The Alzheimer's Action Plan: A Book Review and Interview
If you just found out that your mother has Alzheimer disease, what information would you want? This is the perspective that physician-researcher P. Murali Doraiswamy and social worker Lisa Gwyther, both at Duke University Medical Center in Durham, North Carolina, took in compiling an authoritative guidebook with science writer Tina Adler.
Called The Alzheimer's Action Plan, the book offers cutting-edge information about diagnosis, care, and clinical trials. Despite its imposing length of almost 500 pages, the book is organized into a bite-sized format; bullet points, boxes, and checklists make the information readily accessible.
This book is one of the first to address people with memory diseases and their families dealing with early stages of the disease, as well as people with impaired cognition who worry about having early-stage Alzheimer's. The book does not address late-stage disease; the authors feel that this topic is covered in other books, such as The 36-Hour Day by Nancy Mace and Peter Rabins.
The authors aspire to give readers the tools to take charge of their diagnosis and medical treatment, to continue living with their loved ones at the highest possible level of social and emotional functioning, to understand clinical research, to enroll in a clinical trial if they wish, and to understand what to expect and how to prepare.
With its broad scope, the book offers an interdisciplinary overview of medical, scientific, psychological, and personal perspectives on AD. To this reviewer, reading this book felt like having a best friend who works in the field of Alzheimer's and gives insider information about navigating the medical system.
ARF: What inspired you to write this book?
MD: I see a change happening in the field. We traditionally think of Alzheimer's as a disease of old people, that is, people being diagnosed in their late seventies, eighties. A lot of these people got diagnosed at very advanced stages. The majority of individuals today are still in this age group, but over the last decade there has been a big shift, an increasing emphasis on early recognition and early diagnosis. The availability of four newer FDA-approved treatments combined with increased advocacy efforts and a steady stream of new clinical trials and new diagnostic tests has contributed to this change. The kinds of people who are being diagnosed now are younger and younger. Plus, you're likely to get people being diagnosed more at the very early stages when they are still highly functional; many of them either still work or, even if they are retired, are leading very active lives. Their attitudes are different from those of the previous generation of patients. They want much more of a say in how their illness is managed, such as in choosing treatments, or whether they want to take part in a trial. They are more likely to go to the Internet and research their options to do everything possible to maintain their brain health. Even the term "caregiver" is really not applicable to individuals at early stages, so their social support needs are also different.
I felt that there was a need for a very high-quality informational resource for such individuals and their families. Our book is targeted at three specific groups: 1) people with early signs of memory problems and their families, who are wondering if this could be Alzheimer's and if so, what to do about it, 2) adult children or the spouse of someone who has been diagnosed with Alzheimer's and seeks the highest level of care, and 3) anyone wanting credible information on prevention.
LG: We believe there is a need to address individuals living with this problem in a way that offers them consumer-specific information that isn't available in the general literature. We are aware that many people do not understand the reasoning behind the need to identify this problem early. We observed that in hindsight families said 'oh I only wish I knew then what I know now.' It seemed to us that reaching families at earlier points in the disease process could insure decision-making, would have the greatest impact. Families can benefit most from clear and complete information when subtle and confusing changes in the individual are becoming worrisome to the person and/or family. This is the time when families are most confused and in disagreement, hence when the book could make a real difference in individual and family outcomes. Is this a disease or is this normal aging? Will it stay the same or get worse? Why is she doing this but not that? The focus needed to change also because we are unsuccessful in encouraging research participation at the stage where we can learn the most about how to detect, delay, and/or modify the disease process.
A primary impetus for the book was the opportunity to combine the evidence-based biomedical information with the psychosocial and non-pharmacologic information. We offer a physician/social worker collaboration resulting in a common story and a common list of recommendations that made sense from a medical and quality-of-life standpoint. Families complain that doctors and social workers don't take a stand. No one will say: 'Based on the available evidence, our clinical experience, and your current concerns, we recommend this at this point in our knowledge base.'
