Marijuana-Like Compound May Slow Alzheimer's
And the club drug Ecstasy is giving scientists clues to Parkinson's disease

A new U.S. study finds that marijuana may help slow the progression of Alzheimer's disease, while a second report suggests the "club drug" Ecstasy could yield insights into Parkinson's disease.

Both findings were presented Wednesday at the annual meeting of the Society for Neuroscience, in Atlanta.

In the first presentation, researchers from Ohio State University in Columbus found that marijuana may contain compounds that can slow memory loss associated with Alzheimer's disease.

In their study involving rats, a team led by psychology professor Gary Wenk searched for ways to reduce Alzheimer's-linked brain inflammation.

Wenk was already familiar with data that found that long-term marijuana users had lower rates of Alzheimer's disease than the general population. His team sought to find a compound that might reduce disease-linked brain inflammation but avoid the drug's psychoactive effects.
"We are using a component of marijuana that stimulates the same centers in the brain that marijuana does," Wenk said. The synthetic compound, which is very similar in composition to marijuana, is called WIN-55212-2 (WIN).

Experiments conducted on young and old rats revealed that WIN is "a very effective anti-inflammatory, it reduces brain inflammation," Wenk said.

What makes this discovery special is that this compound can cross the blood-brain barrier, Wenk explained. The results of a special rat "maze test" suggested that WIN "also reversed the memory impairment in the older rats," he said.

Brain inflammation is characteristic of many diseases other than Alzheimer's, including multiple sclerosis, ALS, AIDS, Huntington's and Parkinson's, Wenk noted. "We are beginning to notice that brain inflammation is always in the background as people get older," he said. "Inflammation doesn't cause the disease, it contributes to the pathology," he said.

WIN is not appropriate for use in humans because it still contains substances that may trigger a "high." However, Wenk hopes that some form of this compound might be used to benefit people with neurological diseases.

"We have the added advantage that millions of doses [of marijuana] have been taken by millions of people over the past centuries," he said. "We already know a lot about its actions in the body and its toxicity, or lack of toxicity. The only problem we have is that it's illegal."

Wenk is not suggesting that Alzheimer's patients start using marijuana. "Patients would have to be so careful not to get too much," he said. "That would only worsen the symptoms of their dementia."

The challenge is to find a dose that has an anti-inflammatory effect but does not make patients high, Wenk said. "It's hopeful," he said, "but it's not a therapy until we find a way to make it work in humans."

One expert believes it may be possible to derive therapeutic benefits from marijuana without inducing other effects that could be harmful to Alzheimer's patients.

"These are still early days for thinking about drugs derived from cannabis," said Dr. Samuel Gandy, director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia.

"Still, we know the structure of tetrahydrocannabinol (THC) [the active ingredient in cannabis] in detail, and it is not inconceivable that helpful THC-based drugs could be created chemically that benefit brain function but lack the 'high' that currently stigmatizes the compound," Gandy added.

In the second report, researchers from the University of Cincinnati found that, in rats, MDMA (methylenedioxymethamphetamine) -- more commonly known as the illegal drug Ecstasy -- increases the survival of dopamine-releasing cells in the brain during fetal development.
"The club drug Ecstasy can cause dopamine neurons to grow and prevent them from dying off," explained lead researcher Jack Lipton, a professor of psychiatry.

Dopamine cells are critical to the regulation of voluntary movement. This discovery might lead to better therapies for neurological diseases such as Parkinson's, the researchers said.
Ecstasy, as is, is not beneficial for Parkinson's patients, Lipton cautioned. But a part of MDMA may be.

The trick now is to find the components of MDMA that have this effect on dopamine cells and develop ways to use it to help Parkinson's patients, Lipton said. It could also be used as an adjunct to stem cell transplantation, something that's now being studied in Parkinson's patients.
"It could help transplants take better and have more cells survive," Lipton said.

There's more on Alzheimer's disease at the Alzheimer's Association.

This is a story from HealthDay, a service of ScoutNews, LLC.

'Mediterranean' Diet May Cut Alzheimer's Risk
Omega-3 fatty acid supplements might also help, another study shows

People who eat a "Mediterranean" diet rich in fruits, vegetables, olive oil, legumes, cereals and fish have a lower risk of developing Alzheimer's disease, U.S. researchers report.

