit at Cruces Hospital in Bilbao was created with neurologists, neurosurgeons, neurophysiologists, anaesthetists, neuropsychologists and radiologists. Since its creation, more than 100 surgical operations have been carried out, the majority on patients with Parkinson's Disease. Currently it is a centre of reference for functional surgery in the Autonomous Community of the Basque Country (CAPV), and even receives patients from other autonomous communities.
The PhD the neurologist Juan Carlos Gómez-Esteban presented at the University of the Basque Country (UPV/EHU), Results of clinical research at a movement disorders unit, brings together a number of different lines of research undertaken at the Cruces Hospital Movement Disorders Unit between 1998 and 2007. Mr Gómez-Esteban graduated in Medicine and General Surgery and his PhD, having received excellent ratings cum laude, was led by Dr. Juan José Zarranz Imirizaldu and Dr. Elena Lezcano García, both from the Department of Neurosciences of the Faculty of Medicine and Odontology at the UPV/EHU.
Results of the operations
The initial part of the thesis presented by Dr. Gómez-Esteban reviews the operations carried out at the Movement Disorders Unit; in concrete, analysing deep brain stimulation, a surgical procedure that acts on the nuclei deep inside the brain that do not function correctly in patients affected by different movement disorders. From his research he deduced that what is involved is an effective therapy for patients with advanced Parkinson's and that the subthalamic nucleus (a small nucleus located at the base of the brain) is the surgical target that provides a more complete answer to an improvement in the symptoms of the illness. The operation involves implanting microelectrodes in this nucleus and which are controlled by a battery similar to a pacemaker.
Dr Gómez-Esteban states that the benefit of this type of operation for the symptoms affecting movement is similar to that obtained with dopaminergic pharmaceutical drugs (those containing dopamina precursors or behave similarly to them), with the exception of trembling, which responds better to surgical treatment rather than to pharmaceutical medicines. Another of the benefits of deep cerebral stimulation is the enhancement of the quality of life not only for the patient, but also for the carer. It also produces improvements in verbal memory, but changes in verbal fluency or executive functions have not been detected. Although initially symptoms of depression may be produced as a reaction related to patient expectation and to the surgical process itself, Dr. Gómez-Esteban affirms that, in the medium and long term, there is an improvement in the symptoms of depression.
This research also showed that patients suffering from the illness known as Parkinson-type multiple system atrophy as well as those with a specific mutation of the LRRK2-Dardarina gene, do not respond to surgery as well as those suffering from Parkinson's of unknown cause or from other, hereditary Parkinson's.
Genetic research: new mutations
Hereditary forms of Parkinson's and dementia with Lewy bodies (a recently discovered illness previously confused with Parkinson's or Alzheimer) are not frequent. In fact, Dr. Gómez-Esteban states that genetic defects associated with this last illness have not been found to date. However, the Movement Disorders Unit has discovered a new mutation in Parkinson's Disease (a specific mutation in the gene known as alpha-synuclein), which is also associated with Lewy Body Dementia. Also notable is the fact that patients registering such a mutation do not have a primary sleep disorder, a reduction in the REM phases (in which dreams are produced) and NREM (in which dreams are not produced), which could even precede motor symptoms.
Sleep fragmentation, psychotic symptoms and analysis of pharmaceutical drugs
Another problem for Parkinson's sufferers is the fragmentation of sleep or the impossibility of continuous sleep and nicturia (orinating frequently during the night). According to Dr. Gómez-Esteban, the drugs acting directly on the Dopamine receptors appear to improve nicturia, although not improving night time sleep nor the presence of daytime hypersomnia (difficulty in staying awake). 21.9% of patients studied at the Movement Disorders Unit suffer, moreover, from restless legs syndrome, which gives rise to a worsening in the quality of night time sleep and the quality of life.

High cholesterol may up Parkinson's disease risk

06 june 2008--High cholesterol levels are associated with an increased risk of Parkinson's disease, according to findings from a Finnish study.
While it's well established that high cholesterol increases heart disease risk, "the association between serum cholesterol level and neurodegenerative diseases risk has been debated," write Dr. Gang Hu, of the National Public Health Institute, Helsinki, Finland, and colleagues.
The researchers examined this relationship in a cohort of 24,773 Finnish men and 26,153 women between the ages of 25 and 74 years. A total of 321 men and 304 women developed Parkinson's disease during an average follow-up of 18 years, the researchers report in the medical journal Neurology.
Compared to people with the lowest cholesterol, those with the highest had an 86 percent greater likelihood of developing Parkinson's disease.
This increased risk applied to people 24 to 54 years of age. "However, no association was found among subjects aged 55 years or older at baseline," Hu's team explains.
SOURCE: Neurology, May 20, 2008.

