Several Therapies Show Promise for Vascular Depression

WEDNESDAY, May 7 (HealthDay News) -- New treatments for a type of depression in the elderly related to blood vessels -- called vascular depression -- are under development, and researchers have discovered why some patients with this condition fail to respond to current medications.

Details of the findings were to be presented Wednesday during a news conference by researchers taking part in U.S. National Institute of Mental Health symposiums at the annual meeting of the American Psychiatric Association, in Washington, D.C.

Vascular depression is a recently recognized type of depression that usually develops in patients older than age 60. The condition is associated with loss of blood supply to the brain.

"Mental health practitioners and patients should be aware of the relationship between vascular problems and depression, and should understand the value of preventing vascular changes that might lead to difficult-to-treat depressions, for example, through early recognition and treatment of high blood pressure," Dr. John Newcomer, of Washington University in St. Louis, said in a prepared statement.

Several research teams are reporting progress in understanding and treating vascular depression.

Dr. George Alexopoulos of Weill Cornell Medical College in White Plains, N.Y., and colleagues are investigating the specific brain abnormalities associated with blood vessel problems. Using a new MRI technique called diffusion tensor imaging, the researchers found that, in late life depression, higher blood pressure readings are linked to tiny white matter abnormalities, mainly in the brain's frontal lobes and in subcortical areas. Some of these abnormalities are associated with impairment in specific frontal lobe functions.

The same team also found that patients with major depression treated with the antidepressant citalopram were less likely to recover if they had cardiovascular disease or did poorly on a test of cognition requiring frontal lobe function.

They also found that patients with major depression who took the antidepressant escitalopram (which is more potent than citalopram) were less likely to recover if they had more of the tiny structural abnormalities in several areas of the frontal lobes and in subcortical structures.

"With further refinement, the findings may improve physicians' ability to predict who will fail to respond to antidepressants. Such patients may need close follow-up and different treatments such as psychotherapy or novel medications. Second, our findings can be used in the development of new treatments for those who do not respond to classical antidepressants," Alexopoulos said in a prepared statement.

He and his team are currently studying how parts of the frontal lobes are activated when depressed patients do cognitive tasks that activate this area.

Preliminary findings show that depressed older patients cannot activate these frontal lobe parts as efficiently as non-depressed older adults," Alexopoulos said.

In other research, a team at the University of Iowa found that vascular depression can be treated with an experimental technique called repetitive transcranial magnetic stimulation (rTMS). They found that rTMS led to better remission rates than standard medication treatment, and that increasing the number of magnetic pulses significantly improved remission rates.

"These findings suggest that this new method of treatment may be particularly useful for these late life onset depressions and that even greater response rates might be achieved by utilizing more pulses of magnetic stimulation," Dr. Robert Robinson, a professor of psychiatry, said in a prepared statement.

In other reports presented at the conference, scientists urged caution in the use of antipsychotic drugs in elderly people and other patients in order to minimize metabolic, heart and stroke risks
source:news.yahoo.com

Health Tip: Good Shoes Can Prevent Falls

(HealthDay News) -- The shoes you wear can play a big part in how steady you are on your feet, which is a big concern for many seniors.

Here are guidelines for choosing safe shoes, and other ways to help reduce the risk of falls, courtesy of the American Academy of Orthopaedic Surgeons:

* Make sure your shoes fit correctly. Always measure your feet before you buy new footwear.
* Choose shoes that are comfortable and sturdy, avoiding those with very thick soles or high heels.
* Look for shoes with soles that won't skid or slip.
* Keep laces tied tightly all the times. If you have trouble tying laces, look for shoes with Velcro.
* Always wear well-fitted, non-skid slippers at home. Throw away slippers that have become too stretched. Avoid walking barefoot or in your socks.
* Don't let your toenails get too long.
source:news.yahoo.com

Flavonoids May Help Treat Alzheimer's

By Steven Reinberg
HealthDay Reporter Fri May 9, 11:46 PM ET

FRIDAY, May 9 (HealthDay News) -- Flavonoids, compounds found in many fruits and vegetables, may be able to battle the ravages of Alzheimer's disease, a new study suggests.

