SUFFERING WITH THE STARS

When Seth Rogen first learned of his mother-in-law’s diagnosis, he was shocked. “I had no idea that someone that young could even get Alzheimer’s,” he tells Newsweek. “The speed and aggressiveness with which it attacked was something I really didn’t have any context for… My image of it was like, You forgot stuff. But that is really the tip of the iceberg. You forget how to walk and move and talk.”

Nearly one quarter of American adults mistakenly believe the disease is hereditary. When asked about which illness they were most fearful of getting, Americans 60 and older rank Alzheimer’s or dementia (35 percent) above cancer (23 percent) and stroke (15 percent).

“There’s a disease that’s killing our parents and grandparents and no one seems to be doing anything about it,” Rogen says. “One day it’s going to kill us. It hasn’t become trendy to care about… Part of that is because it’s really depressing and there’s not a lot of hope associated with it.”Trojanowski and other doctors say there’s a stigma to the disease. “It’s shameful. You don’t want to talk about the fact that your parents have Alzheimer’s,” he says. “Another reason is, the patients themselves are demented; they can’t advocate for themselves. There isn’t a Michael J. Fox equivalent for Alzheimer’s.”

In today’s media-centric world, a celebrity diagnosis, though no more devastating than anyone else’s, has the ability to raise awareness—and dollars—for a disease. Angelina Jolie, Katie Couric and Lance Armstrong have become public faces for the fight against cancer. Magic Johnson did the same for HIV/AIDS. Christopher Reeve became a crusader for stem cell research. Michael J. Fox started his own foundation dedicated to finding a cure for Parkinson’s disease, with which he was diagnosed in 1991.

Alzheimer’s has struggled to keep pace with these monster marketing and fund-raising machines. Former president Ronald Reagan was among the most notable sufferers. Country music star Glen Campbell, 77, and the University of Tennessee women’s basketball coach Pat Summitt, 61, went public with their diagnoses in more recent years.

“People think it’s an old-age person’s disease,” Petersen says. “It’s like cancer was 25 years ago: You didn’t mention the C word. Cancer activists have done an excellent job of destigmatizing it, putting it out there, and making it a disorder that needs attention. Alzheimer’s is still behind the eight ball on that score.”

White family photograph. Elinor Carucci

TURNING THE TITANIC

Where progress has been made is in detection. When the disease develops, two abnormal structures—called plaques and tangles—disrupt nerve cells’ all-important workflow in the brain, contributing to cell death. Almost everyone develops some plaques and tangles as they grow older, but those with Alzheimer’s have far more. Until recently, the only way scientists could tell, for sure, if a person had Alzheimer’s was to conduct an autopsy. Now, they can use new brain scan technology or test spinal fluid to test for signs before symptoms show up.

New studies focus on delaying onset and slowing progression. A large clinical study, known as A4, targets healthy seniors who do not show signs of memory problems but do have a silent buildup of plaques in the brain. TheAlzheimer’s Prevention Initiative focuses on the few people with a high genetic risk of developing Alzheimer’s. One trial will test a new drug among the world’s largest extended family to experience Alzheimer’s disease, a group of thousands of relatives in Colombia who carry a specific gene mutation. Another trial, called DIAN-Trial Unit, investigates a new drug for people with genetically based, young-onset Alzheimer’s.

Rare, inherited forms of the disease have been linked to three genetic mutations that guarantee a person will develop Alzheimer’s, probably before the age of 65 and sometimes as young as 30. Yet these mutations are the only known definitive cause of the disease, and they account for less than 1 percent of cases. Having one or more first-degree relatives with the disease increases your risk, as do a host of other conditions, including obesity, diabetes, high cholesterol and smoking. Physical activity, healthy diet, mental exercise, social engagement and education may all help reduce the risk.

In another new study, Harvard scientists discovered that a protein called REST—which, in healthy older adults, protects neurons in the brain from the stresses of aging—seems to be significantly diminished in people with Alzheimer’s and other dementias. There is a chance that REST could lead to new drugs for treatment, but considerable testing and further studies must come first.