Adjusting electrodes may help Parkinson's patients

13 may 2008--Patients with Parkinson's disease who have a poor response to brain stimulation therapy may improve if the electrodes are repositioned, even by just a few millimeters.
A poor response can be caused by the misplacement of the electrodes by even just a few millimeters, physicians in France report.
Dr. Mathieu Anheim, at University Hospital, Strasbourg, and colleagues studied seven patients with Parkinson's disease who underwent this procedure in which electrodes are positioned to stimulate the region of the brain called the subthalamic nucleus, a procedure that has been shown to relieve symptoms for many patients.
After the procedure, the seven patients were able to reduce their medication dosage by only a small amount and had little relief from their symptoms. Brain imaging tests showed that 12 of 14 electrodes were misplaced.
The patients underwent a second operation approximately 1.5 years after the first to reimplant the electrodes. One year later, six of the seven patients showed improvements, the authors report in the Archives of Neurology.
The average distance between the contacts and the theoretical effective target decreased from 5.4 to 2.0 mm. Motor symptom scores during stimulation and while off medication fell from 40.1 before reimplantation to 22.2 afterwards, decreasing in parallel with the distance between the electrodes and the target.
The patients' dose of levodopa fell from 1,202 mg per day to 534 mg per day.
For carefully selected patients who have poor results following electrode stimulation and misplaced electrodes are shown on imaging studies, reimplantation closer to the target area should be considered, Anheim and associates advise.
However, they point out that there still will be rare patients who have no clear explanation for poor results on the electrode stimulation technique.
SOURCE: Archives of Neurology, May 2008.

Antioxidant Linked to Parkinson's Disease Progression

By Crystal Phend
BOSTON, 14 april 2008-- For patients with Parkinson's disease, progression may be directly linked to blood levels of the antioxidant urate, researchers found. Patients with the highest urate levels were half as likely to wind up needing dopaminergic therapy as those with the lowest levels (P<0.001 for trend), reported Alberto Ascherio, M.D., Dr.Ph., of the Harvard School of Public Health, and colleagues online in the Archives of Neurology. This would make urate the first biomarker for Parkinson's progression, Dr. Ascherio said. Other factors linked to worsening of the condition have centered on complex behavioral characteristics, the researchers said.
Targeting urate or its precursors, they suggested, could be a way to therapeutically modify the course of the disease, although urate itself may not inform treatment decisions or risk prediction. Measurement of urate on its own in patients with newly diagnosed Parkinson's disease as an indicator of an individual patient's future rate of progression is likely to be of modest clinical utility," they wrote.
As a potent antioxidant, urate may delay the oxidative destruction of dopaminergic neurons that occurs as Parkinson's disease worsens, the researchers speculated.
Animal models of Parkinson's have supported a protective role of urate, a derivative of uric acid. But the best evidence in humans has been the lower Parkinson's risk among healthy adults with higher uric acid levels consistently found in prospective epidemiological studies.
So, the researchers looked for a link between serum urate concentrations and subsequent Parkinson's progression in the randomized Parkinson Research Examination of CEP-1347 Trial (PRECEPT), which was originally designed to test the investigational agent CEP-1347 as a neuroprotectant.
The trial randomized 806 men and women with early Parkinson's disease that did not yet require dopaminergic therapy to active or control treatment.
Dr. Ascherio's group focused on serum urate concentration data from patients' baseline visit collected as part of routine safety monitoring.
During an average 21.4 months of follow-up, 61% reached the primary endpoint of disability sufficient to require dopaminergic therapy.
Higher urate levels were associated with lower likelihood of progression to dopaminergic therapy (P<0.001 for trend).
This advantage was significant for patients in the two highest urate quintiles. Compared with patients in lowest quintile averaging 3.8 mg/dL urate, risk of progression was 35% lower for those with urate levels averaging 6.3 mg/dL (P=0.006) and 49% lower for those with levels averaging 7.5 mg/dL (P<0.001).
The association between urate and disease progression was substantially stronger among men than women. Men had a modestly but significantly slower rate of disease progression measured by scores on the Unified Parkinson's Disease Rating Scale for those in the highest versus lowest urate groups (P=0.02 for trend) whereas the same was not true for women (P=0.52).
The authors had no explanation for the differences observed between the sexes.
Despite these indications that lower urate levels were predictive of neurodegeneration, "that information alone is not sufficient to change the course of treatment or to provide specific advice to patients," Dr. Ascherio said.
Further study is needed to determine whether higher serum urate itself is neuroprotective or simply serves as an indirect marker of protection, he and colleagues wrote.
Meanwhile, urate testing could be useful in designing neuroprotective trials in Parkinson's disease because potential neuroprotectants targeting
oxidative stress pathways might be most effective in patients whose urate and other antioxidant levels are lowest at baseline, they said.
The real hope, though, is that urate may offer a new pathway for Parkinson's disease-modifying therapy, Dr. Ascherio said. But he cautioned there may be a tradeoff in risk.
"Increasing urate could have adverse effects on the cardiovascular system and increase the risk of kidney stones and gout," he said. "So this is not a risk-free intervention."
The analysis was supported by National Institutes of Health grants and the Beeson Scholars Program of the American Federation for Aging Research. The PRECEPT study was supported by Cephalon and H. Lundbeck A/S.
The researchers reported no conflicts of interest.
Primary source: Archives of NeurologySource reference:Schwarzschild MA, et al "Serum urate as a predictor of clinical and radiographic progression in Parkinson disease" Arch Neurol 2008; DOI: 10.1001/archneur.2008.65.6.nct70003.

