“The Big Four” dementias – AD, LBD, FTD, and Vascular

There’s a wonderful article in the November/December 2009 issue of Neurology Now magazine.  It features Jerome and Renata Rafferty; Jerome had Lewy Body Dementia and Renata was his caregiver.

The “Other” Dementias (featuring Lewy Body Dementia story)

A companion article is titled “The Big Four.”  It gives short descriptions of four types of dementia – Alzheimer’s, Lewy Body Dementia, Frontotemporal Dementia, and Vascular Dementia.  The article notes that there are over 100 types of dementia.

Below the full text of the article, and a link to it online. You can also download the PDF of the article.

Robin
————————————

journals.lww.com/neurologynow/Fulltext/2009/05060/The__Other__Dementias.14.aspx –> HTML version

The Big Four
Neurology Now
November/December 2009 – Volume 5 – Issue 6 – p 26-27,31-34

More than 100 types of dementia have been found, but four of them account for nearly 98 percent of all cases of dementia in the United States.

ALZHEIMER’S DISEASE (AD)

DESCRIPTION: People with AD develop memory problems, often followed by confusion, apathy, depression, emotional volatility, and other problems.

CAUSE: People with AD develop two types of dysfunctional protein in the hippocampus, the part of the brain essential for creating new memories. Tau protein accumulates within neurons in that region, while clumps of amyloid protein develop between neurons in that region. Some researchers, however, suspect that the toxic proteins may be the result of the disease rather than the cause.

TYPICAL CASE: The first symptom of AD almost always involves memory problems, such as forgetting familiar names and misplacing items. As the disease progresses people may have trouble finding their way home or keeping up with routine obligations such as doctor appointments, paying bills, and preparing meals. Later stages may affect the frontal lobes, resulting in erratic emotions, loss of normal inhibition, and hallucinations.

TREATMENT: Since AD results in decreased levels of acetylcholine, a neurotransmitter essential for memory and learning, drugs that boost acetylcholine, such as donepezil and memantine, often help, at least for a while. Other treatments are available for specific symptoms such as depression, hallucinations, and movement disorders, but nothing seems to slow development of the disease.

ON THE HORIZON: Several drugs and vaccines designed to inhibit the production of toxic tau and amyloid protein, or remove it once it appears, are in development. However, people who have tried the drug experimentally failed to improve significantly, even though protein levels declined, sometimes dramatically.

LEWY BODY DEMENTIA (LBD)

DESCRIPTION: Like Alzheimer’s, LBD produces cognitive decline, but with three additional traits. Instead of declining continuously, people with LBD tend to fluctuate in terms of attention, alertness, ability to speak coherently, and other symptoms. They also tend to have visual hallucinations, often benign. Finally, they tend to develop symptoms of Parkinson’s disease, including rigidity, tremor, and slowness of movement.

CAUSE: A type of protein known as alpha-synuclein clumps into Lewy bodies, which appear inside of cells, or neurons. Lewy bodies may result from the inability of the cell to break down and recycle alpha-synuclein efficiently. As the protein accumulates, it sticks together, as though the cell is trying to gather its own debris to keep it out of the way.

TYPICAL CASE: People with LBD often act out violent dreams that involve being pursued or attacked. They may develop benign hallucinations involving, for example, children or animals running around the house. Attention and concentration may fluctuate, and patients may start to have trouble with visual-spatial abilities-they may misjudge the height of a step or miss a cup when they reach for it. Some people with LBD experience an overwhelming urge to sleep during the day. Their movements also may become rigid and slow, like the symptoms of Parkinson’s disease, and they may develop problems with memory, judgment, and mood, like the symptoms of AD.

TREATMENT: No treatment specifically for LBD exists. However, since LBD affects nearly every neurochemical system in the brain, specific aspects of the disease can be treated. Memory problems can be treated with donepezil and other drugs for AD. Movement disorders may respond to L-dopa and other medications for Parkinson’s disease. Modafinil may alleviate daytime sleepiness.

ON THE HORIZON: No drug yet exists that affects the synuclein protein, although some drugs exist for daytime sleepiness, and another, which resembles methylfenidate, is in development.

FRONTOTEMPORAL DEMENTIA (FTD)

DESCRIPTION: FTD includes several disorders that cause the frontal lobes behind the forehead, and the temporal lobes at the sides of the brain, to atrophy and shrink. Patients either develop speech difficulties, known as aphasia, or they display inappropriate social behavior. Aphasia may involve halting, effortful speech with the patient struggling to produce the right word. Behavioral changes may involve indifference to the concerns of others. Some patients developing FTD may start shoplifting or become attracted to shiny objects or fire.

CAUSE: In FTD, a protein known as TDP-43 accumulates within cells at the front of the brain. In one form of FTD known as Pick’s disease, tau protein, found in the hippocampus of people with AD, accumulates within cells in the frontal lobes.

TYPICAL CASE: A person developing FTD generally exhibits personality or mood changes. An outgoing person may become withdrawn and depressed, while an introverted person may become loud and outgoing. Socially inappropriate behavior may also become more common. Later, FTD patients may develop speech difficulties as they lose the ability to recall the meaning of words, or they may start to speak with great fluency while making no sense.

TREATMENT: Only symptomatic treatments are available with medications developed for other disorders, such as psychiatric medications for behavioral problems or mood disorders. There are no treatments for language problems.

ON THE HORIZON: Methylene blue, a drug in development for AD, inhibits the aggregation of tau protein, so it may help patients with Pick’s disease. Another tau aggregation inhibitor known as AL-108, or davunetide, is in clinical trials, and may soon become the first tau-active drug available in the U.S. TDP-43, the offending protein in other forms of FTD, was discovered only three years ago, leaving little time for the development of effective treatments.

VASCULAR DEMENTIA

DESCRIPTION: Since this dementia results from several small strokes, and strokes can affect any part of the brain, the symptoms of vascular can vary widely. However, they usually include declines in problem-solving ability, memory, and socially appropriate behavior.

CAUSE: Vascular dementia is believed to result from damage to brain cells caused by lack of oxygen when the blood supply is cut during a series of mild strokes. However, one study of 1,000 brains from demented patients who had died found only six that had pure vascular dementia, with the slow progression typical of the disorder. The rest also had another form of dementia.

TYPICAL CASE: To be diagnosed with vascular dementia, a patient must show evidence of a stroke in a location that could affect cognition, and cognitive problems must develop within three to six months of the stroke. A patient who meets these criteria may develop memory problems and have trouble speaking coherently or understanding the speech of others. They may also develop motor difficulties that prevent them from dressing themselves.

TREATMENT: The first goal is to reduce stroke risk by improving cardiovascular health. Statins may be prescribed to lower cholesterol, anti-hypertensives to lower blood pressure, and omega-3 pills to improve triglyceride levels. Low-dose aspirin may be prescribed to inhibit the clotting of the blood, and patients may be urged to give up smoking and drinking and reduce stress.

ON THE HORIZON: Damage from strokes cannot be reversed, but the brain can compensate for some deficits. Physical therapy designed to stimulate brain plasticity may provide some help.

Copyright © 2009, AAN Enterprises, Inc.

Famous amnesic launches a bold, new brain project at UCSD’s Brain Observatory

This post is likely only of interest to those curious about brain tissue analysis. I’ve been watching the slicing of this brain tissue today at UCSD’s Brain Observatory, and agree that it’s “mesmerizing.” The process will produce about 2500 tissue samples for analysis.

Here’s the live video:
http://thebrainobservatory.ucsd.edu/hm_live.php

In the New York Times article from yesterday on this “famous brain” — http://www.nytimes.com/2009/12/03/healt … brain.html — a researcher said “It’s just amazing that this one patient — this one person — would contribute so much historically to the early study of memory.”

