A New Attack on Alzheimer’s

The Obama administration has announced a bold research program to test whether a drug can prevent the onset of Alzheimer’s disease well before any symptoms appear. It is a long shot, but the payoff could be huge.

The prevailing, but not universally accepted, hypothesis is that amyloid plaques in the brain play a major role in causing Alzheimer’s. Crenezumab attacks the formation of such plaques, apparently by binding to amyloid proteins and clearing them from the brain. If the drug fails to work, the trial will probably demolish the amyloid hypothesis and set researchers scrambling to find other targets to attack.

Currently, there is no cure for Alzheimer’s, which steadily robs patients of their memory, followed by full-blown dementia. There is also no diagnostic test to identify who has it, and no treatment to slow patients’ deterioration for more than a few months. 

 

While work continues on those fronts, the new clinical trial will test whether the drug, Crenezumab, made by Genentech, can prevent the disease in a group of people whose genetic heritage guarantees that they will develop it. If the drug successfully prevents the loss of mental capacities as measured by a sensitive new cognitive test there is hope — but no guarantee — that it could do the same for members of the general public. As Pam Belluck described in The Times last week, the trial will focus on members of an extended family in Colombia who carry a rare genetic mutation that causes them to develop Alzheimer’s early in life. They typically experience cognitive impairment at about age 45 and dementia by 51. The trial will also include a smaller number of individuals in the United States with the same genetic mutation. 

Instead of recruiting thousands of volunteers and following them for an extended period as in a customary prevention trial, the researchers in Colombia will give the drug to only 100 people with the early-onset genetic mutation. They will give placebos to another 100 people with the mutation and to 100 family members who do not carry the deadly gene. 

The study will cost more than $100 million and is being financed mostly by Genentech, buttressed by $16 million from the National Institutes of Health and $15 million raised by the Banner Alzheimer’s Institute in Phoenix, which is leading the study. 

A prevention trial of a different drug that was also intended to slow formation of amyloid plaques actually made patients’ symptoms worse, possibly because it interfered with various other proteins needed by the brain. Researchers believe that Crenezumab will be safer and more effective, but again there are no guarantees. The risk is justified given that without the treatment the recipients will inevitably get Alzheimer’s in the prime of their lives. The truly big payoff will come if the drug succeeds in this group and lays the groundwork for preventing or slowing the progress of Alzheimer’s that appears late in life. The researchers will be gathering data on a variety of biomarkers — glucose activity in the brain, shrinkage of the brain, certain proteins in cerebral spinal fluid, for example — to see which if any are related to preventing amyloid plaques and the loss of mental abilities. 

If the drug prevents the deterioration of particular biomarkers and ultimately sustains mental capacity, then the same markers might be useful in identifying and treating older people likely to develop the disease. And federal regulators might be willing to approve other prevention drugs based on their short-term effects on biomarkers, speeding the conduct of clinical trials. 

More than five million Americans currently have Alzheimer’s. Without an effective preventive, the number will rise steadily as the population ages. 

Published: May 20, 2012  by NY Times, Editorial

New Drug Trial Seeks to Stop Alzheimer’s Before It Starts

Brain scans of a member of a Colombian family who has Alzheimer's

In a clinical trial that could lead to treatments that prevent Alzheimer’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.

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.” 

By PAM BELLUCK, NY Times, Published: May 15, 2012

Dabrali Jimenez contributed reporting.

Early Burdens: Eldercare Falls on Young Shoulders

Suzette Armijo, 30, of Phoenix, right, oversees care of her 86-year-old grandmother, Elizabeth Armijo, left, a retired National Park Service ranger. (Courtesy Suzette Armijo)

By JANE E. ALLEN (@JaneEAllenABC) , ABC News Medical Unit

May 4, 2012

At 30, Suzette Armijo cares for her widowed 86-year-old grandmother, a retired National Park Service ranger in the final stages of Alzheimer's disease, while holding down a fulltime job, a part-time job and raising a 4-year-old son.

