Friday, April 13, 2012

Several intriguing new studies about Parkinson's Disease

WEDNESDAY, April 11 (HealthDay News) --

Some of the newer antidepressants can help treat depression in people with Parkinson's disease without aggravating other disease symptoms such as tremor or rigidity, researchers have found.


Nearly 1 million people in the United States are living with Parkinson's disease, a progressive movement disorder marked by tremor, slowness and/or rigidity. Parkinson's disease and depression tend to travel together, and there has been concern that some of the medications used to treat depression may worsen motor symptoms.

A new study published online April 11 and in the April 17 print issue of Neurology shows that this is not the case, at least when it comes to the antidepressants Paxil (paroxetine) and Effexor (venlafaxine).

Paxil is in the class of drugs known as SSRIs (selective serotonin reuptake inhibitors) while Effexor is an SNRI (serotonin and norepinephrine reuptake inhibitor).

In the new study of 115 people with Parkinson's disease, participants received Paxil, Effexor or an inactive "placebo" pill. The researchers followed-up with patients for 12 weeks and found that both antidepressants improved symptoms of depression without worsening some of the motor symptoms associated with the disease.

On average, those people who took Paxil had a 59 percent improvement and those receiving Effexor had a 52 percent improvement in scores on a standardized tool measuring depression. People who received the placebo had a 32 percent improvement. Three other depression-rating scales showed similar results.

The drugs did not lead to any worsening in motor symptoms, the investigators noted. Use of antidepressants did not improve anxiety levels, thought processes or overall health-related quality of life among the study participants.

Sleep problems were among the most commonly reported side effects. Weight gain was seen with Paxil and at the final study visit, an increase in sitting blood pressure was seen with Effexor, according to the report.

"Depression is the number-one factor negatively affecting the quality of life for people with Parkinson's disease," study author Dr. Irene Hegeman Richard, a neurologist at the University of Rochester Medical Center in Rochester, N.Y., said in a university news release. "It causes a great deal of suffering among patients. The great news here is that it's treatable. And when the depression is treated adequately, many of the other symptoms become much more manageable for patients."

Depression in Parkinson's disease is caused by the underlying disease process, not the stress of dealing with a chronic disease, she said.

Commenting on the study, Dr. Joe Verghese, a neurologist at the Albert Einstein College of Medicine in New York City, said the study provides good news for people with Parkinson's disease and depression. "There is always a concern that we may upset the applecart in Parkinson's by adding a new medication."

Dr. Roy Alcalay, an assistant professor of neurology at Columbia University Medical Center in New York City, agreed that treating depression in Parkinson's disease can be a delicate balance. "The new study validates what we have been doing," he said. "The medications used to treat depression in the general population work as well for Parkinson's disease, and there is no evidence that they have bad side effects on motor symptoms."

While the new study only looked at two antidepressants, "this doesn't mean that others don't work," Alcalay said. As to the robust placebo effect seen in the new study, he said that "just thinking that they are getting treated often helps people with depression."

Treating depression in Parkinson's is important, Alcalay said, and "the study helps us do so in a more educated way."

The U.S. National Institutes of Health/National Institute of Neurological Disorders and Stroke and the Johns Hopkins University School of Medicine funded the study. Wyeth Pharmaceuticals provided Effexor XR and the placebo, while GlaxoSmithKline provided Paxil.

SOURCES: Roy Alcalay, M.D., assistant professor of neurology, Columbia University Medical Center, New York City; Joe Verghese, M.D., neurologist, Albert Einstein School of Medicine, New York City; University of Rochester, news release, April 9, 2012; April 11, 2012, Neurology, online

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Statin Use May Slightly Reduce Risk of Parkinson’s Disease

Apr 10 2012 as reported by Parkinson's Disease Foundation

New research suggests that the class of popular cholesterol-lowering drugs called statins may play a role in protecting people from developing Parkinson’s disease (PD). The study, published in the March 2012 edition of the journal Archives of Neurology, found a modest link between statin use and rates of Parkinson’s disease.

Scientists have hypothesized in the past that statins may play both helpful and harmful roles in Parkinson’s. Statins are known to reduce inflammation, which is believed to play a role in Parkinson’s. However, statins have also been shown to reduce levels of co-enzyme Q10, an antioxidant that may protect against Parkinson’s.

Past studies evaluating the link between statins and Parkinson’s have had mixed results, with some showing a significant connection and others showing none at all. However, these studies were limited by design flaws. For example, they were neither large nor prospective (meaning studies that first documented statins use, and only later in follow-up documented which participants developed Parkinson’s).


In the present study, researchers from Harvard University led by Xiang Gao, M.D., Ph.D., carried out a prospective survey study over 12 years of 38,192 men and 90,874 women to determine whether the individuals had been taking statins, and whether those individuals subsequently developed Parkinson’s.

Results:

 In total, 644 people in the study developed Parkinson’s. Statin use was associated with a 25 percent decrease in the risk of developing Parkinson’s. It should be cautioned that this result was only marginally significant. A person’s age when initiating statin therapy was significant in determining their risk of developing Parkinson’s. People who began using statins before age 60 had a 70 percent lower risk of developing Parkinson’s. People who began using statins after the age of 60 did not see a reduced risk. Statins only showed a benefit for those who took the drugs six years or more.

What Does it Mean?

While this study finds a modest relationship between statin use and lower PD risk, the evidence for its use as a preventative therapy remains to be determined.

This study had advantages over previous studies. First, its sample size is quite large, and second, it followed people prospectively for a long time period. But it also has limitations. The researchers were not always able to determine whether the subjects were taking statins or other cholesterol-lowering drugs, and they also were unable to determine which type of statin was being used – a major issue because different statins may not be able to enter the brain as readily as others.