And here’s a good article on the Brain Observatory and the analysis of this particular brain from Monday’s San Diego Union-Tribune newspaper. For me, the last two sections of the article were the most interesting (starting with “The Brain Observatory is divided between…”).

http://www3.signonsandiego.com/news/200 … ld-new-br/

H.M. recollected
Famous amnesic launches a bold, new brain project at UCSD

By Scott LaFee, San Diego Union-Tribune Staff Writer
Monday, November 30, 2009 at 12:04 a.m.

As best he could remember, Henry Gustav Molaison never visited San Diego, spending his entire life on the East Coast. When he died late last year at the age of 82, Molaison was a man almost entirely unknown except by his initials H.M. and the fact that experimental brain surgery had erased his ability to form new memories.

He forgot names, places, events and faces almost immediately. Half an hour after lunch, he couldn’t recall what he had eaten, or that he had eaten at all. His face in the mirror was a constant surprise because he remembered only what he looked like as a young man. Every question was new, even those asked just minutes before.

Yet Molaison bore this strange and unimaginable burden with grace and stoicism, allowing scores of scientists to study, probe and ponder his condition for decades, each seeking to better understand the mysteries of the human brain, memory and personal identity.

“H.M. started a revolution in the study of memory,” said Dr. Vilayanur S. Ramachandran, a professor of psychology and neuroscience and director of the Center for Brain and Cognition at UCSD at the time of Molaison’s death. “His was an unforgettable contribution.”

Molaison died of respiratory failure on Dec. 2, 2008, but his story — and his legacy — does not end in that Connecticut nursing home. Within hours of death, Molaison’s brain would be scanned, removed and placed in the preservative formalin, the first steps on a journey to San Diego and a new kind of immortality.

On a cold night in mid-February, Jacopo Annese returned to San Diego, arriving on Jet Blue Flight 411 from Boston. With him was the brain of H.M. They had flown coach: Annese in the aisle seat, H.M.’s brain in a 19-quart white plastic cooler strapped next to him in the window seat. More than a few fellow travelers looked curiously at the arrangement; some inquired directly.

“I tried not to be coy,” said Annese. “I told them the cooler contained a very important scientific specimen. I didn’t say a brain. I didn’t want to risk upsetting any passengers.”

Sophisticated and articulate, educated and trained in Italy, England and the United States, the 43-year-old Annese came to the University of California San Diego in 2005 to develop and direct the Brain Observatory, with an ambitious plan to create a new and unrivaled collection of human brains for scientific study.

These brains, normal and with various pathologies, will be preserved on thousands of slides that, in turn, are converted into extraordinarily high-resolution digital images freely available online. Researchers around the world will be able to use the material to conduct investigations ranging from parsing basic cognitive functions or the physical effects of diseases like Alzheimer’s to more abstract inquiries such as how memories are created and changed and the organic nature of consciousness.

The project has already begun with a handful of brains. Annese envisions the collection as a kind of library, each brain containing a life story. “We strive to treat the brains we study not as anonymous tissue, but as representations of a person and of a mind. We want to write books about people’s lives, neurological biographies that survive in glass and pixels.”

In this most novel of libraries, Molaison’s brain is the rarest of volumes. He is the most famous amnesic of all time, perhaps the most-studied neurological patient in history.

When he was 10 years old, Molaison began suffering epileptic seizures and blackouts, which increased in severity and frequency until, in his 20s, he was no longer able to work or live alone. In 1953 at the age of 27, Molaison agreed to undergo a radical experimental operation intended to relieve his suffering. Dr. William Beecher Scoville, a noted neurosurgeon at Hartford Hospital in Connecticut who had refined many of the techniques used in lobotomies, suctioned out finger-sized portions of the temporal lobes on both sides of his brain. The removed tissue contained most of Molaison’s hippocampus, a brain region whose function was poorly understood at the time, if at all.

The seizures largely stopped, but so too did Molaison’s ability to form new memories, though he could recall parts of his life before the surgery, a condition called severe anterograde amnesia. Scoville and a Canadian psychologist named Brenda Milner quickly realized that Molaison represented a tragic but rare opportunity to explore how human memory works.

With Molaison serving as willing and genial subject, identified only as H.M. to protect his privacy, they began a series of studies. In a landmark 1957 paper, Scoville and Milner described H.M.’s bifurcated memory for the first time. The paper, which has been cited by other researchers almost 2,000 times, led to the startling realization that memory is not a generalized brain function, but rather is controlled by key regions like the hippocampus, which regulates the flow of information destined to become long-term memory.

In many ways, H.M. appeared to be an ordinary fellow. He liked crossword puzzles and watching TV. He was polite, funny and self-effacing. “He was a very endearing person,” said Annese, who met H.M. once in 2006 during early planning for the Brain Observatory and library. “I was happy to get to know the man.”

Surprisingly, even with no ability to form long-term memories, H.M. could learn new things, in particular new muscle memory skills like drawing or playing golf. He didn’t remember taking lessons or practicing, but the acquired abilities stuck.

That discovery generated another new and fundamental insight into human cognitive function. There are different types of memories: Long-term declarative memories, which H.M. could no longer form; short-term memories which H.M. still possessed to a degree; and motor memories, such as recalling how to ride a bike, which H.M. never lost.

Each kind of memory, scientists deduced, must essentially be created and reside in different parts of the brain. Sometimes H.M. learned and remembered things that happened post-surgery, such as the assassination of John F. Kennedy in 1963. This suggested portions of H.M.’s memory system survived his 1953 surgery or that other regions had taken up some of those duties. No one really knew.

To really understand what was going on inside H.M.’s head, researchers needed to venture more deeply inside the brain itself.

The Brain Observatory is divided between an elaborately equipped wet lab for handling flesh-and-blood brains, and separate areas housing high-powered microscopes and computers for digitizing them.

Converting biology to bytes takes time. It is complex, painstaking and fraught with unprecedented technical challenges. A brain like H.M.’s represents a singular chance to advance scientific knowledge, but there is almost no room for mistakes.

“It’s a huge responsibility that many labs might not want,” said Annese.

Within four hours of his death, Molaison’s body was moved to Massachusetts General Hospital (MGH), where researchers, led by Suzanne Corkin, a professor of behavioral neuroscience at the Massachusetts Institute of Technology who had worked with H.M. for 46 years, conducted an overnight series of magnetic resonance imaging scans, a last chance to record his brain’s structure and condition “in situ.”

The next morning, after Annese had flown overnight to get there, he and MGH neuropathologist Matthew Frosch delicately removed H.M.’s brain from his skull.

“I was sweating bullets,” Annese later told the journal Science.

Like all fresh brains, H.M.’s had the consistency of Jell-O. It could be easily damaged, harm that might render it less useful — perhaps even useless — for further study. But the removal went smoothly and the brain was immediately deposited in formalin, suspended by a string so that it wouldn’t become deformed by resting on the bottom of the container. It would remain in formalin for two months until firm enough to travel safely to San Diego.

After returning in February with the brain, Annese conducted a second, more exhaustive series of MRI scans over two days, producing a more comprehensive anatomical map and a final record of the brain intact.

Next, the brain was immersed for weeks in increasing levels of sucrose solution. As the sucrose (sugar) infused the brain, it replaced water in cells, reducing the risk that ice crystals might later form, which could cause tissue to tear and reduce the brain’s research value.

High-security freezers house the project’s brains. (Annese has 10 so far.) The freezers are constantly and continuously monitored, with emergency backup power and an automatic alert system.

H.M.’s brain is scheduled to be sectioned on Wednesday, with segments of the procedure broadcast live via the Brain Observatory’s Web site (thebrainobservatory.ucsd.edu). Annese has been practicing the procedure on control brains.