Parkinson's burden to increase as world grows older

by Marlowe Hood
Apr 10, 2008--A surge of Parkinson's disease linked to rapidly aging populations worldwide will severely tax health care systems in coming decades, experts warned Thursday ahead of World Parkinson's Disease Day.
The burden of Parkinson's and other neurodegenerative diseases that strike later in life will be amplified, experts say, by breakdown of informal, home-based care networks that are already strained.
"In many countries, overdependence on voluntary care is a key issue caused by lack of appropriate, consistent and affordable institutional resources," said Mary Baker, president of the European Parkinson's Disease Society.
"With an ever-increasing elderly global population, the cost to nations will be astronomical if action is not taken now, at the beginning of the 21st century," she said.
The World Health Organisation (WHO) forecasts a 20 percent jump from 2005 to 2030 in the number of "disability-adjusted life years" (DALYs) attributable to Parkinson's.
DALYs is a measure that combines years of life lost due to a disability, and years of healthy life lost.
The rate of increase over the same period for Alzheimer's and other progressive neurological disorders that typically emerge in old age is even higher at 66 percent.
For 2008, World Parkinson's Disease Day is seeking to overturn myths and misconceptions about the condition, which affects 6.5 million people around the world.
Sufferers of what James Parkinson, the English doctor who first diagnosed the disease, called "the shaking palsy" are sometimes shunned due to awkward and uncontrolled movements, or mistaken for persons under the influence of alcohol or drugs.
Symptoms include muscular rigidity, difficulty with initiating movements, lack of balance, and slowness of voluntary actions.
"In today's world, it is necessary to move fast, and to communicate through body language and emotions," commented French Psychiatrist Philippe Nuss of Saint Antoine Hospital in Paris. "Parkinson's attacks exactly these three areas."
For Marie Vidhaillet, a neurologist at Pitie Salpetriere Hospital, living with the disease is like the fickle weather of March, with an unpredictable sequence of good days and bad days.
"You have to learn to live with it without succumbing to it," she added.
Parkinson's is caused by the death of neurons in the brain that produce dopamine, a chemical neurotransmitter that regulates, among other things, bodily movement.
Several medications compensate for the lack of dopamine that triggers symptoms, but only imperfectly. Neurosurgical treatments also exist, but are only appropriate in five percent of cases.
Among the misconceptions surrounding Parkinson's is the idea that it is "an old person's disease," said Vidhaillet.
At least 10 percent of patients in France are under 45, but "most doctors don't think of Parkinson's if a patient is 40 years old."
"In our society, where one does not have the right to get old, the disease is doubly stigmatising," she said.

