Gammagard Shows Early Promise Against Alzheimer’s...

An immune system drug called Gammagard showed initial promise against stemming the decline of Alzheimer’s disease in an early-stage trial in a very small number of patients. Much more testing will be needed, but scientists are cautiously optimistic that the drug, or ones like it, may offer new help in treating Alzheimer’s disease.

Researchers warn that the results will need to be corroborated in a larger number of patients; the drug was tested in only in a handful of patients. But in four patients who were given the drug intravenously over three years, it appeared to stabilize the disease. It’s the first time a drug appears to have helped stop the underlying disease progression, rather than treating specific symptoms.

While symptoms like memory loss and thinking problems did not improve in these patients, they did not get worse, a noteworthy achievement for an Alzheimer’s treatment. Current Alzheimer’s drugs may ease symptoms for a time, but they do nothing to stop the downward progression of disease, and patients inevitably continue to deteriorate.

Gammagard, also known as Kiovig or intravenous immune globulin, is currently approved to treat a variety of immune system disorders, including an unusual nervous system disorder that causes muscle weakness in the limbs. It contains antibodies that target beta-amyloid, a toxic protein that accumulates and forms plaques in the brains of those with Alzheimer’s disease. It is also thought to quell inflammation, which experts increasingly recognize as a factor in Alzheimer’s and other chronic diseases.

By working through the immune system, scientists hope that Gammagard or related drugs may offer a new avenue for treating Alzheimer’s disease. However, vaccines and other immune-system related therapies have shown exciting initial promise but proved too dangerous, or ineffective, in larger follow-up trials.

For the study, researchers at Weill Cornell Medical College in New York gave varying doses of Gammagard to a small number of patients with mild to moderate Alzheimer’s disease. They were given the drug as a shot every two weeks for up to 36 months. Some patients received a placebo drug for comparison.

All four patients getting an intermediate dose of Gammagard showed stabilization of their disease, with no worsening of symptoms. The drug also appeared to be safe in general.

The drug is obtained by filtering the blood of healthy persons to obtain antibodies and other immune system components. It is expensive, costing thousands of dollars a month.

A larger, advanced-stage trial of the drug in hundreds of people with mild to moderate Alzheimer’s is under way. Results from that study are expected early this year.

But experts caution that the history of Alzheimer’s drug development is littered with promising false starts. Another immune system drug that targets beta-amyloid, called bapineuzumab, for instance, showed much promise in mid-stage trials but offered no benefits in larger follow-up studies. Additional studies of that drug and others are under way.

Source: Baxter International.

By ALZinfo.org, The Alzheimer's Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer's Research Foundation at The Rockefeller University.

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Promoting Independence With Alzheimer’s Care...

Independence can be an important part of living with Alzheimer’s disease. But some caregivers may be inadvertently undermining the independence of those they care for by underestimating their abilities to carry out everyday tasks.

Those are the findings of new research from the University of Alberta in Canada, where a study led by by psychologist Tiana Rust shows that making patients with Alzheimer’s too dependent on their caregivers may make them less likely to contribute to daily activities and, in the process, diminish their sense of self-worth.

Often caregivers are only trying to help by assuming many of the day-to-day tasks that the person with Alzheimer’s needs. But when the caregiver assumes too many duties, it can create a so-called “dependency support script,” Ms. Rust says, in which those with Alzheimer’s are not encouraged to do things for themselves. As a result, the person with Alzheimer’s may feel less inclined to get involved with tasks like helping out in the kitchen or getting dressed that they may well be capable of, particularly in the earlier stages of the disease.

"When we create this excess dependency that doesn't need to be there, this is a problem," Ms. Rust said. "If we're able to maintain and promote independence to the degree permissible by the disease, that's important."

For her study, she observed several caregivers and Alzheimer’s patients as they prepared a meal together. While many of the patients were clearly capable of helping out with some of these duties, she noted that some of the caregivers assumed they were not able to do them and did the tasks themselves.

One woman, for example, was surprised to learn that her husband did many tasks at the day-care center he attended. She had been doing these for him at home for months, unaware that he was capable of doing them.

"People with Alzheimer's disease have varying abilities, so it's important to base [caregiver] interactions on the actual abilities of the person," she said. "Observing the person and gauging what they're capable of before jumping in and supporting the dependence of the person is definitely important."

