Unite in a movement to reclaim the future for millions. Join a team for the Alzheimer’s Association Walk to End Alzheimer’s®, the nation’s largest event to raise awareness and funds to fight Alzheimer’s disease. Together, we can advance research to treat and prevent Alzheimer’s, and provide programs and support to improve the lives of millions of affected Americans.
I personally have lost too many loved ones to this debilitating disease. Join me by finding a walk in your city or state!
By Alice Park, Time, Health & Family Dec. 04, 2012
The lasting impact that concussions can have on the brain is on the minds of anyone involved in football, from parents of the youngest Pop Warner players to those in the professional ranks.
More and more players in the NFL are succumbing to symptoms of memory loss, inability to concentrate and changes in personality that they attribute to repeated blows to the head during play. But as their numbers grow, researchers are struggling to keep up with understanding the brain injuries that concussions can cause. Now, for the first time, scientists are classifying the brain injury from head trauma into four distinct stages.
Most agree that repeated mild trauma to the brain in the form of concussions can result in chronic traumatic encephalopathy (CTE), or a gradual buildup of a brain protein called tau. Just as with Alzheimer’s patients, where accumulation of plaques and tau tangles can space out healthy brain tissue and let nerve connections wither away, damage caused by concussions can trigger the accumulation of tau in CTE cases, eventually forming deposits large enough to interfere with key functions such as learning, planning and organization.
In the latest study, published in the journal Brain, scientists led by Dr. Ann McKee studied the brains of 68 deceased patients with CTE in order to find patterns in the way the disease develops. McKee, a professor of neurology and pathology at VA Boston Healthcare System and Boston University School of Medicine, spent more than two decades researching Alzheimer’s disease. She decided to apply the same order in staging brains that she had become accustomed to in her Alzheimer’s work. The number of CTE brains she and her team studied is the largest to date, and allowed them to see patterns in the way the disease progressed. The patients included football players, hockey players, boxers and veterans (many of whom were athletes) and one who engaged in self-inflicted head-banging behavior.
In order to generate the least biased analysis possible, McKee and her pathology team conducted the autopsy analysis of the brain tissue, while another group led by Robert Stern, a neurologist and neurosurgeon at Boston University School of Medicine, carried out detailed interviews with the deceased patients’ families about the patients’ lives, behaviors and symptoms.
In her first pass at the data, McKee was able to discern a distinct pattern of where and how CTE progressed. She and her team found focal points where the injury to the brain seemed to start. These were concentrated in the frontal lobe, deep in the valleys of the convoluted cerebral cortex. Cortex tissue resembles a crumbled piece of paper with folds that create peaks and valleys, and the lesions of CTE seemed to start in the valleys where small blood vessels also congregate. “There is a fairly stereotyped lesion; where the gray matter dives in to create a valley in the brain is where we see the greatest damage,” says McKee. “We also see over and over in all of these cases that there is a strong tendency of the disease to start around blood vessels, which means the blood vessel is damaged with the injury.”
While it’s not clear what triggers the damage, McKee suspects that the junction of the elastic blood vessels butting up against the more gelatinous cortex tissue may be particularly vulnerable to the shearing forces from an impact.
Once the damage is done, however, it’s difficult to stop. Even after the physical blows no longer occur, a destructive chain of events is already in motion. From these seed points in the frontal lobes, damage to nerves and brain tissue radiates to other parts of the brain, until it eventually engulfs most of the organ, impairing many cognitive functions. “Even if a person doesn’t get additional trauma, the disease progresses, like a lit fire,” says McKee. “The fire takes hold and continues to affect the brain with more lesions the longer the person lives.”
Because the study included the brains of patients who died at a range of ages, between 17 and 98, McKee could see the growing buildup of tau in the brain among the older cases. She could also see distinct stages of the disease, from lesser signs of lesions and tau to greater depositions. She could then correlate later stages of damage to longer play for the football players, and therefore likely more concussions.
While the findings confirm, and perhaps even reinforce how damaging concussions can be, McKee says they could also lead to better treatments for CTE. For one, recognizing that the disease begins with small lesions in the blood vessels could lead to helmets or other equipment that better protect the most vulnerable parts of the brain.
