RedNova News - Health - Study Finds Opiates More Effective in ElderlyOlder pain sufferers and their doctors often shun morphine-based medications such as OxyContin and Percocet, but a new study suggests that those over 60 are often better candidates for the medications than younger patients.

Not only do older people report greater pain relief, but they are much less likely than younger patients to need rapidly escalating dosages to maintain the same pain relief, the research found.

In the first systematic look at age differences among patients taking opioids, researchers at the University of California at San Francisco pain clinic found that on average, patients under 50 required medication twice as strong as that needed by patients over 60. After almost two years, the older patients reported they still got relief on the low doses, while the younger patients reported little pain relief even after their dosages were increased.

"Because of the continuing stigma associated with opioids among many older people, the group that stands to benefit the most from the pain relief they give are getting the least,'' lead author Pamela Palmer said. "Doctors are reluctant to prescribe the opioids, and seniors are reluctant to take them.''

One reason that older people avoid opioids, she said, is they fear they will want higher and higher doses as they become "tolerant'' of the drug and will become addicted. But the study, she said, showed that older patients develop tolerance very slowly.

Palmer said older people in pain are being poorly served by doctors because morphine-based drugs at moderate doses have less- serious side effects than other painkillers. The primary side effects of opioids are nausea and constipation, while the possible risks of COX-2 inhibitors and other anti-inflammatory drugs include heart and kidney damage and gastric ulcers.

LINK While a breakthrough for humans could be years away, a new study in mice suggests some memory recovery may be possible in the early stages of Alzheimer's disease.

"There basically are two prongs and we need to deal with both," said lead researcher Karen Ashe, a University of Minnesota neurologist. "What we're showing is that there are neurons which are affected (by Alzheimer's) but not dead."

New research shows a mutant protein named tau is poisoning brain cells, and that blocking its production may allow some of those sick neurons to recover. It worked in demented mice who, to the scientists' surprise, fairly rapidly regained memory.

There are no drugs yet to block tau, and most of the recent search for Alzheimer's treatments has focused instead on another protein, called beta-amyloid.

But Thursday's study, published in the journal Science, is sure to refocus attention on finding ways to attack this second culprit, too.

preliminary resultsBACKGROUND: Laboratory evidence of cholesterol-induced production of amyloid beta as a putative neurotoxin precipitating Alzheimer disease, along with epidemiological evidence, suggests that cholesterol-lowering statin drugs may favorably influence the progression of the disorder. RESULTS: Atorvastatin reduced circulating cholesterol levels and produced a positive signal on each of the clinical outcome measures compared with placebo. This beneficial effect reached significance for the Geriatric Depression Scale and the Alzheimer's Disease Assessment Scale-cognitive subscale at 6 months and was significant at the level of a trend for the Alzheimer's Disease Assessment Scale-cognitive subscale, Clinical Global Impression of Change Scale, and Neuropsychiatric Inventory Scale at 12 months assessed by analysis of covariance with last observation carried forward. CONCLUSION: Atorvastatin treatment may be of some clinical benefit and could be established as an effective therapy for Alzheimer disease if the current findings are substantiated by a much larger multicenter trial.

LINKBACKGROUND: Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease. Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo.

Alzheimer's PET scans and cognitive tests have suggested that Alzheimer's disease patients with genetically modified tissue inserted directly into their brains show a reduction in the rate of cognitive decline and increased metabolic activity in the brain, according to a study published in the April 24, 2005 online issue of the journal Nature Medicine by researchers at the University of California, San Diego (UCSD) School of Medicine.
In this first-ever gene therapy for Alzheimer's disease, UCSD physician-scientists took skin cells from eight patients diagnosed with early Alzheimer's disease. The tissue was modified in the lab to express nerve growth factor (NGF), a naturally occurring protein that prevents cell death and stimulates cell function. In surgeries that took place in 2001 and 2002 at UCSD's John M. and Sally B. Thornton Hospital, the genetically modified tissue was implanted deep within the brains of the eight patients who had volunteered for the study.

