The Alzheimer's Project

Momentum in Science


By John Hoffman

By Susan Froemke

With Susan K. Golant

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This companion book to the HBO Documentary Films series explores the cutting-edge research on Alzheimer’s disease that is creating new hope for the future.

Alzheimer’s disease is the second most-feared illness in America, following cancer. It affects as many as 5 million Americans, a number that could soar to 16 million by 2050. It is estimated that, unless effective preventions are discovered, 10 million baby boomers will eventually develop this irreversible and devastating brain disorder.

Until recently, medical news on Alzheimer’s disease was not comforting. But in the past few years, advances in many scientific areas — from diagnostic imaging to genetic analysis — have led to an explosion of knowledge with implications for treatment and prevention. This is an exciting time of discovery in Alzheimer’s research.

Through The Alzheimer’s Project film series, HBO Documentary Films illuminates the vital breakthroughs occurring in the field. One of the central films in this series, Momentum in Science, brings us inside the laboratories and clinics of the nation’s top scientists and physicians who are clearing the path to a deeper understanding of Alzheimer’s disease. By capturing the exhilaration of these scientists and casting light on their groundbreaking discoveries, the film seeks to bring a wider understanding of the disease and new hope for future treatment.

This book offers an even closer look at the advances of this scientific frontier. It investigates the complex cascade of events that occurs inside the brain when someone has Alzheimer’s disease and shows how scientists are working to interrupt this process and ultimately prevent the disease. In accessible prose, it examines specific evidence of momentous progress, from the triumphant discovery of the unique role of the beta-amyloid and tau proteins, to the use of PET scans to track changes in the brain and the analyses of cerebrospinal fluid to identify biomarkers that will help us predict who will develop the disease in the future. It also looks at current drug development and at what we can do as individuals to potentially reduce our risk of developing the disease.

The Alzheimer’s Project: Momentum in Science is a fascinating story of scientific discovery that shows what recent breakthroughs might mean for improving our chances of remaining cognitively vital throughout a long life.


Illustration opposite the title page compares a healthy neuron (above) to one damaged by Alzheimer’s disease (below).

I’ve been a child of Alzheimer’s disease since my father, Sargent Shriver, was diagnosed in 2003. When a loved one is diagnosed with Alzheimer’s disease, it affects the entire family, and it affects each member differently.
In the first years of my father’s illness, I approached the disease not only as the daughter of someone who has it, but also as the mother of children who have to deal with it, too. I struggled to find a way to give my four kids a real sense of what a special man their grandfather was and to help them understand what this disease was doing to him.
That struggle resulted in my third children’s book, What’s Happening to Grandpa? It was a way for me to share the questions my children and my nieces and nephews were asking about my dad and give them answers they could understand and internalize. I hoped it would also help the millions of others dealing with this disease. Writing about Alzheimer’s disease helped me, too, because my father has always been such a cheerful and positive person, and I wanted the book to reflect how that attitude lit up his life and ours.
In truth, my children’s questions and concerns also provoked my own anxieties. What were my chances of developing the disease, I wondered? Were there things I could do to prevent it? Were there drugs I could take? Was there something out there that could help my dad and help him now? If not, why not? I learned that there were, in fact, medications that helped maintain his cognitive abilities early on, but the effect lasted only so long. Since then, there’s been no medication to stave off his continuing decline.
Participating in The Alzheimer’s Project has allowed me to explore the answers to all my questions in much more depth than I ever imagined. As an executive producer of the project, I’ve learned how far scientists have come in figuring out the genetic and environmental causes of the disease, imaging the earliest signs of it in the brain, understanding the disease process, and working to develop drugs that could potentially delay its onset or prevent it altogether.
I had the privilege of joining HBO on some of their shoots with scientists at the forefront of these discoveries. I met Dr. Charles DeCarli, a neurologist at the University of California Davis, who is looking into the connection between vascular disease and Alzheimer’s disease. I visited a lab at the University of California Irvine, where Dr. Carl Cotman is researching how exercise and diet may keep the ravages of Alzheimer’s disease at bay and allow us to age more health-fully. I got to enter the futuristic world of biotech innovation in the Bay Area, where Dr. Dale Schenk showed me the promising work he’s conducting on a potential vaccine for Alzheimer’s disease at Elan Pharmaceuticals. As the first lady of California, I’m proud that so much of the trailblazing research is going on in our state.
My father was a great proponent of public service. In the course of his own career in government, he helped found the Peace Corps, Head Start, Job Corps, Legal Services for the Poor, and countless other programs that up to the present day help people who are struggling to live above the poverty line. I believe scientists focusing on Alzheimer’s disease are also performing public service of the highest order. Today, our federal government, through the National Institutes of Health, does enormous public good by funding and conducting one of the world’s most extensive Alzheimer’s disease research programs. Foundations such as the Alzheimer’s Association also play an important role. I’ve come to believe that scientific research is one of the most important investments our government can make—scientific research that may one day produce treatments and prevention strategies, so that fewer families will have to go through what my family has gone through because of Alzheimer’s disease.
I also firmly believe that each and every one of us can play a role in finding a cure. We can walk to raise money. We can visit people in Alzheimer’s disease homes and read to them, play music for them, or just visit. Of course, it’s hard to say what’s going on in the mind of someone with Alzheimer’s disease. But we all know what’s going on in our own hearts when we feel loved. It feels good. Letting people with Alzheimer’s disease know they’re still loved might not bring back all the memories they once had—but I know in my own heart it can bring them the comfort of remembered love.

