Hospices Become Testing Grounds

clipped from blogs.wsj.com As more Americans spend their final days in hospices, drug makers and doctors are asking patients there to take part in tests of new medicines. But the research faces considerable logistical and ethical challenges, this morning’s WSJ reports.

Alzheimer's Disease Could Be A Third Form Of Diabetes

This article intrigues me. I have been thinking about diabetes for sometime in relation to my mother. My grandmother likely died from diabetes and my sister is a diabetic. My mother's sugar readings are very high but none of her doctor's has ever suggested doing anything about it. This fits under the "she's old" model of medicine now being practiced.

The article is worth reading and considering.

Insulin, it turns out, may be as important for the mind as it is for the body. Research in the last few years has raised the possibility that Alzheimer's memory loss could be due to a novel third form of diabetes.

Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer's disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer's removes insulin receptors from nerve cells, rendering those neurons insulin resistant. (The protein, known to attack memory-forming synapses, is called an ADDL for "amyloid ß-derived diffusible ligand.")

With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer's disease, the Northwestern study sheds light on the emerging idea of Alzheimer's being a "type 3" diabetes.

The new findings, published online by the FASEB Journal, could help researchers determine which aspects of existing drugs now used to treat diabetic patients may protect neurons from ADDLs and improve insulin signaling in individuals with Alzheimer's.

In the brain, insulin and insulin receptors are vital to learning and memory. When insulin binds to a receptor at a synapse, it turns on a mechanism necessary for nerve cells to survive and memories to form. That Alzheimer's disease may in part be caused by insulin resistance in the brain has scientists asking how that process gets initiated.

"We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed," said William L. Klein, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, who led the research team. "Instead, they are piling up where they are made, in the cell body, near the nucleus. Insulin cannot reach receptors there. This finding is the first molecular evidence as to why nerve cells should become insulin resistant in Alzheimer's disease."

ADDLS are small, soluble aggregated proteins. The clinical data strongly support a theory in which ADDLs accumulate at the beginning of Alzheimer's disease and block memory function by a process predicted to be reversible.

In earlier research, Klein and colleagues found that ADDLs bind very specifically at synapses, initiating deterioration of synapse function and causing changes in synapse composition and shape. Now Klein and his team have shown that the molecules that make memories at synapses -- insulin receptors -- are being removed by ADDLs from the surface membrane of nerve cells.

"We think this is a major factor in the memory deficiencies caused by ADDLs in Alzheimer's brains," said Klein, a member of Northwestern's Cognitive Neurology and Alzheimer's Disease Center. "We're dealing with a fundamental new connection between two fields, diabetes and Alzheimer's disease, and the implication is for therapeutics. We want to find ways to make those insulin receptors themselves resistant to the impact of ADDLs. And that might not be so difficult."

Using mature cultures of hippocampal neurons, Klein and his team studied synapses that have been implicated in learning and memory mechanisms. The extremely differentiated neurons can be investigated at the molecular level. The researchers studied the synapses and their insulin receptors before and after ADDLs were introduced.

They discovered the toxic protein causes a rapid and significant loss of insulin receptors from the surface of neurons specifically on dendrites to which ADDLs are bound. ADDL binding clearly damages the trafficking of the insulin receptors, preventing them from getting to the synapses. The researchers measured the neuronal response to insulin and found that it was greatly inhibited by ADDLs.

"In addition to finding that neurons with ADDL binding showed a virtual absence of insulin receptors on their dendrites, we also found that dendrites with an abundance of insulin receptors showed no ADDL binding," said co-author Fernanda G. De Felice, a visiting scientist from Federal University of Rio de Janeiro who is working in Klein's lab. "These factors suggest that insulin resistance in the brains of those with Alzheimer's is a response to ADDLs."

"With proper research and development the drug arsenal for type 2 diabetes, in which individuals become insulin resistant, may be translated to Alzheimer's treatment," said Klein. "I think such drugs could supercede currently available Alzheimer's drugs."

Klein, Grant A. Krafft, formerly at Northwestern University's Feinberg School of Medicine and now chief scientific officer at Acumen Pharmaceuticals, Inc., and Caleb E. Finch, professor of biological sciences and gerontology at the University of Southern California, reported the discovery of ADDLs in 1998. Krafft is a co-author of the FASEB Journal paper. Northwestern and USC hold joint patents on the composition and use of ADDLs in neurodisorders.