"This was nothing that I had planned for," says Armijo, who moved her grandmother Elizabeth Armijo into a nearby six-bed assisted living home because veterans' benefits "wouldn't pay for her to live with me." Still, she says, "I have to do everything for her, aside from her bathing. There's always something new going on with her medically."

Besides her fulltime marketing job with a Phoenix retirement community, Armijo supplements her income with outside consulting because "I do have to pay a portion of Grandma's bills."

 

Although she doesn't know anyone else her age doing what she's doing, she comes to her caregiving out of love for a woman who took care of so many others: "I don't feel torn because I know this is the way my Grandma was," Armijo said Thursday. "She took care of her parents. She took care of my grandfather. She took care of my little brother who had cancer when he was little. I grew up seeing that."

Suzette Armijo is among a generation of young adult caregivers, the majority of whom are women, navigating tough turf without a roadmap. Few of their contemporaries shoulder equivalent responsibilities. Members of the so-called sandwich generation, squeezed by parental caregiving and child-rearing, are a good 20 to 30 years older. As they try to tap into resources to help an ailing grandmother, Mom or Dad, these 20-somethings and 30-somethings are often on a lonely road. Armijo said she's drawn some of her strength from establishing a local young advocates group through the Alzheimer's Association. "You have to find something for yourself, otherwise you lose your mind."

Internet sites like AgingCare.com, which connects caregivers of elderly parents with others, may help this younger caregiving cadre find encouragement, empathy and tips on locating services.

"Other caregivers jump in and help," said Richard Nix, AgingCare.com's 49-year-old executive vice president. The National Stroke Association has launched a free, private Careliving Community with "more than 2,000 caregivers right now," said Taryn Fort, a spokeswoman for the Centennial, Colo.-based organization. Support groups for young caregivers have sprouted within some local chapters of the Alzheimer's Association, said Toni Williams, a spokeswoman for its public policy office in Washington, D.C.
Even the best-laid plans among 20-somethings can be thrown off course by a loved one's catastrophic illness and disability. After graduating from Purdue University in Indiana last May, Lauren Erickson spent six weeks in a competitive pre-medical enrichment program in Cincinnati. In September, she moved to Minneapolis to begin work as a hematology-oncology clinic assistant at Children's Hospitals and Clinics of Minnesota while studying for the Medical College Admission Test, which she hoped to take May 12.


Lauren Erickson, 23, left, moved back home to Prescott, Wis., from Minneapolis, to help care for her dad Jim Erickson, 71, right, following his stroke in March.

 

But on St. Patrick's Day, her father Jim Erickson, 71, suffered a massive stroke at home in Prescott, Wis., which left him unable to speak or move his right side. Because Erickson's mother, 61, was still recuperating from a Feb. 2 hip replacement, the couple's only child stepped in.

"I had to move home and help my Mom," Erickson, 23, said. As a result of new demands on her time, including a significant daily commute to Minneapolis, "I haven't opened an MCAT book or anything," Erickson said. She signed up to take the MCAT in July, but said her taking the test then will depend upon how her father is faring.

Even with a "very helpful" boyfriend and some free counseling through work, Erickson keeps wishing she could do more for her mother. "Through this whole process, I couldn't really break down or cry in front of her. I had to be the strong one." Still, she feels more rushed than ever about achieving her many life goals, including med school admission, "so that I can have my Dad present for all those events."
Having her father David Jenkins nearby was the only solution that Tara Leigh Adams, 28, found acceptable after he suffered a major stroke in November 2010. Adams, married and teaching second grade in Greenville, S.C., raced to her hometown of Charlottesville, Va., to help her 65-year-old father, a widower since Adams was a child.


Tara Leigh Adams, 28, right, a wife, expectant mother and second-grade teacher, moved her father David Jenkins, 65, seated, from Virginia.
 
"I think from the start I kind of, in my heart, knew that was just the way. I always knew he had to be near me," said Adams, who is expecting her first child in October. Aides help her father while she's at work, but once she walks back in the front door, she takes over everything, including getting him to the restroom.
Friends just don't understand, she said. "A lot of people my age look and say 'why do you do this? Why not a nursing home?'"

But for Adams, "there's no other option for me that would ever be as good."