When HBO producers John Hoffman and Susan Froemke came to us at the National Institute on Aging about contributing our scientific expertise to a large-scale public health outreach project on Alzheimer’s disease, we gave a great deal of thought to how to approach it. We are working very hard on the prevention and treatment of Alzheimer’s disease and have made enormous strides in understanding its origins and developing potential routes for prevention and therapy. However, research has yet to achieve success, as defined by the ability to prevent Alzheimer’s disease or, if it develops, to slow its progression. Although the research challenge remains significant, there is a very important, informative, and compelling story to tell—about the dedication of all the scientists and families who are on the front lines of the fight against Alzheimer’s disease and the progress we are making, and will make, together. It is, in a word, a story of hope.
In the three decades since the scientific study of Alzheimer’s disease began in earnest, an increasingly productive research program has been established. It approaches the study of age-related cognitive change and dementia on several different fronts—the basic biology of the disease, genetic and non-genetic influences, drug development and clinical aspects, and approaches to caregiving. Today, innovative technologies in imaging and genetics in particular are allowing exploration in ways we never imagined before. And we have a well-developed infrastructure of academic research centers and consortia to carry out this critical work. What we’ve learned is generating new excitement about the potential for intervening and making a difference in the disease.
Our efforts come none too soon. The world’s population is aging at an accelerating rate, a critical trend because aging is the best established risk factor for Alzheimer’s disease. Studies indicate that the probability of developing the disease doubles every five years after age sixty-five. Among people age eighty-five and older, as many as half may suffer from Alzheimer’s disease. The baby boomers, the first of whom reaches that milestone sixty-fifth birthday in 2011, will soon be entering the ages of increasing risk. In sheer numbers, the statistics are daunting. In 2000, thirty-five million people were older than sixty-five. By 2050, according to one census estimate, the number of older people will double, led by growth in the numbers of people age eighty-five and older, those at most risk for Alzheimer’s disease.
These demographics press the urgency to address Alzheimer’s disease. The first concern is the human toll for the greater number of people who will develop the disease and, with it, an increase in the ranks of caregivers. Add the financial and broader societal burden, and the costs will simply be unsustainable if we fail over the next twenty years to reduce the risk to older people. In dollar terms, it is estimated that the direct and indirect costs of Alzheimer’s disease in the United States today are at least one hundred billion dollars annually, including medical care, caregiving, and lost productivity.
We cannot predict exactly how and when we will turn the corner to find a truly effective intervention against Alzheimer’s disease. But I can report that enormous progress in understanding the disease is leading to development of experimental drugs and to clinical testing of a number of compounds. We have learned much about the complexity of factors involved in Alzheimer’s disease. But there is also new thinking about how to address the combination of genetic and environmental influences that may put us at risk or, conversely, might protect us from developing dementia.
One of the most rapidly moving areas of research is genetics, examining the most basic influences on our health. Our genes direct the production of proteins that make up body structures like organs and tissue, as well as controlling chemical reactions and carrying on signaling between cells. A first step in determining the start of any disease process is pinpointing relevant genes and genetic mutations.
Over the past few decades, we have discovered some of the genetic clues to Alzheimer’s disease. Three genetic mutations are responsible for causing a very rare, early-onset form of the disease, which accounts mostly for cases that occur under age sixty. For late-onset disease, in those aged sixty-five and older, which affects the vast majority of people with Alzheimer’s disease, the genetic picture is much less clear. In these cases, genes may increase the risk of Alzheimer’s disease, but no single gene has been shown to directly cause disease. One gene, apolipoprotein E (ApoE), is such a risk factor for late-onset Alzheimer’s disease, with one form of the gene appearing more often in people with Alzheimer’s disease than in those without. It is likely that other genes are in this class of risk factors.
Today, a major search effort is under way to find additional genetic associations for Alzheimer’s disease. To do so, scientists must compare data from thousands of people who have the disease with data from people who do not have it, to see whether there are particular genetic correlations. To expand and accelerate discovery, the National Institute on Aging launched the Alzheimer’s Disease Genetics Initiative, which brings together investigators at multiple centers to conduct highly sophisticated genetic analyses on at least one thousand families. In 2008, the Alzheimer’s Disease Genetics Consortium was established to take advantage of new technologies for genome-wide association studies. That effort involves rapidly scanning markers across the complete sets of DNA, or genomes, of many people to find genetic variations associated with the disease. Data from both of these projects will be shared with qualified investigators for further analysis. The discoveries from these initiatives should provide important clues to the Alzheimer’s disease process and, ultimately, reveal potential targets for drugs and other interventions.