The patent rights have been licensed to Acumen Pharmaceuticals, based in South San Francisco, for the development of drugs that treat Alzheimer's disease and other memory-related disorders.

In addition to Klein, De Felice and Krafft, other authors on the paper are Wei-Qin Zhao, a former visiting scientist at Northwestern, now with Merck & Co., Inc. (lead author); Hui Chen, from the National Center for Complementary and Alternative Medicine at the National Institutes of Health; Michael Quo, from Blanchette Rockefeller Neurosciences Institute; and Sara Fernandez and Mary Lambert, from Northwestern University.

Note: This story has been adapted from a news release issued by Northwestern University.

Source Science Daily, research Nothwestern University.

The 36-Hour Day: A Family Guide to Caring for People with Alzheimer Disease and Memory Loss in Later Life

Brain Activity Might Point to Early Alzheimer's

A team at Duke University Medical Center in Durham, N.C., used functional magnetic resonance imaging (fMRI) to study the brains of 13 patients with mild Alzheimer's disease, 34 patients with mild cognitive impairment, and 28 healthy people (averaging about 73 years of age) as they did a memory task.

A specific pattern of brain activity could be a sign of early Alzheimer's disease, U.S. researchers report.

They noted that as new treatments for Alzheimer's become available, spotting the disease early will become critical.

A team at Duke University Medical Center in Durham, N.C., used functional magnetic resonance imaging (fMRI) to study the brains of 13 patients with mild Alzheimer's disease, 34 patients with mild cognitive impairment, and 28 healthy people (averaging about 73 years of age) as they did a memory task.

Participants with mild Alzheimer's and mild cognitive impairment showed impaired activity in the medial temporal lobe (MTL), an area of the brain associated with episodic memory that normally turns on during a memory task. Previous research had found that structural changes in the MTL are among the earliest known brain changes in people with Alzheimer's disease.

More surprisingly, the researchers found impaired deactivation in the posteromedial cortex (PMC), a brain area involved in personal memory that's usually suppressed during a memory task. The degree of PMC deactivation was closely related to the level of a patient's memory impairment and significantly correlated with their neuropsychological testing scores.

"In other words, the brain not only loses its ability to turn on in certain regions, but also loses its ability to turn off in other regions, and the latter may be a more sensitive marker. These findings give us insight into how the brain's memory networks break down, remodel and finally fail as memory impairment ensues," study lead author Dr. Jeffrey R. Petrella, an associate professor of radiology at Duke, said in a prepared statement.

He said the findings "implicate a potential functional, rather than structural, brain maker -- separate from atrophy -- that may help enhance diagnosis and treatment monitoring of Alzheimer's patients."

The study is published in the October issue of the journal Radiology.

More information

The Fisher Center for Alzheimer's Research Foundation has more about Alzheimer's diagnosis.

Source Health Day, U.S. News

Subscribe to The Alzheimer's Reading Room

Bob DeMarco is the editor of the Alzheimer's Reading Room and an Alzheimer's caregiver. Bob has written more than 1,200 articles with more than 9,000 links on the Internet. Bob resides in Delray Beach, FL.

Popular articles on the Alzheimer's Reading Room

• Advice and Insight -- Alzheimer's Reading Room
• Dealing with Difficult Behavior Caused by Dementia and Alzheimer's
• Communicating in Alzheimer's World
• Dr Oz Alzheimer's Memory Quiz (Test)
• What is Alzheimer's Disease?
• Does the Combination of Aricept and Namenda Help Slow the Rate of Decline in Alzheimer's Patients
• Test Your Memory (TYM) for Alzheimer's or Dementia in Five Minutes
• Alzheimer's World -- Two Circles Trying to Intersect
• Baby Boomer Alzheimer's Perspective
• Alzheimer's Disease -- The Front Row
• Is it Really Alzheimer's or Something Else?
• Alzheimer's Clock Draw Test -- Detect the Signs of Alzheimer's Early
• 60 Good Reasons to Subscribe to the Alzheimer's Reading Room

"I Remember Better When I Paint"