Another important strategy, she notes, is to assist the person by breaking up tasks into smaller, more manageable steps.

"The task we had given the caregivers and the residents to do was set the table, make grilled cheese sandwiches, mix juice and clean up afterwards. All of those tasks are quite big in themselves, but they can all be broken up into small activities," she said. "These are all small tasks that these people with Alzheimer's disease were still capable of doing, even though they might not have been able to do the full task.

"It's a hard role as a caregiver to try to gauge what the person can do, to know what the patient is capable of, how much they can break up these tasks. But these were all things that the caregivers mentioned in the interviews, so they're definitely wanting to promote their independence."

By ALZinfo.org, The Alzheimer's Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer's Research Foundation at The Rockefeller University.

Source: University of Alberta, Research Services.

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The Decades-Long Slide of Alzheimer’s...

Memory loss and personality changes are clear signs of Alzheimer’s, though scientists have become increasingly aware of subtle changes in the brain and body that appear years before the disease is diagnosed. Now researchers have mapped out a sequence of events that precedes overt Alzheimer’s, with some appearing decades before symptoms become obvious.

"A series of changes begins in the brain decades before the symptoms of Alzheimer's disease are noticed by patients or families, and this cascade of events may provide a timeline for symptomatic onset," said lead author Dr. Randall Bateman of Washington University School of Medicine in St. Louis. "As we learn more about the origins of Alzheimer's to plan preventive treatments, this Alzheimer's timeline will be invaluable for successful drug trials."

Scientists hope that treating Alzheimer’s early, before the disease has damaged the brain extensively, may offer the most promise for slowing or halting the disease’s progress, or even preventing it in the first place. Current Alzheimer’s drugs can provide modest benefits for a time, but do not stop the progression of Alzheimer’s.

For the study, published online in the New England Journal of Medicine, researchers closely followed 128 men and women who lived in families that were genetically predisposed to the form of Alzheimer’s that strikes people at a relatively young age. They had a 50 percent chance of inheriting one of the genes that causes early-onset Alzheimer’s.

Even though most people who get Alzheimer’s have the far more common late-onset form which strikes in a person’s 60s, 70s or older, the scientists believe that studying this early-onset group, who tend to get overt Alzheimer’s in their 40s or even younger, will provide vital clues about how the disease progresses.

The study participants, most in their 30s and 40s, were given extensive memory and thinking tests, as well as brain scans and blood and spinal fluid tests to look for markers of Alzheimer’s, over a period of several years. Fifty-one of them carried an early-onset gene for Alzheimer’s (either presenilin 1, presenilin 2, or a gene called APP), which guarantees that they would get the disease.

The researchers also took detailed family histories to determine when parents developed Alzheimer’s. In this group, early-onset disease had been diagnosed among parents around age 45.

From these tests, the researchers ran statistical analyses to estimate when changes signaling Alzheimer’s disease first became evident. They found that in spinal fluid tests, drops in levels of beta-amyloid, a toxic protein linked to Alzheimer’s, occurred up to 25 years before Alzheimer’s was likely to become evident to patients and family members.

They also found that beta-amyloid brain plaques, a hallmark of Alzheimer’s, began to appear up to 15 years before disease became apparent. The researchers are planning follow-up studies to see whether new drugs that are designed to block or remove plaques in the brain, even before symptoms become disabling, may help slow or halt progression of the disease.

The researchers also found that 15 years before Alzheimer’s symptoms became apparent, parts of the brain critical for memory began to shrink. Spinal fluid levels of tau, a protein that forms tangled clumps in the brains of those with Alzheimer’s, also began to rise.

A decade before disease onset, the brain was less able to take up glucose, or blood sugar, an indication of a slowing brain. Those who were destined to get Alzheimer’s also had slight impairments in episodic memory, critical for remembering times, places and other contextual knowledge, though the changes would be too subtle to be recognized by family members or friends.

"These exciting findings are the first to confirm what we have long suspected, that disease onset begins years before the first sign of cognitive decline or memory loss," said Laurie Ryan, clinical trials program director at the National Institute on Aging, which funded the study. "And while [these] participants are at risk for the rare, genetic form of the disease, insights gained from the study will greatly inform our understanding of late-onset Alzheimer's disease."