Just prior to cutting, H.M.’s brain will be dipped in a liquid bath of isopentane at minus 40 degrees Celsius until frozen solid. The actual slicing is reminiscent of a delicatessen. The prepared brain is locked inside a cuff containing circulating ethanol to keep it precisely frozen. Too cold and the tissue might shatter during cutting; too warm and the tissue becomes sloppy. The cuff and brain are then mounted atop a commercial microtome modified by Annese with help from machinists at the Scripps Institution of Oceanography. Every component has been meticulously measured and engineered. A razor-sharp blade of tempered steel glides over the exposed brain, cutting from the front of the brain to the back, producing opaque, whitish slices that crinkle and wad on the blade’s edge like slivers of cut ginger.

Each brain slice is approximately 70 microns thick, about the width of a hair. An average-sized brain produces 2,600 to 3,000 such slices. Once the cutting begins, it continues until the brain is completely sectioned, a 30-hour endeavor.

A camera mounted above methodically records every slice, though a human operator must constantly attend to gently dab up each crumpled slice off the blade and deposit it into a sequentially numbered container filled with buffer solution.

“There’s something mesmerizing about doing this,” said Natalie Schenker, a postdoctoral research associate as she dabbed and deposited slices of control brain. “It’s like going on a journey, each slice getting you to another place in the brain.”

The majority of slices will be left untouched, cryogenically preserved for future experiments. Some slices, perhaps every 30th to 50th, will be mounted on postcard-sized glass slides. Mounting is an exacting process. A technician uses fine arts brushes to tease a wadded slice floating in a tray of buffer solution to lie flat upon an underlying slide, a physical match to the photo taken of that same slice during the cutting procedure. One mounting can take up to an hour.

The slides are then dried and some sequentially stained, what Annese calls “the club sandwich idea.” Different stain colors reveal different components of the brain. Blue shows individual neurons; brown highlights myelin-coated connective structures and support cells.

Finally, the slides are ready to be digitized. Each is placed under a microscope at 20X magnification to distinguish individual cell types. A computerized camera next begins snapping pictures of the microscopic scene. It requires 20,000 such “capture tiles” to produce a mosaic of just one slide, enough digital information to fill 200 DVDs.

Annese and colleagues have designed an automated system to do this demanding but tedious work. The data are sent to UCSD’s California Institute for Telecommunications and Information Technology (Calit2) and the San Diego Supercomputer Center, where it will be managed and stored for future use.

A fully sliced, mounted, stained and digitized brain is, in some ways, a return to wholeness, a brain reassembled in cyberspace. “We’re taking all of the two-dimensional image data (from the slides) and reconstructing them in a 3-D system,” said Alain Pitiot, a computer scientist at the University of Nottingham in England. “We’re reforming the brain so that researchers can see things in context.”

The intended result will be a bit like Google Earth. Scientists will be able to zoom in and out of a digitized brain; focusing down to the level of individual neurons or pulling back to examine whole brain circuits or regions.

When fully up and operating, the project will be an interactive affair. All data will be online and open to viewing and discussion. Neuroscientists will be able to watch procedures, make recommendations and observations, suggest experiments or request tissue samples. Nonscientists will have similar, if more limited, access.

For obvious reasons, H.M.’s brain holds special interest. It’s the catalyst for the entire endeavor. But more importantly, researchers are eager to compare what they learned about Molaison while he was alive with what they can discover in his digitally revealed brain.

“The extraordinary value of H.M.’s brain is that we have roughly 50 years of behavioral data, including measures of different kinds of memory as well as other cognitive functions and even sensory and motor functions,” said Corkin at MIT.

“We know what he was able to do and not do. Our goal is to link his deficits to damaged brain areas and his preserved functions to spared areas.”

H.M.’s brain will also be compared with those of other amnesic patients. Larry Squire, a professor of psychiatry and neurosciences at UCSD, has donated the brains of three much-studied patients. Some of Ramachandran’s patients have also agreed to donate their brains after death.

But the Brain Observatory and library project is about more that just H.M. and the mystery of memory. It promises the chance to investigate all things that ail the brain. For example, Annese is already processing brains that are part of an HIV study. And he has established partnerships with Lifesharing and the San Diego Eye Bank, which handle organ and tissue donations in San Diego County, to secure new donors.

Annese is quick to note that he’s not solely interested in afflicted or particular brains. He hopes people who have no known neurological issues will donate their brains to the Observatory, too.

“Healthy brains for study are very rare, but they are essential if we want to understand how brains age and why some people avoid neurological disease and dysfunction. We want to know what a normal brain is.”

But more profoundly, Annese hopes the Observatory and the future research that flows through and out of it will help answer the enduring question of what exactly makes each of us human and unique.

“We know that the human brain has a basic pattern,” said Annese. “We’re all born with the same kind of instrument, let’s say a violin. But how we play this violin and what we decide to play shapes this instrument during our lives. We can learn a lot by the wear-and-tear of life on our violins, how each of us has modified it. These could prove to be anatomical fingerprints of individuality, biological clues of what makes us who we are.”

OBSERVING LIVING DONORS IS PART OF STUDY

The Brain Observatory and its related brain library project will necessarily rely upon donated brains, primarily through the services of two regional organ and tissue banks, Lifesharing and the San Diego Eye Bank.

Much of the emphasis will be on finding donors who are able to participate in a monitoring, data-gathering program while they are still alive and well, people like Clint and Maggie Spangler.

The La Jolla couple is reasonably healthy. “I’m told I have the brain of a 60-year-old,” said Clint, who is 81. Nonetheless, he and his wife both suffer from essential tremor, a progressive neurological condition characterized by uncontrollable trembling, typically of the hands though it can affect many parts of the body.

Often confused with Parkinson’s disease, essential tremor is not life-threatening. “It’s more of a nuisance,” said Maggie. But it is common. According to the National Institutes of Health, the condition affects up to 14 percent of Americans over the age of 65.

The exact cause of essential tremor is not known, but there’s a clear genetic component. Two of the Spangler’s four children have the condition; a third appears likely to develop it. Clint and Maggie have promised their brains to the observatory, hoping that the donations might help researchers solve their condition and others.

“We’re not too philosophical about it,” said Maggie. “We’d like to be able to help, and we’re certainly not going to need our brains after we’re dead. Besides, do you know what a funeral costs these days?”

To learn more about organ and tissue donations, visit Lifesharing at lifesharing.org or the San Diego Eye Bank at sdeb.org

Dealing with anosognosia (unawareness of decline)

AlzOnline.net is a caregiver support forum for Alzheimer’s caregivers. They have an interesting article on their website about anosognosia, which is a lack of self-awareness about one’s decline or condition. The best part of the article are “examples of how to approach, interact and speak to someone who has anosognia.”

Here’s the summary from the article: “The person who has anosognosia is unaware of deficits or the progressive decline in abilities to manage tasks and self-care. The person with anosognosia is not in denial; they have limited awareness or are unaware of the decline. When people with anosognosia confabulate, they believe what they are saying; they are not lying. Their remarks should be treated with respect, followed by a smooth transition to whatever tasks or activities need to occur next. Regular help for the home and family, planning ahead and working with a positive, partnership approach will help with the long-term, daily care management.”

Here’s a link to the full article and some additional excerpts.

http://alzonline.phhp.ufl.edu/en/readin … gnosia.pdf

“A lack of awareness of impairment, not knowing that a deficit or illness exists, in memory or other function is called anosognosia. The term anosognosia refers to brain cell changes that lead to a lack of self-awareness. … The impairment may be in memory, other thinking skills, emotion, or movement.”

“Anosognosia differs from denial. Denial is a strategy used to reject something that a person wants to ignore, partially avoid, or reject outright because it is too difficult or causes too much stress. The person may minimize a problem or accept part of the truth, for example, the person may accept the fact of being chronically ill but want to avoid dealing with it by not taking medicine. Sometimes a person is in denial in order to avoid taking any responsibility for an issue or situation. Anosognosia is not denial.”

“Anosognosia may occur in different progressive memory disorders. Often the progressive dementia (sometimes referred to as a progressive memory disorder) is of the Alzheimer’s disease type, sometimes it fits into the category of Lewy body disease or a frontal-temporal lobar degeneration.”