"We have confirmed the association of a Mediterranean diet with Alzheimer's disease," said lead researcher Dr. Nikolaos Scarmeas, an assistant professor of neurology at Columbia University Medical Center in New York.

This benefit does not appear to be due to the diet's effect on blood vessels, Scarmeas added. "The diet could be helping avoid Alzheimer's disease by protection from oxidative stress or by reducing inflammation in the brain," he said.

Another study finds that taking omega-3 fatty acid supplements slows cognitive decline in some patients with very mild Alzheimer's disease. However, supplements do not appear to affect people with more advanced cases of the disease, according to a team of Swedish researchers.
Both reports appear in the online October issue of the Archives of Neurology.

For the diet study, Scarmeas's team collected data on almost 2,000 people averaging 76 years of age. Of these, 194 had developed Alzheimer's. The researchers analyzed each person's diet during the previous year and scored the diet based on how closely it followed what's known as the Mediterranean diet, which also includes mild-to-moderate drinking and little intake of red meat. Scores ranged from zero to 9. Higher scores were given for closely following a Mediterranean diet.

People who closely followed that regimen had a significantly lower risk for Alzheimer's disease, the researchers found. For each additional point on the diet score, risk for Alzheimer's was reduced by 19 to 24 percent.

In fact, people in the top one-third of diet scores had 68 percent lower risk of developing Alzheimer's disease, compared with people in the bottom third. In addition, people in the middle third had a 53 percent lower risk of developing the disease.

While the jury is still out on whether a Mediterranean diet actually protects people from developing Alzheimer's disease, Scarmeas believes that the other health benefits of the diet are clear.

"It seems that this diet is [health] protective," Scarmeas said. "Taking into account that this diet is protective for other conditions such as coronary heart disease, heart attack, high blood pressure, obesity and a series of cancers, it seems to make sense to follow this diet anyway, and the diet may also protect from Alzheimer's disease."

In the second report, a team led by Dr. Yvonne Freund-Levi from the Karolinska Institutet in Stockholm, looked at the effects of omega-3 fatty acids supplements on 204 patients with Alzheimer's disease.

After six months, among the 174 people who completed the trial, the researchers found no difference in cognitive decline among people taking omega-3 fatty acids supplements at different doses or placebo.

However, for a subgroup of 32 patients with very mild cognitive impairment at the beginning of the study, those taking the supplements experienced less cognitive decline compared with those who took placebo, the researchers found.

And when patients who took placebo during the first six months were given omega-3 fatty acids supplements, their cognitive decline decreased during the second six months of the trial.

"The mechanisms by which omega-3 fatty acids could interfere in Alzheimer's disease pathophysiologic features are not clear, but since anti-inflammatory effects are an important part of the profile of fish oils, they are conceivable also for Alzheimer's disease," the researchers write. "It is possible that when the disease is clinically apparent, the neuropathologic involvement is too advanced to be substantially attenuated by anti-inflammatory treatment."
One expert said that, given the other health benefits of fish oil, it certainly can't hurt patients to take supplements.

"I am happy to tell people that if they want to reduce their risk for Alzheimer's, they should reduce their cardiovascular disease risk factors and take fish oil," said Greg M. Cole, a neuroscientist at the Greater Los Angeles VA Healthcare System, and the associate director of the Alzheimer's Disease Research Center at UCLA's David Geffen School of Medicine.
A second expert agreed that diet probably does influence the disease.

"The papers share a focus on the idea that diet plays a role in Alzheimer's, a consensus that has been building for the past five or six years," said Dr. Sam Gandy, the chair of the Medical and Scientific Advisory Council at the Alzheimer's Association and director of the Farber Institute for Neurosciences at Thomas Jefferson University.

"The common thread is that both papers point toward intervention at the earliest moment having a greater effect and the suggestion that prevention may have the greatest effect of all," Gandy said.

"Once the gooey amyloid material has accumulated and poisoned nerve cells and the cells have died, it is very hard to think seriously about repairing damage that severe," he added.
More information

There's more on Alzheimer's disease at the Alzheimer's Association.

This is a story from HealthDay, a service of ScoutNews, LLC.

Alzheimer's Study Raises Warning Flag
Target of drug development also critical to protection of neurons

Some bad news has emerged from a study of an enzyme that is a major target in the effort to find new drugs to fight Alzheimer's disease.