By ALZinfo.org, The Alzheimer's Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer's Research Foundation at The Rockefeller University.

Source: R. J. Bateman, C. Xiong, T.L.S. Benzinger, et. al. Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease. The New England Journal of Medicine, July 11, 2012.

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Berries Are Good for the Brain...

Older women who regularly ate blueberries and strawberries had slower rates of cognitive decline than those who ate berries infrequently, a new study found. The findings, part of the large and ongoing Nurses’ Health Study, were published in the Annals of Neurology.

The study analyzed results from some 16,000 women who had completed extensive questionnaires about the foods they ate, beginning in middle age and then every four years thereafter. They also underwent tests of memory and thinking skills every two years, starting at age 70.

Over the next four years, the researchers found, those women who ate the most strawberries and blueberries had the lowest rates of memory decline. The greatest benefit occurred in women who ate at least one serving of blueberries or at least two servings of strawberries per week. Including berries in your regular diet, the researchers estimated, was associated with a delay in cognitive aging of up to two-and-a-half years.

"Among women who consumed two or more servings of strawberries and blueberries each week, we saw a modest reduction in memory decline,” said study author Dr. Elizabeth Devore, a researcher at Harvard Medical School. “This effect appears to be attainable with relatively simple dietary modifications."

Berries are rich in health-promoting flavonoids, the pigments that give them their color. Flavonoids are also found in other fruits and vegetables, as well as herbs, grains, legumes and nuts at well. In the study, total flavonoid intake was also associated with less decline in brain function.

The authors noted that there is "substantial biologic evidence" to support a diet rich in berries and other foods rich in flavonoids in protecting the brain. Several flavonoids have been to reduce levels of inflammation, which scientists increasingly link to Alzheimer’s and other forms of dementia. Flavonoids are also potent antioxidants, which prevent cell damage from the reactive forms of oxygen known as free radicals, and have been shown to have other protective effects on brain cells as well.

Dietary studies can be unreliable, experts caution, since people may not fill our food surveys accurately, and it can be difficult to tease out the cause-and-effect relationship between what we eat and the many factors that contribute to sound health. But "what makes our study unique is the amount of data we analyzed over such a long period of time,” said Dr. Devore. “No other berry study has been conducted on such a large scale."

By ALZinfo.org, The Alzheimer's Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer's Research Foundation at The Rockefeller University.

Source: Elizabeth E. Devore ScD, Jae Hee Kang ScD, Monique M. B. Breteler MD, PhD, Francine Grodstein ScD: “Dietary intakes of berries and flavonoids in relation to cognitive decline.” Annals of Neurology online, 25 April, 2012.

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Eating Fish, Chicken, and Nuts Tied to Lower Levels of Alz...

Eating foods like fish, chicken, nuts and salad dressings – all high in the heart-healthy fats known as omega-3’s – are linked to lower blood levels of beta-amyloid, a toxic protein that builds up in the brains of those with Alzheimer’s disease. The findings, reported in the medical journal Neurology, add to a growing body of evidence linking dietary omega-3s to a reduced risk for Alzheimer’s.

“While it’s not easy to measure the level of beta-amyloid deposits in the brain in this type of study, it is relatively easy to measure the levels of beta-amyloid in the blood, which, to a certain degree, relates to the level in the brain,” said study author Dr. Nikolaos Scarmeas of Columbia University Medical Center in New York.

Increasing evidence suggests that diet may play an important role in preventing or delaying the onset of Alzheimer’s disease. Other studies have shown that a Mediterranean-style diet, rich in fish, fresh fruits and vegetables and olive oils, for example, is associated with a lower risk of Alzheimer’s and memory problems.

For the current study, researchers looked at 1,219 seniors, all of whom were free of dementia. They completed surveys about what they ate for an average of 1.2 years before their blood was tested for beta-amyloid.

The scientists looked at a variety of nutrients in addition to omega-3s. They include saturated fats (the kinds found in fatty meats), omega-6s (polyunsaturated fats found in many vegetable oils), vitamins C and E and beta-carotene (antioxidants), and vitamin B12 and folate (B vitamins linked to nervous system health).

