Higher Iron Levels in Blood May Protect Against Parkinson's Disease

Christine Hsu
Counsel & Heal - A new study has found an association between higher iron levels and lower risk of developing Parkinson's disease.

The latest research, published in the journal PLOS Medicine, looked at whether there was a link between serum iron levels and the risk of Parkinson's disease.

The causes of Parkinson's disease are currently unknown. However, previous studies have revealed that Parkinson's patients have lower blood levels of iron.

In the new study, scientists estimated the effect of blood iron levels on the risk of Parkinson's disease by looking at three polymorphisms in two genes, HFE and TMPRSS6. Polymorphism occurs when two or more clearly different phenotypes exist in the same population of a species.

Researchers performed a meta-analysis combining the results of studies investigating the genetic effect on iron levels and a meta-analysis of studies investigating the genetic effect on the risk of Parkinson´s disease for each polymorphism.

Afterwards, investigators performed three separate Mendelian randomization analyses to estimate the effect of iron on Parkinson disease for the three polymorphisms.

The findings revealed a statistically significant odds ratio of 0.97 for Parkinson's disease per 10 μg/dl increase in iron, corresponding to a 3% reduction in the risk of Parkinson´s disease for every 10 μg/dl increase in blood iron.

Researchers explained that because genotype influences on blood levels represent difference that generally persist throughout adult life, the latest findings reflects an effect of iron over the course of a lifetime.

Investigators said the latest findings suggest that increased iron levels in the bloos are associated with a 3 percent relative reduction in the risk of Parkinson's diease for every 10 μg/dl increase in iron.

Study authors conclude that increased blood iron levels may have a protective effect against Parkinson's disease.                        

Health Care Barriers Hinder Parkinson's Care for Latinos

Cristina Fresquez
El Semanario - Aside from dealing with an illness that has so many unanswered questions, Latino elders suffering from Parkinson’s disease also carry the burden of tackling barriers that hinder their healthcare and treatment.

“My Mom is proficient with her English – when she wants to. But she doesn’t read very well-- she only has an eighth grade education -- so one of us always has to sit in with her on doctor visits and make sure the doctor understands what’s going on with her and so that Mom understands the doctor’s orders,” said West Denver resident Allende, who asked to be identified by last name only because of her immigration status.

Allende, the primary caregiver for her elderly mother, who suffers from Parkinson’s, added, “The fact that she can’t read and understand things like her prescriptions makes it more difficult for all of us.”

Medical Culture Clash

Cultural barriers for Latinos are vaguely acknowledged, if at all, by doctors practicing Western medicine.
Many Latino elders were raised with homeopathic healing methods, Curanderismo, or Santeria, all cultural forms of healing connecting the mind, body and spirit. This different conception of healing often creates a lack of understanding and problems in communicating medical issues and treatment options between doctors and patients.

“Right now, we are struggling with helping my Mom understand that her sickness and bouts of dementia are actually medical issues and unfortunately are not going away. She is convinced that someone has placed a curse on her,” explained Allende.

“To make things worse,” she went on, “some lady told my Mom she could remove the curse for $800. We have even brought her doctor in to help explain, but he wasn’t very helpful -- he just attributed her claims to her dementia and basically wrote off the situation.”

Double Parkinson’s Rate for Latinos

Studies show that among the estimated 1 million people with Parkinson’s in the United States (with about 60,000 new patients diagnosed each year) Latinos and whites have nearly double the rate of developing the condition over Asians and African Americans.

However, because there is still so little known about the cause of Parkinson’s, scientists don’t exactly understand why Latinos have a greater risk of developing this incurable, degenerative disease marked by such symptoms as tremors or shaking, slowed movement, rigid muscles, impaired balance and difficulty speaking.

Parkinson’s was once considered mainly a genetic disorder. But research in recent years has shown environmental factors appear to play a key role for increased risk of developing the ailment.
For instance, the largest Parkinson’s study -- conducted to date--based on data from 36 million Medicare recipients--concluded that genetics play a relatively small role. T

he study by researchers at the Washington University School of Medicine in St. Louis, instead pointed to environmental factors, such as long-term exposure to pesticides, herbicides and farming metals (particularly copper and manganese), which might explain the disproportionate rates of Latinos afflicted with the disease. The study called for further research to confirm these suspicions.

Poverty Complicates Disease

According to UCLA’s Center for Health Policy Research, data from 2009 shows Latino elders age 65 and older rank the highest (29 percent) of those living below 200 percent of the federal poverty level, or about $24,000 a year and struggle to make financial ends meet.