The human clinical trial was undertaken following extensive studies in primates conducted by Tuszynski and colleagues, which showed that grafting NGF-producing tissue into the brains of aged monkeys restored atrophied brain cells to near-normal size and quantity, and also restored axons connecting the brain cells, essential for communication between cells. The recent human studies were a Phase I clinical trial, designed to test safety and toxicity. The procedure was initially performed while patients were awake but lightly sedated, and two patients moved as the cells were being injected, resulting in bleeding in the brain. One of these patients died five week later. As a result of the bleeds, the protocol was redesigned to perform the procedure under general anesthesia and all subsequent procedures were performed without complication.
Based on the positive findings of this Phase I trial, a new Phase I/II study using direct NGF gene delivery to the brain, thereby eliminating the need for grafting cells, is currently underway at Rush University Medical Center in Chicago, sponsored by the San Diego biotechnology company Ceregene, Inc. The Chicago trial is under the direction of David Bennett, M.D., director of the Rush University Alzheimer's Disease Center, and Zoe Arvanitakis, M.D., a Rush neurologist.

USATODAY.com - The Alzheimer's Association says 4.5 million Americans have the disease, and up to 16 million are expected to be diagnosed with it by 2050. As Alzheimer's becomes more prevalent, more people, including spouses, will become caregivers.

In the past several years, prominent Americans, including Ronald Reagan, have gone public with their diagnosis.

Now caregivers, who often remained behind closed doors, are emerging publicly as well. An estimated 60% to 70% of people with Alzheimer's are living in family homes.

This month, Supreme Court Justice Sandra Day O'Connor said she was retiring to spend more time with her husband, John O'Connor, who has had Alzheimer's disease for many years.

Caring for someone with Alzheimer's always is difficult. But spouses and partners deal not only with the ravages of an illness that slowly eats away at the brain and causes countless losses, including memory and physical control; they also have to cope with losing the person who would perhaps be the very one to whom they would turn to for comfort in such a crisis.

Experiences vary from person to person, but caregivers and professionals say all spouses and partners in O'Connor's position will face similar problems. They offer the following pieces of advice and bits of wisdom:

•Learn about Alzheimer's. Begin on the day of diagnosis or pretty soon after, says Donna Schempp, program director for the Family Caregiver Alliance, a national information clearinghouse. "They have to get very, very educated about the illness. And not just on the here and now but what happens over time."

•Don't delay legal arrangements. Prepare documents immediately, while the person with Alzheimer's is still relatively lucid. That includes wills, powers of attorney and end-of-life decisions. "All the mechanical things have to happen sooner rather than later," Schempp says.

•Think about what kind of help you will need. Alzheimer's is a long road, averaging seven or eight years from diagnosis to death, says Kathleen O'Brien of the Alzheimer's Association. "There's a huge emotional toll that families will face," she says.

"To watch the person you relied on emotionally and for all kinds of support and cooperation and companionship just disappearing in this bizarre way is hard," says Maxine Fredericksen, 58, of Walnut Creek, Calif., whose husband was diagnosed with early Alzheimer's in 1997 and now lives in a nursing home.

Carl Fredericksen, 62, was a Renaissance man. A high school teacher and seminary graduate, he had a passion for religion, history, theater, poetry and music. Now he hardly speaks.

"To see him as he is now tends to be an out-of-body experience," says his wife, a graduate student adviser at the University of California-Berkeley. "It's an endless grief."

Those who have been there say the best way to cope is to get help. Lots of it. Many recommend support groups. "Sharing helps," says Terri Jo Barron of Tallahassee, Fla., whose husband died of Alzheimer's. "Anything you can talk about and bring into the light of day, it loses some of its scariness."

•Take care of yourself. Studies have shown that caregivers often neglect their own health. Some even end up dying before their spouses.

Mary Mittelman, an epidemiologist at New York University School of Medicine, is conducting a study about caregivers. "It's very hard to disentangle health, support and depression," she says. "They're all interrelated. And it's very important to take care of the totality of your own needs while caring for the other person."

•Don't take Alzheimer's behavior personally. "You can't get mad," Roth says. "You can't get frustrated. You can't get your feelings hurt if the person yells at you or shoves you or cusses you out and does all kinds of things. They don't know what they're doing or saying. ... It's just like handling a baby."

Mornings are hard. He goes through the routine of waking his wife, cleaning her up — she's totally incontinent, as are many people with Alzheimer's — and dressing and feeding her.

But, he says, "I do it with love. It's not a burden. She was always there for me.

"I have so many men friends whose wives got cancer. And they suffered. And they went through chemotherapy. And then they died. Don't feel sorry for me. That's the attitude I have. I'm thankful for what I've got. My men friends lost their wives. They don't have their wives to hug and kiss. They'd give anything to have what I have."

Ivanhoe A new research approach to understanding the cellular processes of degenerative brain diseases could lead to the development of new drugs to treat these illnesses.

