What We Talk About When We Talk About Alzheimer's Disease
By Jason Karlawish, MD, professor of medicine and medical ethics at the University of Pennsylvania, and recipient of a Robert Wood Johnson Foundation Investigator Award in Health Policy Research
Just one year after President Obama signed the National Alzheimer’s Project Act into law, the U.S. is beginning to talk about Alzheimer’s disease. With input from 23 federal departments and agencies, the Department of Health and Human Services has issued the nation’s first National Alzheimer’s Plan, and the President’s budget proposes to increase funding for Alzheimer’s research and care by at least $156 million.
Alzheimer’s disease is now a national problem that we will tackle guided by a plan with five goals. Goal #1 is ambitious—to prevent and treat Alzheimer’s by 2025. The other goals are far reaching. They include detailed proposals to change the delivery of health care for patients and families, evaluate new models of care and housing for people with Alzheimer’s, and to provide services for their caregivers’ health and well-being.
Health care reform is hotly contested, and may even be repealed, but so far, this disease specific expansion of federal interventions and spending has largely escaped the recurrent and bitter partisan disputes over the role of the federal government in solving the nation’s health care problems, and the size of the federal budget and its deficit.
Alzheimer’s may, like other diseases of aging, largely remain free of partisanship at least in part because America is aging. Studies show that the chief risk factor for developing Alzheimer’s is something we can little change: our age. Demography is destiny, and as the number of Americans over 65 steadily grows, so too will the number of Americans with Alzheimer’s.
National action is needed, but as the U.S. is about to dive into tackling the Alzheimer’s problem, it is worth considering a fundamental guide of ethics. Before you decide what to do about something, you have to know what it is, otherwise, your plan may fail. Alzheimer’s disease is called the most common cause of dementia. But what we talk about when we talk about Alzheimer’s disease is changing. How might this changing language impact the success or failure of our national plan?
A fundamental task of medicine is stratifying people into clinically meaningful categories. The term “stratifying” describes how physicians divide the sick from the well and then divide the sick into different stages of disease. In other words, the job of medicine is to put people into boxes. Doctors and policy-makers then decide how much time and attention they should devote to each box.
For much of the last half of the 20th century, brain aging fit into two big boxes: normal or demented. A person was either aging normally, or he had dementia. In much of the industrialized world, the cause of dementia was, and remains, Alzheimer’s disease. By the close of the 20th century however, brain researchers began to see that these two big boxes needed to be broken into smaller and smaller boxes. Their research had discovered a set of revolutionary results. Long before a person is demented, Alzheimer’s pathology is present; persons with mild but measurable deficits in short term memory are at heightened risk to develop dementia, and, most importantly, some cognitively normal persons have subtle changes in brain imaging that may predict future cognitive decline.
These results are changing how we talk about Alzheimer’s disease. What was once a disease we understood based on a history of declining cognition and function is becoming a problem foretold. The categories are collapsing. Older adults who were either normal or demented will occupy points along a continuum of the risk of future cognitive decline.
Alzheimer’s shares a theme with other diseases the exponentially expanding numbers of older adults face. They are about managing the risk of future problems such as a fractured hip, weakened heart, and soon, if the National Alzheimer’s Plan achieves its goals, memory loss.
Goal #1 – to prevent and treat Alzheimer’s by 2025—is necessary. It reflects how medicine is moving from the bedside of the suffering patient to the desktop of the person at risk of suffering. To achieve it, not only the Alzheimer’s community, but health care policy-makers should read the Institute of Medicine’s (IOM) short but provocative recently issued “Alzheimer’s Diagnostic Guideline Validation: Exploration of Next Steps.”
This summary of a workshop presented at a seminar held at the International Alzheimer’s meetings in Paris, France in July 2011 explores the two new diagnostic criteria for Alzheimer’s disease. One, from researchers in the U.S. under the auspices of the National Institute on Aging and the Alzheimer’s Association, breaks Alzheimer’s disease into three stages: dementia, mild cognitive impairment, and pre-clinical. The other, from a consortium of researchers in Europe, proposes much the same criteria. Common to both criteria is the assertion that Alzheimer’s disease is best thought of as a continuum of decline and that clinicians need new measures to fit people along this continuum. These new measures are standardized biological measures—typically, molecules such as genes, proteins, and drug metabolites—called “biomarkers.” They are the lingua franca of the emerging model of medicine called “personalized medicine.”
Alzheimer’s is a relatively late-comer to this new world order of biomarker driven medicine. In contrast, since the 1980’s, internal medicine has been using biomarkers to slice and dice its disease categories and thereby transform what was once normal aging into diseases in urgent need of diagnosis and treatment. The leader in the revolution has been cardiovascular disease.