Adams, who calls her husband the "rock that I lean on" said there is no substitute for "waking up and telling my Dad how much I love him in the morning."

PBS Documentary: You’re Looking at Me Like I Live Here and I Don’t

Many of you know the work I do with my Young Advocates group, YAAA! Young Advocates for the Alzheimer's Association.  Kathy Ritchie found me through this group last year and has had her own, massive, family struggles with dementia.  I want to help spread the word about this documentary airing THIS THURSDAY, March 29th, 2012 AT 10PM (check local listings) on PBS.  Anyone able to re-post via Facebook, Twitter, blogs, etc...  Please do so!  Kathy interviewed the filmmaker and her personal blog, www.MyDementedMom.com contains a Q&A with him.  I am sure it is a great documentary and I think and hope it will help shed some light on the disease and what it's like living with it.

Thank you for sharing Kathy!

Film Description:

You’re Looking at Me Like I Live Here and I Don’t is the first documentary filmed exclusively in an Alzheimer’s care unit, told from the perspective of someone suffering from the disease.

Lee Gorewitz's search is for more than a word, or a memory, or a familiar face. It is a quest for understanding. She wanders through her unit. She gazes through windows, examines other residents’ rooms, and strains to see outside the front entrance.

She scours family photographs in her bedroom, unable to identify herself in the pictures. Combing through the items in her closet, she mistakes an everyday outfit for her wedding dress. She finds a birthday card but cannot recognize that she is the “Mom” to whom the card is addressed. Exasperated and missing her children, Lee embraces a make-believe family of stuffed animals.

Although she lacks the ability to grasp memories, Lee’s attempts at recollection demonstrate unusual and poetic candor. Reflecting on her birthplace, she says, “Brooklyn, it’s right behind you.” Regarding her deceased husband, she professes, “How do I even say it? The air — was very good.” Considering love, she intones, “That’s a damn good thing to work with.”

The Science Behind Frontotemporal Dementia

When Times staff photographer Rob Gauthier and I first visited the Bryant family last April to begin reporting a story, (“Little-known brain disease rips apart lives of victim, loved ones,”), about a rare type of dementia, known as frontotemporal dementia, we realized that we needed to explore the science behind the malady. FTD, as the disease is known, is similar to Alzheimer's but affects the front portions of the brain and leads to behavioral problems such as the Bryants experienced with Stu.
I knew about Phineas Gage, the railroad foreman who in 1848 lost the front portion of his brain in a terrible construction accident and who survived as a radically changed man. I had read the work of Hanna and Antonio Damasio, neuroscientists who almost 20 years ago pioneered our understanding of the biology of emotions, and I was eager to see how frontotemporal dementia was being studied to further this research.
In the course of our reporting, Rob and I took a number of trips to UCLA and the West Los Angeles Veterans Affairs hospital to interview Mario Mendez, the physician and neuroscientists treating Stu. In our conversations, Mendez helped us understand what Oliver Sacks meant when he wrote, “Without the great development of the frontal lobes in the human brain, civilization could never have arisen.”
By studying the effects of frontotemporal dementia – and its slow diminishment of personality – Mendez is able to see more clearly the so-called social brain, a portion of our frontal and temporal lobes that plays a role in allowing us to successfully interact with each other and build relationships. Take away this portion of the cortex and we are no longer able to moderate our emotions.
Moderation – the inhibition of emotional impulses – can take the form of empathy and embarrassment and is critical in helping us negotiate complex social environments. Without either, as Rob and I learned during the time we spent with Stu, humans grow untethered to the world, unable to read feelings or behave in an appropriate manner.

By steering the discussion about morality, normally the providence of ethicists and philosophers, away from the symposium and putting it inside the laboratory where thoughts are considered to be not so much conscious choices, but instead reflexes based on a neurological network, Mendez and other neuroscientists are furthering the inquiry into the nature of right and wrong. In this light, religion, family, even Freud's notions of superego, ego and id matter less than biology.

