recent news on Alzheimer's/dementia

New clue to Alzheimer's found

Wired

2008-06-24

Researchers have uncovered a new clue to the cause of Alzheimer's disease.

The brains of people with the memory-robbing form of dementia are cluttered with a plaque made up of beta-amyloid, a sticky protein. But there long has been a question whether this is a cause of the disease or a side effect. Also involved are tangles of a protein called tau; some scientists suspect this is the cause.

Now, researchers have caused Alzheimer's symptoms in rats by injecting them with one particular form of beta-amyloid. Injections with other forms of beta-amyloid did not cause illness, which may explain why some people have beta-amyloid plaque in their brains but do not show disease symptoms.

The findings by a team led by Dr. Ganesh M. Shankar and Dr. Dennis J. Selkoe of Harvard Medical School were reported in Sunday's online edition of the journal Nature Medicine.

The researchers used extracts from the brains of people who donated their bodies to medicine.

Forms of soluble beta-amyloid containing different numbers of molecules, as well as insoluble cores of the brain plaque, were injected into the brains of rats. There was no detectable effect from the insoluble plaque or the soluble one-molecule or three-molecule forms, the researchers found.

But the two-molecule form of soluble beta-amyloid produced characteristics of Alzheimer's in the rats, they reported.

Those rats had impaired memory function, especially for newly learned behaviors. Studies were also done on mice and when their brains were inspected, the density brain cells were reduced by 47 percent. The beta-amyloid seemed to affect synapses, the connections between cells that are essential for communication between them.

The research, for the first time, showed the effect of a particular type of beta-amyloid in the brain, said Dr. Marcelle Morrison-Bogorad, director of the division of neuroscience at the National Institute on Aging, which helped fund the research.

It was surprising that only one of the three types had an effect, she said in a telephone interview.

Morrison-Bogorad said the findings may help explain the discovery of plaque in the brains of people who do not develop dementia. For some time, doctors have wondered why they find some brains in autopsy that are heavily coated with beta-amyloid, but the person did not have Alzheimer's.

The answer may lie in the two types of beta-amyloid that did not cause symptoms.

Now, the question is why one has the damaging effect and not others.

"A lot of work needs to be done," Morrison-Bogorad said. "Nature keeps sending us down paths that look straight at the beginning, but there are a lot of curves before we get to the end."

Dr. Richard J. Hodes, director of the National Institute on Aging, said that "while more research is needed to replicate and extend these findings, this study has put yet one more piece into place in the puzzle that is Alzheimer's."

In addition to the Institute on Aging, the research was funded by Science Foundation Ireland, Wellcome Trust, the McKnight and Ellison foundations and the Lefler Small Grant Fund.

Important FLU and atypical antipsychotic information

Two things to keep your elderly parents away from: Being drugged at their elderly facility and the flu shot that has high levels of mercury, causes dementia and actually does not work which in some facilities are required.
If so, demand the flu shot without Thimerosal but not the live virus vaccine called "Flu mist". Eileen

See 5 minute University of Calgary video on our site: www.ProgressiveConvergence.com (how mercury degenerates the brain neurons)

and check out the 2500 suicide and homicide stories: http://www.ssristories.com/index.php

Letters to the editor: letters@nytimes.com

New York Times

Doctors Say Medication Is Overused in Dementia

By LAURIE TARKAN

June 24, 2008

Ramona Lamascola with her mother, Theresa Lamascola.

Ramona Lamascola thought she was losing her 88-year-old mother to dementia. Instead, she was losing her to overmedication.

Last fall her mother, Theresa Lamascola, of the Bronx, suffering from anxiety and confusion, was put on the antipsychotic drug Risperdal. When she had trouble walking, her daughter took her to another doctor — the younger Ms. Lamascola's own physician — who found that she had unrecognized hypothyroidism, a disorder that can contribute to dementia.

Mrs. Lamascola no longer takes antipsychotics.

Theresa Lamascola was moved to a nursing home to get these problems under control. But things only got worse. "My mother was screaming and out of it, drooling on herself and twitching," said Ms. Lamascola, a pediatric nurse. The psychiatrist in the nursing home stopped the Risperdal, which can cause twitching and vocal tics, and prescribed a sedative and two other antipsychotics.

"I knew the drugs were doing this to her," her daughter said. "I told him to stop the medications and stay away from Mom."

Not until yet another doctor took Mrs. Lamascola off the drugs did she begin to improve.