“We don’t fully understand what causes Alzheimer’s, so in a sense we’re shooting in the dark,” says Doraiswamy. “When drug companies start their clinical drug programs, there’s often a 10-year lag period. In the eight or nine years it takes the drug to move… into human trials, the science simultaneously progresses to where we’ve learned something new. A lot of these companies are like the Titanic; they can’t change directions quickly.”

Pam and Ed with their grandchildren. Elinor Carucci

ONE LITTLE GLITCH

For Pam White, it happened slowly. A model-turned-social worker, she started buying books she already had at home. Sometimes she got lost driving. Other times she couldn’t do simple calculations. Mail disappeared. She was always losing her keys. Little things, like her cooking, seemed to be off.

“My dad took over many tasks and roles that used to be my mom’s, but it happened so gradually and naturally, none of us ever made much of it,” says Pam’s youngest son, Luke White, 32, a psychiatrist.

In 2009, when Pam was 61, she was diagnosed with early-onset Alzheimer’s. The news came just one year after she had started writing a book about her mother, renowned painter Marian Williams Steele, who had died of Alzheimer’s in 2001 at 89.

“There is so much tension in loving someone who is in the process of changing, who will inevitably die because of this disease,” says Banker White, 40, Pam’s eldest son, a documentary filmmaker who starting rolling his camera right after she was diagnosed.

The result of all that footage is The Genius of Marian, a documentary about the Whites’ experience, co-produced with his wife Anna Fitch. Spanning the first three years of Pam’s illness, the film (named after the book she was writing) weaves together footage of her everyday life and progressive illness with old family videos and Marian’s whimsical paintings that hang on the walls of the Whites’ home in Dedham, Mass. The film debuted last year at New York’s Tribeca Film Festival, will be released theatrically this month byTUGG and will air on PBS in September.

In the film, nothing is off-limits—not the bleak doctor visits nor tense conversations about medication nor the countless confused, absent stares that cross Pam’s face. We watch her forget how to dress herself. At an appointment with her neurologist, she can’t name the image on a flash card (a bench) and doesn’t know what year it is (“19-something”—it was 2011).

For years, the White family kept Pam’s condition a secret, while she vacillated between denial and acceptance. “I don’t have it. Yes I do. I do. I have it,” she says in the film.

Women in their 60s are on average twice as likely to develop Alzheimer’s disease over the rest of their lives as breast cancer. Elinor Carucci

In December, her husband, Ed White, 69, retired from his investment management business to care for her at home. Their daughter, Devon, 37, who lives in neighboring Brookline, visits often with her own family. Ed also hired a part-time caregiver to help. Still, he only takes four to six days off every couple of months to play golf with friends.

“My biggest problem is, I sometimes feel like I’m caged. I can’t even go buy a paintbrush without going through the big rigmarole of getting Mom dressed up and getting in the car,” Ed says in the film. “So I just have to—forget it. So? Remember the phenomenal life that she’s given me…. So I sure as hell owe her this, even if it gets frustrating.”

Some of the most intimate scenes in the film come from Pam’s video diary, including the ending.

“I live for my family and my children,” Pam says, “and one little glitch is that I have developed Alzheimer’s. Initially, I was quite distressed and upset about it, but it doesn’t really matter. It doesn’t really change anything, so I don’t feel sad and I don’t feel regret. I feel blessed that I have this wonderful family and a husband who is extraordinarily wonderful. I just feel like, maybe the way my mother did before she was dying. It just was the way it was. And remembering, keeping, cherishing all the times I had with friends and family. So it’s all good. No regrets.”

Watching the clip, Ed pumps his fist in the air.

“It’s very important that that movie got made,” Rogen says. “That’s the exact type of thing that’s going to help: people sharing their personal experiences, making people realize that the disease is not how it’s perceived.”