“Interaction Tips
Providing regular assistance with daily chores, transportation, and personal care and restricting unsafe activities are important. For example, someone may need to make sure that meals are readily available, that spoiled food is discarded, and that alcoholic beverages are not accessible. The controls for operating the stove and water heater should be inaccessible. Someone should be responsible for setting the home thermostat at an appropriate temperature and then locking the thermostat so that the person who is not accurately interpreting body temperature cannot reset the room temperature at too high or too low. Soiled clothing should be laundered immediately or kept unavailable (out of sight ­ out of mind) until the clothing is clean.”

“The Checklist for Family Matters, located at www.AlzOnline.net is a useful tool to help families with planning for long-term care management. Regular respite for the family caregiver(s) is essential!”

“Examples of how to approach, interact and speak to someone who has anosognosia:

1. Down-size and decrease unnecessary chores and responsibilities.

Use a positive approach, such as, “It is time to plan ahead about moving to a retirement community where there are kind people and some of your friends so you have more time to do what you like, such as read and go for a walk every morning.”

Don’t use a negative approach, such as, “This house and yard are too much work for all of us. It is hard for you to take care of the house, the yard, and yourself. You need to move to a place where people are always around to help you.”

2. Partner with the person.

Use a positive approach, such as, “Let’s work together on the front porch, then go out for a nice dinner.”

Don’t use a negative approach, such as, “You really need to clean up that mess of old magazines, newspapers and piles of trash on the front porch.”

3. Focus on the person’s concern and subtly include your concern.

Use a positive approach, such as, “When you take this multi-vitamin, how about taking these “brain-vitamins” that the doctor prescribed to keep your memory strong?”

Don’t use a negative approach, such as, “The doctor prescribed these pills and you have to take them every morning.”

4. A gentle, positive voice should be part of a positive empathic approach.

Use a positive approach, such as, “To keep up with these bills, we should work as a team. I will come over on Saturday mornings with your favorite breakfast and we will write out the checks together. After you sign the checks, we will put them in their envelopes and take them to the mailbox.”

Don’t use a negative approach, such as, “You have to pay these bills on time. The utility companies have sent notices threatening to shut off the gas and electricity. I’ll handle the bills from now on.”

5. Provide available assistance and a structured schedule of tasks including personal care, activities including chores and leisure
activities, and “down-time” including a favorite activity or no activity.

Use a positive approach, such as, “After we walk the dog, we will finish the laundry and then sit down for some of that applesauce I cooked this morning.”

Don’t use a negative approach, such as, “There is so much to do? What do you want to do this morning? We have to walk the dog, finish the laundry, and clean the kitchen. The work really piles up fast around here.”

“Instead of Saying X, Trying Saying Y”

This is a nice article with a helpful chart on using techniques of validation and redirection to deal with memory loss, repetitive questions, delusions or aggressive behaviors, when speaking with those with dementia.

This article is from care ADvantage, a free publication of the Alzheimer’s Foundation of America (alzfdn.org) for caregivers of people with AD and similar illnesses.
(Reprinted with permission from the Fall 2009 issue of care ADvantage magazine, a publication of the Alzheimer’s Foundation of America. For a free subscription, please visit www.afacareadvantage.org or call 866-232-8484.)

http://www.afacareadvantage.org/issues/ca_fall09.pdf –> article starts on page 9

Instead of Saying X, Try Saying Y
Use Validation and Redirection to Manage Daily Challenges
by Susan London, LMSW, QDCP
care ADvantage, Fall 2009

Let’s face it: caring for an individual with Alzheimer’s disease isn’t always a walk in the park; in fact, it can be downright stressful. Between memory loss, repetitive questions, false thinking or aggressive behaviors, each day often brings new challenges.

As a caregiver, your understanding of the disease as well as your attitude about the illness can have a great impact on the way you manage day-to-day caregiving responsibilities. And just because this illness has taken over someone close to you, it doesn’t mean you should let it conquer you as well. So what do you do when your loved one blames you for something you didn’t do or becomes paranoid that you are plotting against him or her? How about when someone sees objects that aren’t there or says things that simply don’t
make any sense?

If your gut reaction is to try to orient the person back to reality, you’re not alone. Many caregivers spend endless hours trying to prove who they are, where they are and what they are doing, but to no avail. They believe if they would just show a wedding album or have other family members confirm information that the person with Alzheimer’s disease will catch on and it will “click” for them. Even though a caregiver’s heart is in the right place, these efforts are often fruitless. Their loved ones may continue to press the issue, and sometimes even get angry or hostile at the “evidence” presented to them.

Fortunately, there are ways to manage daily challenges in order to minimize a caregiver’s stressful feelings and improve the odds that an individual with dementia will respond positively.

One of the best approaches to use with people with dementia is Validation—a technique that confirms their right to feel a certain way and express their emotions regardless of the situation. The Validation theory, developed by Naomi Feil, suggests that an individual
could be revisiting past events or trying to solve unfinished business. This helps explain why some people feel the need to go to work years after they retire or pay off a debt from decades ago. By validating their experience, you are meeting them where they are and sending a message that you still accept them no matter what. Another powerful approach to utilize is redirection—a behavioral intervention that shifts the individual’s focus, by distracting the person or moving away from an undesired topic or behavior to something more pleasant. See the chart on the following pages for some role-playing ideas that tap basic validation and redirection techniques to handle some of the most difficult situations.

When
Your mother says, “I want to go home!”

Instead of Saying
“This is your home! Don’t you remember? You’ve only lived here for 30 years!”

Try Saying
“Of course you want to go home! Your house was the prettiest on the block. Why don’t you tell me about those tulips you planted in your front yard?”

Why?
Memory impairments and disorientation can cause people to forget where they are. When they want to go “home,” it really signals a desire for a sense of safety and familiarity. Bring mom “home” by reuniting her with her favorite memories of what home represents.

When
Your wife says, “Get away from me, you’re not my husband!”

Instead of Saying
“But I am your husband! Look at our matching wedding rings. You know, you really upset me when you don’t remember who I am.”

Try Saying
“You must love your husband very much. I can tell by the way you talk about him. Why don’t you tell me about your wedding day?”

Why?
Memory loss can cause individuals to forget even their closest loved ones. When your wife becomes agitated, respect her space,
validate the love she feels for her spouse, and allow her to talk about “him” while you are sitting right beside her. Even though she may
have forgotten you today, hearing her talk about you will demonstrate that you are still very close to her heart.

When
During meals, your father refuses to eat and says, “You’re trying to poison me.”

Instead of Saying
“That’s ridiculous! Why would I ever do such a thing? Eat your meal and stop making up crazy stories!”

Try Saying
“Dad, I understand if you are feeling afraid, but I want you to know that I would never let anything bad happen to you. You are safe with me. By the way, this meatloaf is delicious. I am having a big plate of it myself. Let’s have some together and you can tell me all about
the fishing trip.”

Why?
It is difficult, if not impossible, to rationalize with people with dementia. Instead of trying to orient Dad back to reality, instill a sense of safety, and demonstrate it by eating the same meal as him or taking a bite from his plate. Once you’ve established trust, you can quickly refocus him by shifting the conversation to something more pleasant, such as a fun day he had by the docks.

When
Your sister says, “You stole my money! Give it back!”

Instead of Saying
“I’m sick and tired of you accusing me every time you hide your money. You stuffed it in your drawer five minutes ago. I saw you do it, so stop blaming me.”

Try Saying
“Oh no, your money is missing? I can see why you’re upset. Well, don’t you worry because I am going to help you look for it.”

Why?
It is common for people with dementia to hide items and forget where they are moments later. Since it can be embarrassing to admit this, individuals sometimes accuse others to take the focus off themselves. Rather than trying to deflect blame, simply let your sister know that you understand how she feels and that you want to help her resolve the situation. Then walk her over to the drawer and ask her to open it. When your sister finds her money, allow her to take pride in finding it all by herself.

