Alzheimer's Club

We hope that someday soon a cure for Alzheimer's disease will be found so that future generations won't have to experience the heartache millions of Americans now know all too well. But until then, let each of us do our part to focus attention on the problem and to give generously to help fund the research that one day will lead to a cure.

"Chances are most people know someone who either has Alzheimer's disease or a family member who does.

Some with early stage Alzheimer's are able to go about their normal daily routine with little evidence of the progressive, degenerative disease which destroys parts of the brain that control memory, learning, communication and reason. Others, however, have advanced to the point they have experienced changes in their behavior and personality, as well as having their cognitive abilities impaired so that they no longer can adequately care for themselves and perhaps even fail to recognize their closest family members, including their spouse and children.

While those with advanced Alzheimer's may not be aware of the toll the disease has taken on them, their families, friends and loved ones are all too aware as they watch them slowly withdraw into themselves and become increasingly dependent on others for their every need.

Nationally, an estimated 4.5 million Americans have Alz-heimer's, including some 74,000 in Kentucky. Age is the greatest risk factor, and according to the National Institute on Aging, the percentage of people who develop Alzheimer's doubles for each five-year age group beyond 65, with nearly half of those over 85 affected. Estimates are that as many as 8.5 million Americans will develop the disease in the next few decades, with as many as 14 million Americans having it by 2050.

Sadly, there is no known cure for Alzheimer's disease, or certain treatment, although researchers are learning more about what causes it and how to at least control its symptoms. Certainly that's critical if meaningful progress is to someday be made.

November is National Alzheimer's Disease Month, an event first proclaimed by President Ronald Reagan in 1983. At the time, an estimated 2 million people suffered from Alzheimer's, less than half the number with it today. Ironically, Reagan developed Alzheimer's later and his candor in telling the nation “I now begin the journey that will lead me into the sunset of my life,” helped focus new attention on a growing problem.

Typically, a person with Alzheimer's will live with it for eight years, although death can occur within three years and as long as 20 or more years after the onset of symptoms. Because Medicare and much private insurance does not cover the type of long-term care Alzheimer's patients need, most remain at home. Consequently, spouses, children and other loved ones must assume the role of caregivers.

That can be an emotionally and financially draining experience. Fortunately, help is available. The Generations Center offers a respite care program from noon to 4 p.m. Monday, Wednesday and Friday for those with Alzheimer's or dementia. Transportation and a meal are provided, and equally important, caregivers receive a very welcome break from their ongoing responsibilities. A few slots are available and those needing more information about the program may call 744-3235.

The Winchester Board of Commissioners included funds in this year's city budget for Project Life Saver, a program that sees participants fitted with a transmitter that will greatly facilitate tracking them should they wander off. The devices, worn around the wrist, are to be ordered soon. The county also is considering the program, which has an outstanding track record.

Help for families with Alz-heimer's patients also is available by calling the Alzheimer's Association in Lexington at (859) 266-5283 or in Kentucky at (800) 272-3900.

We hope that someday soon a cure for Alzheimer's disease will be found so that future generations won't have to experience the heartache millions of Americans now know all too well. But until then, let each of us do our part to focus attention on the problem and to give generously to help fund the research that one day will lead to a cure."

Source: Cure for Alzheimer's is needed. Winchester Sun Online Edition (30 November 2005) [FullText]

"LOGAN, Utah, Nov. 29 (UPI) -- Utah State University scientists say they are finding indications there may be a link between diet and Alzheimer's disease.

Specifically they believe there might be a link between eating fruits and vegetables and reducing memory loss in elderly people. The researchers are also asking questions, such as will cholesterol-reducing drugs protect memory and are people at a higher risk of developing Alzheimer's if they have diabetes?

Investigators from the Cache County Study on Memory, Health and Aging based at the university have found people with the highest intake of fruits and vegetables score better on memory tests than do people with the lowest consumption of such foods.

Heidi Wengreen, a lead investigator in the study, said the research is the first of its kind specifically geared to dementia prevention. The study is a collaborative effort between researchers at Utah State, Duke University, Johns Hopkins University and the University of Washington.

A study update was presented during the Alzheimer's Association's International Conference on Prevention of Dementia, in Washington, D.C., earlier this year."

Source: Diet link sought in Alzheimer's disease. United Press Inter (UPI) (29 November 2005) [FullText]

"Editor's note: Part one of this two-part series on dementia illnesses such as Alzheimer's disease centered on the experience of caring for a patient. Part two concerns taking care of the caregiver — how to seek help and avoid the stress and burnout that are common to caregivers.

In her role as training and consultation director and dementia specialist for Family Alliance, Woodstock, and as co-author of a new book titled "Dementia Caregivers Share their Stories," Lynda Markut is a strong voice for more education and awareness of dementia-related illnesses.

November is National Alzheimer's Awareness Month, and one awareness issue that needs to be raised is that caregivers of dementia patients need to learn to ask for and accept help in order to keep their own stress levels manageable.

Markut cared for her mother, Helen, for 15 years after Helen was diagnosed with vascular dementia. Markut's book, written with co-author Anatole Crane, is a collection of the stories of family members of dementia patients who have come together in support groups at Family Alliance to find help and share experiences.

Keeping it in perspective

Becoming totally involved in the care of a dementia patient can easily become overwhelming, said Markut. But overextending oneself and never taking time off to walk away from the situation from time to time can have an adverse effect on the health of the caregiver.

"It's when you lose sight of your own life ... if your life has become disease-focused, then I would say you are stressed out and need to start the process of caring for yourself," said Markut.

"The most calls that we get (at Family Alliance) are about starting someone in a day care program," said Markut. There is help available, but the caregiver has to be creative and persistent in looking for it.

That help differs from patient to patient, according to the capabilities of the patient and the family. It will involve a combination of home care, the help of family members, friends, paid caregivers, day care programs and sometimes a residential care facility such as a nursing home.

Family issues

"If you want to work together as a family, you need to realize that every person has a certain level of capability to respond," said Markut. "Some can, some can't. The act of caregiving, by itself, does not enhance family connections. All the ways your family worked together before, and all the ways they did not work together before, all that still applies.

"What works, often, is to have a family meeting with an outside professional, an objective person," said Markut. "What that does is to help everyone get the words out and listen."

You don't have to do it alone

Markut explained the concept of "rent a friend."

"It can be a friend, a next-door neighbor, someone the patient knows," said Markut. Asking that friend to stop in and check on a patient as a paid service can reduce stress for both the patient and the caregiver. When the relief caregiver is a familiar face, the patient won't know they are being taken care of.