As in other epidemiological studies, an association does not necessarily mean causation. For example, it is possible that people who use statins regularly are more likely to adhere to the Mediterranean type diet (which, in the same groups, has shown to be linked to lower risk of Parkinson’s). Nevertheless, this link between statin use and lower Parkinson’s risk may provide direction for research that could perhaps lead to a better understanding of Parkinson’s in general.

Reference: Gao, X., Simon, K.C., Schwarzschild, M.A., Ascherio, A. Prospective Study of Stain Use and Risk of Parkinson Disease. The Archives of Neurology, March 2012, 69(3):380-384; doi: 10.1001/archneurol.2011.1060. Source Date: Dec 31 1969





Gene Mutation May Lead to Cognitive Symptoms in Parkinson’s

Parkinson's Disease Foundation- Apr 10 2012


Mutations in a particular gene may lead to cognitive deficits in people with early-onset Parkinson’s disease (PD), according to new research published in the May 1 issue of the journal Neurology. The findings suggest that mutations to the gene, called GBA, are risk factors for the development of cognitive symptoms in people with Parkinson’s. Mutations in GBA are found in roughly five percent of all people with Parkinson’s, and are more common in Ashkenazi Jews, where one in four or five people with Parkinson’s are carriers a GBA mutation.

Research has shown that over 80 percent of people with Parkinson’s eventually develop cognitive symptoms as a result of the disease. However, little has been known about how such cognitive symptoms develop and why they occur in some people with Parkinson’s but not others.

Research has also shown that mutations to the GBA gene are a risk factor for developing Parkinson’s, and lead to the development of Lewy bodies in the brain, which have been related to cognitive symptoms in people with PD. But no study had demonstrated a link between mutations to the GBA gene and changes in cognitive behavior.


In this study, a large team of scientists from the PDF Research Center at Columbia University Medical Center led by Roy Alcalay, M.S., M.D., studied the effects of mutations to the gene GBA on behavior. To study this, the Columbia team administered a range of behavioral and cognitive tests to people with PD, some of whom had mutations to the GBA gene and some of whom did not.

Results:

Of 147 total people with Parkinson’s that were enrolled in the study, 33 had mutations in the GBA gene. To age match the two groups, researchers studied a final group that included 33 people with GBA mutations and 39 non-carriers of such mutations.

There were no differences in demographic details such as age, gender, or education between the two groups.

People with GBA mutations had lower scores on the Mini-Mental State Exam, a common test of cognitive function.

In particular, carriers of GBA mutations performed significantly worse on tests of memory and visuospatial function than those who did not have GBA mutations.

What Does it Mean?

These results provide strong evidence that mutations to the GBA gene contribute to the development of cognitive symptoms in people with Parkinson’s. While it is likely that there are other genetic mutations and environmental factors that also contribute to cognitive decline in Parkinson’s, these findings represent an important step toward understanding this particularly concerning set of symptoms for people with Parkinson’s.

The implications of these findings are that clinicians may be able to use genetic testing to better predict the risk of cognitive problems in people with Parkinson’s. In addition, this study highlights the importance of the GBA pathway in cognitive function in people with Parkinson’s.

There is currently no known treatment to aid the symptoms that result from mutations to the GBA gene. However, it is possible that treatments will be developed in the future that specifically target the pathology and symptoms of GBA mutations. Future studies – for example, testing whether interventions targeting the GBA pathway may help cognitive function in PD – are required.

The results of this study could allow for a behavioral means to determine which people with Parkinson’s are likely to benefit from such treatments.

Reference: Alcalay, R. N., Caccappolo, E., Mejia-Santana, H., Tang, M. X., Rosado, L., Orbe Reilly, M., Ruiz, D., et al. (2012). Cognitive performance of GBA mutation carriers with early-onset PD: The CORE-PD study. Neurology. doi:10.1212/WNL.0b013e318253d54b

Source Date: Apr 10 2012, Parkinson's Disease Foundation

1 comment:

  1. Here is a more recent article in regards to the statin/PD relationship (which challenges the above article):

    http://onlinelibrary.wiley.com/doi/10.1002/mds.26152/abstract

    Abstract
    Previous findings on the association of statins, plasma lipids, and Parkinson's disease (PD) are confounded by the fact that statins also affect lipid profiles. We prospectively examined plasma lipids and statin use in relation to PD in the Atherosclerosis Risk in Communities (ARIC) Study. Statin use and plasma lipids were assessed at baseline (visit 1, 1987-89) and at three triennial visits thereafter (visits 2-4) until 1998. Potential PD cases were identified from multiple sources and validated where possible. The primary analysis was limited to incident PD cases diagnosed between 1998 and 2008. Odds ratios and 95% confidence intervals were derived from multivariate logistic regression models. Statin use was rare at baseline (0.57%) but increased to 11.2% at visit 4. During this time frame, total-cholesterol levels decreased, particularly among statin users. Fifty-six PD cases were identified after 1998. Statin use before 1998 was associated with significantly higher PD risk after 1998 (odds ratio = 2.39, 95% confidence interval 1.11-5.13) after adjusting for total cholesterol and other confounders. Conversely, higher total cholesterol was associated with lower risk for PD after adjustment for statin usage and confounders. Compared with the lowest tertile of average total cholesterol, the odds ratios for PD were 0.56 (0.30-1.04) for the second and 0.43 (0.22-0.87) for the third tertile (Ptrend = 0.02). Statin use may be associated with a higher PD risk, whereas higher total cholesterol may be associated with lower risk. These data are inconsistent with the hypothesis that statins are protective against PD.

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