In addition, it could help scientists develop higher-resolution brain scans to detect these early signs of the disease. Current technology is not able to find such small abnormalities, but researchers are testing a tracer that could detect the tiniest deposits of tau protein that would alert doctors to the potential for CTE. Patients could then be warned to avoid repeated head trauma like those that might occur on the football field.
Understanding that the damage occurs in the blood vessels could also lead to ways of protecting those vessels and preventing the damage from spreading to the rest of the brain. It’s not clear yet what is causing the initial lesions to seed damage to other parts of the brain, but if the damage causes leakage of agents that are toxic to nerve cells, for example, drugs or other interventions may block the added injury these lesions can cause.
The insights from CTE could also help researchers develop better treatments for other neurodegenerative conditions as well. “I’m optimistic that this disease gives us lots of insights into other diseases like Alzheimer’s,” says McKee. “If we could reduce tau somehow or wall off the early stages of the disease, we can prevent the degenerative part from developing.” Avoiding head trauma may not always be possible, but stopping the damage it can cause may one day be more realistic.
Originally posted by By Alice Park, Staff Writer at Time, in Health & Family Dec. 04, 2012
New Drug Trial Seeks to Stop Alzheimer’s Before It Starts
In a clinical trial that could lead to treatments that preventAlzheimer’s, people who are genetically guaranteed to develop the disease — but who do not yet have any symptoms — will for the first time be given a drug intended to stop it, federal officials announced Tuesday. A version of this article appeared in print on May 16, 2012, on page A1 of the New York edition with the headline: Drug Trial Aims For Prevention of Alzheimer’s.
Experts say the study will be one of the few ever conducted to test prevention treatments for any genetically predestined disease. For Alzheimer’s, the trial is unprecedented, “the first to focus on people who are cognitively normal but at very high risk for Alzheimer’s disease,” said Dr. Francis S. Collins, director of the National Institutes of Health.
Most participants will come from the world’s largest family to experience Alzheimer’s, an extended clan of 5,000 people who live in Medellín, Colombia, and remote mountain villages outside that city. Family members with a specific genetic mutation begin showing cognitive impairment around age 45, and full dementia around age 51, debilitated in their prime working years as their memories fade and the disease quickly assaults their ability to move, eat, speak and communicate.
Three hundred family members will participate in the initial trial. Those with the mutation will be years away from symptoms, some as young as 30.
“Because of this study, we do not feel as alone,” said Gladys Betancur, 39, a family member. Her mother died of Alzheimer’s, three of her siblings already have symptoms, and she had a hysterectomy because of her fears that she has the mutation and would pass it on to her children. “Sometimes we think that life is ending, but now we feel that people are trying to help us.”
The $100 million study will last five years, but sophisticated tests may indicate in two years whether the drug helps delay memory decline or brain changes, said Dr. Eric M. Reiman, executive director of the Banner Alzheimer’s Institute in Phoenix and a study leader.
Alzheimer’s experts not involved in the study said that though only a small percentage of people with Alzheimer’s have the genetic early-onset form that affects the Colombian family, the trial was expected to yield information that could apply to millions of people worldwide who will develop more conventional Alzheimer’s.
“It offers a tremendous opportunity for us to answer a large number of questions, while at the same time offering these people some significant clinical help that otherwise they never would have had,” said Dr. Steven T. DeKosky, an Alzheimer’s researcher who is vice president and dean of the University of Virginia School of Medicine. Dr. DeKosky was part of a large group consulted early on, but is not involved in the study.
Some 5.4 million Americans have Alzheimer’s, and the numbers are expected to swell as the baby boom generation ages. Dr. Reiman’s team is planning a similar trial for people in the United States considered at increased risk for conventional late-onset Alzheimer’s. The study announced Tuesday will include a small number of Americans with gene mutations guaranteed to cause early-onset Alzheimer’s.
The drug trial is part of the federal government’s first national plan to address Alzheimer’s, which was unveiled Tuesday by Kathleen Sebelius, the secretary for health and human services. The government took the unusual step of assigning $50 million from the current year’s N.I.H. budget to research considered too promising to wait, including the Colombia trial and a study on whether inhaled insulin can ease mild cognitive impairment, Dr. Collins said. Another $100 million is proposed for 2013, mostly for research, but also for education, caregiver support and data collection.