"There are places that will take a person for the weekend, or a 24-hour period, like nursing homes. They may have an empty bed, to offer respite care, like a stay for a weekend," said Markut.

"No one said that caregiving has to be a solo journey," Markut added. "Statistics show that only 11 percent of (caregivers) use support groups across the United States. What we are taught in this country is that we are supposed to be independent. I blame John Wayne," Markut said with a laugh. "We are taught that, when we are really all interdependent."

Giving permission

"What we try to do is give caregivers permission to take care of themselves," said Markut. "Think about what they tell you on a plane, for parents to put the oxygen mask on themselves first, so they can then take care of their children."

According to Markut, without relief, the nonstop stress of being a caregiver will result in serious health consequences. Ironically, research shows that it is factors such as high stress, lack of creative mental stimulation, lack of connection to a larger group of people, poor diet and lack of exercise that can make a person more susceptible to dementia-related illnesses.

Life after caregiving

"When people are so much into caregiving, they are lost when they let go of it," Markut said. "For a long time, their life was solely caregiving for that person, and that person is no longer there ... they are lost. Life is empty, and they have to work hard to get those connections again."

The bottom line, Markut said, is that, "We try to give caregivers permission to take care of themselves. We all need somebody. When you are caring for someone with dementia, you need a lot of somebodies."

Support for caregivers

Family Alliance offers support groups for caregivers, drop-in day care for dementia patients and a host of other services and resources. For information, call Family Alliance at 338-3590.

The book "Dementia Caregivers Share Their Stories" is currently available at Read Between the Lynes book store, 129 Van Buren, Woodstock; and online at Amazon.com. The book is also available at the Woodstock Public Library."

Source: Eileen Millard. It is important to take care of the Alzheimer's caregiver. The Woodstock Independent (23 November 2005) [FullText]

"The amyloid beta ptoein may not be the only monster, or even may not be the monster at all. My reasearch showed that reducing the amyloid precursor protein expression using antisense did improve the memory in mice considerably. If amyloid peptide has no role to play in AD, how would we explain the famous mutations in APP that enhance the accumulation of betaprotein also cause AD?. I think, formation of insoluble plaques may be the way in which the brain fights a soluble toxic agent or it indirectly generates. It is almost impossible to get a few dollars for alternate studies any way. I have lipid theory and complement theory, both were shot in their heart, dispite reasonable evidence I presented. If some one who sees this letter gives me a lead to which agency I may approach for few dollars to conduct AD research that involves other theories, I would be obliged."

Vijaya B. Kumar, Ph.D.

Source: Reader comment. Wall Street Journal Covers Alzheimer's Research. AlzClub.Org (16 November 2005) [FullText]

"PORTSMOUTH — Penny. Apple. And what was the third word the exam-giver had said to remember?

Oh yeah, table. Or was it desk?

Thousands of Americans received a free screening Tuesday, Nov. 15, as part of National Memory Screening Day, an Alzheimer's Association of America event to promote early detection of the disease and related illnesses. Locally, at the Brichel Center for Neurodevelopment, cofounder William Mautz and center clinical director Sandra Lovell administered the 10- to 15-minute screenings to walk-ins and those who had set up appointments. The screening included a series of memory-related questions involving time, place, subtraction and word recall. Test-takers lost points for incorrect answers.

For some it offered reassurance; for others, it pointed to a need for more examination. The screening did not offer a diagnosis. If visitors wanted, the center forwarded the results to their primary care physician, he said. For those who seek a complete dementia exam, it can take four or five hours, said Mautz, who holds a doctorate in neuropsychology.

Interest in and research into memory are growing with the aging of the baby boomer generation, typically described as those born between 1946 to 1964, a time of increased birth rates and prosperity.

Mautz speculated that boomers' interest stems from having seen parents experience memory loss, and because the boomers have been very health conscious, as a generation. In any case, because many of this generation are approaching an age when Alzheimer's disease develops — most victims are more than 65 — more people will be actively dementing in the coming years, said Mautz. In the last five years research has emerged about a condition called mild cognitive impairment, he said.

Those identified with this do not have full-blown dementia, but will develop the disease in three to six years. The Alzheimer's Association says early diagnosis of Alzheimer's gives patients a better chance of benefiting from treatment and more time to plan for the future. While there is no cure for Alzheimer's, drug treatments may stabilize symptoms, and care strategies and activities may prevent behavioral problems, the association says.

Memory problems, however, are not necessarily a product of Alzheimer's. Factors including depression, anxiety, or head injury can contribute to memory loss, Mautz said. Still, the sheer number of people expected to develop Alzheimer's recommends greater awareness, a goal of the national screening day, he said.

Another reason to continue research into and test for the disease is society's planning for the high cost of caring for people with the end stages of the disease. An estimated 5 million Americans have the disease, according to a Brichel Center news release. One in 10 of those 65 and older have it, and almost half of those 85 and older. The incidence is expected to triple by mid-century

The Brichel Center, located at 20 Ladd St., was also founded by psychiatrist Joshua Gear. It offers a variety of psychiatric and neuropsychological services. Its memory services include consultation, baseline memory testing, comprehensive diagnostic evaluation and individual memory training and education."

Source: Terry Gate. Baby boomers' interest grows in monitoring memory. Democrat (23 November 2005) [FullText]

Also see: Statins have Mind-Boggling Effects (AlzClub.org13 November 2004)

"A new study has found evidence that suggests use of statins, commonly used in the regulation of cholesterol levels, may be associated with a reduction in cognitive decline in the elderly.

23 Nov 2005, 17:56 GMT - Researchers in the Cardiovascular Health Study Collaborative Research Group monitored the cognitive abilities of 3,334 people over the age of 65 without dementia for an average of seven years and found that regular statin use was associated with a rate of cognitive decline less than half of that of untreated patients.

These new results published in medical journal Neurology follow on from other positive results concerning Alzheimer's disease and statin drugs which were released recently. In the first study, statins were found to slow the progression of Alzheimer's disease in a new three-year study of 342 patients.

Source: New study suggests efficacy of statins in cognitive decline. Pharm Business Review Online (23 November 2005) [FullText]

As part of activities for Alzheimer's Disease Awareness Month, Coventry resident Mary Reardon will be honored by the Alzheimer's Association.

In Rhode Island, 25,000 people suffer from Alzheimer's disease, and even more are caregivers of people with the disease. The Alzheimer's Association's Rhode Island chapter has organized a week long schedule of activities to commemorate the month Ronald Reagan declared Alzheimer's Disease Awareness Month. "Alzheimer's is a devastating disease that robs people of their memory, personality, and takes a toll on the entire family," said Camilla Farrell, development director for the Alzheimer's Association Rhode Island chapter.