Armed with knowledge of basic disease processes already gained from genetic insights and the study of factors like protein conformation, inflammation, and oxidative stress, we know about important fundamentals of the Alzheimer’s disease process and how it damages and ultimately destroys brain cells and communications. We have aimed our sights squarely at one of the best-developed areas of research thus far, the formation of the beta-amyloid plaques characteristic of Alzheimer’s disease, which are formed by fragments of a larger protein found in brain cells and which interfere with how neurons talk to one another. We have also discovered that the tangles in the brains of people with Alzheimer’s disease, the second hallmark pathology of the disease, are made up of the protein tau, whose normal role in supporting cell structures is compromised.
As we peer deeper at the molecular and cellular level, what other factors could influence our chances of getting Alzheimer’s disease? A great deal of evidence from large-scale epidemiological studies suggests that the factors affecting heart health, such as blood pressure, cholesterol, and blood glucose, may overlap with the risk and protective factors for brain health and function. These include observations that link exercise, maintaining a healthy weight, and controlling blood pressure in midlife to a lower risk of developing Alzheimer’s disease later in life. Studies in animal models also associate exercise and healthy diet with reduced risk of cognitive decline. Additional clinical trials of these interventions are being conducted in humans to determine definitively whether they reduce the risk of cognitive decline. But they are clearly important for controlling cardiovascular disease and diabetes, and so we recommend healthy lifestyle factors for both their known and potential benefits.
This productive portfolio of basic, epidemiological, animal, and clinical research has led to the development and testing of a number of potential interventions to prevent or delay the onset of Alzheimer’s disease or slow its progression. The institute is also building a robust translational research program that supports the discovery and development of new treatments for Alzheimer’s disease to the stage where they can be tested in clinical trials supported by the government or private sector. It is estimated that there are ninety-one new drugs in clinical trials. Overall, more than two hundred clinical trials of interventions are under way, including the testing of new drugs, natural products, and lifestyle interventions such as exercise. These studies involve thousands of individuals across the United States and are supported by both the public and the private sector.
Research in caregiving is finding better ways to manage care at home and in an institutional setting. This is a vital area of study for families now coping with the disease. Pilot testing is being done to see how the innovative REACH (Resources for Improving Alzheimer’s Caregiver Health) program of successful interventions for caregivers might be adopted more widely. The effort involves over a dozen Department of Veterans Affairs programs around the United States (REACH-VA) and several statewide programs funded by the Administration on Aging.
Our progress so far—and prospects for the future—depends in important ways on coordination and collaboration among the research community, with the private sector, and across the government. The network of twenty-nine Alzheimer’s Disease Research Centers supported by the National Institute on Aging undertake basic and clinical research as well as training, education, and the dissemination of technology, with a key function being the coordination of studies and sharing of data. The institute also manages the nation’s foremost clinical trials network in this area, the Alzheimer’s Disease Cooperative Study.
We recognize the importance of collaboration between the public and the private sector to advance research and knowledge. A model partnership is the Alzheimer’s Disease Neuroimaging Initiative. This sixty-million-dollar multi-year project includes the government, academia, the Alzheimer’s Association and Institute for the Study of Aging, and a number of pharmaceutical and imaging companies. It is designed to demonstrate how brain imaging techniques and biomarkers in blood and cerebrospinal fluid may be able to signal Alzheimer’s disease before clinical symptoms appear. That would help detect the disease at its earliest stages, track progression, and monitor the effect of interventions. What we learn will enable us to conduct clinical trials more quickly and efficiently. Already, preliminary findings from this and other studies suggest that we can “see” Alzheimer’s disease plaques in the living brain and that there may be markers for Alzheimer’s disease, in the same way that cholesterol signals cardiovascular disease.
It is in the spirit of such collaborations that we at the National Institute on Aging accepted HBO’s invitation to provide scientific input and technical guidance for The Alzheimer’s Project. As part of the National Institutes of Health at the U.S. Department of Health and Human Services, the institute has the leading responsibility in the United States government for research in Alzheimer’s disease. Along with our sister NIH institutes and centers and other federal agencies, including the Administration on Aging, with its interest in caregiver research and support, and the Food and Drug Administration, which evaluates the safety and efficacy of new drugs and devices used in diagnosis and treatment, we are the taxpayers’ primary investment in Alzheimer’s disease programs. As such, it is the National Institute on Aging’s mission, in addition to research, to report on research progress and to promote understanding of science and health with respect to aging and Alzheimer’s disease.
I am pleased that we have been able to work with the Alzheimer’s Association, Fidelity Charitable Gift Fund, and the Geoffrey Beene Gives Back Alzheimer’s Initiative, in collaboration with HBO’s Sheila Nevins and John Hoffman, and with Executive Producer Maria Shriver, to provide a front-row seat at the laboratory bench. We dedicate our efforts to the millions of people touched by Alzheimer’s disease—those supporting research, those participating in studies, and, especially, those with Alzheimer’s disease and their families and friends.
Director, National Institute on Aging
National Institutes of Health
U.S. Department of Health and Human Services