“They say Alzheimer’s is a caretaker’s disease, and it really is. It requires a lot of work and it lasts a very long time,” Rogen adds. “One of the reasons my speech got so much attention is because people were shocked that’s what I was actually talking about. In a way, that was a major victory,” he says. “But it shows how much people weren’t talking about Alzheimer’s—the mere fact that [my testimony] was a story.”

Harvard researchers have found evidence that Alzheimer’s disease, long known for the toxic clumps and tangles that build up in the brain, may also be caused by the failure of a natural system that protects brain cells.

The protein deposits that are hallmarks of Alzheimer’s disease have turned out to be puzzlingly unreliable, suggesting the devastating illness might have additional causes. Studies have found the protein clumps clogging the brains of some people with no cognitive impairment.

In the new study, published Wednesday in the journal Nature, scientists identified a protein called REST that flips genes on and off and naturally increases during aging. REST, they found, represses genes involved in Alzheimer’s disease, and its levels are reduced in key brain areas of people diagnosed with Alzheimer’s or the mild cognitive impairment that precedes dementia.

In laboratory tests, REST protected brain cells from dying when exposed to a number of stresses, including the beta amyloid protein that accumulates in the brains of Alzheimer’s patients.

“One very positive, optimistic note from this study is that it suggests that dementia can be resisted by some people, and it provides the first molecular inklings of how that might occur,” said Bruce Yankner, a professor of genetics at Harvard Medical School.

The finding highlights a different approach to understanding neurodegenerative diseases: instead of focusing on the negative changes that cause disease, researchers looked for lapses in the brain’s protective mechanisms.

“It’s an amazing idea that neurons that you’re born with will function for 100 years or more, in a very high-stress situation … until the day a person dies,” Yankner said. “The brain is a pretty tough organ and we should strive to find out what makes it so tough and capitalize on this.”

Outside scientists said that the study was important and meticulously done, but warned that it is basic research and will need to be repeated. Translation of such insights into experimental treatments that can be tested in patients typically takes years.

“One of our concerns is the fact there are 5 million Americans living with Alzheimer’s disease, but we have no treatments to slow, stop, or prevent the disease,” said Dean Hartley, director of science initiatives for the Alzheimer’s Association. “It’s basic research like this that we think will be important not only to understand this disease, but the biggest risk factor for Alzheimer’s is aging — and that’s what intriging” about the new study’s focus.

Yankner did foundational work in the Alzheimer’s field, describing in the 1990s how the protein deposits that form in the brains of Alzheimer’s patients are toxic. In the intervening years, however, he has become broadly interested in what happens to the brain during aging.

It was a search for those changes that led his team to the REST protein. Yankner and colleagues used a computer program to search for genetic switches that might account for the characteristic differences in gene activity between the brains of young adults and older adults. The REST protein leaped out from the data.

Because genetic studies are not feasible in humans, the team created genetically manipulated mice that lacked the REST protein. When the researchers compared month-old mice with and without REST, they had similar numbers of neurons in key brain areas, but by the time they were eight months old, more brain cells had degenerated and been lost in mice lacking the protein than in those with it. The scientists also found that among brain cells exposed to a toxin, cells with extra REST were less likely to die.

Next, they created roundworms that lacked proteins that are analogous to REST, and found that the ones lacking the protein were less likely to survive when subjected to an herbicide that causes oxidative stress. That suggested the REST mechanism for protecting brain cells is very basic to survival, because it had been conserved in starkly different species by evolution.

The researchers then analyzed human databases, including a study that has tried to eliminate some of the natural variability in people’s environment by studying clergy who have lived similar lifestyles. Those clergy in the Religious Orders Study had detailed cognitive assessments performed and also donated their brains for study after death.

The researchers found that higher levels of REST in the prefrontal cortex — a portion of the brain involved in decision-making, planning ahead, and coordinating activities — were correlated with greater ability to remember autobiographical information and events.