ARF: You talked about dealing earlier in the disease process. What was lacking specifically?
LG: Help in getting people to the point of seeking a thorough diagnosis and treatment. Families were telling us, 'I see it, no one else sees it, my dad thinks it is just aging, my brother thinks it's a marital communication problem, my sister thinks it's job stress or menopause gone wild.' Families were asking, 'Based on the testing and examination of my mother right now, what can you tell us to expect next or down the road? That's what people need for planning and for daily living modifications, and that's what was missing.
ARF: Is it a matter of motivation?
LG: It's not just that—people are motivated to solve immediate problems in their daily lives. One issue is how to help someone who is scared or reluctant or in denial to find a responsive medical professional and a socially supportive community system. Once a person and his/her family are at the clinic or physician's office, they want to know what to ask, what are reasonable expectations of the physician or clinic, and how to apply what they learn during a diagnostic or treatment visit in their daily lives and in planning.
They must be told that this is a complex disease. People respond differently based on what else is going on in their lives and what other chronic illnesses they have simultaneously. They must be told that there is no simple or linear system of care; they must advocate for themselves within fragmented or no-care systems. Finally, they must be told that there is sufficient information from population and clinical studies, that we can tell them which issues are likely to be important for them as individuals and families.
ARF: What is contributing to earlier diagnosis?
MD: Increased awareness, a lot of public campaigns, media, a lot more education. Anytime you have an FDA-approved treatment it gives people incentive to go out and get tested. Also we are an aging society and age is the biggest risk for Alzheimer's. The Alzheimer's Association estimates that 10 million boomers may be at risk over the coming decades. So naturally, as a society we are all more conscious of it.
But it's important to ensure that early diagnosis is accompanied by preservation of high quality of life. Society needs to put in the resources to make sure our ability to diagnose early is matched by our ability to halt or prevent disease. That is why early diagnosis has been effective in prostate cancer or breast cancer. So we need to resist inappropriate stigmatization of normal aging and encourage people to maintain their brain health. Our book has several sections on coping with early diagnosis as well as things we all can do to keep our brains healthy.
ARF: The book struck me as being an insider's view.
MD: Yes. I really wanted to do a book that if a beloved family member had Alzheimer's and I wanted to provide the highest level of care, and I knew every secret in the medical system that there was, that I could leverage all that to access the best possible resources, the latest drugs, the experimental drugs that you only get via trials, how to find the best specialist, how to protect yourself in clinical trials, how to avoid the common mistakes that inexperienced doctors make, where to get the latest tests. This can be daunting for an average family.
I gained my insights from having conducted dozens of clinical trials and having been an advisor to many diagnostic and drug companies as well as consumer advocacy groups. The idea for the book arose after I did a series of public lectures, or town hall meetings, in 2006 and compiled the several hundred most common questions people always asked me, and their frustrations. It's sad to see even a single missed opportunity to help someone. That's also why I wanted Lisa to be my coauthor since she is one the world's top experts in family support issues, a huge part of helping families dealing with Alzheimer's. We packed our book with hundreds of practical tips and insider insights to guide families through every step.
ARF: Does the book help people assess clinical trials?
MD: Yes. I wanted to make this book the single best one-stop resource for families on clinical trials. In addition, our book has information on all FDA-approved therapies, as well as dozens of medications used to treat changes in mood, sleep, anxiety, and it covers common supplements and herbal remedies.
It also tells people how to spot something that's too good to be true. It tells people how to increase their chances of getting into a clinical trial, how to pick a trial, how to read between the lines of the clinical trial documents they have to sign, and how to tell a bad research center from a good one. We even have a section on how to detect fraud, which is not much talked about at all. It's really important for people to consider clinical trials, because if no one signed up today we would have no new drugs tomorrow.