It is fitting then that the crux of the IOM report is a talk by Dr. Robert Mahley from the San Francisco-based Gladstone Institute for Cardiovascular Disease and Neurological Disease. Mahley’s talk “Validating the new diagnostic guidelines: Lessons learned from cardiovascular disease and cholesterol” is a brief history of the cholesterol hypothesis. He describes the drug-powered looping effect between a biomarker (the LDL cholesterol) and a clinical outcome (a heart attack). Clinical trials involving hundreds of persons with high cholesterol showed that reducing the LDL level reduced the chance of a heart attack. Subsequent experiments pushed the levels lower and, in turn, further reduced the chance of a heart attack. The statistics are compelling. From 1980 to 2000, successive iterations of guidelines dropped the cutoffs for a normal LDL, and in that time, the death rate from coronary heart disease was reduced by nearly half.
One lesson the world of Alzheimer’s should take from the cholesterol history is that drugs and the biomarkers they manipulate are key actors. They redraw the border between normal and disease. They push a diagnosis into earlier and earlier stages, even pre-clinical stages. The cholesterol story is an example of what the physician and historian Jeremy Green has called “prescribing by numbers.” Signs and symptoms of heart disease no longer drive the prescription pad. Biomarkers do.
Progress in achieving Goal #1 of the National Alzheimer Plan—effective treatment by 2025—will reshape what we say when we talk about Alzheimer’s disease. Drugs and biomarkers won’t simply treat the disease. They will redefine it. Someday you will not have to be demented to be diagnosed with Alzheimer’s disease.
Another lesson of the cholesterol hypothesis is the value of a story that has both an obvious villain and a clear and coherent event to show when that villain has struck. LDL is the bad cholesterol and a heart attack is a vivid event that marks the fall from health to disease, or even death. When a researcher counts these heart attacks, she starts to transform a disease into a public health problem. She also has a clear way to talk about the benefits of experiments on patients that lower their cholesterol. Success is fewer heart attacks.
Alzheimer’s may someday have its villain—perhaps brain amyloid—but it lacks a clear and common dramatic event that can show how big the problem is and whether a drug has worked to reduce that problem.
The story of a patient with Alzheimer’s disease is not that his memory was fine in the morning and then, suddenly in the afternoon, it was lost. Instead, it is a long story of on-again, off-again, day-to-day sufferings. The vision statement of the National Plan opens with a quote from President Obama. “Alzheimer’s burdens an increasing number of our nation’s elders and their families.” Alzheimer’s disease is like Tolstoy’s proverbial unhappy family, “unhappy in its own way.”
Without a clear and coherent measure like a heart attack, the field of Alzheimer’s disease has a measurement problem. The brain is all around us—you are using yours to read this—but it is a tough organ to measure.
The field faces a challenge: how to tell patients, families and policy-makers a story that makes sense. Researchers will have to correlate change in a biomarker to change in measures of cognitive and functional decline. The size or worth of this correlation has to measure up against not only the risks of treatment but also its costs. Someone needs to decide how much change in what kinds of measures are worth patients taking a drug.
This decision gets complex. The label “Alzheimer’s disease” will soon capture a spectrum of disability—from disabled persons who require a caregiver, to persons with pre-clinical disease who are simply at risk of needing a caregiver. How big is the Alzheimer’s problem? The answer depends on how you count it. Alzheimer’s disease will become a problem of accounting.
It is the fifth goal of the National Plan where the federal government steps into this problem. Compared to the ambitious first goal—prevention by 2025—or the more basic and essential goals to optimize care quality, support patients and their families, and enhance public awareness, Goal #5 seems dull. “Goal 5: Improve data to track progress” proposes to expand and enhance data infrastructure and make data easily accessible to federal agencies and other researchers and to monitor progress of the National Plan. This could be called the scorekeeping goal.
It is all very well and good to gather data; a fair and public body needs to make decisions that use these data, decisions that will reshape what is Alzheimer’s. Patent protection means drugs and biomarkers are privately owned. Hence, private interests have a stake in what we talk about when we talk about Alzheimer’s disease. This together with the degradation of health care into a partisan slugfest means that the politics of what we say when we talk about Alzheimer’s are potentially huge.
Read a post Karlawish wrote for the RWJF Human Capital Blog about continuing to work after being diagnosed with dementia caused by Alzheimer’s disease.
Read his essay Desktop Medicine, published in the Journal of the American Medical Association (JAMA).