In addition, REST levels were significantly higher in study participants who had signs in their brain of Alzheimer’s disease but no recorded memory issues. That, along with the laboratory tests in animals, suggested the protein was helping preserve cognitive abilities.

For years, experimental drugs aimed at the known pathological signs of Alzheimer’s disease have been largely ineffective, and Yankner thinks that perhaps this variability in people’s REST levels during aging could help explain those results. His team found that REST appears to be activated in response to stress, but further work needs to be done to understand precisely why some people have higher rest levels during aging and some do not.

Already, his group is searching for experimental drugs that can turn up REST levels, and he said one intriguing finding so far is that an approved drug, lithium, appears to activate it.

Yankner cautioned that no one should try and take lithium to prevent memory loss, but said that it may help guide the development of drugs that can be tested in people. Jeffrey Kelly, chairman of molecular medicine at Scripps Research Institute, said that what intrigues him about REST is that it is part of a signaling mechanism in cells that has been thoroughly studied in cancer research, thus it might make drug development quicker.

“What I love about this study, first and foremost, is it’s some good news for Alzheimer’s, and it connects that good news with an immediate therapeutic strategy,” Kelly said. “There aren’t a lot of steps between this” and the development of experimental drugs.

Li-Huei Tsai, director of the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology, who was not involved in the study, said that the work could help fill in many questions about complex neurodegenerative diseases. Perhaps if researchers could understand patient’s natural levels of REST, they could target treatments to people based on whether they had high or low levels of the protein, similarly to how oncologists treating some cancers can tailor treatments based on the genetic cause of the cancer.

“I think this is an amazing, heroic piece of work,” Tsai said. “We always talk about why certain individuals get Alzheimer’s disease, and why some other people don’t. … But so far nobody can really put a finger on, say, a particular biological pathway and say look, if you have higher activity of this pathway you can be more protected, or vice versa.

The Harvard study, she added, appears to do so.

Alzheimer’s disease affects many more women age 65 and older than men of that age, a new report suggests.

Wednesday’s report from the Alzheimer’s Association in the U.S.  estimates a woman’s lifetime risk of developing Alzheimer’s at age 65 is 1 in 6 or 17 per cent compared with nearly 1 in 11 or nine per cent for a man.

The differences in lifetime risk between women are men are mainly due to women’s longer life expectancy.  Age is considered the greatest risk factor for the mind-robbing disease.

“Alzheimer’s disease takes a stronger toll on women than men,” the report’s authors conclude. “More women than men develop the disease, and women are more likely than men to be informal caregivers for someone with Alzheimer’s disease or dementia.”

Alzheimer’s disease is still largely misunderstood by the public,  said Angela Geiger,  the association’s chief strategy officer, based on the group’s poll findings. Everyone, male or female, family history or not, is at risk.

The impact of Alzheimer’s is expected to increase as baby boomers age.

The National Alliance for Caregiving and AARP, formerly the American Association of Retired Persons, said more than half of unpaid caregivers — usually immediate family members — said they provide help with getting in and out of bed and one-third offer help with bathing, feeding, getting to and from the toilet and managing incontinence.

In 2011, 747, 000 Canadians were living with Alzheimer’s or related dementias, according to the Canadian Institutes of Health Research. In 2031, 1.4 million Canadians are expected to have the disease.

A blood test can accurately predict the onset of Alzheimer’s disease, according to US researchers.

They showed that testing levels of 10 fats in the blood could predict – with 90% accuracy – the risk of the disease coming on in the next three years.

Their findings, published in Nature Medicine, will now be tested in larger clinical trials.

Experts said the results needed to be confirmed, but such a test would be “a real step forward”.

The number of people living with dementia stands at 44 million around the globe and is expected to treble by 2050.

The disease silently attacks the brain for more than a decade before any symptoms emerge. Doctors think drug trials are failing because patients are simply being treated too late to make a difference.

This is why discovering a test that predicts the risk of dementia is a major priority for the field.