In the sections on the approved Alzheimer drugs (such as cholinesterase inhibitors and memantine), as well as drugs to treat behavior problems (such as antidepressants or sleeping pills), we give not only lots of new information but also the pro and con viewpoints. We really want to present all sides of the equation. But at the end of the day we can't just have a consumer book that's completely theoretical. Families want to know what I would do if they saw me in my office, so I also give some favorites and drugs that are not as much my favorites.
ARF: How do you feel about the promise of new treatments?
MD: I am definitely an optimist, but one needs to separate the hype from reality. The book discusses the most promising drugs in late-stage trials. Dimebon is a drug that is most advanced in clinical trials, and if all goes well in its next trial, it might come to market as the next new treatment in two years. Unfortunately every new press release of preliminary findings creates high expectations in families who don't realize that most drugs in clinical trials will fail. Also, side effects get buried in the hype. Expectations are also unrealistic for existing drugs, since people often hope the drugs will produce a cure. Everyone wants a magic bullet, so it's human nature to emphasize the positive side and somewhat overlook the negative side. Plus, with the Internet it is easy for consumers to be misled given the hundreds of memory cures being touted.
So a major emphasis throughout The Alzheimer's Action Plan is to offer hope and credible information but also to help consumers separate hype from reality. I do feel that realistic optimism is a good thing for families. The combination of family support and biologic therapy is unbeatable. Longevity studies suggest that people who are optimistic are more likely to live longer and have better quality of life.
ARF: What do you think is most promising?
MD: The most promising thing is that with a growing pace of research we are coming up with so many new targets. Drug development for this condition has dramatically changed with increasing use of biomarkers, such as spinal fluid assays or brain scans, to help determine efficacy. Both neurotransmitter approaches as well as approaches targeting pathology (plaques, tangles, nerve cell viability) are equally promising, since we will probably use combinations of drugs in the future to both improve symptoms and slow progression.
think we are at a point where we are getting very close to determining the true role of β amyloid plaques in Alzheimer's. That's a very important thing we have to do, because for many years this has been a leading theory. A critical test of the hypothesis will come if we can target the plaque with different drugs acting via three or four different mechanisms. If they work, that will be a giant step forward. And if none of those drugs succeed clinically, i.e., make people better, despite clearing plaques, then we're going to have to step back and revisit this theory. The research field remains excited about anti-amyloid therapy, but expectations are a bit more realistic and even the hypothesis is already evolving. We are sensing that once a lot of plaques have accumulated in the brain, maybe it is too late for an anti-plaque immunization therapy to be effective. Maybe we will need to try these therapies in very early stages of the disease. Also, we now know that amyloid has a relatively rapid turnover in the brain, which has implications for how often one needs to give a drug to inhibit its production.
Moving away from amyloid, there are at least a dozen other promising drugs, including some targeting tangles and nerve growth factor receptors. The hope is that it would be great if we could get an anti-tangle drug and an anti-amyloid drug and we could combine the two, and for the first time we would be able to target the two pathological processes that occur in Alzheimer's. As with any experimental drug, each of these agents also needs to undergo safety testing. Our book guides consumers through each of these.
ARF: What phase are they in?
MD: Dimebon is in Phase 3; they've got a successful Phase 2 trial. It acts on the mitochondrial level as well as on neurotransmitters. That could be the next new drug that would come to market if all goes well in their next trial. [Editor's note: see ARF related news story.]
ARF: How have the anti-tau drugs done?
MD: There's one called Rember given orally already in human trials [see ARF related conference story], as well as a second one given intranasally. Immunologic therapies are still in early stages of development. I looked at the trial data for Rember. Rember is an old antibiotic that's been reformulated. In laboratory studies they found that it has effects against tangles. The preclinical science seems strong. They have gone as far as conducting a Phase 2 clinical trial in London and Asia. They've shown that it might have some cognitive benefits on some measures, even though it wasn't a consistent effect seen across all cognitive tests. They are in the stage where they are considering initiating Phase 3 trials. So I am cautiously optimistic, though I have yet to vet the full package.
ARF: Thank you for this interview.
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