Parkinson's brain cell transplants last for years

By Maggie Fox
Transplants of brain cells given to Parkinson's disease patients survive for 10 years or more, three teams of researchers reported on Sunday, but at least some of the transplants were damaged.
The researchers disagree about whether this damage shows that Parkinson's disease is a long-term, ongoing process that continues to attack the brain into old age, or the result of the transplants themselves.
But they agree that their studies, published in the journal Nature Medicine, demonstrate the benefits of the sometimes controversial brain cell transplants.
"I think these findings lend much optimism to future work," said Dr. Ole Isacson of McLean Hospital and Harvard Medical School in Massachusetts, who worked on one of the studies.
Parkinson's disease, which affects more than a million patients in the United States alone, is marked by the death of brain cells that produce dopamine, a message-carrying chemical associated with movement. Drugs can delay symptoms for a while but there is no good treatment and no cure.
Patients report shakiness, which progresses to paralysis and sometimes dementia and death.
A few teams tried transplanting brain cells, some from aborted fetuses, to replace cells destroyed by the disease.
Jeffrey Kordower of Rush University Medical Center in Chicago and colleagues described the case of a 61-year-old woman who died 14 years after she got a transplant.
She initially got better but then deteriorated until she died. Her brain showed signs of damage similar to that caused by Parkinson's, Kordower's team reported.
"This case reveals that pathological changes typical of Parkinson's disease can develop in human fetal neurons grafted into a host with Parkinson's disease," they wrote.
ONGOING PROCESS?
Patrik Brundin of Wallenberg Neuroscience Center in Lund, Sweden, and colleagues found some damage to cells transplanted into the brains of patients. But they said the transplants had survived for as long as 16 years and the patients had reported relief from their symptoms.
Kordower believes the findings suggest that Parkinson's is caused by an ongoing process that lasts for years. "Whatever the offending agent is, it is still present in the Parkinson's brain," he said in a telephone interview.
He said only about 5 percent of the cells were damaged.
"If you ask me whether this spells doom and gloom for cell replacement, the answer is absolutely not," said Kordower, who is pursuing another treatment for Parkinson's by using gene therapy to repair the damaged cells.
Isacson found no such damage in the brains of five patients who died nine to 14 years after getting transplants.
He said transplanting purified brain cells may provide better results. Isacson, who examined brain tissue from the patient studied by Kordower's team, said whole chunks of brain tissue had been transplanted into her -- including cells that could have provoked damaging inflammation.
"I think that the transplant is basically triggering an immune reaction," Isacson said in a telephone interview.
Isacson wants to continue to try to treat Parkinson's patients with brain cell transplants, perhaps using stem cells that have been trained to grow into the specific brain cells affected in Parkinson's.

New studies raise questions over foetal grafts for Parkinson's

Sun Apr 6
Two investigations published on Sunday place a question mark over pioneering treatment to treat Parkinson's disease by grafting foetal cells into the brain.
In several patients examined in the studies, the transplanted cells appear to have been attacked by the protein aggregates that cause this tragic degenerative disease, the papers said.
A third study, though, into five other individuals found no evidence of such a problem.
Parkinson's is an incurable disease of the central nervous system that causes uncontrollable shaking, along with impaired speech and movement. In approximately one third of cases it also results in dementia. The disease affects at least one percent of people over the age of 65.
Well-known people with the disease include Pope John Paul II and the movie actor Michael Fox.
The cause is a loss of dopamine, a chemical messenger that helps direct movement. The substance is provided in a part of the brain called the substantia nigra.
Treatment paths have focussed essentially on providing a pharmaceutical substitute for dopamine or on restoring or protecting dopamine-producing cells.
Another experimental route, launched in the 1990s, has been to inject dopamine-making brain cells from foetuses into the brain.
Post-mortems of three individuals with the grafts found evidence that so-called Lewy bodies -- the protein that accumulates in the substantia nigra and kills dopamine cells -- had spread to the implanted cells, according to two letters published in the journal Nature Medicine.
The patients, who did not die from effects of Parkinson's disease, had had the implants 11, 14 and 16 years earlier.
But a third study, in which five subjects who had had the grafts between nine and 14 years earlier were autopsied, found no evidence of any spread of Lewy bodies.
The mixed picture reflects the complexity of Parkinson's, a disease whose causes and propagation remain fuzzy.
Although the discovery of Lewy bodies in the grafted cells is troubling, "available data suggest that the majority of grafted cells are functionally unimpaired after a decade," said one of the studies.
"Recipients can still experience long-term symptomatic relief."