"Our goal during the month of November," Farrell said, "is to, number one, raise awareness of the disease, but also to recognize the dedication of caregiving, emphasize the importance of finding and funding treatments, and to find preventative measures and a cure by hosting free educational and appreciation events for the public." "We work with patients and their families in various ways
and we offer education and training to health care professionals who care for people with Alzheimer's," she said. This week, the association held several events, including a tree dedication at Slater Mill Historic Site in Pawtucket.
"We have the tree dedication because we feel it is a nice way to commemorate our loved ones who have died from the disease," Farrell said. "You don't ever want to forget them, so we think that the tree is a nice way to remember them."
Yesterday, the association held what Farrell referred to as one of its most prominent events - the annual Dr. Brian Ott Research Symposium and Lecture.
Tomorrow, the association will honor some of its outstanding volunteers, several of whom are from the Kent County area.

Coventry resident Mary Reardon and her family, active supporters of the Alzheimer's Association, will be recognized for their most recent contribution of $2,400, which they raised for the association's annual Memory Walk. "You get so many solicitations to donate to, but my mother had Alzheimer's and she passed away in 2001, so we decided ... this was the cause that we wanted to support," Reardon said. "We each wrote letters and sent them out to our extended family, friends and co-workers and managed to raise $2,400 for the Memory Walk, which we were pretty proud of."
Terry Leal, owner of Tebeca's Jewelry in Warwick, is another volunteer honoree. Leal is one of the association's biggest supporters. In the past she has made monetary donations, offered the association a diamond for its "diamond-in-a bag" raffle, and started a half-and-half fund raiser for the association. Leal takes half the proceeds from the store's sale of clock and watch batteries and donates them to the association.

"There is a woman who worked for me (Judy Enos) whose father died of Alzheimer's," Leal said. "There was a lot of listening to her about her dad. That is how I really learned about the disease. That is why I like to try to help out the association when I can." Both women said they are humbled by being selected as honorary volunteers, but are more interested in using their honor to bring awareness to the association. "I can't say enough about the association," said Reardon. "They are a wonderful group of people that give way more than 100 percent. "They are the source of incredible resources for many people, and I am so very impressed with them. I just can't say enough about them," she said. For more information on Alzheimer's disease or the association, visit www.alz-ri.org."

Source: Jessica Carr. Local resident receives honors from Alzheimer's Association. Daily Times (17 November 2005) [FullText]

"Nov. 20 - Predix Pharmaceuticals, an Israeli drug discovery and development company, announced that PRX-03140, its highly selective, proprietary serotonin 4 (5-HT4) receptor agonist, showed the desired alterations in brain wave activity in patients with mild-to-moderate Alzheimer's disease and was well-tolerated in a recently completed 14-day Phase Ib clinical trial. "The results of this Phase Ib trial in patients with Alzheimer's disease suggest that PRX-03140 is stimulating the 5-HT4 receptor in the brain and is eliciting the desired effects on brain waves consistent with approved drugs for Alzheimer's disease," said Stephen Donahue, M.D., vice president of clinical and regulatory affairs. "The excellent tolerability profile of PRX-03140 at all doses studied, combined with these early indicators of activity, are exciting preliminary results and warrant further evaluation in a Phase II trial." Michael G. Kauffman, M.D., Ph.D., president and CEO of Predix, added, "We expect to initiate a Phase II dose-ranging trial in Alzheimer's disease patients early next year." In parallel with these clinical development efforts, several positive studies of PRX-03140 in key preclinical models for memory, cognition, and disease modification were the subject of four poster presentations at the 35th Annual Meeting of the Society for Neuroscience in Washington, D.C. last week."

Source: Israel21C. November 20-25, 2005 News [FullText]

Beware simplicity of Lay reports, Check major subject journal now. Neurobiology of Lipids, ISSN 1683-5506

"Cholesterol treatment, including statins, may slow down the progression of Alzheimer's disease, the results of a new study indicate. A team of researchers assessed the degree of brain function loss caused by Alzheimer's disease in 342 patients attending a memory clinic. The progress of the disease among the group was then monitored for a further three years. The average age of the patients was 73. Altogether, 129 of the participants had abnormal cholesterol levels, almost half of whom were being treated exclusively with statins. Statins are a group of drugs used in the treatment of people with high cholesterol levels. A further 105 of the participants had abnormal but untreated cholesterol. The remaining 108 participants had normal cholesterol levels.

The researchers found that during the three years, all of the patients deteriorated as a result of Alzheimer's. However the disease progressed significantly slower in the patients who were being treated for abnormal cholesterol levels. In fact, progression of the disease was rated at 1.5 points a year in those given cholesterol drugs, 2.4 in those whose cholesterol was untreated and 2.6 in those with normal cholesterol levels. The research team concluded that cholesterol lowering drugs effectively slow down the progression of the disease. However they emphasised that a larger study would be required to confirm these findings. Details of this study are published in the Journal of Neurology Neurosurgery and Psychiatry..."

Source: Deborah Condon. Statins may slow down Alzheimer's. Irish Health (17 November 2005) [FullText]

Among the hallmarks of Alzheimer’s, which include neurofibrillary tangles and amyloid plaques, Abbott Laboratories Inc., Abbott Park, Ill., researchers now say they found a new species of amyloid beta-peptide that selectively binds to nerve cells in the brain and is an important causal factor for the disease.
“For years researchers have focused on finding ways to stop the formation of the plaque, believing that the plaques themselves were toxic,” says James Sullivan, PhD, vice president, neuroscience discovery, Abbott. “Over the last five years, however, more and more research suggests that we did not have the whole story.”

Preclinical research, Sullivan says, now shows that cognitive function, such as memory retention, started being impaired long before amyloid plaques formed. Clinical research also shows that amyloid plaques are present in the brains of aged people without Alzheimer’s.

Thus, the focus has turned to finding other forms of amyloid protein that may represent a toxic or pathologic species. One such form, Sullivan says, is a soluble amyloid, in contrast to the insoluble form found in plaques.

Abbott identified a new soluble globular beta-amyloid species, which they call globulomer, present in the brains of Alzheimer’s patients. “These globulomers are structurally distinct from the [fibrous] form of amyloid that dominates in plaque,” says Sullivan.

Using highly selective antibodies for the globulomers, he says, they were able to prove the presence of this new form of amyloid in the brains of Alzheimer’s patients, which were not present in age-matched controls.