The use of antipsychotic drugs to tamp down the agitation, combative behavior and outbursts of dementia patients has soared, especially in the elderly. Sales of newer antipsychotics like Risperdal, Seroquel and Zyprexa totaled $13.1 billion in 2007, up from $4 billion in 2000, according to IMS Health, a health care information company.

Part of this increase can be traced to prescriptions in nursing homes. Researchers estimate that about a third of all nursing home patients have been given antipsychotic drugs.

The increases continue despite a drumbeat of bad publicity. A 2006 study of Alzheimer's patients found that for most patients, antipsychotics provided no significant improvement over placebos in treating aggression and delusions.

In 2005, the Food and Drug Administration ordered that the newer drugs carry a "black box" label warning of an increased risk of death. Last week, the F.D.A. required a similar warning on the labels of older antipsychotics.

The agency has not approved marketing of these drugs for older people with dementia, but they are commonly prescribed to these patients "off label." Several states are suing the top sellers of antipsychotics on charges of false and misleading marketing.

Ambre Morley, a spokeswoman for Janssen, the division of Johnson & Johnson that manufactures Risperdal, would not comment on the suits, but said: "As with any medication, the prescribing of a medication is up to a physician. We only promote our products for F.D.A.-approved indications."

Nevertheless, many doctors say misuse of the drugs is widespread. "These antipsychotics can be overused and abused," said Dr. Johnny Matson, a professor of psychology at Louisiana State University. "And there's a lot of abuse going on in a lot of these places."

Dr. William D. Smucker, a member of the American Medical Directors Association, a group of health professionals who work in nursing homes, agreed. Though the group encourages doctors to conduct a thorough assessment and prescribe antipsychotics only as a last resort, he said, "Many physicians are absent without leave in the nursing home and don't take an active role in the assessment of the patient."

Some nursing homes are trying a different approach, so-called environmental intervention. The strategies include reducing boredom, providing intellectual and physical stimulation, exercise, calming music, bringing in pets for therapy and improving how the staff approaches and talks to dementia patients.

At the Margaret Teitz Nursing and Rehabilitation Center in Queens, social workers do life reviews of patients to understand their interests, lifestyle and former occupations.

"I had a patient who used to be in fashion," said Nancy Goldwasser, the director of social services. "So we got her fabric samples. And she'd sit and look through the books, touch the fabric, and it would calm her."

But such approaches are time consuming, they do not help all patients, they can be prohibitively expensive and they will be more difficult to provide as Alzheimer's continues to increase.

"Our health care system isn't set up to address the mental, emotional and behavioral problems of the elderly," said Dr. Gary S. Moak, president of the American Association for Geriatric Psychiatry.

Nursing homes are short staffed, and insurers do not generally pay for the attentive medical care and hands-on psychosocial therapy that advocates recommend. It is much easier to use sedatives and antipsychotics, despite their side effects.

The first generation of antipsychotics, like Haldol, carry a significant risk of repetitive movement disorders and sedation. Second-generation antipsychotics, also called atypicals, are more commonly prescribed because the risk of movement disorders is lower. But they, too, can cause sedation, and they contribute to weight gain and diabetes.

Used correctly, the drugs do have a role in treating some seriously demented patients, who may be incapacitated by paranoia or are self-destructive or violent. Taking the edge off the behavior can keep them safe and living at home, rather than in a nursing home.

If patients are prescribed an antipsychotic, it should be a very low dose for the shortest period necessary, said Dr. Dillip V. Jeste, a professor of psychiatry and neuroscience at the University of California, San Diego.

It may take a few weeks or months to control behavior. In many cases, the patient can then be weaned off of the drugs or kept at a very low dose.

Some experts say another group of medications — antidementia drugs like Aricept, Exalon and Menamda — are underused. Research shows that 10 to 20 percent of Alzheimer's patients had noticeable positive responses to the drugs, and 40 percent more showed some cognitive improvement, even if it was not noticeable to an observer.

"Sometimes, it's enough to take the edge off the behavioral problems, so the family and patient can live with it and you don't expose people to much risk," said Dr. Gary J. Kennedy, director of geriatric psychiatry at the Montefiore Medical Center in the Bronx.

Other experts cite a lack of research backing these drugs for behavioral problems.

If patients begin showing behavioral symptoms of dementia, doctors said, they should have complete medical and psychiatric workups first, especially if symptoms develop suddenly.