Impaired Olfaction May Point to Impending Parkinson's

By Charles Bankhead
HONOLULU, March 21 -- One of the earliest signs of impending Parkinson's disease could be right under a patient's nose, according to a study here.Impaired olfactory function predated clinical Parkinson's disease by at least four years and conferred as much as a five-fold increased risk of the neurologic disorder, G. Webster Ross, M.D., of the University of Hawaii, and colleagues reported in the February issue of Annals of Neurology."Olfactory testing together with screening for other potential early indicators of Parkinson's disease . . . could provide a simple and relatively economic means of identifying individuals at high risk for development of Parkinson's disease who could participate in trials of medications designed to prevent or slow disease progression," the authors concluded.
Olfactory dysfunction has a well-recognized association with Parkinson's disease. Moreover, an accumulation of evidence suggests that impaired olfaction may precede classic motor manifestations of the condition by several years, the authors said. However, proof of the association in a general population has been lacking.
Seeking the missing confirmation of the olfactory link, Dr. Ross and colleagues reviewed data from the Honolulu-Asia Aging Study, which began in 1965 as the Honolulu Heart Program. Evaluation of dementia Parkinson's was incorporated during 1991-1993, with three follow-up assessments from 1994 to 2000.
The current study comprised data on 2,267 men who underwent olfaction assessment during 1991 to 1996 by means of the Brief Odor Identification Test. The men were ages 71 to 95 at the time of olfaction testing and were free of clinical Parkinson's disease and dementia at the time.
During eight years of follow-up, 35 study participants had Parkinson's diagnoses, a rate of 24.6 per 10,000 person-years. The average age at diagnosis was 82.9, and the time from olfaction assessment to diagnosis was four years.
After stratification of the men by olfactory test results, patients in the lowest quartile of odor identification had an age-adjusted incidence of Parkinson's disease of 54.5 per 10,000 person-years. That compared with rates of 26.6, 8.2, and 8.4 per 10,000 person-years among men in the second, third, and fourth quartiles (P<0.001). To rule out the possibility that undiagnosed dementia might have affected olfaction tests, investigators excluded men with low scores on a standardized test of cognitive function.
Adjustment for potential confounders resulted in a Parkinson's odds ratio of 5.2 (95% CI 1.5 to 25.6) for men in the lowest quartile of odor identification versus men in the top two quartiles. The association between olfactory function and Parkinson's disease was not evident beyond four years of follow-up.
"This is the first population-based prospective study to demonstrate that odor identification deficits can predate the development of clinical Parkinson's disease in men by at least four years," the authors said. "These results remained significant when restricting the at-risk population to those without cognitive impairment."
The authors noted several potential limitations to the study including that the population studied was all male and that the smell test may not be completely applicable to Japanese-American men.
The authors reported no disclosures.
Primary source: Annals of NeurologySource reference:Ross GW, et al "Association of olfactory dysfunction with risk for future Parkinson's disease" Ann Neurol 2008; 63: 167-173.

Test rates driving ability in Parkinson's patients

By Michelle RizzoWed Oct 17, 4:50 PM ET
A short screening test, developed by a Belgian team, which measures four clinical variables can accurately predict the fitness of patients with Parkinson's disease to drive, according to findings published in the current issue of the journal Neurology.
"Physicians often rely on a medical history and an interview with the patient and the next of kin regarding driving problems," lead author Dr. Hannes Devos noted in comment to Reuters Health. However, "physicians often overestimate the driving skills of their patients."
Devos of Catholic University in Leuven and colleagues developed a brief, efficient screening system to help physicians assess the fitness of Parkinson's disease patients to drive a car.
Eighty individuals, including 40 with Parkinson's disease and 40 healthy subjects matched to the patients for age and other variables, were assessed using a driving simulator, a driving history survey, and the Clinical Dementia Rating scale.
In addition, the Parkinson's patients underwent a screening test and an evaluation designed by the Belgian Road Safety Institute. This included visual, intellectual and on-road testing.
The combination of assessments that included disease duration, sensitivity to contrasts, Clinical Dementia Rating, and the motor part of the Unified Parkinson's Disease Rating Scale provided the best screening test to predict fitness to drive.
Overall, 36 (90 percent) patients with Parkinson's disease were correctly classified as pass or fail using this screening method.
"When the result on the formula is positive, the patient can continue to drive without further restrictions," Devos explained. When the patient fails, he may be allowed to drive with restrictions or be considered unfit to drive, he said. "Further assessment at an official driving assessment center then seems to be the right course of action."
Parkinson's disease "is often regarded as a disease that mainly affects motor functions, while visual and cognitive functions are often disregarded," Devos noted. "Nonetheless, problems with attention, visuospatial organization, planning and judgment, and contrast sensitivity are also seen in Parkinson's disease."
"It is my opinion that the driving performance of Parkinson's disease patients is often overestimated and that they should be evaluated on a more regular basis," Devos concluded.
SOURCE: Neurology October 2, 2007.