Amyloid formation, or the twisting of cellular proteins into abnormal shapes, is linked to Alzheimer's, Huntington's, Parkinson's and other degenerative diseases but has left scientists puzzled as to how it kills the cells and leads to disease.

Researchers, including Ratnesh Lal, a scientist from the Neuroscience Research Institute at the University of California, Santa Barbara, examined the three-D structure of several different proteins associated with the diseases. They noticed misfolded proteins in the cell membrane -- resembling ion channels -- and changes in the electrical properties of cells.

The researchers found that the proteins were capable of producing electrical currents when embedded into artificial membranes, confirming their similarity to ion channels. It was previously known that abnormal ion balance disrupts cell function and causes degeneration, proving the possibility that amyloid formation may lead to the cellular destruction associated with neurodegenerative diseases.

"These ion channels could serves as a model system for designing preventive and therapeutic drugs," said Lal. "You don't need large aggregates of these amyloid proteins, the plaque, to have this disruption. Rather, small aggregates, when in contact with membrane, form ion channels and allow passage of ion current. By controlling activity and designing specific drugs to regulate these channels, we might be able to prevent and/or treat various diseases related to the amyloids."

link

Oregon Research Institute Home walking on a cobblestone mat surface resulted in significant reductions in blood pressure and improvements in balance and physical performance among adults 60 and over. An article published in an early online publicationof the Journal of the American Geriatrics Society summarizes the study results in a randomized trial.

These are very exciting results,%u201D notes John Fisher, Ph.D., one of the lead scientists on the study. %u201CCompared to conventional walking, the experience of walking on the river rock-like surface of these manufactured cobblestone mats improved participants%u2019 balance, measures of mobility, as well as reducing their blood pressure.

link: "A ground-breaking new research approach to understanding the cellular processes of Alzheimer's and other degenerative diseases has revealed a promising pathway to the development of new types of drugs for these diseases.

The discovery, made in the laboratory of Ratnesh Lal, research scientist in the Neuroscience Research Institute (NRI) at the University of California, Santa Barbara, is published in this week's online issue of the Proceedings of the National Academy of Sciences (PNAS).

The research describes a new way of understanding the degeneration of brain cells in patients with Alzheimer's, Huntington's, and Parkinson's diseases, as well as other degenerative diseases. Misfolded proteins in the cell membrane, and subsequent changes in the electrical properties of cells, provide the explanation for the cell degeneration. Specific three-dimensional structures of misfolded proteins are embedded in the cell membrane.
'It has long been thought that amyloid plaque, which has been studied for 30 years, was the cause of Alzheimer's disease,' said Lal. 'Plaque isn't the cause.' He explained that the fibers of plaque are too large to directly affect small cells.

The answers may come from small globs of misshapen, misfolded proteins that make well-defined holes in cell membranes and disrupt their electrical activity, according to the study.

Amyloid protein is a sticky, globular substance created when normal cellular proteins become twisted and contorted into abnormal shapes. While amyloid formation has been associated with diseases like Alzheimer's, Parkinson's, and Huntington's, scientists have puzzled over whether and how it actually kills cells and causes disease. To gain insight into this mysterious process, Lal and his research team examined the three-dimensional structure of several different proteins associated with these diseases. The researchers observed that all of the proteins folded into structures resembling ion channels, or pores within cell membranes. These pores control the electrical properties of the cell by regulating the flow of charged particles (ions) such as calcium."

Reuters.comJapan's biggest drug maker, Takeda Pharmaceutical Co. Ltd (4502.T: Quote, Profile, Research), said on Monday it is on track to release a sleeping pill as early as September in the United States and may extend its use to treat Alzheimer's disease and other illnesses.

The Osaka-based drug maker plans to launch its insomnia drug Ramelteon in the U.S. market in September or October, marking its entry into the central nervous system disease segment, Takeda President Yasuchika Hasegawa told an analysts' meeting.

To be marketed as Rozerem, it will be Takeda's first new drug in the United States in six years, and will compete with existing drugs such as Sanofi-Aventis's (SASY.PA: Quote, Profile, Research) Ambien and Sepracor's (SEPR.O: Quote, Profile, Research) Lunesta. Takeda's Ikeya also said the company is considering extending the drug's use to other illnesses such as Alzheimer's disease or depression, and may start clinical development for these purposes after the launch of the sleeping pill. In an bid to fill its sparse drug cabinet, Takeda has sealed four licensing deals with U.S. and British biotech companies since last October, and it bought U.S. biotech venture Syrrx in March.