Success for the Colombia trial is, of course, no sure thing. Many trials fail, and Alzheimer’s research has so far found no treatment effective for more than several months. But experts say that trying drugs years before symptoms emerge could have greater potential because the brain would not yet be ravaged by the disease. The trial will be financed with $16 million from the National Institutes of Health, $15 million from private donors through the Banner Institute and about $65 million from Genentech, the drug’s American manufacturer.
The drug, Crenezumab, attacks amyloid plaques in the brain. If it can forestall memory or cognitive problems, scientists will know that prevention or delay is possible and appears to lie in targeting amyloid years before dementia develops. Many, but not all, Alzheimer’s researchers believe amyloid is an underlying cause of Alzheimer’s.
In 2010, The New York Times reported on the pervasiveness of dementia in this large Colombian family and scientists’ hopes of testing prevention drugs. But persuading pharmaceutical companies to invest took months. There are scientific and ethical issues involved with giving drugs to people who are healthy and people who live in a developing country, some of whom have little education, paltry incomes and longstanding superstitions about the disease they call La Bobera — the foolishness.
“The first thing I did was to ask myself the question, Are we taking advantage of these folks?” said Richard H. Scheller, Genentech’s executive vice president of research and early development. “The answer was clearly no.”
The risks, he said, are balanced by the fact that if nothing is done, “they’re going to get this terrible, terrible disease for sure.”
The few trials of prevention therapies — involving ginkgo biloba, women’s hormone replacement treatment and anti-inflammatory drugs — have involved people not guaranteed to get the disease. These therapies either failed or caused adverse side effects.
Testing drugs on that kind of population takes “too many healthy volunteers, too much money, and too many years,” Dr. Reiman said.
The Colombian population is ideal because it is large enough to provide solid results, and it is easy to identify whom the disease will strike and when.
Crenezumab was chosen for the Colombia trial partly because it appears to have no negative side effects, unlike other drugs designed to clear amyloid from the brain, said Dr. Francisco Lopera, a Colombian neurologist who has worked with the family for decades and is a leader of the study. Other anti-amyloid treatments have caused edema in the blood vessels, an imbalance of fluid that can have serious consequences.
Crenezumab is currently being given in two clinical trials to people with mild to moderate symptoms of dementia in the United States, Canada and Western Europe to see if it can help reduce cognitive decline or amyloid accumulation, according to Genentech.
In the Colombia study, expected to start early next year, 100 family members with the mutation will receive the drug every two weeks in an injection at a hospital. Another 100 carriers will receive a placebo. And because many people do not want to know if they have the mutation, researchers will include 100 noncarriers in the study; they will receive a placebo.
Researchers have developed a sophisticated battery of five memory and cognitive tests that have been shown in other studies to detect subtle alterations in recall and thinking ability that usually go unnoticed. Dr. Pierre N. Tariot, director of the Banner Institute and a leader of the study, said the measurements would involve recalling words, naming objects, nonverbal reasoning, remembering time and place, and drawing tests involving copying complex figures.
Dr. Tariot said researchers would also assess changes in people’s emotional state, “irritability, sadness, crying, anxiety, impulsivity — these are cardinal features of the disease as it emerges.”
The scientists will take physiological measurements, including PET scans that measure amyloid and how glucose is metabolized in the brain, M.R.I. scans that measure whether the brain is shrinking, and cerebral spinal fluid tests that measure amyloid and tau, a protein in dying brain cells.
If any of these indicators are improved by the drug, Dr. Reiman said, scientists may then be able to treat one of these early physiological changes, just as high blood pressure and cholesterol are treated to prevent heart disease.
In Medellín, Marcela Agudelo, 17, has Alzheimer’s on both sides of her family because her parents are distant cousins. Marcela watched her maternal grandmother die, and her father, 55, once a vibrant livestock trader, has deteriorated so much that he can no longer walk, talk or laugh.
With the research, “we have more hope for a cure,” Marcela said, “or at least a better life.”