Statins may not lower Parkinson's risk, experts say

Date:

February 19, 2015

Source:

Penn State

Summary:

The use of statins may not be associated with lowering risk for Parkinson's disease, according to a new study. The findings cast doubts

 on reports suggesting that the cholesterol-lowering medications may protect against this neurodegenerative brain disorder.

The use of statins may not be associated with lowering risk for Parkinson's disease, according to a new study led by researchers at Penn State College of Medicine and National Institute of Environmental Health Sciences. The findings cast doubts on reports suggesting that the cholesterol-lowering medications may protect against this neurodegenerative brain disorder.

According to the National Parkinson Foundation, Parkinson's disease affects about one million Americans and an estimated four to six million people worldwide. Although the cause of PD is unknown, damage to dopamine-producing neurons eventually leads to the movement disorders that are a hallmark of the disease.

Xuemei Huang, professor of neurology and vice chair for research, Penn State College of Medicine, previously reported an association between high blood cholesterol levels and lower incidence of PD. A low incidence of heart attack and stroke in PD patients in movement disorder clinics, despite their usually advanced age motivated these studies. Other studies also reported similar findings.

However, evidence has been somewhat inconsistent. The use of statins has also been associated with a lower incidence of PD in several recent epidemiology studies, leading some researchers to hypothesize that these medications, which lower levels of LDL -- bad cholesterol -- may protect against PD. Those studies, however, failed to account for cholesterol levels prior to the widespread use of statins in the U.S. population, Huang said, noting that as a strength of the new study.

The researchers looked at blood cholesterol levels, medications and PD status in participants in the ongoing, long-term Atherosclerosis Risk in Communities study. Cholesterol readings were taken at three-year intervals over the course of a decade from 1987 to 1989, before widespread statin use began.

"We confirmed our previous finding that high total cholesterol and LDL cholesterol were associated with a lower risk of PD," Huang said. "Moreover, statin use over the course of the study did not protect against PD, and in fact appeared to increase PD risk in the long term. Although the analysis on statin use and PD was based on a fairly small number of PD cases, this preliminary data argues against the hypothesis that statins protect against PD."

The researchers reported their finding in the journal Movement Disorders.

"One possibility," Huang said, "is that statin use can be a marker of people who have high cholesterol which itself may be associated with lower PD risk. This could explain why some studies have found an association between use of these medications and low incidence of PD. Most importantly, this purported benefit may not be seen over time."

Future research should focus on if and why cholesterol may protect against PD. Although blood cholesterol is not indicative of cholesterol in the brain, there is increasing evidence that PD may begin outside the brain. Statin-induced decreases in blood cholesterol levels may have unknown consequences in these peripheral areas. A compound called coenzyme Q10 that is produced alongside cholesterol may also be an area of future PD research. Statins reduce coenzyme Q10, which helps produce energy for cells and is hypothesized to have protective qualities in nerve cells.

"Statins have been proven to be effective in the primary and secondary prevention of cardiovascular events and stroke. Although some have proposed that statins might be a 'cure-all' drug," Huang said, "this might be a case where what's good for the heart isn't good for the brain."

An estimated 43 million Americans currently take statins or are eligible for statin therapy. Recent updates to American Heart Association guidelines are expected to increase that number to 56 million or more. The new guidelines recommend statin use for some patients without high cholesterol but who have other risk factors for heart disease and stroke.

"Statins have been very important for preventing and treating vascular disease, but we need more research to understand if in some cases there is collateral damage," Huang said.

Until more epidemiological and basic research can be conducted to further parse out the associations between PD, cholesterol and statins, physicians and scientists should be cautious in promoting health benefits of statins for PD without a good understanding of clinical evidence and potential biological mechanisms, Huang advises.

Patients and physicians considering statins for cardiovascular health and stroke prevention should consider their individual cases.

"This is evidence that personalized medicine is better than a one-size-fits-all approach," Huang said.

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Story Source:

The above story is based on materials provided by Penn State. The original article was written by Jennifer Abbasi. Note: Materials may be edited for content and length.

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Journal Reference:

1. Xuemei Huang, Alvaro Alonso, Xuguang Guo, David M. Umbach, Maya L. Lichtenstein, Christie M. Ballantyne, Richard B. Mailman, Thomas H. Mosley, Honglei Chen. Statins, plasma cholesterol, and risk of Parkinson's disease: A prospective study. Movement Disorders, 2015; DOI: 10.1002/mds.26152

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Penn State. "Statins may not lower Parkinson's risk, experts say." ScienceDaily. ScienceDaily, 19 February 2015. <www.sciencedaily.com/releases/2015/02/150219115734.htm>.