Reuters.comJapan's biggest drug maker, Takeda Pharmaceutical Co. Ltd (4502.T: Quote, Profile, Research), said on Monday it is on track to release a sleeping pill as early as September in the United States and may extend its use to treat Alzheimer's disease and other illnesses.

The Osaka-based drug maker plans to launch its insomnia drug Ramelteon in the U.S. market in September or October, marking its entry into the central nervous system disease segment, Takeda President Yasuchika Hasegawa told an analysts' meeting.

To be marketed as Rozerem, it will be Takeda's first new drug in the United States in six years, and will compete with existing drugs such as Sanofi-Aventis's (SASY.PA: Quote, Profile, Research) Ambien and Sepracor's (SEPR.O: Quote, Profile, Research) Lunesta. Takeda's Ikeya also said the company is considering extending the drug's use to other illnesses such as Alzheimer's disease or depression, and may start clinical development for these purposes after the launch of the sleeping pill. In an bid to fill its sparse drug cabinet, Takeda has sealed four licensing deals with U.S. and British biotech companies since last October, and it bought U.S. biotech venture Syrrx in March.

- Forbes.com Roche Holding AG and GE Healthcare, a unit of General Electric Co, are to collaborate to help diagnose and treat Alzheimer's disease as well as develop personalised medicines, GE said.

Roche and GE are to conduct joint clinical trials. GE will provide a specially developed diagnostic imaging agent Positron Emission Tomography (PET) which Roche will use to test the response of its six early-stage Alzheimer's drugs.

MSNBC.comStatin drugs, which are designed to lower elevated cholesterol levels, also may stave off dementia in patients thought to have Alzheimer’s disease, a preliminary study said on Monday. The year-long study concluded that prescribing 80 milligrams of Lipitor daily to patients diagnosed with mild to moderate Alzheimer’s “may have a positive effect on the progressive deterioration of cognitive function and behavior” compared to patients taking a placebo, lead author Larry Sparks wrote.

Previous animal research has suggested high blood cholesterol levels play a role in the progression of Alzheimer’s, which is identified after death by the tangled plaques that form in victims’ brains, the report said.

Sparks believes high cholesterol leads directly to the brain plaques. But he wrote the beneficial effects from statins -- which have also been found to lower the risk of prostate and breast cancer -- could be due to their anti-inflammatory properties, the increased blood flow that results, or other effects.

MSNBC.comAricept, a drug long used to treat Alzheimer’s disease, can delay its onset a bit but does not prevent it, U.S. researchers said on Wednesday.

And vitamin E has no effect, they reported in the New England Journal of Medicine.

“These findings, from the Memory Impairment Study, are the first to suggest than any agent can delay the clinical diagnosis of Alzheimer’s Disease in people with mild cognitive impairment,” the National Institute on Aging, which helped pay for the study, said in a statement.

Aricept, known generically as donepezil, is made by Pfizer and Japan’s Eisai Co. Ltd. and also generically by India’s Ranbaxy Laboratories Ltd.

“These findings give me a great deal of hope,” said Dr. Ronald Petersen of the Mayo Clinic in Rochester, Minnesota, who led the study.

“We have not answered the question of whether donepezil reduces the underlying brain changes in Alzheimer’s disease, but now we know that for some people, drug therapy did make a real, clinical difference. I think there will be real opportunities in the future to test other therapies for patients with mild cognitive impairment.”

MSNBC.com A %u201Cpassive%u201D vaccine against Alzheimer%u2019s, a drug designed to filter out brain-clogging proteins and inhaled insulin may all offer ways to treat Alzheimer%u2019s disease in the future, researchers said on Monday.

No single treatment showed dramatic effects, and certain patients with Alzheimer%u2019s benefited more than others -- which suggests the disease may need to be fought on several fronts, they told a prevention conference sponsored by the Alzheimer%u2019s Association.

PittsburghLIVE.com
Missing teeth and gum disease at an early age may be linked to an increased risk of Alzheimer's disease, researchers have found, bolstering the increasingly strong connection between early exposure to chronic inflammation and the degenerative brain disorder.
The study, among the findings presented recently at the first Alzheimer's Association International Conference on Prevention of Dementia, examined lifestyle factors of more than 100 pairs of identical twins. All of the pairs included one twin who had developed dementia and one who hadn't. Because identical twins are genetically indistinguishable, the study involved only risk factors that could be modified to help protect against dementia