An immunofluorescent imaging technique was used to find the specific sites in the brain where the globulomers bind and found them binding to neurons in the hippocampus, a key region of the brain involved in learning and memory and one of the first areas affected by Alzheimer's disease. Research in mice, Sullivan says, suggests that globulomers inhibit the ability to form and retain memory. They are now conducting research to find the proteins on these neurons, with which the globulomers are interacting.

“The identification of this unique amyloid species provides the opportunity to generate selective antibodies directed against globulomers,” says Sullivan. “Such antibodies have the potential to address the underlying disease pathology, not just the symptoms, and to be safe because of their selective interaction with this toxic species of amyloid.”

Source: Elizabeth Tolchin. Abbott Finds New Amyloid in Alzheimer’s. Drug Discovery and Development. (16 November 2005) [FullText]

"Brain scan, cerebrospinal fluid analysis may help predict Alzheimer's disease
St. Louis, Nov. 15, 2005 -- A combination of brain scanning with a new imaging agent and cerebrospinal fluid (CSF) analysis has left neuroscientists encouraged that they may finally be moving toward techniques for diagnosing Alzheimer's disease before its clinical symptoms become apparent. "When clinical symptoms start, the disease process has already been at work in the patient for many years and possibly even decades," explains Anne Fagan Niven, Ph.D., research associate professor of neurology at Washington University School of Medicine in St. Louis. "Up to 30 percent of neurons in vulnerable areas are already dead, and you can't get them back. So finding markers that can help us identify patients prior to symptoms is really our big push now."

With colleagues Mark Mintun, M.D., professor of radiology, and David Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology, Fagan studied a group of 24 people that included individuals diagnosed with very mild and mild Alzheimer's disease, and cognitively normal subjects. As expected, in patients with cognitive impairments, believed to be attributable to Alzheimer's disease, researchers found low CSF levels of amyloid beta 42 (A-beta 42), the principal ingredient of the brain plaques that are characteristic of Alzheimer's disease. In the same individuals, brain scans with a new imaging agent that reveals the presence of amyloid plaques in the brain were positive. What scientists didn't anticipate was that three cognitively normal subjects would have both low CSF levels of A-beta 42 and positive results from the brain scans. Fagan stressed that although this aspect of their findings was very intriguing, it doesn't prove that the three normal subjects will one day develop clinical Alzheimer's disease.

"For now, definitive diagnosis of Alzheimer's disease still cannot be made until autopsy," she says. "It's going to take a number of years for us to fully assess these results, because all we can do now is follow the participants closely to see if they eventually develop Alzheimer's dementia." Fagan presents the results of the study at 10:15 a.m. on Nov. 15 at this year's annual meeting of the Society for Neuroscience in Washington, D.C. The study will also appear in an upcoming issue of Annals of Neurology. Many prior studies have found that A-beta 42 levels drop in the cerebrospinal fluid of Alzheimer's disease patients. A-beta 42 is naturally produced in the brain, and researchers suspect that the creation of amyloid plaques may be linked to breakdowns of the processes that degrade or normally clear A-beta 42 from the brain via the CSF and the bloodstream.

However, natural variations occur in CSF A-beta 42 levels in healthy subjects, and the amount this level drops in Alzheimer's patients also varies. And that left no distinct level scientists could identify as a diagnostic marker characteristic of Alzheimer's disease. Fagan wanted to see if useful distinctions could be made by combining data on CSF A-beta 42 levels with results from brain scans with a new imaging agent, PIB (for Pittsburgh compound B). Developed by researchers at the University of Pittsburgh, PIB temporarily sticks to amyloid plaques in the brain but washes clean in 30 to 60 minutes. Scientists can detect this sticking with a PET scanner. Using PIB data available from ongoing studies of research volunteers at the Memory and Aging Project at the Alzheimer's Disease Research Center at Washington University, Fagan compared PIB scan results and levels of CSF A-beta 42.

"When I realized that everyone who was PIB positive also had lower CSF A-beta 42 levels, I had one of those 'aha!' moments that makes it so exciting to be a scientist," Fagan says. Other CSF factors, such as levels of another form of A-beta and of a molecule found in the brain cell tangles created by Alzheimer's disease, did not correlate with positive PIB scan results. "The hope is that 10-20 years from now, we'll give people a PIB scan, draw and analyze their CSF, and combine that with other factors to get a global score for their personal risk of Alzheimer's disease," Fagan says. "We have disease-modifying treatments on the way to clinical trials right now, and tests that can help us detect Alzheimer's earlier will both help us put those treatments to better use and assess the results they produce in patients."

Fagan AM, Mintun MA, Mach RH, Dence CS, Shah AR, LaRossa G, Spinner ML, Klunk WE, Mathis CA, Morris JC, Holtzman DM. Correspondence between in vivo amyloid imaging and CSF A-beta 42 levels in humans: implications for antecedent biomarkers of Alzheimer's disease. Society for Neuroscience annual meeting, November 15, 2005. Funding from the National Institute on Aging supported this research. Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

View online at this link . Source: EurekAlert.org

Public release date: 15-Nov-2005
Contact: Michael C. Purdy , purdym@wustl.edu (314) 286-0122 , Washington University School of Medicine

"Alzheimer's disease, depression and epilepsy share a problem with a single brain chemical: glutamate. A neurotransmitter, glutamate is critical to the process by which individual brain cells send messages to one another, and it plays a key role in learning and memory.

Under normal conditions, glutamate keeps the brain humming. But if the glutamate signaling process doesn't shut off at the appropriate time, neurons in the brain become overstimulated and damaged, leading to the development of brain diseases. New research by Rockefeller University's Bruce McEwen explores how the brain uses a specific protein, neuropeptide Y, to protect itself from glutamate damage.

One area of the brain that is particularly sensitive to glutamate is the memory center, called the hippocampus. Nozomu H. Nakamura, a postdoc in McEwen's lab, focused on one type of cell, called interneurons, within the hippocampus. These neurons are regulated by estrogen, which scientists know has protective effects on the brain. McEwen and Nakamura wanted to know how estrogen affected the interneurons and how it could protect them from excessive glutamate.

Looking specifically at interneurons that express the estrogen receptor, they found that neuropeptide Y, already known to regulate glutamate signaling, was present in many of the cells with an estrogen receptor.

When Nakamura gave estrogen to female rats lacking their ovaries, he saw that more cells in the hippocampus began to make neuropeptide Y, and the cells that already made it made more. Alternatively, when he blocked estrogen signaling, he could also block the increase in neuropeptide Y, showing that neuropeptide Y is controlled by estrogen.

"Neuropeptide Y may help restrain the overactivity of the glutamatergic system, which can cause seizures and stroke," says McEwen, the Alfred E. Mirsky Professor and head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology. "Regulation of neuropeptide Y might be one way estrogen protects the brain from damage and over-excitation, and understanding how those pathways work could lead to therapeutic strategies."