Through the experience of producing The Alzheimer’s Project: Momentum in Science, I lost my fear of developing the disease.
This was not the first time I was confronted with the prospect of producing a campaign on Alzheimer’s disease. Ten years ago my father, Emanuel Hoffman, died of the disease at the age of eighty. Manny was a newspaper journalist and editor and his decline into dementia was long and slow. My father’s illness frightened me as much it saddened me. Would I share his fate? Was his father’s, my grandfather’s, senility just another word for the same condition? A short while after his death, Sheila Nevins, the president of HBO Documentary Films, asked if I thought the time was right to do a film on Alzheimer’s disease. My gut reaction was to say no. I had a difficult time considering the notion of spending two years immersed in the disease that destroyed my father. The truth was, I was terribly reluctant to learn more about it. Over the course of my father’s illness and well beyond his death, I was filled, right or wrong, by a pervasive sense of hopelessness about Alzheimer’s disease.
Two years ago, I was forced to confront my fears of Alzheimer’s again after HBO premiered The Addiction Project, and we began our search for the next public health campaign for HBO to produce. The Addiction Project was a considerable HBO-National Institutes of Health effort to educate the American public about advances in the understanding of addiction as a treatable brain disease. We conveyed life-changing information to more than fifty million Americans via a wide array of media platforms. With this success, Sheila Nevins asked me and Susan Froemke (my producing partner) to return to the NIH. As a pay cable network, HBO has an invitation into thirty million homes and, when all cable households are invited to watch certain events for free, that audience grows to as many as one hundred million homes. It’s important to recognize Sheila’s and HBO’s belief that such reach must sometimes be used for public health purposes. After The Addiction Project, Susan’s and my task was to explore other ways we could combine the medical and scientific expertise of the National Institutes of Health with the scope and excellence of HBO programming. The goal was to find a medical problem affecting millions of Americans for which science had made great advances of which the public was unaware. Where had the National Institutes of Health and the research community found hope for solving a disease where little hope was perceived? The resounding answer was Alzheimer’s disease.
How was it that such advances in Alzheimer’s research had escaped me? I read the Science Times avidly, I listen to NPR, I make science films! I had gradually taken my head out of the sand about this disease, yet I believed incorrectly that Alzheimer’s disease research was still in its infancy, that the biggest controversy in the field revolved around the risks of cooking in aluminum pots (a long-disproved theory), and that the most I could do to minimize my chance of getting the disease was to solve crossword puzzles—which I do anyway.
I now know that I was not alone in my anxiety about developing Alzheimer’s disease. According to a recent study, it is the second most feared illness among the general U.S. population, and it is the most feared illness among women. The baby boomers are seeing nearly 50 percent of their parents’ generation struggle with Alzheimer’s disease by the time they reach eighty-five, and in 2011 the first boomers will themselves reach retirement age, setting off a precipitous rise in the incidence of the disease, which already affects as many as five million Americans.
Through our collaboration with the National Institute on Aging (NIA) of the National Institutes of Health and the Alzheimer’s Association, we achieved a remarkable level of access to the scientific community. The National Institutes of Health spend about half a billion dollars on Alzheimer’s disease research each year, funding the work of the nation’s greatest minds, who are applying their brilliance toward unraveling the genetics, neuroscience, pathology, prevention, and treatment of Alzheimer’s disease. While the Alzheimer’s Association has a smaller research funding profile, they do publish the definitive research journal Alzheimer’s & Dementia and host the International Conference on Alzheimer’s Disease. The seventy-two chapters of the Alzheimer’s Association are the support lifeline for people with the disease and their families. Susan Froemke and I, along with our pair of dedicated young associate producers, Matt Heineman and Ali Moss, could not have become educated students of Alzheimer’s disease without the support of these two organizations. And, of course, The Alzheimer’s Project could not have grown to the level we’ve achieved without the support of the Geoffrey Beene Gives Back Alzheimer’s Initiative and the Fidelity Charitable Gift Fund.