Original content Bob DeMarco, the Alzheimer's Reading Room

Testing of Alzheimer’s Drugs Remains a Puzzle

clipped from blogs.wsj.com Alzheimer’s is a brutal disease, and it’s been brutally resistant to treatment. There are plenty of experimental drugs in development now, but the drawn-out, inexorable decline for patients with the disease makes it tough for researchers to tease out whether a drug is having an effect. That’s especially true in the early, small trials of medicines that have just started on their journey out of the lab. “Unless it’s a Lazarus drug, the only way to see the results is to do a Phase III study,” Peter Davies, an Alzheimer’s researcher at the Albert Einstein College of Medicine, said Monday in a briefing sponsored by New York City Chapter of the Alzheimer’s Association. As a result, he said, companies are forced to push potential drugs into late-stage trials that enroll more than 1,000 patients, last for years and cost millions. “It puts you in a huge gamble,” Davies said. Davies and Rudolph Tanzi of Harvard were speakers at a meeting of the Alzheimer’s group last night.

ARR

The Alzheimer's Reading Room is the number one source of information for the entire Alzheimer's community.
The site focuses on Alzheimer's disease, dementia, Alzheimer's caregivers, and the art of Alzheimer's caregiving.
Each day, 1,232 people are diagnosed with Alzheimer's disease.

Aricept & Severe Alzheimer's

The only thing I can say is Aricept definitely helps my mother. Is it a cure, NO!

clipped from www.google.com A research study for people living in nursing homes with severe Alzheimer's disease showed those taking Aricept (Donepezil) improved slightly. But do minimal improvements mean that a medication used in the early and moderate stages of Alzheimer's should be used in the later stages of dementia? Aricept & Severe Alzheimer's

Unitedhealth to offer an Alzheimer's plan

This is important news and we will be following up on this story as it develops.

clipped from www.startribune.com UnitedHealth Group Inc. said it will offer the first government-subsidized plan devoted to the care of patients with Alzheimer's disease and chronic dementia. Nurse-managers will customize plans for policyholders in the Phoenix, Ariz., area starting Jan. 1 as a first step toward offering the Alzheimer's program nationwide, the company said Monday. The policies will be funded by Medicare. UnitedHealth, based in Minnetonka, said the program is aimed at improving services for the estimated 5 million Americans suffering from Alzheimer's. Nurses serving as case managers will help members stay out of hospitals, said John Mach, chief executive officer of UnitedHealth's Evercare unit.

Diagnosing Alzheimer's Disease In Earliest Stages: New Method

clipped from www.sciencedaily.com The proposed criteria are based on examining the structure and function of the brain using advanced brain imaging techniques as well as looking at spinal fluid for the imprint of the disease. Early detection will allow researchers to test vaccines that might be used preventively or to treat fully affected individuals, or other drug treatments that are directed at the earliest stages of the disease -- the best time to reduce symptoms.

Alzheimer's disease a ticking time bomb

clipped from timesofindia.indiatimes.com Ranjan Goel was a gregarious and fun-loving person, a top executive with an MNC till recently. Without any warning, life did a turnabout. He started forgetting things, got agitated easily and little-by-little began withdrawing into a shell. His family was worried. A couple of visits to psychiatrists and neurologists confirmed his wife's worst fears — Goel had developed Alzheimer's disease. Now, four years later, as he sits with a vacant look with his wife and children, their animated conversation has no effect on him. "It's heart-wrenching to watch him in this state," says his wife Indu, fighting back tears. "Every day is a battle for us." <BR>

More Drug Side Effects, or Just More Reports of Problems?

clipped from blogs.wsj.com Reports of serious injuries and deaths that may have been caused by prescription drugs skyrocketed between 1998 and 2005, says a paper published today in the Archives of Internal Medicine. But it’s unclear if the jump in reports to FDA reflects a true increase in the number of people who suffered serious side effects. First, the numbers. In 1998, the FDA received 34,966 reports of serious adverse events, including 5,519 reports of deaths, possibly related to the use of prescription drugs. By 2005, those figures more than doubled, to 89,842 events including 15,107 deaths.

Silent Seizures May Cause Alzheimer's Dementia

The surprising finding indicates that antiseizure medications given to epilepsy patients may also help lower or even reverse cognitive decline in Alzheimer's disease, a treatment option that could be available relatively quickly.