The more omega-3s someone ate, the lower their blood levels of beta-amyloid. Eating just 1 gram of omega-3s per day – equal to the amount found in just half a salmon fillet per week – reduced blood beta-amyloid levels by 20 to 30 percent compared to those who ate less omega-3s. The benefits persisted, even after controlling for other known Alzheimer’s risk factors like age, education levels, calories consumed and the presence of the APOE-E4 gene. Other nutrients did not have a similar effect on beta-amyloid levels.

In the study, those who had the highest omega-3 blood levels tended to get the nutrient from salad dressings, fish, poultry, margarine and nuts.

High levels of beta-amyloid in the brain have been linked to formation of brain plaques, a hallmark of Alzheimer’s. The more plaque in the brain, in general, the worse someone’s memory. While the relationship between beta-amyloid blood levels and brain levels remains uncertain, studies suggest that high levels of beta-amyloid in the brain will be linked, over time, to high levels in the blood. Conversely, low blood levels of the toxic protein are thought to be linked to low brain levels.

Animal studies, for example, consistently show that animals fed diets rich in omega-3s have reduced levels of beta-amyloid in the brain and fewer plaques than those fed normal diets. Other scientists have shown that taking fish oil supplements rich in omega-3s may be associated with a reduced Alzheimer’s risk and a more robust brain.

By ALZinfo.org, The Alzheimer's Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer's Research Foundation at The Rockefeller University.

Sources: Y. Gu, N. Schupf, S.A. Cosentino, et al: “Nutrient Intake and Plasma Beta-Amyloid.” Neurology Vol 78: 1:1, 2012.

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La Batería eterna de EDISON

Elderly men and women who were the slowest walkers were at increased risk of mild cognitive impairment, a form of memory loss that sometimes precedes Alzheimer’s disease and other forms of dementia. Slowing down could precede dementia by many years, the findings suggest, and be an early warning sign of more serious memory and thinking problems down the road.

Having trouble walking can, of course, result from many common ailments, such as arthritis or fluid retention due to diabetes or heart disease. This study looked at 93 generally healthy volunteers, aged 70 and older, who were living alone in the Portland, Oregon area. Among the participants, 54 were free of memory problems, while the others had varying degrees of mild cognitive impairment, or MCI.

Researchers at the Oregon Health and Science University installed heat-sensitive sensors in their homes. The system was designed to detect how fast they moved down hallways and other areas of the home.

“By using this new monitoring method, we were able to get a better idea of how even subtle changes in walking speed may correlate with the development of MCI,” said study author Hiroko Dodge, Ph.D. The findings were published in Neurology, a journal from the American Academy of Neurology.

The study volunteers were given memory and thinking tests and had their walking speed monitored at their homes unobtrusively over a three-year period. Participants were placed in groups of slow, moderate or fast based on their average weekly walking speed and how much their walking speed fluctuated at home.

The researchers found that people with MCI were nine times more likely to be slow walkers than moderate or fast walkers. Variations in walking speed were also more common in those with MCI.

Earlier studies have found that slower walking speed are associated with mild cognitive impairment, and may be one of many possible predictors of who will ultimately go on to develop dementia. Problems with gait, posture and balance have likewise been linked to declines in attention, memory and other cognitive skills.

The researchers note that the number of study participants was small, and few developed MCI during the actual study period. “Further studies need to be done using larger groups of participants to determine whether walking speed and its fluctuations could be a predictor of future memory and thinking problems in the elderly,” said Dr. Dodge. “If we can detect dementia at its earliest phases, then we can work to maintain people’s independence, provide treatments and ultimately develop ways to prevent the disease from developing.”

By ALZinfo.org, The Alzheimer's Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer's Research Foundation at The Rockefeller University

Source: H.H. Dodge, N.C. Mattek, D. Austin, et al: “In-Home Walking Speeds and Variability Trajectories Associated With Mild Cognitive Impairment.” Neurology Vol. 78, June 2012, pages 1946-1952.

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How to defend against dementia

Many forms of dementia are untreatable, but Tiffany Chow believes that patients do not need perfect cognitive function to feel safe, productive and loved.
As a neuroscientist and clinician at Toronto’s Sam and Ida Ross Memory Clinic at Baycrest, Chow has made it her mission to help families struggling with dementia to experience meaningful moments, even when the illness is irreversible.