New growth factor indicates possible regenerative effects in Parkinson's disease

Researchers have long sought treatments that can slow the progression of Parkinson's disease. Current treatments have for decades been only symptomatic in nature, supplying the neurotransmitter dopamine, which the dying nerve cells can no longer produce. Results from a recent clinical study offer hope that future therapies could take advantage of the brain's own protective mechanisms to limit neuronal cell death and restore dopamine production to natural levels.

Researchers at Lund University and Karolinska Institutet have, in a first-in-man clinical study with twelve participating patients, applied a growth factor to the brain with the hope of preserving dopaminergic cells and fibers.

The growth factor, PDGF (platelet-derived growth factor), has previously demonstrated, in studies in animals with Parkinson-like symptoms, reparative effects on both neurons and nerve fibers, while also leading to improved motor skills.

The results of the current study in patients show that applying the growth factor does not cause any serious unresolvable side effects. Perhaps even more encouraging are the images of the patients' brains, produced four months after the delivery of the growth factor.

Using a PET scanner, researchers have seen that in patients who received the growth factor the signaling of dopamine not only stayed at the same level, but even increased.

"In Parkinson's disease patients lose nerve cells continuously, which means that we see signals indicating dopamine processing constantly decreasing. What we have seen is that the patients who received the highest dose did not have the same decrease in these signals as the placebo-treated patients. Instead, we have actually seen an increase in signaling here. This indicates that we may have managed to reverse this process which is obviously very exciting", says Gesine Paul, research group leader at Lund University who is the first author of the study.

Experiments when researchers first tested the growth factor in animals were launched over ten years ago and the journey towards clinical trials has been a long one. It is now hoped that the positive results can speed up the process towards broader clinical studies where treatment effects in patients will be evaluated further. Gesine Paul and her colleagues also hope to identify in detail the mechanisms underlying the complex process of reparation that the growth factor seems to initiate.

"There are currently no drugs that can repair the structures in the brain that are lost in Parkinson's disease. Although we still have a long way to go our study suggests that it may be possible to stimulate the brain's built-in protective mechanisms in order to slow or halt disease progression. If we are to fully take advantage of the growth factor's restorative properties we now need to better understand the underlying molecular processes. Next, we proceed with new clinical studies in Sweden, England and Germany", says Gesine Paul.

The published study and forthcoming studies are performed in collaboration with the Swedish biotech company Newron Sweden (former Neuronova) and financial support has been received from Vinnova and the European Commission. 

Having Parkinson's since I was 13 has made me an expert in self-care

When I was 13 years old, I experienced the first symptoms of what almost 20 years later would be diagnosed as Parkinson’s disease. Getting Parkinson’s in your teens is pretty unusual, if not rare. Nevertheless, I am happy that I wasn’t diagnosed with an “old person’s disease” in my teens. I am convinced that if I had known when I was 16 that the problems I experienced with movement, gait and balance were due to Parkinson’s, I would not have gone to university, got my driver’s licence or dared to start a family with the man I met at university.

In Sweden, as in the UK, Parkinson’s is mainly managed with medication prescribed by a neurologist, preferably combined with physical activity. But most of the care in chronic diseases is not delivered in healthcare. I visit my neurologist two times a year, for about 30 minutes. The rest of the year’s 8,765 hours, I spend in self-care, taking care of myself the best way I can. During the one hour per year with my neurologist, he assesses my symptoms, answers my questions and prescribes the medication I take six times a day, in five different combinations. But frankly, he doesn’t know if I take my medications or not.

Compassionate care – a superpower or just part of the job?

Maria Davison

Read more

This is why self-care is so important. I am the only person with the whole picture. To me, self-care is everything I do to stay as healthy as possible with a disease that is a difficult life companion. It entails everything from making sure I take my medication in the optimal way, to eating healthily, getting enough sleep, to making sure I stay physically active. I also make an effort to learn as much as I can about my condition; my neurologist says that I know more about Parkinson’s research than he does. I don’t find that odd, since he needs to try to stay on top of research in probably hundreds of neurological diseases, whereas I focus on just one.