When
Your grandmother says, “I have to leave now. I need to pick up Jimmy from school.”

Instead of Saying
“Grandma, Jimmy is a grown man. He’s 60 years old. You’re not going anywhere.”

Try Saying
“Oh Grandma, you have always been such a loving mother to Jimmy. Why don’t you come with me to get a drink of water and tell me all about what you love to do with Jimmy after school?”

Why?
People with Alzheimer’s disease often live in the past by re-creating experiences that happened long ago. Despite the fact that Grandma hasn’t picked Jimmy up from school in decades, her maternal instinct is still very strong, and she feels an urgency to follow the same routine she did while he was growing up. Take this as an opportunity to reunite your grandmother with those happy memories: while you are distracting her from going to the front door, she will tell you all about those wonderful times she had with Jimmy and will forget all about wanting to leave.

When
Your uncle believes he’s still at work. He treats you like an employee and tells you he needs the paperwork finished by the end of the hour.

Instead of Saying
“Are you starting with that nonsense again? You retired in 1985. How many times do I have to keep reminding you?”

Try Saying
“You really run a tight ship around here! I guess that’s what makes you such a good boss. I’ll make sure to get the paperwork to you, but I could use a little help. Can you assist me with one of the documents?”

Why?
It is not uncommon for people with Alzheimer’s disease to strongly affiliate with important roles they have taken on in the past. The fact that your uncle thinks he’s at work suggests that a job is still very meaningful to him. Use this moment to create an activity that can contribute to a sense of purpose. Bring him a phone bill or other document and allow him to “help” you interpret it. Support his efforts and remind him what a great boss he has always been.

SUSAN LONDON, LMSW,QDCP, is a social worker and project coordinator at the Alzheimer’s Foundation of America (AFA). As a member of AFA’s social services team, she regularly responds to calls and e-mails from caregivers across the country, walking them through both daily challenges and crisis situations.

Research findings: clearing tau in mice by targeting Hsp70

This is a report on some basic research involving the protein tau and an update of sorts of the tau-busting drug Rember.

This University of South Florida press release was posted earlier this week to EurekAlert! Byrd Alzheimer’s Institute neuroscientist Chad Dickey studies how the protein tau can be removed from the brain through drugs or gene therapy. Tau is the protein involved in Alzheimer’s Disease, PSP, CBD, and some other disorders.

A study in mice (genetically modified to develop tau tangles) revealed that inhibiting the protein Hsp70 rapidly reduced the level of tau in the brains. “Hsp70 is a one of several ‘chaperone’ proteins that supervises the activity of tau inside nerve cells. The normal function of tau is to support the structure of nerve cells, much like the skeleton provides a scaffold to support the body. Tau is inside nerve cells, while another hallmark protein associated with Alzheimer’s, beta amyloid, is outside the neurons.”

Several compounds were tested in cell models and genetically modified mice to see if they had any effect on Hsp70. According to the abstract of the journal article about this research, this is the first time that Hsp70 has been targeted and the first time a “newly developed high-throughput screening system” was utiilized.

“One of the more effective Hsp70-inhibitor drugs the researchers discovered was a derivative of methylthioninium chloride, or Rember™, the first experimental medication reported to directly attack the tau tangles in patients with Alzheimer’s disease. Rember™ was heralded as a major development in the fight against Alzheimer’s when results in early clinical trials were announced last year at the International Conference on Alzheimer’s disease. But Rember™ and its derivatives do have some inherent problems; they’re not very potent so effective therapy would require fairly high doses, Dickey said.”

“The drug does help prevent the protein (tau) from clumping together, but that in itself doesn’t mean it’s actively getting rid of the toxic tau,” he said. “Now that we know Hsp70 is a target of Rember™, we can develop similarly-acting drugs that will more specifically target this chaperone protein in affected areas of the brain, resulting in fewer side effects.”

I’ve copied the USF Health press release below. This research was supported by a Pollin CBD research grant from CurePSP. (Abe Pollin has a clinical diagnosis of CBD.) Too bad that the press person at USF couldn’t get the acronym for the disorder spelled correctly (“CDB”) or the disorders CBD and PSP put into the article. (I guess money doesn’t buy accurate publicity.)

I’ve also copied the abstract of the Journal of Neuroscience article.

Robin

http://www.eurekalert.org/pub_releases/ … 092809.php

University of South Florida Health Press Release

Protein inhibitor helps rid brain of toxic tau protein
Laboratory study shows drug targets chaperone Hsp70 to reduce Alzheimer’s protein

Tampa, FL (September 30, 2009) — Inhibiting the protein Hsp70 rapidly reduces brain levels of tau, a protein associated with Alzheimer’s disease when it builds up abnormally inside nerve cells affecting memory, neuroscientists at the University of South Florida found. The study is reported online today in the Journal of Neuroscience.

“Now that we’ve discovered that targeting the chaperone protein Hsp70 can clear tau, it could be helpful in finding more effective drugs for Alzheimer’s disease,” said the study’s senior author Chad Dickey, PhD, assistant professor of molecular medicine who works out of the Byrd Alzheimer’s Institute at USF Health “The therapeutic strategy may also be applicable to other neurodegenerative diseases involving Hsp70, such as Huntington disease, amyotrophic lateral sclerosis (ALS), and some cancers.”

Hsp70 is a one of several “chaperone” proteins that supervises the activity of tau inside nerve cells. The normal function of tau is to support the structure of nerve cells, much like the skeleton provides a scaffold to support the body. Tau is inside nerve cells, while another hallmark protein associated with Alzheimer’s, beta amyloid, is outside the neurons.

Working with researchers at the University of Michigan, the USF team tested the effects of several compounds on Hsp70 in cell models and brain tissue from mice genetically modified to develop the memory-choking tau tangles. Some compounds activated Hsp70, and others were Hsp70-inhibitors.

One of the more effective Hsp70-inhibitor drugs the researchers discovered was a derivative of methylthioninium chloride, or Rember™, the first experimental medication reported to directly attack the tau tangles in patients with Alzheimer’s disease. Rember™ was heralded as a major development in the fight against Alzheimer’s when results in early clinical trials were announced last year at the International Conference on Alzheimer’s disease.

But Rember™ and its derivatives do have some inherent problems; they’re not very potent so effective therapy would require fairly high doses, Dickey said.

“The drug does help prevent the protein (tau) from clumping together, but that in itself doesn’t mean it’s actively getting rid of the toxic tau,” he said. “Now that we know Hsp70 is a target of Rember™, we can develop similarly-acting drugs that will more specifically target this chaperone protein in affected areas of the brain, resulting in fewer side effects.”

The USF researchers originally thought activating Hsp70 would direct the chaperone protein to decrease the tau gone bad — preventing tau from stacking up into tangles inside cells involved in memory and destroying them. But instead of restoring tau to its normal supportive function, activating Hsp70 actually led to tau’s preservation and even more accumulation, Dickey said. “Basically we think the chaperone binds to the tau, and somehow in the process of trying to fix things decides to keep holding onto tau when it shouldn’t. So, activating Hsp70 is not necessarily what we want to do; we ultimately want to inhibit Hsp70 to promote the release or clearance of tau …to kill the bad tau.”

Dr. Dickey emphasizes that problems with Hsp70 alone do not cause Alzheimer’s. It likely develops from a convergence of various factors in the brain, he said, including deposits of the other featured Alzheimer’s protein beta amyloid, or a genetic defect; disruption of cell signaling; a breakdown in the neuron’s support structure, and then accumulation of tau into the memory-choking tangles.

Dr. Dickey’s team at USF focuses on how to manipulate with drugs or gene therapy the chaperone proteins that regulate tau’s fate ­ determining whether it’s preserved or cleared from the brain. The University of Michigan team works on identifying and developing compounds that may be effective against Alzheimer’s disease and other tauopathies.