In experiments with mice, two flavonoids called luteolin and diosmin reduced levels of beta-amyloid, which forms the harmful plaques that build up in the brains of those with Alzheimer's disease.

"Our lab has been investigating beta-amyloid, which is associated with Alzheimer's, and how we can reduce it using natural compounds," said lead researcher Kavon Rezai-Zadeh, from the Rashid Laboratory for Developmental Neurobiology at Silver Child Development Center at the University of South Florida.

The research team would like to use the two flavonoids to see if they can reduce amyloid plaque in humans, since they believe flavonoids would be safe and have few side effects compared with drugs that are being developed to reduce amyloid plaque.

Rezai-Zadeh also thinks that flavonoids, which have strong antioxidant properties, might guard against Alzheimer's. "A lot of these compounds can be derived from the diet, and they may have preventive effects against Alzheimer's disease," he said. "Increasing the flavonoids in your diet may help reduce the risk of Alzheimer's."

"The question is, can we use these flavonoids in people that have cognitive impairment?" Rezai-Zadeh said. "That's the million-dollar question."

The report was published in the May 8 online edition of the Journal of Cellular and Molecular Medicine.

In the study, Rezai-Zadeh's team used a mouse model of Alzheimer's disease to test their theory. Using, luteolin and diosmin, the researchers were able to reduce the levels of beta-amyloid in the rodents' brains.

In addition, the researchers found these two molecules were targeting a protein called presenilin-1, which has been linked to a genetic cause of Alzheimer's disease. These findings could lead to a new approach for treating Alzheimer's patients, they said.

One expert is concerned this potential treatment could also affect a patient's cognitive functioning.

"The authors of this study believe that they have identified a drug with a reasonable safety record that could reduce both plaques and tangles," said Greg M. Cole, associate director of the Alzheimer's Disease Research Center at the UCLA David Geffen School of Medicine in Los Angeles.

However, the enzyme (GSK3) targeted by these flavonoids has many important functions, including a role in processes required for normal cognitive function, Cole said.

"In fact, complete inhibition of GSK3 causes neurons to degenerate. Since cognitive function was not evaluated in this study, researchers still need to learn how much inhibiting GSK3 will be beneficial and side effect-free. That said, this may be a promising new direction," Cole said.

Another expert cautions that promising findings in mice often do not translate into effective treatments in humans.

"While this paper also shows some promising results in amyloid-depositing mice, we know from our recent experience with Alzhemed [a drug to treat Alzheimer's] and statins that the path from 'mouse cures' to 'human cures' may be a tough path indeed," said Dr. Sam Gandy, chairman of the National Medical and Scientific Advisory Council at the Alzheimer's Association and associate director of the Mount Sinai Alzheimer's Disease Research Center at Mount Sinai School of Medicine in New York City.

"Both Alzhemed and statins were effective in mice, yet failed in the clinic, so the flavonoid data join NSAIDs, vaccines, PBT2, IVIg, secretase modulators, among others, in the queue of interventions that look promising in mice but remain to be thoroughly assessed in humans," Gandy said.
source:news.yahoo.com

Anti-inflammatories did not ward off dementia

CHICAGO (Reuters) - Giving elderly people either Aleve or Celebrex, two anti-inflammatory painkilling drugs, did nothing to ward off the mental decline associated with the onset of Alzheimer's disease, researchers said on Monday.

Several studies have suggested that long-term use of certain painkillers in the class known as non-steroidal anti-inflammatory drugs, or NSAIDs, can lower the risk of developing the memory-wasting disease.

However, using NSAIDs for long periods can pose health risks such as stomach bleeding and kidney problems.

Barbara Martin of Johns Hopkins University in Baltimore and colleagues concluded there was no protective effect from the two commonly used drugs. They added that Aleve, known generically as naproxen, may have had a slightly negative impact.