I have never been one for much exercise and I didn’t enjoy sports growing up, probably because it was really hard work for me getting my body to move. Now, however, I know how important physical activity is for me to stay well and I use an activity tracker to measure how many steps I take every day, how much sleep I get and what quality it is. This makes me feel more in control of my Parkinson’s, because I know more about my condition and better understand why I am feeling really “Parky” after a night of bad sleep. It also enables me to see that the exercise I do really does have a positive effect.

Why can’t patients receive blood results via text or use Skype for appointments?

Michael Seres

My strongest weapon against Parkinson’s is self observation. Sometimes I use technology and sometimes just a pen and paper. I use a finger tapping app to evaluate how the effects of my medication varies over the day and as a result have been able to optimise my medication regime. My neurologist welcomes discussions based on data I bring to appointments. We both agree that it would be ideal if the data I collected could be pulled into my healthcare record, but Sweden is not quite ready for that yet.

Besides being a patient, I am also a doctoral student in health informatics at Karolinska Institute in Stockholm, where I use my self-monitoring experience as the basis of my research. I am working closely with fellow Parkinson’s patients to develop and research tools that can improve our condition. I often present my work to different audiences: other researchers, fellow patients, healthcare professionals or policy makers. And almost every time, someone says: “But Sara, you are not a typical patient! You have to think about the old, the less engaged and the non-techies!”. To some degree, this is a generational issue, since older people tend to see physicians as more of an authority. But it is a myth that older people are reluctant to use new technology.

I am also active in patient advocacy circles internationally. This movement is growing stronger and consists of active, engaged patients, often with serious health challenges, who believe strongly in autonomy. We are convinced that the person with the biggest interest in their health, as well as the opportunity to do something about it, is oneself. And we want to work together with the healthcare system to achieve the best health we possibly can. After all, my health is my responsibility.

Sara Riggare will be speaking at the Nuffield Trust health policy summit on 26 and 27 February.

In the illustration below, the red circle signifies the hour in which I am in direct contact with neurological speciality care. The blue dots are the 8,765 hours in selfcare, applying my knowledge and experience together with what I get from my neurologist to manage a difficult condition as best I can.

Dying former official a focus of Maryland assisted suicide bill

At Ginger Cove Health Center, McShane Glover, left, reads a draft of the death with dignity bill to Richard "Dick" Israel, who has Parkinson's disease. (Algerina Perna / Baltimore Sun)

By Erin CoxThe Baltimore Suncontact the reporter

• Laws and Legislation
• Elections
 
• Trials and Arbitration
 
 
• Euthanasia
• Michael E. Busch
 
• Maryland General Assembly

A friend asks state lawmakers to allow Death with Dignity

Dick Israel, who advised the General Assembly for years, asks them to pass assisted suicide law.

It's been more than 15 years since Dick Israel's body started to revolt.

Back then, in the early days of his Parkinson's disease, Israel still wrote legal opinions in flowery script from an old-fashioned fountain pen, churning out advice for the General Assembly. He charmed political giants with a wry wit, delivered in a baritone that seemed several octaves too deep for his short stature.

Now he never leaves his hospice room.

His booming voice has become a rumble, his clever words tumbling out slowly in a nearly undecipherable growl. A hospital gown has replaced his trademark straw hat and bow tie.

Richard E. Israel, 72, spent more than two decades behind the scenes in Annapolis guiding lawmakers. Now he plans to spend his final months alive lobbying them from afar, advocating for the right to die when he chooses, a final act of control over a disease that robbed him of it.

CAPTIONDick Israel

Algerina Perna / Baltimore Sun

Former Annapolis Ward One Alderman Dick Israel, who has Parkinson's disease, looks through old pictures while in Ginger Cove Health Center.

CAPTIONDick Israel

Algerina Perna / Baltimore Sun

At Ginger Cove Health Center, McShane Glover is pictured with a draft of the death with dignity bill which she read to Richard "Dick" Israel, who has Parkinson's disease.

CAPTIONDick Israel

Algerina Perna / Baltimore Sun

At Ginger Cove Health Center, McShane Glover, left, reads a draft of the death with dignity bill to Richard "Dick" Israel, who has Parkinson's disease.

CAPTIONDick Israel

Algerina Perna / Baltimore Sun

W. Minor Carter, a lobbyist for the Richard Israel "death with dignity" bill, sits by the bedside of its author. Former Annapolis Ward One Alderman Dick Israel, who has Parkinson's disease, is pictured in Ginger Cove Health Center.