Also, higher poverty levels among Latinos may intensify the impact of Parkinson’s. For example, low income tends to limit access to much-needed healthcare and medications.

Poverty stricken elders also face the risk of malnutrition because they lack healthy food options. Diet can be particularly important for managing Parkinson’s symptoms, as well.

The UCLA Health Policy Research Center, using 2009 data, showed that Latinos ages 65 and older have the lowest level of educational attainment among ethnic minorities in the U.S., with an astonishing 57.9 percent having less than a high school education.

“Studies have shown that people who have lower levels of education struggle more with complex things like financial and health literacy,” stated Steven P. Wallace, associate director of UCLA’s center.

He explained that lower literacy directly affects the capacity of patients and family members to understand such things as even simple medication directions to being able to navigate complex healthcare systems, such as Medicare and Medicaid.

Adding language barriers to the mix impacts elders’ ability to understand such things as how diet and exercise affect on health, and may exacerbate effects of the disease.

Eliminating Health Disparities

The need for cultural competence among health care professionals was emphasized in a 2012 article entitled “Social Justice, Health Disparities, and Culture in the Care of the Elderly,” published in the Journal of Law, Medicine and Ethics., by gerontologists at the University of North Carolina, Chapel Hill.

In the report, Peggye Dilworth-Anderson and colleagues stated, “By understanding a group’s values, belief systems, and ways of thinking and behaving, researchers, care providers, and policymakers can be better equipped to identify the cultural influences that serve as barriers and facilitators to eliminating health disparities.”

Other hurdles Latino elders often must overcome may be geographical barriers, and access to technology. Geographical barriers, such as living in rural areas or living with limited transportation options, often restrict elders’ access to getting adequate medical treatment. This scenario is worsened if their Parkinson’s is creating physical limitations, both making a simple trip to the doctor’s office nearly impossible.

A common hurdle for Latinos is the barrier of being undocumented, which stigmatizes this population into a life of living in the shadows, which is fraught with fear of being deported and detained. This fear keeps people from seeking medical assistance unless it is a life-or-death situation. Combinations of language, immigration status and cultural barriers push Latinos further away from seeking medical advice; understanding proper and affective treatment; and willingness to adhere with medical treatment.

“It’s hard to care for my Mom because we are both undocumented, and she doesn’t qualify for things like Medicare or Medicaid, and going to the doctor regularly isn’t something my family can afford to do,” said Allende.                        

New technique for deep brain stimulation surgery proves accurate and safe

OHSU News - The surgeon who more than two decades ago pioneered deep brain stimulation surgery in the United States to treat people with Parkinson's disease and other movement disorders has now developed a new way to perform the surgery — which allows for more accurate placement of the brain electrodes and likely is safer for patients.

The success and safety of the new surgical technique could have broad implications for deep brain stimulation, or DBS, surgery into the future, as it may increasingly be used to help with a wide range of medical issues beyond Parkinson’s disease and familial tremors.

The new surgery also offers another distinct advantage: patients are asleep during the surgery, rather than being awake under local anesthesia to help surgeons determine placement of the electrodes as happens with the traditional DBS surgery.

A study detailing the new surgical technique is being published in the June 2013 edition of the Journal of Neurosurgery, and has been published online at the journal's website.

"I think this will be how DBS surgery will be done in most cases going forward," said Kim Burchiel, M.D., F.A.C.S., chair of neurological surgery at Oregon Health & Science University and the lead author of the Journal of Neurosurgery article. "This surgery allows for extremely accurate placement of the electrodes and it's safer. Plus patients don't need to be awake during this surgery -- which will mean many more patients who can be helped by this surgery will now be willing to consider it."

DBS surgery was first developed in France in 1987. Burchiel was the first surgeon in North America to perform the surgery, as part of a Food and Drug Administration-approved clinical trial in 1991.

The FDA approved the surgery for "essential tremor" in 1997 and for tremors associated with Parkinson's disease in 2002. The surgery has been performed tens of thousands of times over the last decade or so in the United States, most often for familial tremor and Parkinson's disease. Burchiel and his team at OHSU have performed the surgery more than 750 times.

The surgery involves implanting very thin wire electrodes in the brain, connected to something like a pacemaker implanted in the chest. The system then stimulates the brain to often significantly reduce the tremors.