###

The study was supported by the national Alzheimer’s Association, the National Institute on Aging, the Abe and Irene Pollin Fund for CDB from the Society for Progressive Supranuclear Palsy (CurePSP), and the National Institute of Neurological Disorders and Stroke.

The study’s other authors were Umesh Jinwal (lead author), Yoshinari Miyata, John Koren III, Jeffrey Jones, Justin Trotter, Lyra Chang, John O’Leary, David Morgan, Daniel Lee, Cody Shults, Aikaterini Rousaki, Edwin Weeber, Erik Zuiderweg, and Jason Gestwicki.

USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $380.4 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching. For more information, visit www.health.usf.edu

Here’s the abstract of the recently-published research article:

Journal of Neuroscience. 2009 Sep 30;29(39):12079-88.

Chemical manipulation of hsp70 ATPase activity regulates tau stability.

Jinwal UK, Miyata Y, Koren J 3rd, Jones JR, Trotter JH, Chang L, O’Leary J, Morgan D, Lee DC, Shults CL, Rousaki A, Weeber EJ, Zuiderweg ER, Gestwicki JE, Dickey CA.
Departments of Molecular Medicine, USF Health Byrd Alzheimer’s Institute, University of South Florida, Tampa, Florida.

Alzheimer’s disease and other tauopathies have recently been clustered with a group of nervous system disorders termed protein misfolding diseases. The common element established between these disorders is their requirement for processing by the chaperone complex. It is now clear that the individual components of the chaperone system, such as Hsp70 and Hsp90, exist in an intricate signaling network that exerts pleiotropic effects on a host of substrates. Therefore, we have endeavored to identify new compounds that can specifically regulate individual components of the chaperone family.

Here, we hypothesized that chemical manipulation of Hsp70 ATPase activity, a target that has not previously been pursued, could illuminate a new pathway toward chaperone-based therapies. Using a newly developed high-throughput screening system, we identified inhibitors and activators of Hsp70 enzymatic activity.

Inhibitors led to rapid proteasome-dependent tau degradation in a cell-based model. Conversely, Hsp70 activators preserved tau levels in the same system. Hsp70 inhibition did not result in general protein degradation, nor did it induce a heat shock response.

We also found that inhibiting Hsp70 ATPase activity after increasing its expression levels facilitated tau degradation at lower doses, suggesting that we can combine genetic and pharmacologic manipulation of Hsp70 to control the fate of bound substrates.

Disease relevance of this strategy was further established when tau levels were rapidly and substantially reduced in brain tissue from tau transgenic mice. These findings reveal an entirely novel path toward therapeutic intervention of tauopathies by inhibition of the previously untargeted ATPase activity of Hsp70.

PubMed ID#: 19793966 (see pubmed.gov for this abstract, available for free)

Nitrates – Possible Environmental Cause of AD, PD, etc

Here’s an article from yesterday’s MedicalNewsToday website about an association between nitrates (found in fertilizers) and Alzheimer’s Disease and Parkinson’s Disease.

http://www.medicalnewstoday.com/articles/156507.php

Researchers Find Possible Environmental Causes For Alzheimer’s, Diabetes
07 Jul 2009
MedicalNewsToday

A new study by researchers at Rhode Island Hospital have found a substantial link between increased levels of nitrates in our environment and food, with increased deaths from diseases, including Alzheimer’s, diabetes mellitus and Parkinson’s. The study was published in the Journal of Alzheimer’s Disease (Volume 17:3 July 2009).

Led by Suzanne de la Monte, MD, MPH, of Rhode Island Hospital, researchers studied the trends in mortality rates due to diseases that are associated with aging, such as diabetes, Alzheimer’s, Parkinson’s, diabetes and cerebrovascular disease, as well as HIV. They found strong parallels between age adjusted increases in death rate from Alzheimer’s, Parkinson’s, and diabetes and the progressive increases in human exposure to nitrates, nitrites and nitrosamines through processed and preserved foods as well as fertilizers. Other diseases including HIV-AIDS, cerebrovascular disease, and leukemia did not exhibit those trends. De la Monte and the authors propose that the increase in exposure plays a critical role in the cause, development and effects of the pandemic of these insulin-resistant diseases.

De la Monte, who is also a professor of pathology and lab medicine at The Warren Alpert Medical School of Brown University, says, “We have become a ‘nitrosamine generation.’ In essence, we have moved to a diet that is rich in amines and nitrates, which lead to increased nitrosamine production. We receive increased exposure through the abundant use of nitrate-containing fertilizers for agriculture.” She continues, “Not only do we consume them in processed foods, but they get into our food supply by leeching from the soil and contaminating water supplies used for crop irrigation, food processing and drinking.”

Nitrites and nitrates belong to a class of chemical compounds that have been found to be harmful to humans and animals. More than 90 percent of these compounds that have been tested have been determined to be carcinogenic in various organs. They are found in many food products, including fried bacon, cured meats and cheese products as well as beer and water. Exposure also occurs through manufacturing and processing of rubber and latex products, as well as fertilizers, pesticides and cosmetics.

Nitrosamines are formed by a chemical reaction between nitrites or other proteins. Sodium nitrite is deliberately added to meat and fish to prevent toxin production; it is also used to preserve, color and flavor meats. Ground beef, cured meats and bacon in particular contain abundant amounts of amines due to their high protein content. Because of the significant levels of added nitrates and nitrites, nitrosamines are nearly always detectable in these foods. Nitrosamines are also easily generated under strong acid conditions, such as in the stomach, or at high temperatures associated with frying or flame broiling. Reducing sodium nitrite content reduces nitrosamine formation in foods.

Nitrosamines basically become highly reactive at the cellular level, which then alters gene expression and causes DNA damage. The researchers note that the role of nitrosamines has been well-studied, and their role as a carcinogen has been fully documented. The investigators propose that the cellular alterations that occur as a result of nitrosamine exposure are fundamentally similar to those that occur with aging, as well as Alzheimer’s, Parkinson’s and Type 2 diabetes mellitus.

De la Monte comments, “All of these diseases are associated with increased insulin resistance and DNA damage. Their prevalence rates have all increased radically over the past several decades and show no sign of plateau. Because there has been a relatively short time interval associated with the dramatic shift in disease incidence and prevalence rates, we believe this is due to exposure-related rather than genetic etiologies.”

The researchers recognize that an increase in death rates is anticipated in higher age groups. Yet when the researchers compared mortality from Parkinson’s and Alzheimer’s disease among 75 to 84 year olds from 1968 to 2005, the death rates increased much more dramatically than for cerebrovascular and cardiovascular disease, which are also aging-associated. For example, in Alzheimer’s patients, the death rate increased 150-fold, from 0 deaths to more than 150 deaths per 100,000. Parkinson’s disease death rates also increased across all age groups. However, mortality rates from cerebrovascular disease in the same age group declined, even though this is a disease associated with aging as well.

De la Monte notes, “Because of the similar trending in nearly all age groups within each disease category, this indicates that these overall trends are not due to an aging population. This relatively short time interval for such dramatic increases in death rates associated with these diseases is more consistent with exposure-related causes rather than genetic changes.” She also comments, “Moreover, the strikingly higher and climbing mortality rates in older age brackets suggest that aging and/or longer durations of exposure have greater impacts on progression and severity of these diseases.”

The researchers graphed and analyzed mortality rates, and compared them with increasing age for each disease. They then studied United States population growth, annual use and consumption of nitrite-containing fertilizers, annual sales at popular fast food chains, and sales for a major meat processing company, as well as consumption of grain and consumption of watermelon and cantaloupe (the melons were used as a control since they are not typically associated with nitrate or nitrite exposure).

The findings indicate that while nitrogen-containing fertilizer consumption increased by 230 percent between 1955 and 2005, its usage doubled between 1960 and 1980, which just precedes the insulin-resistant epidemics the researchers found. They also found that sales from the fast food chain and the meat processing company increased more than 8-fold from 1970 to 2005, and grain consumption increased 5-fold.