Patients who took two daily doses of Aleve scored slightly lower on tests of mental functioning compared to the groups taking a placebo or celecoxib.

The nearly four-year study, published in the Archives of Neurology, divided 2,117 people aged 70 or older with a family history of Alzheimer's into three groups.

One group received naproxen twice daily in the form of Bayer's Aleve, another Pfizer Inc's Celebrex, known generically as celecoxib, and a third group took a placebo.

Each participant had a close relative with Alzheimer's, a known risk factor for the disease that has no cure and few effective treatments.

The researchers suggested that certain NSAIDs may protect against dementia only when given several years before mental functioning begins to decline.

Some doctors believe persistent inflammation may play a role in mental decline and Alzheimer's, a disease that affects more than 5 million Americans and is the most common form of dementia.

Another study by a different team and published last week in the journal Neurology concluded that taking ibuprofen, commonly sold as Advil or Motrin, for at least five years cut the risk of developing Alzheimer's by 40 percent.

Some other NSAIDs reduced the risk of developing the illness by 25 percent, though Celebrex did not, the team at Boston University School of Medicine said.

Celebrex is one of a class of painkillers that selectively block the COX-2 enzyme, which is linked to inflammation. Other NSAIDS such as aspirin and naproxen affect both COX-1 and COX-2, and the COX-2 drugs were designed to be more specific and thus safer.

Merck & Co. Inc pulled its COX-2 inhibitor, Vioxx, from the market in 2004 after studies showed it raised the risk of heart attacks and strokes in long-term users. Pfizer withdrew a similar drug, Bextra, but has continued to market Celebrex.

The latest study was ended early because of the heart attack and stroke concerns about this class of drugs.
source:news.yahoo.com

Adjusting electrodes may help Parkinson's patients

NEW YORK (Reuters Health) - 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.

Celebrex, Naproxen Won't Prevent Mental Decline

By Amanda Gardner
HealthDay Reporter Mon May 12, 11:47 PM ET

MONDAY, May 12 (HealthDay News) -- Contrary to prior studies, a new trial shows that daily use of two popular pain-relieving drugs, Celebrex and naproxen, does not prevent cognitive decline in people with a family history of Alzheimer's disease.

In fact, naproxen, which goes under the brand names Aleve and Naprosyn, may even have a deleterious effect on cognitive function, the study found.

"The drugs we studied did not seem to improve cognitive function and, if anything, there was some weak evidence for a detrimental effect," said Barbara Martin, an investigator on the trial and assistant professor of epidemiology at the Johns Hopkins School of Public Health in Baltimore. "So we don't at this time recommend taking NSAIDs for the purpose of preventing Alzheimer's or cognitive decline."

Added Dr. John Morris, director of the Alzheimer's Disease Research Center at Washington University School of Medicine in St. Louis and a member of the medical and scientific advisory council for the Alzheimer's Association: "My strong recommendation is I would not take any drug for a hoped-for effect until it has been demonstrated to have such an effect. Drugs potentially have side effects and unless there's a documented benefit, just because it's popular, I wouldn't rush to do that."

Both Celebrex and naproxen belong to the class of pain-killing drugs known as non-steroidal anti-inflammatory drugs (NSAIDs).

The study, to be published in the July issue of Archives of Neurology, was funded by the U.S. National Institute on Aging. The drug maker Pfizer provided the supply of Celebrex used in the study, plus a matching placebo, while Bayer Healthcare provided naproxen and a matching placebo.

Inflammatory processes may play a role in Alzheimer's disease and in cognitive decline in general.

"In addition to the plaques and tangles which are pathological hallmarks of Alzheimer's, there also seem to be signs of inflammation in the brains of people with the disease," Martin said.

That observation has led scientists to speculate that anti-inflammatory drugs may have an effect on the disease and, in fact, some previous observational studies have shown an association between NSAID use and a reduced risk of developing Alzheimer's.

In May 2007, the same group of researchers published findings that Celebrex and naproxen did not prevent Alzheimer's disease.