Gene Mutation Linked to Parkinson's Disease

By Alan MozesHealthDay ReporterMon Sep 17, 7:02 PM ET
MONDAY, Sept. 17 (HealthDay News) -- People who carry a certain gene mutation appear to have a greater risk for getting Parkinson's disease and for getting it at a relatively early age, new research suggests.
The study authors also found that because Ashkenazi Jews -- those with an Eastern European background-- are more likely to carry this gene mutation, this population may run an even higher risk for the disease. An estimated 90 percent of American Jews are of Ashkenazi lineage.
Study lead author Lorraine N. Clark, a researcher at Columbia University, described her team's findings as "unique and different."
"We specifically compared patients who had an early onset Parkinson's before age 50 with patients who had a later onset after age 50, and also with patients with and without Jewish ancestry," she said. "And we showed that mutations are twice as common among early onset Parkinson's and also that they're more frequent among patients with Jewish ancestry."
Clark serves as an assistant professor in the department of clinical pathology with the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, as well as the Center for Human Genetics, both at Columbia University.
The findings are published in the Sept. 18 issue of the journal Neurology.
Parkinson's disease is a brain disorder that affects 1.5 million Americans, according to National Parkinson Foundation estimates. Approximately 60,000 news cases occur each year, striking men and women equally, usually over the age of 65.
The disease is characterized by widespread damage to dopamine-producing nerve cells, impeding their ability to regulate body movement and muscle control. Key signs of the disease include tremors, stiffness, balance problems, and slowness of movement. Patients may also experience difficulty with speech and depression. There is no known cure.
To explore potential genetic underpinnings to the onset of Parkinson's, Clark and her colleagues decided to focus on the GBA gene. Mutations of this gene have already been identified as the cause of Gaucher disease, a rare fat-storage disorder that disrupts spleen and brain function.
Gaucher's and Parkinson's have some links, the study authors noted. In some cases, Gaucher's patients have a family history of Parkinson's, while others actually develop neurological features of Parkinson's. It is also one of the most prevalent genetic illnesses among Ashkenazi Jews.
For the new study, the researchers conducted a sequencing analysis of the GBA gene among 278 Parkinson's patients, 178 of who were of Jewish ancestry dating back to all four grandparents. A similar analysis was done among 179 men and women without Parkinson's.
Clark and her team found that 14 percent of the Parkinson's patients had GBA mutations, compared to just 5 percent of the healthy patients. And, while GBA mutations were found among 22 percent of Parkinson's patients who were diagnosed with their illness before the age of 50, only 10 percent of patients diagnosed after 50 had such abnormalities.
Teasing out information on Jewish patients, the researchers found that while nearly 17 percent of Jewish Parkinson's patients had GBA mutations, the figure was 8 percent among non-Jewish Parkinson's patients.
Clark called the study findings preliminary, and she cautioned that it remains unclear whether a single GBA mutation is a cause of Parkinson's or merely a part of a larger puzzle.
Still, she believes the findings could prove helpful in opening up new avenues of research into the disease.
"This is a gene we hadn't really thought about before," she said. "And it implicates new pathways that might be important in the pathogenesis of Parkinson's disease which could lead to the development of new treatment strategies. I do think, however, that further studies are needed in larger patient populations before we could use this work in diagnostic testing and counseling."
Robin Elliott, executive director of the Parkinson's Disease Foundation in New York City, called the new research "very interesting and very worthwhile, solid work in one of the most fruitful areas of Parkinson's research.
"Genetics and the study of genetics has been one of the most exciting areas of Parkinson's in the last 10 years," he said. "In 1996, we had not a single gene associated with the disease, and now it's up to 12 or 13. So, this is a very important study that pushes the science even further, and gives us the basis for more work."
More information
To learn more, visit the Parkinson's Disease Foundation.