The authors state that the time course of the increased prevalence rates of Alzheimer’s, Parkinson’s and diabetes cannot be explained on the basis of gene mutations. They instead mirror the classical trends of exposure-related disease. Because nitrosamines produce biochemical changes within cells and tissues, it is conceivable that chronic exposure to low levels of nitrites and nitrosamines through processed foods, water and fertilizers is responsible for the current epidemics of these diseases and the increasing mortality rates associated with them.

De la Monte states, “If this hypothesis is correct, potential solutions include eliminating the use of nitrites and nitrates in food processing, preservation and agriculture; taking steps to prevent the formation of nitrosamines and employing safe and effective measures to detoxify food and water before human consumption.”

Notes:
Other researchers involved in the study with de la Monte include Alexander Neusner, Jennifer Chu and Margot Lawton, from the departments of pathology, neurology and medicine at Rhode Island Hospital and The Warren Alpert Medical School of Brown University.

The study was funded through grants from the National Institutes of Health. Two subsequent papers have been accepted for publication in the near future that demonstrate experimentally that low levels of nitrosamine exposure cause neurodegeneration, NASH and diabetes.

De la Monte, Suzanne M., Alexander Neusner, Jennifer Chu and Margot Lawton. “Epidemilogical Trends Strongly Suggest Exposures as Etiologic Agents in the Pathogenesis of Sporadic Alzheimer’s Disease, Diabetes Mellitus, and Non-Alcoholic Steatohepatitis.” Journal of Alzheimer’s Disease, 17:3 (July 2009) pp 519-529.

Source:
Nancy Cawley Jean
Lifespan

“Revealed: how Alzheimer’s infects the brain”(tau)

Here’s an excerpt from a newspaper article on a breakthrough discovery in Alzheimer’s Disease: “It is the first time that scientists have detected infectious properties in the so-called tau protein which causes aggregates of particles known as ‘neurofibrillary tangles’ to build up inside the brain cells of Alzheimer’s patients. The tangles lead to the disease’s symptoms. [The] researchers emphasised that the discovery does not mean that the disease itself is infectious, only that the tau protein seen in Alzheimer’s disease is able to convert otherwise healthy brain proteins into the defective form associated with the disease.”

PSP and CBD, like AD, are tauopathies – disorders of tau protein.

http://www.independent.co.uk/news/scien … 99214.html

Revealed: how Alzheimer’s infects the brain
Breakthrough may lead to new treatments for senile dementia
By Steve Connor, Science Editor
The Independent (UK newspaper)
Monday, 8 June 2009

A scientific breakthrough in the understanding of how Alzheimer’s disease may spread across the brain of elderly patients might lead to novel ways of treating senile dementia, scientists have announced.

A study has discovered that a key brain protein linked with Alzheimer’s disease has infectious properties that allow defects in the protein to be transmitted through the brain and so leads to debilitating neuro-degeneration.

It is the first time that scientists have detected infectious properties in the so-called tau protein which causes aggregates of particles known as “neurofibrillary tangles” to build up inside the brain cells of Alzheimer’s patients. The tangles lead to the disease’s symptoms.

But the researchers emphasised that the discovery does not mean that the disease itself is infectious, only that the tau protein seen in Alzheimer’s disease is able to convert otherwise healthy brain proteins into the defective form associated with the disease.

Alzheimer’s disease is one of the fastest growing and most costly medical conditions. About 700,000 people in the UK have some form of dementia and this will grow to about 940,000 by 2015, rising to more than 1.7 million by 2051 as a result of the demographic time bomb of an ageing population.

Medical researchers believe that the latest findings – which have so far been shown in laboratory mice rather than human patients – could open up new ways of treating Alzheimer’s disease by developing drugs that block the tau’s infectious properties.

The results of the study also show that Alzheimer’s disease has underlying similarities to Creutzfeldt-Jakob disease (CJD), a brain disease that is believed to be caused by other kinds of infectious proteins called “prions” which can, under certain circumstances, be transmitted from one person to another.

Scientists have known for many years that the brain cells of Alzheimer’s patients experience a build up of tau protein in the form of complicated tangles and that these tangles spread in a characteristic fashion through the brain.

The latest study, published in the journal Nature Cell Biology, offers the first proper explanation for how these tangles spread and suggests a possible target for drug companies hoping to develop ways of slowing down the progression of Alzheimer’s disease.

“This opens new avenues in dementia research that will aim to understand how abnormal tau can spread. We can also investigate how diseases caused by tau aggregates and prions are similar,” said Michel Goedert of the Medical Research Council’s Laboratory of Molecular Biology in Cambridge.

“We have looked at whether tau tangles can spread in mice. The injection of brain extract from tangle-bearing mice into animals without tangles caused their tau to tangle and spread from the sites of injection to neighbouring brain regions,” said Dr Goedert, who took part in the study.

The scientists used a strain of genetically modified mouse with a gene for the human form of the defective tau protein. When the tau of this mouse was injected into the brain of ordinary laboratory mice, it caused a build-up of the same sort of tangles seen in Alzheimer’s patients.

“This research in mice does not show that tau pathology is contagious or that it can spread easily from mouse to mouse. What it has revealed is how tau tangles spread within brain tissues of individual mice,” Dr Goedert said.

“It suggests that tangles of proteins that build up in the brain to cause symptoms could have some contagious properties, within brain tissue but not between mice that haven’t been injected with tissue from another mouse and certainly not between people,” he said.

There is no epidemiological evidence that brain diseases like Alzheimer’s or Parkinson’s can spread from one person to another and the latest study does not suggest that such disorders are caused by an infection, said David Allsop, professor of neuroscience at Lancaster University.

“This is interesting because it could explain how tangles spread from one region of the brain to another during the course of Alzheimer’s disease and some other ‘tangle’ diseases,” Professor Allsop said.

Susanne Sorensen, the head of research at the Alzheimer’s Society, said that the study could result in a greater understanding of how tau tangles form and spread through the brain.

“There is still so much we do not understand about the changes in tau that lead to tangle formation in humans and, eventually, widespread cell death,” Dr Sorensen said. “Each new piece of knowledge helps to build a better picture and takes us closer to the point where we can stop loss of brain tissue and dementia for good.”

Rebecca Wood, the chief executive of the Alzheimer’s Research Trust, said: “This greater understanding of how tangles spread in Alzheimer’s may lead to new ways of stopping them and defeating the disease.”

16 patients with clinical DX of CBS (11 had CBD, 5 had AD)

This research by Mayo Rochester (including CBD expert Dr. Brad Boeve) was published a couple of days ago. In this study, 16 patients had a clinical diagnosis of CBS (corticobasal syndrome). After death, 11 were pathologically diagnosed with CBD (corticobasal degeneration) and 5 with Alzheimer’s Disease (AD). Here are the key differences in the two patient groups, after correlating the clinical record with the pathological results:

* “Patients with AD pathology had an earlier age of onset than patients with CBD pathology (58 vs. 68 years).”
* “Tremors were only present in CBD cases (73%)…”
* Interestingly, “myoclonus was more common in AD than CBD (80 vs. 18%).”
* “SPECT imaging demonstrated parietal hypoperfusion in AD patients and frontotemporal hypoperfusion in CBD patients.”

The authors conclude that: “Functional brain imaging may have greater utility than the clinical and neuropsychological features in differentiating AD presenting as CBS from CBD.”

We need more articles like this, with bigger patient numbers!

Robin

——————————

Movement Disorders. 2009 May 7. [Epub ahead of print]

Alzheimer’s disease and corticobasal degeneration presenting as corticobasal syndrome.

Hu WT, Rippon GW, Boeve BF, Knopman DS, Petersen RC, Parisi JE, Josephs KA.
Department of Neurology, Mayo Clinic, Rochester, Minnesota.

The aim of this article is to compare patients with Alzheimer’s disease (AD) pathology and corticobasal degeneration pathology (CBD) presenting as corticobasal syndrome (CBS).