CAPTIONDick Israel

Algerina Perna / Baltimore Sun

Regina Brady, a friend of and helper to former Annapolis Ward One Alderman Dick Israel, who has Parkinson's disease, pulls out earlier pictures of him from a file in his room at Ginger Cove Health Center.

"It's about having a choice for others, not just for me," Israel said, each word taking a full second to articulate. "Death is inevitable. The question is when and how."

Israel volunteered for the legislative fight, but only reluctantly agreed to lend his name to a bill that would legalize "death with dignity" in Maryland. His friends convinced him that the measure would be more likely to pass in his memory than on the strengths of its arguments alone. It was a tough sell for the legal scholar who also served two terms as an Annapolis alderman and values the true meaning of the law above politics.

In all likelihood, even if the bill passes, Israel's medical struggle will end before anyone benefits from a law that bears his name.

A wave of such bills has garnered support across the country, sparked by the high-profile advocacy of 29-year-old Brittany Maynard, who had a terminal brain tumor and moved to Oregon to legally end her own life.

Legislatures from New York to Oklahoma, Wyoming to California are also considering bills this year — more than 15 in total. Lawmakers in another five states plan to introduce bills, too, a rapid reversal from the nationwide tide of physician-assisted suicide bans that followed the infamy of Dr. Jack Kevorkian in 1999.

That same year, Israel was dispensing legal advice on the budget when the Maryland legislature voted to make physician-assisted suicide a felony. It was also the year he first noticed symptoms of Parkinson's.

National advocates say Israel's choice to lead the movement here made Maryland one of four East Coast states where they'll target resources. Activists used to focus on one state at a time, and so far have passed laws in three states in the past two decades. But the tremendous shift in the political landscape has them rethinking strategy this year.

Maryland strips doctor of license for assisting in six suicides

"Maryland came in because of Dick Israel," said Peg Sandeen, executive director of the Death with Dignity National Center. The state was under consideration as a target anyway, but "when you add someone who is willing to give a face to the campaign, who people know and understand, that makes a big difference."

The proposed law would allow a doctor to prescribe a life-ending drug for certain terminally ill patients, under a wide-ranging list of conditions and after a waiting period.

The bill also is named after former Annapolis Mayor Roger "Pip" Moyer, a political mentor to both House Speaker Michael E. Busch and Senate President Thomas V. Mike Miller. Moyer, renown for his ability to quell racial tensions in the late 1960s, died Jan. 10, two decades after he was diagnosed with Parkinson's.

But it's Israel and his painful decline that's expected to resonate most with lawmakers.

Former Annapolis Alderman Richard Israel, who is battling Parkinson's Disease, has lent his name to a right-to-die bill that is being presented during the General Assembly. (Algerina Perna/Baltimore Sun)

The medication that diminishes his tremors also weakens muscle control. He has a small window each afternoon when the drugs wear off enough to let him regain his speech before he takes the next dose. A lifelong bachelor, he packs that hour with visits from the many friends accumulated in Annapolis — lobbyists, top legislators and judges smitten with the Kansas-raised lawyer who chose to speak with the elongated cadence of a British aristocrat.

"You have to call ahead to make a reservation, no doubt about it," said Robert A. Zarnoch, a Court of Special Appeals judge who was Israel's boss for 25 years.

He said Israel's dry, cerebral humor resonated with the Annapolis political elite, including his frequent quip: "You should never say it writing when a wink will do."

"It's not like he's dying alone," Zarnoch said. "His friends are around him, and they want to take care of him."

He needs help, in part, to dictate his final wishes. His dry eyes, a condition related to Parkinson's, make it impossible for him to read a computer screen, which meant that late last year, he lost the ability to communicate by email. Friends read books and articles to him, and they write down, word for word, how he thinks Maryland should legalize death with dignity.

At the end of his long list of legal conditions that must be met to qualify for the program, Israel dictated his philosophy on the subject, directed more by his pragmatism than his life as a devout Episcopalian.

"Modern science has prolonged life without giving us insight into the meaning or purpose of life," he said. "The purpose of this legislation is to restore the role of science as a servant of humanity, not the master."

Modeled after the law in Washington state, the bill would apply only to a patient who is mentally competent and likely to die from terminal illness within six months. The patient must undergo a 15-day waiting period and be able to take the drug without help, among many other conditions. Old age and disabilities alone would not qualify someone for an aid-in-dying drug.