For most of the last two decades, the DBS patient was required to be awake during surgery, to allow surgeons to determine through monitoring the patient’s symptoms and getting other conscious patient feedback whether the electrodes were placed in the right spots in the brain.

But the traditional form of the surgery had drawbacks. Many patients who might have benefitted weren't willing to undergo the sometimes 4 to 6 hour surgery while awake. There also is a small chance of hemorrhaging in the brain as the surgeon places or moves the electrodes to the right spot in the brain.

The new technique uses advances in brain imaging in recent years to place the electrodes more safely, and more accurately, than in traditional DBS surgery. The surgical team uses CT scanning during the surgery itself, along with an MRI of the patient's brain before the surgery, to precisely place the electrodes in the brain, while better ensuring no hemorrhaging or complications from the insertion of the electrode.

The Journal of Neurosurgery article reported on 60 patients who had the surgery at OHSU over an 18-month period beginning in early 2011.

"What our results say is that it's safe, that we had no hemorrhaging or complications at all — and the accuracy of the electrode placement is the best ever reported," Burchiel said.

Burchiel and his team have done another 140 or so surgeries with the new procedure since enrollment in the study ended. OHSU was the first center to pioneer the new DBS procedure, but other surgical teams across the U.S. are learning the technique at OHSU, and bringing it back to their own centers.

The positive results with the new DBS technique could have ramifications as medical researchers nationwide continue to explore possible new uses for DBS surgery. DBS surgery has shown promising results in clinical trials with some Alzheimer's patients, with some forms of depression and even with obesity.

If the early promising results for these conditions are confirmed, the number of people who might be candidates for DBS surgery could expand greatly, Burchiel said.

The length of the new surgery for the 60 patients involved in the study was slightly longer than traditional DBS surgery. But as Burchiel and his team have developed the new surgical technique, the new DBS surgeries are usually much shorter, often taking half the time of the more traditional approach. Given that, and that the electrodes are placed more accurately and the surgery is cheaper to perform, the new DBS surgery likely will be the technique most surgeons will use in coming years, Burchiel said.

DBS surgery often helps significantly reduce tremors in patients with familial tremor and tremors and other symptoms in Parkinson’s disease. A parallel study is ongoing at OHSU to assess how symptoms of the patients have improved since their DBS surgery using this new method.

Study finds proof that immune defenses amplify Parkinson’s disease damage

Greg Williams
UAB News - The same mechanism that lets the immune system mount a massive attack against invading bacteria contributes to the destruction of brain cells as part of Parkinson’s disease, according to a study published online today in the Journal of Neuroscience.

Researchers from the University of Alabama at Birmingham (UAB) found that shutting down production of a key group of immune proteins, major histocompatibility complex II (MHCII), completely protected mice that displayed a “human version” of the disease from related nerve cell death.

The MHCII protein complex enables cells that first respond to infections to display pieces of bacteria or viruses on their surfaces for notice by a second part of the immune system. These displayed pieces of invaders trigger a massive, second wave of immune reactions led by T cells and B cells. While vital to body’s ability to combat infectious disease, full-scale immune responses cause disease-related inflammation and cell death when unleashed in the wrong place.

“We were surprised to find that blocking MHCII action rescued nerve cells from Parkinson’s disease mechanisms so quickly and completely,” said Ashley Harms, Ph.D, a postdoctoral scholar in the UAB Department of Neurology within the UAB School of Medicine, and lead author of the study. “The completeness of the rescue argues that this mechanism is at the heart of the immune-mediated aspect of Parkinson’s disease.”

The idea that the immune system plays a major role in Parkinson’s disease has been gaining momentum since September 2010, when a paper published by another group in Nature Genetics found that small changes in the gene for human leukocyte antigen, one piece of the MHCII complex, occurred much more often in patients with Parkinson’s disease.

Parkinson’s disease is the most common neurodegenerative movement disorder, with the steady loss of nerve cells eventually causing patients’ limbs to shake or become rigid. While much about its cause is still unknown, researchers agree than an early step in the disease is the build-up of a protein called alpha-synuclein in nerve cells, which causes them to self-destruct.

Once alpha-synuclein builds up, the question becomes whether immune cells in a given person’s brain will handle the buildup well or ramp up a misplaced, cell-killing immune response. The current study suggests that genes in microglia, the first-responder immune cells of the brain, are triggered to make many more MHCII complexes on their surfaces. This, in turn, enables more T cells to release chemicals called cytokines designed to kill bacteria, but that also destroy nearby human cells.