"Just because someone is 95 does not mean one should not do a workup, especially if she's been healthy," Dr. Kennedy said.

Common causes of the symptoms include ministrokes, reparable brain hemorrhage from a mild bump on the head, hypothyroidism, dehydration, malnourishment, depression and sleep disorders.

Some doctors point out that simply paying attention to a nursing home patient can ease dementia symptoms. They note that in randomized trials of antipsychotic drugs for dementia, 30 to 60 percent of patients in the placebo groups improved.

"That's mind boggling," Dr. Jeste said. "These severely demented patients are not responding to the power of suggestion. They're responding to the attention they get when they participate in a clinical trial.

"They receive both T.L.C. and good general medical and humane care, which they did not receive until now. That's a sad commentary on the way we treat dementia patients."

To family members looking at a nursing home for an aging parent, experts recommend seeking out homes with low staff turnover, a high ratio of staff members to patients, and programs with psychosocial components.

The Medicare Web site has basic information on individual homes at www.medicare.gov/NHcompare. The National Citizens' Coalition for Nursing Home Reform, at www.nccnhr.org, offers a consumer guide to choosing a nursing home.

If medications are necessary, a family member should communicate with the prescribing doctor, learn the goal of each medication and be involved in making the decision.

Dr. Moak, of the psychiatry association, emphasized seeking out the doctor. Family members, he said, "often speak through the nursing staff, and that's a huge mistake."

Family members who are not convinced that a relative is receiving the best care should get a second opinion, as Ramona Lamascola did.

The physician she consulted, Dr. Kennedy of Montefiore, stopped her mother's antipsychotics and sedatives and prescribed Aricept.

"It's not clear whether it was getting her hypothyroid and other medical issues finally under control or getting rid of the offending medications," he said. "But she had a miraculous turnaround."

Theresa Lamascola still has dementia, but she went from confinement in a wheelchair — unable to sit still and screaming out in fear — to being able to walk with help, sit peacefully, have some memory and ability to communicate, understand subtleties of conversations and even make jokes.

Or, as her daughter put it, "I got my mother back."

Link to article: http://www.nytimes.com/2008/06/24/health/24deme.html?pagewanted=1&_r=1

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MORE on zyprexa ..

Antipsychotic Drugs Triple Risk of Death for

Dementia Patients
>
> By Elizabeth Lopatto
>
> May 26 (Bloomberg) -- People with dementia more than tripled their
risk of death or hospitalization within a month of taking antipsychotic drugs
to silence their agitation, according to a study.
>
> Those taking a class of antipsychotic drugs including generics
haloperidol and loxapine were 3.8 times more likely to be hospitalized or die,
> according to research published today in the Archives of Internal
> Medicine. People taking newer medicines including Eli Lilly & Co.'s
> Zyprexa and Johnson & Johnson's Risperdal had 3.2 times more risk of
> complications or death.
>
> Antipsychotic drugs, often prescribed as a short-term treatment for
> dementia's confusion and rages, have been associated with falls, hip
> fractures, strokes and death in other scientific studies. The new
research collects the potential for death and all other serious risks together
for the first time.
>
> ``You have to think very carefully before you start these
therapies,'' said lead author Paula Rochon, a senior scientist at the Institute
for Clinical Evaluative Sciences in Toronto. ``Is the risk worth the
potential > benefit? For many patients, there are probably other approaches you
could take that are equally effective and much safer.''
>
> The U.S. Food and Drug Administration in 2005 required makers of all
five of the newer antipsychotic drugs to include a ``black box'' warning
of death risk in elderly dementia patients.
>
> Even Worse?
>
> The risk to people taking the drugs is probably even higher than the
study of 41,000 dementia patients aged 66 and older, the authors said. The
study followed participants for 30 days and didn't include people with
severe injuries who weren't hospitalized.
>
> Alzheimer's disease is the most common cause of dementia, according
to the National Institutes of Health. Other causes include stroke and brain
> tumors. Previous research has shown that Alzheimer's patients who are
given antipsychotics die six months earlier than patients who don't
take the drugs.
>
About 17 percent of dementia patients in nursing homes are prescribed
an antipsychotic drug within 100 days of their admission, the study
said.  Nursing home patients taking the medications were twice as likely to
die or be hospitalized as those not taking the medicine, the study said.

``These therapies can be useful,'' Rochon said. ``The problem is when
they're used outside of their indication.''