Source: Study shows potential for curbing brain disease. (9 November 2005) myDNA News [FullText]

"Most people in America approve of allowing patients with Alzheimer's disease to be enrolled in research studies, even when they are not able to provide their own consent, new research has shown.

Ninety per cent of 229 participants in a study carried out by the University of Michigan/University of Rochester in the US said it would be appropriate to allow family members to enroll Alzheimer patients in research that involved mild-to-medium risks, including the testing of new drugs.

A majority of participants in the study also approved of the surrogate decision-making in studies that would involve procedures such as spinal taps, brain tissue sampling and gene transfers.

All the study participants were aged over 70 and at heightened risk of developing Alzheimer's. All had had at least one close blood relative diagnosed with dementia and all were taking part in a study looking at the use of anti-inflammatory drugs to prevent dementia.

Their study authors believe national standards are needed for this type of research issue and that their research may help policy-makers."

Source: Research ethics in Alzheimer's. Irish Health. (9 November 2005) [FullText]

Also see an essay on Alzheimer's corruption by Chris Masterjohn [FullText]

"Researchers trying to crack one of medicine's most perplexing unsolved mysteries can now keep abreast of late-breaking developments via the Schizophrenia Research Forum, a website launched this month with funding from the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH). Sponsored by NARSAD, The Mental Health Research Association, the site bills itself as a "virtual community" where researchers can link-up with colleagues and potential collaborators, learn about new findings, meetings and funding opportunities, and critique each other's articles and ideas.
"We're hoping that the Forum will become a catalyst for creative thinking that will speed the pace of discovery," said NIMH Director Thomas Insel, M.D.

The site (www.schizophreniaforum.org) includes original news stories and interviews with leading scientists in the field. Among specific forums that invite contributions from the field, "Current Hypotheses" presents theory reviews, while an "Idea Lab" posts less formal treatments. Most features of the site are interactive and solicit comment.

There will also be live chats with experts that will be archived for later viewing. For example, NIMH senior advisor Mayada Akil, M.D., who represents the Institute to the Forum, is tentatively scheduled to co-lead a discussion with Dr. Irving Gottesman, University of Virginia, on "Identifying Quantifiable Phenotypes in Schizophrenia Research."

Citations of current schizophrenia-related papers, with links to PubMed abstracts are posted each week ­ the newest in a searchable database going back to 2000. Among research tools, the site offers an extensive annotated index of relevant web sites with information, downloadable software, databases, and other web-based technologies for scientists. Future plans include a searchable database called SchizophreniaGene.

Registered researchers are listed in a member directory with links to their profiles, containing affiliations, contact information and research interests. Other resources include jobs listings and links to journals and departments and institutes involved in schizophrenia research worldwide.

Members of the Forum's Scientific Advisory Board are William T. Carpenter, Jr.,
University of Maryland School of Medicine, Joseph T. Coyle, McLean Hospital, Anthony A. Grace, University of Pittsburgh,. Stephan Heckers, McLean Hospital, James L. Kennedy, University of Toronto, June Kinoshita, Alzheimer Research Forum, David A. Lewis, University of Pittsburgh, Carol A. Tamminga, University of Texas Southwestern Medical Center at Dallas, and Daniel R. Weinberger, National Institute of Mental Health.

NIMH is providing $700,000 in initial funding for the Schizophrenia Research Forum for 2005-2007. The site's executive editor Hakon Heimer is assisted by a team of science communicators and web designers who helped develop a similar website for Alzheimer's disease, after which it is modeled.

NIMH will be co-hosting an event during the Society for Neuroscience annual meeting Washington, D.C. in late November that will acquaint neuroscientists with the Schizophrenia Research Forum and its offerings.

NIMH and is part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services.

Contact: Jules Asher, NIMHpress@nih.gov , (301) 443-4536, NIH/National Institute of Mental Health

Source: Web Forum launched for schizophrenia researchers. News release by NIH/National Institute of Mental Health (31 October 2005) [FullText]

"European researchers, publishing in a leading scientific journal, show a biological link between cholesterol and Alzheimer’s disease. Authors of the paper acknowledge the EU’s contribution to their work through the Lipidiet project, which investigated the role of lipids in neurodegeneration.

Alzheimer’s, or the ‘memory disease’, as it is sometimes called, is a fatal condition affecting higher brain function. Around one-third of the EU population develops it during their lifetime. It generally affects the elderly but early onset is known. Its prevalence in older people has led to the misconception that “losing your mind” is just part of ageing. Scientists are keen to dispel this, showing that Alzheimer’s is a disease and not a process of normal ageing. On average, it progresses from the first clinically apparent symptoms to death in about nine years. But this can vary.

The disease starts with minor memory problems and ends with patients completely forgetting even friends and family and becoming dependent on full-time care. Until now, the only treatments have been for the symptoms. More active treatments and possibly a cure will take the burden of Alzheimer’s off healthcare systems and families who have to watch this tragic degradation of the mind.

While the cause of Alzheimer’s is still not fully understood, science is well on the way to providing some answers. It is already known that, in most cases, the disease is not inherited but may depend on environmental and genetic factors ­ in around 5% of cases, it is inherited through mutations in three different genes. These cases have revealed much about the disease, according to the Lipidiet project team.

Lipidiet ­ which stands for ‘Role of Lipids in Neurodegeneration and their Preventive Potential in Diet’ ­ was funded by the EU’s Fifth Framework Programme (FP5). The project’s coordinator, Tobias Hartmann of Heidelberg University, Germany, is the senior author of a recent publication in Nature Cell Biology which shows that regulation of cholesterol and another fat called ‘sphingomyelin’ (SM) involves a protein ­ called amyloid precursor protein (APP) ­ which is found in the brain, but also other organs like the heart, kidneys and lungs.

Lipidiet sought to better understand the basic cellular principles at work in the disease. The seven partners in the project cover an array of specialties, including molecular biology, neurobiology, lipid metabolism, physiology and medicine, and behavioural sciences, as well as a private firm specialising in health-targeted food.

What’s cholesterol got to do with it?
APP contains a small region ­ the amyloid beta domain. This domain is cut off from APP by certain enzymes, known as secretases. Accumulation of amyloid beta forms, over time, a hard plaque in the human brain which is difficult to break down. Everyone produces this but the quantity and its effects are not all the same. This is an area that has traditionally stumped scientists. But using mouse models to firm up the relationship between this accumulation and the onset of Alzheimer’s, the European team is now closer to understanding the sequence of events.