Beta-secretase plays an important role in development of the protein clumps called beta-amyloid that form in Alzheimer's disease and damage mental function, so researchers are looking for compounds that might inactivate it.

But now, scientists in Germany, Belgium and the United States report in the Sept. 21 online issue of Science that beta-secretase is also involved in myelination, the formation of a protective covering for nerve cells early in life. Interfering with that activity could cause lifelong nerve
damage, the researchers speculated.

The report is "a cautionary tale for scientists developing drugs today," but hardly a death blow to overall drug development for this neurodegenerative disorder, said Dr. Sam Gandy, director of the Farber Institute for Neurosciences in Philadelphia and chairman of the Alzheimer's Association medical and scientific advisory council.

The study was done in infant mice, when the protective covering forms, and "there may be no serious effects in adult life," Gandy noted.

Efforts to develop a beta-secretase inhibitor have run into problems anyway, he said. "It's very difficult to get inhibitors that are fully active and nontoxic," he explained. One practical problem is to get a pill that is small enough to be swallowed.

Furthermore, drug development efforts aren't limited to enzymes, Gandy noted. The new finding doesn't affect programs for other anti-clumping approaches or for immunotherapy, Gandy said. But, he added, "we have to be doubly cautious now that this has emerged."
Another paper in the same issue of the journal described animal experiments on the formation of the beta-amyloid clumps. The studies showed that injecting the abnormal proteins collected from Alzheimer's patients caused Alzheimer-like protein clumps in the animals.

Alzheimer's disease thus resembles brain conditions such as mad cow disease that are caused by prions, molecules which cause abnormal folding of proteins, said Lary C. Walker, a research professor in neurology at Emory University and a member of the research team.

The experiments in which abnormal beta-amyloid protein from the brains of Alzheimer's disease patients were injected into mice are part of an effort "to take our understanding of what causes the disease as far back as possible," Walker said.

The work, most of which was done at the University of Tubingen in Germany, might eventually have an application in treatment of the condition, he said. "If we can learn how the seeding process initiates these changes, we can think about different therapeutic possibilities," Walker said.

The formation of beta-amyloid protein clumps in the brain is a basic feature of Alzheimer's disease, he noted. "We have no idea now how these proteins are corrupted," Walker said. "That is what this animal model will be useful for."

More information
The latest on Alzheimer's research is available from the Alzheimer's Association.

This is a story from HealthDay, a service of ScoutNews, LLC.

Statin Therapy Linked to Regression of Coronary Atherosclerosis - CME Teaching Brief® - MedPage Today

Statin therapy was associated with a 5% or greater regression of coronary atherosclerosis when LDLs dropped substantially in the face of rising HDLs, according to researchers here.

These findings, derived from an analysis of four big clinical trials, suggest that statins led to both a reduction in LDLs and an increase of at least 7.5% in HDLs, Stephen Nicholls, M.B.B.S., Ph.D., of the Cleveland Clinic, and colleagues, reported in the Feb. 7 issue of the Journal of the American Medical Association.

"This, to our knowledge, is the first time that increases in HDL-C levels have been shown to be an independent predictor of a beneficial outcome with statin therapy," they said.

Nevertheless, it remains to be seen whether the atherosclerosis regression will translate to meaningful reductions in cardiovascular events, they added.

A large body of evidence supports a central role for lowering LDLs in the prevention of atherosclerotic cardiovascular disease. However, no data exist describing the relationship between statin-induced HDL increases and disease progression, Dr. Nicholls said.

To investigate the relationship between changes in LDL and HDL cholesterol and the atheroma burden in patients with coronary artery disease, the researchers combined the raw data from four prospective randomized trials in the U.S., North America, Europe, and Australia from 1999 to 2005.

In these trials, 1,455 patients (mean age 57.6) with angiographic coronary disease underwent serial intravascular ultrasonography while receiving statin treatment for 18 months or 24 months.

Of the patients 73% were men, 92% were white, the average body mass index was 30; 24% were current smokers, 76% had a history of hypertension, and 19% had a history of diabetes.