Clinicopathologic series was used. Five patients with AD and 11 patients with CBD were clinically diagnosed with CBS. Patients with AD pathology had an earlier age of onset than patients with CBD pathology (58 vs. 68 years, P = 0.004), but the two groups had similar disease duration and core features of CBS. Tremors were only present in CBD cases (73%, P = 0.026), but myoclonus was more common in AD than CBD (80 vs. 18%, P = 0.036). Neuropsychological testing showed similar degrees of memory impairment and attentional deficits. (99m)Tc-HMPAO SPECT imaging demonstrated parietal hypoperfusion in AD patients and frontotemporal hypoperfusion in CBD patients. AD patients with clinical CBS have similar characteristics to CBD patients. Functional brain imaging may have greater utility than the clinical and neuropsychological features in differentiating AD presenting as CBS from CBD.

PubMed ID#: 19425061 (see pubmed.gov for this abstract only; you can also link to the full article for which the publisher probably charges $30)

“The Alzheimer’s Project” (HBO and free online)

I received this announcement from the Alzheimer’s Association:

http://www.alz.org/news_and_events_16202.asp

The documentary that will change the way America thinks about Alzheimer’s disease.

On May 10, 11 and 12, tune into HBO’s “THE ALZHEIMER’S PROJECT” to take a look at the faces behind the disease – and the forces leading us to find a cure. This multi-platform series reveals groundbreaking Alzheimer discoveries and the effects this debilitating and fatal disease has on those with Alzheimer’s and their families.

As the leading voluntary health organization in Alzheimer’s care, support and research, the Alzheimer’s Association has been an active partner in “THE ALZHEIMER’S PROJECT,” providing expert insight and leading community engagement.

Air dates and times

Sunday, May 10 at 9 p.m. EST
“The Memory Loss Tapes”

Monday, May 11 at 7:30 p.m. and 8 p.m. EST
“Grandpa, Do You Know Who I Am? With Maria Shriver”
“Momentum in Science, Part 1”

Tuesday, May 12 at 7 p.m. and 8 p.m. EST
“Caregivers”
“Momentum in Science, Part 2”

For additional details, please visit hbo.com/alzheimers.

Be a part of something big.

HBO’s “THE ALZHEIMER’S PROJECT” will expose the Alzheimer crisis facing our nation and drive concerned citizens to take action.

“THE ALZHEIMER’S PROJECT” is a presentation of HBO Documentary Films and the National Institute on Aging at the National Institutes of Health in association with the Alzheimer’s Association, The Fidelity® Charitable Gift Fund and Geoffrey Beene Gives Back® Alzheimer’s Initiative.

All films will stream free of charge on www.hbo.com/alzheimers and will be offered for free on multiple platforms by participating television service providers.

Delirium (from hospitalization or illness) accelerates memory loss

This press release out of Beth Israel Deaconess Medical Center (bidmc.org) in Boston will be of interest to those dealing with dementia.

The press release reports on a study that:

“…confirms that an episode of delirium rapidly accelerates cognitive decline and memory loss in Alzheimer’s patients. … Delirium often develops in elderly patients during hospitalization or serious illness, and this acute state of confusion and agitation has long been suspected of having ties to Alzheimer’s disease and other dementias.”

The press release is copied below.

Robin
_____________________________

www.bidmc.org/News/InResearch/2009/April/DeliriumandDementia.aspx

Delirium Accelerates Memory Loss in Patients With Alzheimer’s Disease
Acute state of confusion and disorientation often complicates hospitalizations for patients with dementia
Beth Israel Deaconess Medical Center, Boston, MA
Press Release
Date: 5/4/2009

BOSTON ­ Delirium often develops in elderly patients during hospitalization or serious illness, and this acute state of confusion and agitation has long been suspected of having ties to Alzheimer’s disease and other dementias. Now a study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and Hebrew Senior Life confirms that an episode of delirium rapidly accelerates cognitive decline and memory loss in Alzheimer’s patients. The findings are reported in the May 5 issue of the journal Neurology.

“The cognitive rate of decline was found to be three times more rapid among those Alzheimer’s patients who had had an episode of delirium than among those who did not have such a setback,” according to lead author Tamara Fong, MD, a staff neurologist at BIDMC and Assistant Scientist at the Institute for Aging Research, Hebrew Senior Life. “In other words, the amount of decline you might expect to see in an Alzheimer’s patient over the course of 18 months would be accelerated to 12 months following an episode of delirium.”

Alzheimer’s disease is an irreversible, progressive form of dementia that gradually destroys a person’s ability to carry out even the simplest of tasks, and affects as many as 4.5 million individuals in the U.S. according to figures from the National Institute on Aging. There is currently no cure for Alzheimer’s disease.

Delirium, on the other hand, is a potentially preventable condition, which often develops following a medical disturbance, surgery or infection and is estimated to affect between 14 percent and 56 percent of all hospitalized elderly patients.

The investigators performed a secondary analysis of data gathered from 408 patients examined between 1991 and 2006 at the Massachusetts Alzheimer’s Disease Research Center (MADRC). Over this 15-year period, MADRC staff conducted a number of memory tests on patients. Testing was done on at least three occasions, separated by intervals of approximately six months. Seventy-two of the participants developed delirium during the course of the study.

In their final analysis, the authors found that among patients who developed delirium, the average decline on cognitive tests was 2.5 points per year at the beginning of the study; following an episode of delirium, decline nearly doubled to 4.9 points per year.

“Although each dementia patient declines at his or her own individual rate, the results of our study tell us that this rate can increase three-fold following an episode of delirium,” says Fong. “As an example, suppose an Alzheimer’s patient begins with mild symptoms, such as forgetting appointments or details of conversations, but over a period of the next 18 months, loses the ability to identify relatives, becomes lost while driving familiar routes, or can no longer balance a checkbook or manage financial transactions. This same patient, were he or she to experience an episode of delirium, might experience this same rate of decline in only 12 months.”

While further investigations are needed to determine the mechanism behind this turn-of-events, Fong explains that delirium may, in fact, be a key link in a chain of events that results in injury to brain cells. “Older patients may be at greater risk of developing delirium ­ particularly in the hospital setting ­ because they tend to have less ‘reserve’ or ability to compensate in settings of increased stress. Consequently, infections, new medications and other stressors put the patient at risk for delirium.”

All elderly patients, but particularly patients who have already been diagnosed with Alzheimer’s disease, can benefit from a number of preventive measures if they are hospitalized, notes Fong.

“As much as possible, it’s important to try and orient the patient to his or her surroundings [i.e. frequently remind the patient that he or she is in the hospital], to allow for as much uninterrupted sleep as possible by not waking patients to take vital signs or do blood draws at night, and to get patients out of bed and walking as soon as their medical condition allows,” notes Fong. Also, important, she adds, is to avoid use of unnecessary medications.

“Twenty percent of all elderly patients who develop delirium go on to experience complications, whether it’s a prolonged hospital stay, a move to a rehabilitation center or long-term care facility, or even death,” notes Fong. “Our current study now shows that delirium can also adversely impact the state of cognitive decline in patients with Alzheimer’s disease. Because up to 40 percent of delirium episodes can be prevented, taking steps to avoid delirium could result in significant improvements.”

This study was funded, in part, by grants from the Massachusetts Alzheimer’s Disease Research Center, the National Institute on Aging, and the Alzheimer’s Association, and the VA Rehabilitation Career Development Award.

Study coauthors include BIDMC investigators Edward Marcantonio and Sharon Inouye; Hebrew Senior Life investigators Richard Jones, Peilin Shi, James Rudolph, Frances Yang and Douglas Kiely; and Liang Yap of Massachusetts General Hospital.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks in the top four in National Institutes of Health funding among independent hospitals nationwide. BIDMC is a clinical partner of the Joslin Diabetes Center and a research partner of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.