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In her new book, The Memory Clinic: Stories of Hope and Healing for Alzheimer’s Patients and Their Families, she offers advice for patients and caregivers on how to cope, from delaying the onset of cognitive decline to managing expectations.
Chow shares some of her advice with The Globe and Mail:
In the book, you discuss various defences against dementia, from mental stimulation and maintaining social networks to diet and exercise. But how much can you really do to prevent it?
That’s an important point that has some subtlety to it. In this day and age, we have some ability to detect the abnormal proteins that are markers for dementia. But there are quite a few people among us with these abnormal proteins, yet who are still doing everything the way they used to without extra help and who don’t look to the casual observer as if they have dementia. I think the goal for more people should be to be like them. So you might have some of the abnormal proteins of dementia, but the idea is to not have symptoms of dementia.
How can someone tell if they have dementia or just absent-mindedness?
There are times in our life when we have some transient lapses in our memory because we’re distracted or we’re sleep deprived or we’re ill. But when it’s happening more consistently and you’re forgetting the kinds of things that you think are really important, that can be one of the major symptoms of the illness. For healthy individuals, whatever intelligence or talents you had before, you should be able to keep those up until the end of your life.
Can you explain why education is a strong defence against dementia?
There is a correlation between having a high level of formal education and being able to have abnormal proteins in your brain without showing symptoms. But, in fact, building your cognitive reserves has to do more with constantly expanding your repertoire as you age.
It turns out reading can be helpful in sustaining your cognitive function and it’s not clear yet whether that’s reading non-fiction or fiction. The idea is you want to introduce your brain to new stories and episodes and have new things to discuss with people.
How does does calorie reduction – reducing one’s energy intake by 33 per cent – benefit the brain?
There are cellular organisms, the mitochondria, which help scan protein products as they’re made, like a quality-assurance team. As we get older, that machinery slows down, so a few more rejects get through. And with time, we get the deposition of abnormal proteins. With calorie reduction, there’s a message sent to the quality-control team that says, “We’re in a little bit of a crisis here. It’s not huge, but would you please get back on the job and do some overtime.” So in that way, you might be able to key up the vigilance for abnormal proteins.
Your late grandmother had Alzheimer’s disease. How has your family history affected your perspective on the illness?
First, I have to take my own advice. The other part of it has to do with pursuing more of a meditative life and focusing more on equanimity, which I think will play into how I am going to react if I feel like I’m losing it later in life. We’re all open to pleasant surprises, but it’s so important to remain open to something that is not going to go the way you want it to.
Yet being diagnosed with dementia can be devastating.
Yes. However, by the time patients come see me, it’s not a surprise. They’ve been worried for a long time. When I do give the diagnosis, more times than not, as opposed to shock, there is a certain sense of relief. They feel, “Now it’s settled. We have a name for this and we have a direction we can go in.”
You emphasize the importance of compassion when caring for patients. But what are some of the biggest mistakes caregivers make?

The No. 1 one mistake is thinking, “I can do this all by myself.” That’s a guaranteed recipe for burnout. Caregiving has to be done with some allies, whether it’s your personal friends, neighbours, other family members or professional care providers. There are couples who have been together forever and the wife or husband has gotten used to the idea that they’re a unit: They can handle everything on their own. But they forget that the other half of the unit now can’t contribute as much. It’s hard to compensate for the other person for the 15 to 20 years for the dementia to run its course.
What is the best way for caregivers to deal with patients who are aggressive or agitated?
This is one of the most stressful things for a caregiver. In order for us to figure out how to address aggression or agitation, we have to take a fearless and honest appraisal of what the patient is doing, and what may be triggering that behaviour.
There are some behaviours that are caused by the dementia itself. But sometimes it’s the only way the patient has of stating that an important need is not being met, such as boredom. They may be craving stimulation or interaction. If you can create some kind of activity – it may be very simple but meaningful – it may give that person a feeling of having accomplished something that day. Then, everybody wins.
This interview has been edited and condensed.
Editor's note. This is an updated version of the story, correcting the name of the Ross Memory Clinic to Sam and Ida Ross Memory Clinic.

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