The chill I still felt at the mention of Alzheimer’s disease began to dissipate in the spring of 2007 with our immersion in the science of Alzheimer’s disease. We studied hundreds of research papers, journal articles, and, in particular, the National Institute on Aging’s annual Progress Reports. We carefully examined twenty hours of taped presentations by a select gathering of scientists in Tübingen, Germany, recognizing the one hundredth anniversary of Dr. Alois Alzheimer’s historic discovery of plaques and tangles in the brain of a deceased fifty-six-year-old demented patient, Auguste D. Each scientist at that gathering had made one or more historic discoveries in Alzheimer’s disease research. Frankly, with all this new information, I was amazed to find myself swimming in a calming pool of scientific discovery and optimism.
Throughout the rest of 2007, with the encouragement and tutelage of the expert staff of the National Institute on Aging’s Division of Neuroscience, under the guidance of Marcelle Morrison-Bogorad, PhD, and the Alzheimer’s Association’s highly respected chief medical and scientific officer, William Thies, PhD, our small team spoke with more than two hundred of the most active and cutting-edge American scientists and physicians working on this problem. We acknowledge with gratitude the spirit of generosity and enthusiasm of all those who helped educate us. Time and time again this research community reinforced our belief that now was the right time to inform the public about progress being made in Alzheimer’s disease research. We learned about the research being conducted in multiple areas of basic science, drug development, and, to our surprise, lifestyle factors such as diet, exercise, and education that might mitigate the expression of the disease or delay its onset.
The scientists featured in the resulting documentary film, Momentum in Science, along with their discoveries and their present-day investigations, represent a near-complete portrait of the state of Alzheimer’s disease research. Out of this film and all our research has come this book. Like the film, the book captures the excitement among scientists today, and explains their work in ways that we hope are easy to understand. We have placed the scientific discoveries in the broader context of the research field, highlighting what’s most important and showing how it all fits together.
Part I of the book describes amazing breakthroughs in the basic science of Alzheimer’s disease. Part II shows how new imaging technologies are making discoveries possible. Part III explores possible pathways to the disease, reflecting the new thinking that Alzheimer’s disease is a disease of the whole body, not just the brain. Finally, Part IV looks at current work related to changing the disease process, including cutting-edge research on cognitive reserve and lifestyle factors, as well as the development of new drugs.
Working on the film and book has completely transformed the way I think about Alzheimer’s disease. In the past, I had always assumed that my risk was very high because my father had the disease. In the course of this project, however, I learned that, while the general population has a 10 percent chance of developing Alzheimer’s disease by age eighty-five, my father’s illness increases my risk to 20 percent. Optimist that I am, I consider it that I have an 80 percent chance of not developing Alzheimer’s. I find further comfort in the new term “susceptibility genes” to describe the role genetics plays in personal risk. Late-onset Alzheimer’s accounts for 97 percent of cases and is not completely determined by inheritance. Rather, a number of small genetic variations are believed to contribute to late-onset risk. Susceptibility, not inevitability. A vibrant worldwide race is under way to identify these susceptibility genes.


On Sale
May 12, 2009
Page Count
224 pages

John Hoffman

About the Author

In addition to producing The Alzheimer’s Project, John Hoffman and Susan Froemke produced the 2007 Emmy® Governors Award- winning documentary series Addiction. Hoffman, vice president of HBO Documentary Films, has spent the past thirteen years creating, producing, and supervising documentary programming for HBO. Froemke has more than twenty-nine nonfiction films to her credit, including the 1976 classic Grey Gardens.

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