The trials included REVERSAL (Reversal of Atherosclerosis With Aggressive Lipid Lowering), CAMELOT (Comparison of Amlopidine vs Enalapril to Limit Occurrence of Thrombosis), ACTIVATE (ACAT Intravascular Atherosclerosis Treatment Evaluation), and ASTEROID (A Study to Evaluate the Effect of Rosuvastatin in Intravascular-Ultrasound Derived Indices of Coronary Atheroma Burden).

During statin therapy, the researchers reported that mean LDL cholesterol levels were reduced 23.5%, (P<0.001). Levels went from 124.0 mg/dL to 87.5 mg/dL.

HDL levels increased 7.5% (P<0.001). Levels increased from 42.5 mg/dL to 45.1 mg/dL.
Accordingly, the ratio of LDL-to HDL-C was reduced by 26.7%, from a mean of 3.0 to 2.1 (P<0.001). [MORE]

"PRESS RELEASE FROM JOHNS HOPKINS UNIVERSITY: CALL MADE FOR CHANGES IN WOMEN'S HEART DISEASE RISK-FACTOR LIST"
-- Family history and blood C-reactive protein should be added to traditional risk factors for all older women

Johns Hopkins cardiologists are calling for an expansion of the criteria widely used by physicians to detect and assess a postmenopausal woman's chances of developing cardiovascular disease, the leading cause of death among women in the United States.

In an editorial appearing in the Journal of the American Medical Association (JAMA) online Feb. 14, Roger Blumenthal, M.D., and colleagues say that a family history of heart disease and blood levels of a protein tied to vessel inflammation, C-reactive protein, should quickly be added to traditional assessments of women's risk of suffering a heart attack, stroke or severe chest pain (angina).

"Physicians should incorporate these factors into their testing and decision-making about which women are most likely to develop cardiovascular disease," says Blumenthal, an associate professor and director of the Ciccarone Preventive Cardiology Center at The Johns Hopkins University School of Medicine and its Heart Institute. "And physicians should intervene with lifestyle changes and drug treatment before symptoms start to appear," he adds. "Our best means of prevention is through early identification of those most at risk."

Blumenthal says these changes could help ameliorate the discrepancy between the death rate for men and women from cardiovascular disease, which has steadily declined for men over the last 20 years, but has remained relatively the same for women.

The new risk-factor list would strengthen existing assessment tools, including the Framingham Risk Estimate, which gauges how likely a person is to suffer a fatal or nonfatal heart attack within 10 years and calculates risk based on a summary score of such factors as age, blood pressure, cholesterol levels and smoking.

The Johns Hopkins experts base their editorial call on research conducted elsewhere and published in the same issue of JAMA, which looked at the predictive value of more than 35 risk factors not included in the Framingham score but reported to play a role in heart disease and stroke.

They found clear evidence that only family history and C-reactive protein, or hsCRP for short, had significant, additional predictive value in determining women really at moderate or high risk of future cardiovascular disease. The new method changed risk scores for at least 20 percent of the women studied.

"These are the best data yet to show how we should be assessing our female patients," says Blumenthal, whose own research showed in 2005 that the gold standard Framingham tool failed to identify approximately one-third of women over age 60 who had advanced hardening and narrowing of the arteries for their age and sex.

The latest findings are not surprising, the Johns Hopkins team says. Family history - where either a parent or a sibling suffered a coronary event - doubles a woman's own chances of arterial disease. High blood levels of C-reactive protein, in excess of 3 milligrams per liter, also double the risk. And the effects are multiplied if both factors are present, with a woman's risk rising almost fourfold.

Also in 2005, Blumenthal and his team suggested additional screening, using CT scans of the arteries and calcium scoring to better find women who would likely benefit from aspirin and statin therapy. Such additional tests, he says, should still be considered for those women with no symptoms and at least two traditional risk factors who are also undergoing lifelong drug therapy with aspirin and lipid-lowering drugs.

But, he notes, the latest analysis, which was funded by the Donald W. Reynolds Foundation, provides a thorough review of many potential risk factors and should be applied for all postmenopausal women. Results are available online at http://www.reynoldsriskscore.org/

Evaluation of the women in the current study included analysis of race, age, body mass index, menopause status, frequency of exercise, alcohol use, postmenopausal hormone use and dietary supplements of vitamin E, other multivitamins and aspirin. Blood factors studied were equally varied and included levels of homocysteine, creatinine, fibrinogen and hemogloblin A1C levels.