The team’s newly-published findings show that amyloid beta, while toxic and disease causing when over produced, has a normal and non-toxic function. And this normal function is to regulate cellular lipid levels. Their function results in regulatory cycles in which the amyloid beta reduces cholesterol synthesis and sphingomyelin levels, the team writes in a recent statement.

The very same lipids control the activity of the enzyme which produces amyloid beta, resulting in altered amyloid-beta levels, leading to the troubling plaque. Altering these regulatory cycles ­ with drugs, genetics, or even diet ­ changes amyloid-beta production and thus the risk for Alzheimer’s, say the researchers.

“Knowledge of the natural amyloid-beta peptide function allows us to re-evaluate therapeutic and preventive approaches to Alzheimer’s disease and to generate more effective and safer novel therapies,” notes the team. What’s more it explains the link between Alzheimer's and cholesterol, and how statins (cholesterol-lowering drugs) work to prevent it.

How does this relate to food and the Lipidiet project? Well, Lipids are an insoluble fat found in the blood and organs, including the brain. We eat foods with varying fat content and types. A strong case had already been presented for the use of lipid- and cholesterol-lowering drugs to either prevent or slow down Alzheimer’s. But non-drug approaches are equally promising.

A ‘designer diet’ that can delay the onset of Alzheimer's had earlier been devised by Lipidiet, according to a CORDIS News story. The consortium is testing it in clinical trials to validate its effectiveness and provide a more convincing case for diet’s potential to prevent, delay or slow down Alzheimer’s disease."

Source: DIET, MEDICINE: Adding another dimension to ‘brainfood’. Europa.Eu.Int (28 October 2005) [FullText]

Also see:

Brain Cholesterol Pathology is the Cause of Alzheimer's Disease. Alzheimer's Research Forum: Current Hypotheses [FullText]

Koudinov AR, Koudinova NV. Amyloid beta protein restores hippocampal long term potentiation: a central role for cholesterol? Neurobiol. Lipids Vol.1, 8 (2003) [FullText]

Koudinov AR, Berezov TT. Alzheimer's amyloid beta (Ab) is an essential synaptic protein, not neurotoxic junk. Acta Neurobiol Exp. 64, 71-79 (February 2004) [.PDF FullText]

Also, please see below the references for publications questioning integrity of American Academy of Neurology

"ST. PAUL, Minn. ­ Grandma has Alzheimer's disease ­ should you sign her up for a new research study, even if she doesn't really understand what it entails? What if the research has real risks, is unlikely to benefit her, but could lead to advances that will help future patients with Alzheimer's? A new study sheds light on these questions, which may come up more often as potential treatments require more involved and invasive research.
"As potential new therapies such as vaccines, gene therapy, and new drugs are being tested, the need for research must be balanced with the need to protect vulnerable adults," said Scott Y. H. Kim, MD, PhD, of the University of Michigan Medical School in Ann Arbor. "This continues to be an area with unsettled policy, and there is little data to guide policymakers. It doesn't seem ideal to leave these important ethical questions solely to politics. This study shows that it's possible to learn the views of key stakeholder groups, and they can provide important insights."

People at heightened risk for Alzheimer's disease ­ 229 people who were over 70 and had at least one close relative with the disease ­ took part in the study, which is published in the November 8, 2005, issue of Neurology, the scientific journal of the American Academy of Neurology.

The participants were given 10 research scenarios and asked if the research portrayed was acceptable when it involves people with Alzheimer's who cannot give their own informed consent and are enrolled with a family member's permission.

They were asked to consider three perspectives: whether the research was acceptable from a societal perspective, from their own perspective (whether the participants would want a loved one to make the decision for them), and from the perspective of a surrogate (how they would make a decision for a loved one).

The 10 scenarios ranged from low-risk studies involving observation or routine blood draws to higher-risk studies like testing a potential vaccine or a neurosurgical gene-transfer intervention. The survey participants were told about the risks and any potential benefits to subjects or to society.

More than 90 percent of the participants felt that minimal risk studies as well as randomized clinical trials of new medicines should be allowed with incompetent Alzheimer's subjects if family members give permission. A smaller proportion, but still a majority, felt that even the scenarios with the most risk (for example, early phase experiments testing gene-transfer) were acceptable.

In general, participants endorsed family consent for research most strongly when applied to themselves as future research subjects and least strongly when placing themselves in the position of the surrogate having to decide for a loved one. For example, for a study that would involve a lumbar puncture (also known as a spinal tap), family consent for research was endorsed by 69 percent when applied to themselves as future subjects, by 65 percent from a social policy perspective, and by 61 percent as something they would allow for a loved one.

Participants were more likely to find the research scenarios acceptable if they had a generally supportive attitude toward biomedical research. The study participants were already taking part in an Alzheimer's disease anti-inflammatory prevention research study. The researchers note that the participants could be more supportive of research than the typical person at risk for Alzheimer's.

"However, those taking part in the study were fairly typical demographically to people taking part in other studies of Alzheimer's disease, so they may be quite similar to those likely to be considered for future research studies," Kim said.

The study was supported in part by a grant from the National Institutes of Health."

The American Academy of Neurology, an association of nearly 19,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer's disease, epilepsy, Parkinson's disease, multiple sclerosis, and stroke.

For more information about the American Academy of Neurology, visit www.aan.com , Marilee Tuite mtuite@aan.com (651) 695-2789

Source: Is it okay to sign Alzheimer's patients up for research studies? American Academy of Neurology Press Release. (7 November 2005) [FullText at EurekAlert]


Also, make sure you read the following publications questioning integrity of American Academy of Neurology:

Dr Alexei Koudinov correspondence with Murray Sagsveen of AAN (13 Nov. 2002 - 26 March 2003, eight items)[FullText]

Open letter to President George W. Bush on conduct by scientists, STM journals, and Scientific Institutions. (Neurobiology of Lipids, 10 March 2004) [FullText]

See below three references questioning Dr. Floyd Bloom science integrity!

"The Institute of Medicine of the National Academies has awarded the 2005 Rhoda and Bernard Sarnat International Prize in Mental Health to Floyd E. Bloom, chairman, chief executive officer, and chief scientific officer of Neurome Inc., La Jolla, Calif. Consisting of a medal and $20,000, the prize was presented at the IOM's annual meeting.