For the new study, 2,117 men and women over the age of 70 with a family history of Alzheimer's disease were randomly assigned to receive 200 milligrams of Celebrex twice a day, 220 milligrams of naproxen twice a day, or a placebo. Participants did not have a diagnosis of Alzheimer's, other dementias or mild cognitive impairment at the March 2001, start of the trial.

The participants' cognitive function was tested annually, but therapy was stopped in December 2004 because another study had reported an increased risk of cardiovascular problems in people taking Celebrex.

Analysis of this trial found that people taking naproxen had lower overall scores on measures of cognitive function than did men and women taking the placebo. Individuals taking naproxen or Celebrex had lower scores on a specific mental exam than did those taking a placebo.

The differences in results between this trial and previous research may have to do with the design of the study, or the results here may apply only to Celebrex and naproxen and not to other anti-inflammatory drugs such as ibuprofen, the researchers said. Or NSAIDs may only confer protection when given much earlier.

"This is speculative but there is increasing evidence that it may be a matter of timing, so by the time older adults take these drugs, if there is a protective effect, it may be past that time," Morris explained.

At this point, however, experts don't know what the best time would be to start the drugs.

"Increasingly we see that if we're going to want to understand how the process of Alzheimer's disease begins in the brain, we cannot limit our studies simply to older adults," Morris said. "We have to begin to study people even in middle age because the disease process may have its origins decades before people actually develop it."

Dr. Gary Kennedy is director of geriatric psychiatry at Montefiore Medical Center in New York City. Regarding this particular area of anti-inflammatory research as it pertains to cognitive problems, he said, "It's not strike three, but it's strike two for sure. The inflammatory model was a reasonable shot to begin with, but it was a long shot. [Inflammation] may be a side effect."
source:news.yahoo.com

Older brains don't benefit from painkillers

By CARLA K. JOHNSON, Associated Press Writer Tue May 13, 4:31 PM ET

CHICAGO - Results from a large government experiment are dimming hopes that two common painkillers can prevent Alzheimer's disease or slow mental decline in older people.

The arthritis drug Celebrex and the over-the-counter painkiller Aleve showed no benefit on thinking skills, new findings show. Earlier results from the same research showed the two drugs didn't prevent Alzheimer's, at least in the short term.

The experiment was halted several years early in 2004 when heart risks turned up in a separate study on Celebrex. Researchers also had noticed more heart attacks and strokes in the people taking Aleve in the Alzheimer's prevention study.

Despite the study's early end, there was still enough data to hint at how the drugs act on thinking and memory. The findings were posted online Monday and will appear in July's Archives of Neurology.

"These were not the results we were hoping for," said co-author Barbara Martin of the Johns Hopkins Bloomberg School of Public Health. "We designed this study hoping we would see a protective effect of these drugs."

Researchers hope to continue monitoring the participants to see if they find any delayed benefit.

Scientists have speculated that nonsteroidal anti-inflammatories, such as Aleve and Celebrex, might prevent Alzheimer's by reducing inflammation in the brain or by other means.

"The drugs have several effects in the brain and the different effects could be important at different stages in the illness," said study co-author Dr. John Breitner of the University of Washington in Seattle.

Previous studies had found that people who took the drugs ran a lower risk of developing Alzheimer's. But those were observational studies, meaning they observed people's behavior and health. The people who took the pills may have had other healthy habits that lowered their risk.

The halted study included more than 2,000 people ages 70 and older with a family history of Alzheimer's but no thinking problems themselves. People were randomly assigned to take standard daily doses of either Celebrex, Aleve, also known as naproxen, or a dummy pill.

At the start and annually for up to three years, they took a battery of tests. In one, they named as many grocery items as they could in one minute.

All three groups scored about the same at the start. But over time, the Aleve takers scored on average slightly lower than the people who took placebos. The Celebrex takers scored slightly lower than the placebo takers on most, but not all, of the tests.

"There's no evidence that people should be on these drugs to prevent Alzheimer's disease," said Dr. David Bennett of Chicago's Rush University Medical Center, who was not involved in the study but does similar research. "With the side effects of these drugs, people shouldn't be taking them for this reason."