Conversely, mice genetically engineered to have alpha-synuclein build-up were protected against Parkinsonian nerve cell death when the current study authors shut down their gene coding for the MHCII complex in microglia.

Moving forward Harms and colleagues will seek to learn more about the relationship between MHCII and alpha-synuclein in hopes of informing drug design efforts. The team will, for instance, seek to learn whether it is a piece of alpha-synuclein, or of some related protein, which MHCII displays to trigger a larger immune reaction. They will also shut down the function of each protein in the MHCII complex to see which is most involved in the immune escalation.

“Alpha-synuclein may light the fire, but it appears that inflammation keeps it burning and may be responsible for the progression of Parkinson’s disease from year to year,” said David Standaert, M.D., Ph.D., chair of the UAB Department of Neurology and the study’s corresponding author.

He added that understanding the role of the immune system in Parkinson’s disease is a major research focus with the UAB Department of Neurology. Along with the work on the MHCII complex, another team is looking at whether interfering with an enzyme called leucine-rich repeat kinase 2 or LRRK2 can stop disease progression. LRRK2, like MCHII, is a critical player in the body’s immune response to alpha-synuclein buildup.

Along with Harms and Standaert, Shuwen Cao, Aaron Thome and Xinru Li in the UAB Center for Neurodegeneration and Experimental Therapeutics, Amber Rowse in the UAB Department of Microbiology, Leandra Mangieri and John Shacka in the UAB Department of Pathology, Chander Raman in the UAB Department of Medicine, and Randy Cron in the Division of Rheumatology, part of the Department of Pediatrics at Children’s Hospital of Alabama, made important contributions to the study. The work was supported by the RJG Foundation and the National Institutes of Health.                        

UF study finds brain-imaging technique can help diagnose movement disorders

Allison Vitt
University of Florida - A new University of Florida study suggests a promising brain-imaging technique has the potential to improve diagnoses for the millions of people with movement disorders such as Parkinson’s disease.

Utilizing the diffusion tensor imaging technique, as it is known, could allow clinicians to assess people earlier, leading to improved treatment interventions and therapies for patients.

The three-year study looked at 72 patients, each with a clinically defined movement disorder diagnosis. Using a technique called diffusion tensor imaging, the researchers successfully separated the patients into disorder groups with a high degree of accuracy.

The study is being published in the journal Movement Disorders.

“The purpose of this study is to identify markers in the brain that differentiate movement disorders which have clinical symptoms that overlap, making [the disorders] difficult to distinguish,” said David Vaillancourt, associate professor in the department of applied physiology and kinesiology and the study’s principal investigator.

“No other imaging, cerebrospinal fluid or blood marker has been this successful at differentiating these disorders,” he said. “The results are very promising.”

Movement disorders such as Parkinson’s disease, essential tremor, multiple system atrophy and progressive supranuclear palsy exhibit similar symptoms in the early stages, which can make it challenging to assign a specific diagnosis. Often, the original diagnosis changes as the disease progresses, Vaillancourt said.

Diffusion tensor imaging, known as DTI, is a non-invasive method that examines the diffusion of water molecules within the brain and can identify key areas that have been affected as a result of damage to gray matter and white matter in the brain. Vaillancourt and his team measured areas of the basal ganglia and cerebellum in individuals, and used a statistical approach to predict group classification. By asking different questions within the data and comparing different groups to one another, they were able to show distinct separation among disorders.

“Our goal was to use these measures to accurately predict the original disease classification,” Vaillancourt said. “The idea being that if a new patient came in with an unknown diagnosis, you might be able to apply this algorithm to that individual.

He compared the process to a cholesterol test.

“If you have high cholesterol, it raises your chances of developing heart disease in the future,” he said. “There are tests like those that give a probability or likelihood scenario of a particular disease group. We’re going a step further and trying to utilize information to predict the classification of specific tremor and Parkinsonian diseases.”

Vaillancourt and his team are part of the National Institute of Neurological Disorders and Stroke Parkinson’s Disease Biomarkers Program, an effort that was launched in 2012 and awarded nine grants to scientists across the U.S., totaling more than $5 million in the first year. The program gives researchers access to a much broader community of individuals and patients as part of a biomarker initiative for Parkinson’s disease.

Vaillancourt’s team is engaged in a longitudinal study at UF that will assess between 150 and 180 people over the next few years. His team will be using DTI as well as other MRI-based techniques to classify subjects and track their progression, he said.