Del. Shane Pendergrass had been debating whether to introduce legislation this year or next, when Israel's friends approached her. The Howard County Democrat said the conversation brought back searing memories of her grandfather's battle with Parkinson's in the 1960s.

She volunteered to sponsor the Richard E. Israel and Roger "Pip" Moyer Death with Dignity Act, which was introduced Friday with 37 co-sponsors. In the Senate, Sen. Ron Young, a Frederick County Democrat, also sponsored a version.

Pendergrass anticipates a debate with religious groups and disability advocates who tend to oppose such measures across the country.

Howard legislator is primary House sponsor for death with dignity bill

"This is about people who need to exit pain at the end of life," Pendergrass said. "This is law and not religion. I would hope this is kept as an issue of human dignity."

Mary Ellen Russell, executive director of the Maryland Catholic Conference, said her group also believes it's a matter of dignity to help people nearing death feel as though their life still has value.

She said the Catholic lobby doesn't plan to make fighting the bill a top priority, although they don't support it. Beyond religious objections, Russell predicted it could spark a "suicide contagion" effect, in which condoning the hastened death of the terminally ill undermines the value of life. "It sends a message that it's OK to do this."

Suicide rates in Oregon, which has had a death with dignity law since 1997, are as much as 40 percent above the national average and have been climbing since 2000, according to a 2012 report by that state's health department.

Gov. Larry Hogan, who is Catholic, told the Catholic Standard in September that he would oppose any efforts to legalize assisted suicide in Maryland. "I believe in the sanctity of human life, and I believe a physician's role is to save lives, not terminate them," he said.NATION/WORLD

On Thursday, the new Republican governor was less clear about his administration's view of the issue, saying, "We'll let you know if we've taken a position on it."

In decline

At Ginger Cove Health Center, on a day when Israel again could not speak, a friend handed him a worn piece of paper with the alphabet on it. Letter by letter, holding a pencil he used as a pointer, Israel spelled out the story of how he first noticed his muscles would not obey him. He was walking to work along West Street, watching other people swinging their arms. His right arm was motionless.

As he spelled, another friend took down each letter and tried to take a short cut. Israel spelled the entire sentence twice more, until she replaced "wasn't moving" with "was not moving."

Flags and a name plate sit on top of a file cabinet in Dick Israel's room at Ginger Cove Health Center. Former Annapolis Ward One Alderman Dick Israel, has Parkinson's disease. His "death with dignity" bill will be introduced in the senate. (Algerina Perna / Baltimore Sun)

Miller, who has known Israel for three decades, burst into laughter at the retelling of the anecdote. "That's Dick. He's so precise."

Israel's room is festooned with paraphernalia from Maryland law and his years in Annapolis, interspersed with medical devices.

As his health declined, he continued to serve as an alderman, poring over stacks of documents each weekend and hanging out for hours every Saturday at an Annapolis coffee shop in case an constituent wanted to visit.

Once he toppled out of his seat during city council meeting. Another time, he missed a meeting because he'd fallen and spent seven hours on floor of his bathroom. Afterward, he wryly joked he was reconsidering budget cuts for the Fire Department that rescued him.

Today, the poster-sized "Dick Israel, Ward 1 Alderman" magnets he made for marching in parades decorate the air conditioning unit in his room. He used them for the last time on July 4, 2013, a few months after he resigned his seat on the Annapolis city council because he had to move into a nursing home outside his district.

For the parade, he insisted the phrase "ex-" be affixed to his title, to be precise and to not detract from the alderman who replaced him.

Richard E. "Dick" Israel

Born: Hutchinson, Kan.

Education: B.A., University of the South; LL.B., Washington and Lee University; M.A., Oxford University

Professional: Lawyer, counsel to Maryland General Assembly for 25 years

Public service: Annapolis alderman, 2005-2013

Personal: Single. 40-year member of St. Anne's Parish, Annapolis

• The humane thing to do is to pass this bill. You never know if you will need to take advantage of it until the time comes.
  NICK SHERIDAN
  AT 4:15 AM FEBRUARY 16, 2015
  
  
  
  
  
  
  
  http://www.baltimoresun.com/news/maryland/politics/bs-md-dick-israel-20150214-story.html#page=1 

  NPR host Diane Rehm emerges as a key force in the right-to-die debate