Both products now carry warnings about heart risks. Anti-inflammatory drugs also can cause serious gastrointestinal bleeding. Experts advise patients to ask their doctors about how long to take the drugs for pain.

The study was funded by the National Institute on Aging. Pfizer Inc. and Bayer Healthcare provided the drugs and matching dummy pills for the study, but did not participate in the research. Some of the authors reported receiving speaking or consulting fees from drug companies, including Pfizer.

"Unfortunately, as this paper demonstrates, research doesn't always translate into successful new treatments," said Dr. Gail Cawkwell of Pfizer in an e-mail. Cawkwell pointed out that the study did not find increased heart risks for Celebrex.

Bayer spokeswoman Tricia McKernan said the early end to the experiment reduces the relevance of the data. She said the findings don't apply to the intended use of Aleve as a short-term pain reliever.
source:news.yahoo.com

O'Connor makes personal plea for Alzheimer's aid

By LAURAN NEERGAARD, AP Medical Writer Wed May 14, 3:41 PM ET

WASHINGTON - The first woman on the Supreme Court is now the nation's most prominent Alzheimer's caregiver.

Retired Justice Sandra Day O'Connor made public her family's private battle with the mind-destroying illness Wednesday as she urged Congress to speed research in hopes of slowing a coming epidemic.

"Our nation is certainly ready to get deadly serious about this deadly disease," she told the Senate Special Committee on Aging.

She has a personal stake: "My beloved husband John suffers from Alzheimer's," she said, her voice briefly wobbling. "He's not in very good shape at present."

Her story resonated with senator after senator who told of mothers and fathers crippled and then killed by Alzheimer's inexorable march — and with a crowd of about 300 onlookers, many wearing purple Alzheimer's Association sashes, who applauded the calls for aid in a Senate hearing room where such emotion is rare.

More than 5 million Americans are living with Alzheimer's disease. The number is poised to skyrocket, with 16 million people forecast to have it by 2050 thanks to a graying population. It already afflicts one in eight people 65 and older, and nearly one in two people over 85.

"I'm getting pretty close to 80, so that gets my attention," O'Connor said wryly. "I think a lot of people will be concerned."

And with that specter of disease comes a bigger question: Who will care for all these patients? Already, 10 million people are estimated to be sharing the overwhelming task of caring for a relative or friend with dementia, juggling jobs and other family responsibilities with little formal training, support or financial help available. The Alzheimer's Association says the unpaid care they provide is valued at $89 billion.

The intensely private O'Connor has said little until now of her personal experience. But it illustrates some of that balancing act: When her husband could no longer stay home alone, O'Connor would take him to work with her at the high court. She announced her retirement in 2005 by saying she needed time to care for him, and eventually moved him to an assisted care center in Phoenix, near two of their three children.

Wednesday, however, her main message was a sharp call to action. She urged better support for caregivers and repeatedly stressed the need to speed quality research, citing the possibility of such treatment approaches as attacking a brain-clogging gunk called beta-amyloid that is the disease's hallmark.

"If we're going to dissolve something in the brain, you want to be sure it isn't the brain itself," she said with a laugh.

"What we have to ask is whether this rapid growth is inevitable," she added. "I think it's not — if we can fund the research."

O'Connor has joined a group of national leaders, including well-known scientists and former House Speaker Newt Gingrich, to create what they call a "national strategy" to battle Alzheimer's, emphasizing both research and improving help for caregivers. The so-called Alzheimer's Study Group will issue its report early next year, but began pushing lawmakers Wednesday to start thinking about the investment despite tight economic times.

Already the nation spends more than $150 billion caring for Alzheimer's patients, a fraction of the true cost thanks to free family care, Gingrich said. But he argued that more research investment would be a good buy — saying if scientists could create a way to merely delay the onset of Alzheimer's by five years, that could save Medicare and Medicare billions a year.
Source:news.yahoo.com