The Sarnat Prize is being given to Bloom in recognition of the international scope and significance of his contributions to biological sciences, neuroscience in particular. Bloom was one of the first neurobiologists to appreciate the need for in-depth study of the roles and functions of the brain's neurotransmitters, and to elucidate the roles and interactions of specific neurotransmitter systems. His research teams were the first to identify a number of genes expressed exclusively in the brain. His work led to key revelations about the interaction between medications and neurotransmitters, as well as how alcohol and other addictive substances act on the brain. Bloom also pioneered applications of software programs and databases that aid in the imaging and analysis of neurological functions. Based on his conviction that pinpointing gene expressions in the brain will lead to new understanding of neurodegenerative disorders such as Alzheimer's and Parkinson's, Bloom co-founded a biotechnology firm called Neurome Inc. in 2000 that seeks new ways to diagnose and treat these diseases.

In addition to his research pursuits, Bloom served five years as editor in chief of SCIENCE, where he led the publication into the Internet age by overseeing the development of an online version of the journal. Bloom further expanded the journal's readership by partnering with scientific associations overseas to appeal to an international audience and make SCIENCE accessible to other nations.

Bloom was elected to the National Academy of Sciences in 1977 and the Institute of Medicine in 1982. From July 1989 until March 2005, Bloom served as chairman and professor of the department of neuropharmacology at Scripps Research Institute in La Jolla, Calif. He has been president of the Society for Neuroscience, the American College of Neuropsychopharmacology, and the American Association for the Advancement of Science. Bloom also has been elected a member of the Royal Swedish Academy of Sciences, the American Academy of Arts and Sciences, and the American Philosophical Society, and received numerous awards and honorary degrees. He has written more than 600 publications and co-authored multiple editions of textbooks on neuropsychopharmacology.

Bloom received his undergraduate degree from Southern Methodist University in Dallas, and went on to receive an M.D. from Washington University in St. Louis. After completing an internship with Barnes Hospital in St. Louis, his interest in pharmacology led him to seek further training at the National Institute of Mental Health's Clinical Neuropharmacological Research Center. It was there that Bloom began his studies of the fundamental mechanisms of the nervous system.

The Institute of Medicine has awarded the Sarnat Prize since 1992 to individuals, groups, or organizations that have demonstrated outstanding achievement in improving mental health. The prize recognizes - without regard for professional discipline or nationality - achievements in basic science, clinical application, and public policy that lead to progress in the understanding, etiology, prevention, treatment, or cure of mental disorders, or to the promotion of mental health. As defined by the nominating criteria, the field of mental health encompasses neuroscience, psychology, social work, public health, nursing, psychiatry, and advocacy.

The award is supported by an endowment created by Rhoda and Bernard Sarnat of Los Angeles. Rhoda Sarnat is a licensed clinical social worker, and Bernard Sarnat is a plastic and reconstructive surgeon and researcher. The Sarnats' concern about the destructive effects of mental illness inspired them to establish the award.

Nominations for potential recipients are solicited every year from IOM members, deans of medical schools, and mental health professionals. Nominations for the 2006 prize can be sent to Leslie Baer at sarnataward@nas.edu.

The Institute of Medicine is a private, nonprofit organization that provides health policy advice under a congressional charter granted to the National Academy of Sciences. "

Michelle Strikowsky news@nas.edu The National Academies nas.edu

Source: Floyd E. Bloom wins 2005 Sarnat Prize in Mental Health. NAS Mental Health News (25 October 2005) [FullText]

Also, make sure you read the following publications questioning integrity of Floyd Bloom science:

Open letter to Donald Kennedy, Science Editor-in-Chief: AAAS, Science, Alzheimer’s disease and academic dishonesty (Science SAGE KE, 16 June 2003) [FullText]

Open letter to President George W. Bush on conduct by scientists, STM journals, and Scientific Institutions. (Neurobiology of Lipids, 10 March 2004) [FullText]

Memorandum from Dr Alexei Koudinov: Select Committee on Science and Technology Written Evidence Editorial and Publisher Corruption. (12 February 2004) [FullText]

"Blocking a signaling lipid can keep nerves from developing the arm-like extensions they need to wire the body and may even cause neurons to die, researchers have found.

The researchers hope this piece of the puzzle of how the central nervous system develops in the first place will one day help them repair loss from injury or disease.

It’s already helped them understand the ailments of a spontaneous mouse mutant that has about 20 percent function of the protein that helps the lipid get to the cell surface so it can help axons grow, says Dr. Wen-Cheng Xiong, developmental neurobiologist and corresponding author on the study published in the November issue of Nature Cell Biology.

The mutant mouse is small and has motor neuron degeneration, with tremors, short limbs and a short life, she says. Before this new work, what the blocked lipid transfer protein regulated was still a mystery.

The lipids in question aren’t those measured during an annual physical exam, rather those that help give shape and function to units within cells such as the nucleus and cell powerhouse, or mitochondria, she says.

“Traditionally people didn’t think these lipids were regulated. They thought they were just there,” says Dr. Xiong. “But what we found is this particular lipid is regulated; it’s like a signaling molecule. Especially during axon growth, the dynamic regulation is more dramatic.”

She and her colleagues found the lipid is transferred to the cell surface at just the right time and place by phosphatidylinositol transfer protein-a, which humans also have. It’s been known that many proteins can be regulated, especially signaling proteins that enable intracellular chatter. “Now we have found this protein regulates lipids and lipids also travel,” Dr. Xiong says.

The mouse mutant is a clear example of what can happen when the lipids don’t travel. The researchers also studied a similar mutant chick embryo that had reduced axon growth. For this paper, they added the zebrafish embryo, which forms most of its major organs within the first 24 hours and remains transparent for the first few days of life, to further document the role of these regulated lipids and their transfer protein.

When they injected an agent that blocks expression of a related lipid transport protein, the next they could see the impact on axon growth and neuron survival, says Dr. David J. Kozlowski, developmental geneticist and director of the MCG Transgenic Zebrafish Core Laboratory. They looked at different levels of suppression, finding the greater the suppression, the greater the resulting defect. “It shows this protein is critical for development,” Dr. Xiong says of repeated findings.

Next they’ll use a version of the transgenic zebrafish that will enable them to watch axon development ­ or lack of it ­ in live embryos and in real time, Dr. Kozlowski says.

They also want to look at what happens to the lipid activity in an injury model. They already know some signaling proteins are disturbed.

MCG contributors included the laboratories of Drs. Xiong and Kozlowski as well as Dr. Lin Mei, program chief in Developmental Neurobiology and Georgia Research Alliance Eminent Scholar in Neuroscience.

Collaborating institutions include the University of Alabama at Birmingham; the Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; Howard Hughes Medical Institute; and the Jackson Laboratory in Bar Harbor, Maine.

The work was supported by the National Institutes of Health."