The information came from the U.S. Women's Health Study, which tracked for a decade more than 24,000 healthy women to see who developed coronary heart disease and who didn't. All women were over age 45.

"Our goal is to make heart attacks less likely to occur, and to do so by strongly considering therapies such as aspirin, cholesterol-lowering medications and, possibly, blood pressure medications for individuals at higher risk," says editorial co-author and cardiologist Erin Michos, M.D., a clinical fellow at Johns Hopkins.

In addition to researchers' call for change, Michos says that existing treatment guidelines, the 2001 National Cholesterol Education Program Adult Treatment Panel, which currently emphasize the Framingham score, should be revised to incorporate family history and hsCRP.

Assistance with the Johns Hopkins editorial was provided by Khurram Nasir, M.D., M.P.H.

Air Pollution Linked to Increased Cardiovascular Events and Death in Postmenopausal Women - CME Teaching Brief® - MedPage Today

Fine-particulate air pollution over time significantly increased the risk of first heart attack or stroke, as well as cardiac mortality, in postmenopausal women, researchers here reported.

Moreover, the risk increased as pollution worsened so that for every 10 µg per cubic meter increase in fine-particulate matter the risk of a cardiovascular event rose by 24% and the risk of death jumped by 76%, found Kristin A. Miller, M.S., of the University of Washington, and colleagues, in an observational study. (MORE...)

BREAKING NEWS: 18 MILLION U.S. MEN AFFECTED BY ER*CT*LE DYSFUNCTION - Lifestyle Changes Could Improve Male Sexu*l Function
(PRESS RELEASE FROM: Johns Hopkins University)

From: Johns Hopkins University
Date: February 1, 2007 3:00:00 AM MST
Johns Hopkins University Bloomberg School of Public Health
Office of Communications and Public Affairs

NOTE: Due to its subject matter, some words in this release have been edited to avoid its being captured by spam filters

FOR IMMEDIATE RELEASE
18 MILLION U.S. MEN AFFECTED BY ER*CT*LE DYSFUNCTION
- Lifestyle Changes Could Improve Male Sexu*l Function
More than 18 million men in the United States over age 20 are affected by er*ct*le dysfunction, according to a study by researchers from the Johns Hopkins Bloomberg School of Public Health.
The prevalence of er*ct*le dysfunction was strongly linked with age, cardiovascular disease, diabetes and a lack of physical activity. The findings also indicate that lifestyle changes, such as increased physical activity and measures to prevent cardiovascular disease and diabetes, may also prevent decreased er*ct*le function. The study is published in the Feb. 1, 2007, issue of the American Journal of Medicine.

"Physicians should be aggressive in screening and managing middle-aged and older patients for er*ct*le dysfunction, especially among patients with diabetes or hypertension," said Elizabeth Selvin, PhD, MPH, lead author of the study and a faculty member in the Bloomberg School of Public Health's Department of Epidemiology. "The associations of er*ct*le dysfunction with diabetes and cardiovascular risk factors may serve as powerful motivators for men who need to make changes in their diet and lifestyle."

For the study, the research team analyzed data from 2,126 men who participated in the National Health and Nutrition Examination Survey (NHANES). Men who reported being "sometimes able" or "never able" to get and keep an er*ct*on were categorized as having er*ct*le dysfunction, while men who reported being "always or almost always able" or "usually able" were not.

The overall prevalence of er*ct*le dysfunction among men in the United States was 18 percent. Men aged 70 and older were much more likely to report having er*ct*le dysfunction compared to only 5 percent in men between the ages of 20 and 40. Nearly half of all men in the study with diabetes also had er*ct*le dysfunction. And, almost 90 percent of all men with er*ct*le dysfunction had at least one risk factor for cardiovascular disease, including diabetes, hypertension, having poor cholesterol levels or being a current smoker. Men with er*ct*le dysfunction were also less likely to have engaged in vigorous physical activity within the month prior to participation in the study.

###
"Prevalence and Risk Factors for Er*ct*le Dysfunction in the U.S." was written by Elizabeth Selvin, PhD, MPH, Arthur L. Burnett, MD, and Elizabeth A. Platz, ScD, MPH. Selvin and Platz are with the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health. Platz and Burnett are with the James Buchanan Brady Urological Institute at Johns Hopkins Hospital.