Source Scientific America

Study identifies nonconvulsive seizures as potential culprit. Already available drugs may stave off and even reverse debilitating symptoms

By Nikhil Swaminathan

The families of the five million Alzheimer's disease sufferers in the U.S. are all too familiar with the erratic neurodegenerative disorder. "Mom seemed almost like herself this morning and then she drifted away form me," recounts senior investigator Lennart Mucke, describing a conversation with a patient's daughters.
The root of these heart-wrenching fluctuations between cognizance and confusion has eluded scientists for years. But Mucke, director of the Gladstone Institute of Neurological Disease at the University of California, San Francisco, and colleagues believe they may finally have pinpointed the cause of these puzzling personality twists as well as other cognitive deficits associated with Alzheimer's: petite mal (nonconvulsive) seizures similar to those exhibited in some types of epilepsy.

They reached this conclusion during studies of mice engineered to build up protein fragments in their brains known to cause the disease. The animals had alternating stages of overexcitement and inhibition in several regions of their brains, seizures of activity that resulted in swift rewiring to dampen the sudden surges.
"We were quite struck to find anatomical and pathological hallmarks of overexcitation" observed in epilepsy without the convulsive, physical reaction, says Mucke. "We would have thought that everything was shutting off."

The surprising finding indicates that antiseizure medications given to epilepsy patients may also help lower or even reverse cognitive decline in Alzheimer's disease, a treatment option that could be available relatively quickly.

A protein fragment called amyloid-beta (Aβ) is known to aggregate and create plaque in the brains of Alzheimer's patients. Plaque hinders neuronal activity by gumming up synapses (spaces between cells through which chemical or electrical information is transmitted), eventually damaging nerve cell branches and leading to neuronal death.

In the current study, a collaborative team of researchers at the Gladstone Institute and the Baylor College of Medicine in Houston, created a strain of mice that overproduces a precursor of Aβ known as amyloid precursor protein. Five to six months after birth, as plaque built up, these animals showed learning and memory deficits illustrated by their difficulty navigating mazes. During autopsies, researchers observed that rewiring had occurred in the late subjects' brains.

"What tipped us off to the excitation was actual anatomical rewiring in the hippocampus—or learning centers—that looked like the cells wanted to protect themselves from overexcitation," Mucke says.

Using electroencephalography (EEG)—in which electrodes placed in the brain measure neural activity—the team saw a sharp wave of action in the mouse brains from the hippocampus in the midbrain to the neocortex (the outermost brain layer). The whole network of nerve cells seemed to activate simultaneously and synchronously. "The hippocampus then clamps down because it doesn't want to receive all that excitation, so it clamps down its portals by engaging its inhibitory cells," Mucke says. "In the process, they probably disable some normal, excitatory functions; part of this inhibitory rewiring that happens probably accounts for the fact that there's no physical seizure activity."

He says it is no doubt difficult for the neurons to do their usual jobs in the face of the sudden bursts of activity and overcompensation to correct them. Given that the hippocampus is associated with episodic memory, he says that this may account for some of the cognitive deficits of Alzheimer's, including the spells of confusion. "I could imagine that this abnormal activity may go on throughout the course of the disease,'' Mucke notes, "and not just mess up cognition but contribute to the neurodegenerative process."





The 36-Hour Day: A Family Guide to Caring for People with Alzheimer Disease and Memory Loss in Later Life

Alzheimer's Patients now being implanted with Microchip

The chip is being positioned by VeriChip as a critical part of emergency medicine. The majority of early adopters are interested in the chip for wandering and identification of lost loved one’s. Opponents are concerned about privacy.

+Alzheimer's Reading Room

Florida-based VeriChip has developed an FDA-approved microchip that can be implanted in an Alzheimer's patient's arm.

The VeriChip contains a unique 16-digit number which allows for wearer identification and immediate access to that persons medical record.

The medical information is contained in a database managed by VeriChip and could be accessed from a hospital emergency room. The microchip about the size of a grain of rice must be scanned in order for the information to become available.

The chip is being positioned by VeriChip as a critical part of emergency medicine. It is obvious that the majority of early adopters are interested in the chip for wandering and identification of lost loved one’s.