Source: Medical College of Georgia News: Lipids play important role in nervous system development. Innovations Report (26 October 2005) [FullText]

Also See: Neurobiology of Lipids News Collection

"Famous people who suffer from the degenerative neurological Alzheimer’s Disease remind us that there is currently no prevention, no cure, and no discrimination when it comes to diagnosis. Political figures, actors, and athletes alike can use their recognition to bring attention to the need for research, early diagnosis, and increased awareness. Ironically, though, the disease makes it extremely difficult for such figures to make public appearances, as they cannot reliably deliver speeches or interact with media when their memory and functionality is on the decline.

Perhaps the most well-known sufferer, of course, was the 40th President of the United States, Ronald Reagan. He drastically increased public awareness for the tragic illness through his personal mission of education and fundraising. In 1983, he declared November National Alzheimer’s Disease month to call attention to the growing numbers of seniors succumbing to debilitation. He founded the Ronald and Nancy Reagan Research Institute, in coordination with the Alzheimer’s Association, to explore the possible causes and courses of treatment, especially focusing on early detection. When he passed away in 2004, he left a lasting legacy of research funds to benefit a country whom now better understood and appreciated the tragic condition.

Other political figures have not been so public about their Alzheimer’s Disease. The modern American conservative of the 60s, Barry Goldwater, who died of Alzheimer’s in 1998, lived his last years in private. Experts still disagree whether Sir Winston Churchill, the Prime Minister of Great Britain, suffered from Alzheimer’s Disease or a dementia associated with strokes. A family doctor insists Churchill did not have the neurological disorder, yet many of his symptoms are consistent with Alzheimer’s. More than anything, this speaks to the shame and uncertainty surrounding a proper diagnosis.

Charlton Heston, an actor and political activist, is among the few celebrities still suffering from Alzheimer’s. Heston became famous in the 50s for epics such as The Ten Commandments. He remained popular for three decades, starring in adventures, westerns, and earning two Oscars. After retiring from acting, he took up conservative causes, most notably as President of the National Rifle Association. He’s advocated for progress in Alzheimer’s Disease after being diagnosed in 2001. On behalf of the Academy of Molecular Imaging, Heston released a public service announcement urging those without symptoms of Alzheimer’s to use a new detection method, PET scans of the brain. Positron Emission Tomography can diagnose Alzheimer’s very early and gives patients a chance to enjoy their symptom-free time.

Other actors, such as the classical Hollywood pin-up Rita Hayworth of the 40s and ultra-masculine Charles Bronson of the 60s, also had Alzheimer’s Disease. Since they were diagnosed late, and didn’t have the kind of public support recently garnered, our country’s climate didn’t permit them to make statements before their deaths. Similarly, the boxer Sugar Ray Robinson and singer Perry Como suffered from advanced Alzheimer’s in the later years of their private life, and succumbed to the disease in 1989 and 2001 respectively."

Source: Who are Some Famous People That Had Alzheimer's Disease? WiseGEEK (last viewed 2 November 2005) [FullText]

"Nymox Pharmaceutical’s AlzheimAlert diagnostic fails to improve the decision-making capability of physicians assessing patients for Alzheimer’s disease, FDA’s Immunology Devices Panel concluded July 15.

The panel voted 5-2 against recommending approval of the clinical test. Both positive and negative test results from the device “appear to have little clinical utility,” panelist James Gulley (National Cancer Institute) said of the clinical data.

The firm suggested its product would be especially useful in assisting general practitioners. However, Gulley was among several other panel members who argued that primary care physicians would likely refer the patient to a specialist following an AlzheimAlert test, regardless of the result.

Nymox wants to position the product as an adjunct to standard Alzheimer’s evaluation procedures such as neurological, radiological and neuropsychological techniques, and as a tool to “help the clinician’s decision for the need of further diagnostic work-up.”

The urine test measures levels of neural thread protein (NTP), which has been shown as elevated in patients with early Alzheimer’s disease (AD).

The panel’s conclusion is consistent with FDA’s statistical review. The agency suggested that Nymox’ data did not offer any clear answers because it was not compared to the “gold standard” for AD diagnosis – histopathological autopsy of the brain after death.

“Should a clinician discard the clinical impression of [definitive] non-AD if the NTP test is positive?” FDA statistician Mariana Kondratovich inquired. “From the submitted data, it is impossible to evaluate the significance of this disagreement.”

Nymox’s application rests on one 200-patient, nine-center study comparing NTP results with standard clinical assessment by neurologists. “First-morning” urine samples were collected from subjects with signs of dementia, but not an AD diagnosis.

Subsequently, physicans – blinded to the test results – employed current best practices to put patients into one of four categories: definite non-AD, mild cognitive impairment, possible AD, and probable AD.

Nymox intends the test to “aid in the diagnosis of definite non-AD versus probable AD, possible AD, or MCI.”

The firm reported that 94 of 98 (96%) patients with NTP values > 22 microg/mL were classified in one of the latter three categories. It also noted that 40 of 44 (91%) def non-AD patients had NTP values < 22 microg/mL (categorized as “normal”).

However, 62 of the 102 patients with “normal” NTP values were not classified into the non-AD group, suggesting that 61% of patients “will be incorrectly categorized as having def non-AD,” FDA reviewers noted in documents released prior to the meeting.

“Given the significant overlap observed in NTP values between the four categories of interest...it is unclear if this device is effective at meeting the stated indications for use,” the pre-panel analysis stated.

Nymox contends that AlzheimAlert is not intended to individually support a physician’s decision, but to add helpful data to the overall clinical picture, which, they say, is a use supported by the submitted study.

“It is infinite, the number of choices in the practice of medicine,” Nymox CEO Paul Averback told the panel. “We are only trying to say that [the product] adds information to the toolbox.”

However, FDA and several panelists agreed that the test does not address the complexities of today’s diagnostic challenges. Agency reps suggested that the definite non-AD category was not clearly defined, and that many assigned to the group were unlikely to be confused for AD patients.

“How useful is a diagnostic test that is only applicable in those instances where a diagnosis is already easy to make?” Division of Neuropharmacological Drug Products Medical Officer Ranjit Mani, who reviewed the PMA clinical data as a consultant.

Several panel members echoed this concern wishing the test would differentiate patients in the probable AD and MCI categories, where more complex signs and symptoms present themselves.

FDA approval would allow Nymox to sell AlzheimAlert as a kit to qualified laboratories and hospitals. Currently, it is offered to physicians through Nymox’s CLIA-certified laboratory in N.J."

Source: Nymox AlzheimAlert Diagnostic Clinical Utility Questioned By Panel. FDA Advisory Committe .com (20 July 2005) [FullText]