Mendez argues that specific behaviors – not harming another person, respecting hierarchy and authority, accepting communal goals, recognizing equity and fairness – evolved among humans. Good manners, therefore, have as much to do with what we are born with as they do with how we were raised and what our parents taught us.
“Much of the social behavior that we take for granted and that we often consider to be learned or cultural or developmental is actually behavior that is deeply ingrained in the nervous system and in the frontal lobes,” Mendez says.
Consider that the next time you’re in a crowded restaurant and watching the kaleidoscope of interactions. Never mind the ability to speak and communicate. Never mind the opposable thumbs. The frontal lobes make humans human.
 
By Thomas Curwen
February 15, 2012

Diabetes...Dementia... Alzheimer's... Pneumonia

Which one would you rather deal with for most of your life? Which one would you rather die from? Which one would you rather your family have to see you die from? Honestly, I pick the one that takes me the soonest, the one that's the least painful for my family. You know why? Because the way you die is the way they remember you... Okay okay, maybe that's not true for every disease or every person. But I see families every day that lose touch with their loved one because mentally that loved one has left the body a long time ago. I see the amazing memory of a person fade away because of disease and a rotting brain, it's disgusting. It's not fair to that person, not fair to the family, it's not fair for our healthcare system. It's not fair to anyone and it's horrible to see in this world. I see people in their 20s and 30s caring for parents with Alzheimer's, I see grandkids that never knew their grandma could talk, that never knew she could walk... And of course they'll never know the amazing person that used to be there. Their grandparents life and memory will be jumbled with this ridiculous disease. And their parents are too busy trying to care for their grandparents!

I see amazing people that are trying to fight against this disease, against the many forms of dementia. But it's not enough, its just not enough.

What are you going to do? Are you going to read this and go to the next page, play the next game? Good luck, it doesn't discriminate. Half the population over 85. No joke.

www.alz.org

Save the Date for the 2012 Alzheimer's Advocacy Forum in Washington, D.C.

Save the Date! Join us for next year's Forum.

April 23-25, 2012

Renaissance Hotel, D.C.

Registration Fees

Registration fees cover only a portion of the total meeting cost. The Association subsidizes the remainder.

Early bird by March 9 $175

ISTAART members $150
March 9 – April 13 $225

After April 13 and on-site registration $275

Monday only $100

Tuesday only $175

Wednesday only $50

Group Registration Policy and Procedures

For every three fully paid registrations from a group, one free registration will be offered. To qualify for group registration: One person from your group must register all four attendees online (no faxed or e-mailed forms). Group must register at the same time with payment to receive the discount. We will not cancel a pre-registered attendee to join a group registration. All group registrations must be entered at the same time to obtain the group discount.
Cancellation and refunds must be made in writing and must be postmarked, emailed (advocacyforum@alz.org) or faxed (866.699.1235) on or before March 8. All refund requests received by March 8 will be refunded, less a $35 processing fee. No refunds will be made for cancellations received after March 8. No refunds for no-shows.


Registration Methods

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Fax registrations ONLY if payment will be made using a credit card. Do not fax group forms. Your email address must be included on the faxed form. Fax completed registration form to 886.699.1235.

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Confirmation letters are sent by email. Please include the email address where you would like to receive the confirmation. Contact Darnella Harris at 312.335.5833 or advocacyforum@alz.org if you do not receive a confirmation.
Pre-Registration

Pre-registrations must be received by Friday, April 13, at 5 p.m. Central. After this time, anyone wishing to register must do so on site at the Advocacy Forum. See registration fee schedule.

Events at Registration

Please indicate on your registration form the meal functions and events you will be attending. All meals will be ticketed. If you wish to make a change to your registration, you may do so by calling 312.335.5833 before April 13 or visit the registration desk on site.

On-Site Registration Hours

Pre-registered attendees may pick up their conference materials, and on-site registrants may complete the registration process, during the following hours:


Monday, April 23 10 a.m.–6 p.m.

Tuesday, April 24 6:30 a.m.–5:30 p.m.

Substitutions

If you are unable to attend but would like to send another person in your place, please email the new information indicating it is a substitution to Darnella Harris at Darnella.Harris@alz.org

For More Information

For registration information, call 312.335.5833 or email advocacyforum@alz.org.