The biomarker revolution has changed the way people view Alzheimer’s disease – and that has its drawbacks, says Jason Karlawish, MD, co-director of the Penn Memory Center at the University of Pennsylvania in Philadelphia.
“In a fairly short amount of time, we’ve gotten a revolutionary redefinition of what we’re talking about when we talk about Alzheimer’s,” said Karlawish in an interview with MedPage Today. “This is really made possible by two events: one is the discovery of biomarkers and the other is the discovery of the idea of mild cognitive impairment.”
In the field of Alzheimer’s disease, science often clashes with politics. Battle lines are drawn about cure versus care. More than six million Americans are living with Alzheimer’s disease, and many more provide unpaid care to patients. And decades after scientists first realized they could clear the brain of amyloid plaques – a hallmark of the disease, along with tau tangles – people with Alzheimer’s don’t have effective treatments.
This is the background for Karlawish’s new book, The Alzheimer’s Problem: How Science, Culture, and Politics Turned a Rare Disease into Crisis and What We Can Do About It MedPage today Senior writer Judy George spoke with Karlawish to learn more about the complexities of Alzheimer’s in today’s society.
George: Let’s start with the biomarker revolution. We can now visualize amyloid and tau in human brains, and blood tests for Alzheimer’s disease are on the way.
Karlawish: When I started, patients had to have dementia to be diagnosed with Alzheimer’s. It was kind of a gothic horror story; I couldn’t tell you what was wrong with you until you died and until then it was at most a probable diagnosis.
Biomarkers have made the invisible visible. But the biomarker revolution will not be without its challenges. One of these is to push the diagnosis of Alzheimer’s disease to a milder and milder and even unaffected state of being – persons who are not or at most mildly cognitively impaired.
This certainly offers opportunities for early diagnosis and treatment. But it presents people with real challenges in terms of their identity, autonomy and threats that stem from stigmatization and the need for monitoring and thus invasion of their privacy.
George: What kind of stigma?
Karlawish: There are three types of stigma in Alzheimer’s disease. There is a self-stigma – the stigma a person feels when they can’t do things. There is a public stigma – the world around them thinks less about them. And there is a stigma that people can feel about the patient or family members, distancing themselves from others.
I am quoting a story in the book about Ronald Reagan. His ambassador to the White House and the United Kingdom, Walter Annenberg, said he preferred to remember Reagan as a powerful guy. He didn’t want to see him with Alzheimer’s because he was just “out”. He actually said, “I’m staying away from Ronald Reagan, I’m getting away from him,” which meant he was also distancing myself from Nancy Reagan, I suppose. To me that is a very poignant example of stigma.
The ground zero of stigma expression in Alzheimer’s is what I call the ‘z’ word – namely, that we cultivate this rhetoric of death before death or the living dead, that humans become zombies.
George: You have said that the Alzheimer’s field has a “strange pit between care and cure.” How did this come about?
Karlawish: It has been wrapped up in a number of events. The Alzheimer’s field struggled to gain legitimacy, and focusing on topics other than “let’s see how to diagnose and cure this disease” was seen as a distraction from that mission.
When the Alzheimer’s Association was founded in 1980, there was no discussion that cancer was a disease; cancer has been recognized for centuries. There was no discussion that cardiovascular disease was a disease. Still, in 1980 there was immense ignorance about the legitimacy of Alzheimer’s disease.
We support research to find a cure, but we disagree on how to care for people with Alzheimer’s. Concern has become embroiled in controversial political debates over the role of the state for long-term care and support, and ideological struggles over the role of the family.
In the 1990s, one party in America said absolutely no tax increases, no expansion of federal programs beyond defense and some related matters, and had deep skepticism about feminism and the creation of equal opportunities for women. While none of those views were formulated to specifically harm or otherwise hurt individuals with dementia or their caregivers, they did so because they thwart a coherent national conversation about how we should deliver care.
You need to build infrastructure for care – for long-term services and support, not just diagnosis and treatment. I see it as a basic infrastructure that enables the American family to function, such as roads and traffic lights: we don’t ask for what we need.
George: The FDA will soon decide the fate of aducanumab. What can we expect from drugs such as aducanumab?
Karlawish: Aducanumab is part of the amyloid story, which is interesting. At the turn of the century, studies first appeared using a very new method that removed transgenic mice from amyloid. Researchers thought they might have to find a new job because Alzheimer’s disease would be resolved.
Well, here we are 21 years later and it hasn’t resolved, and at best we have a treatment that’s controversial. Even the most optimistic view of aducanumab is that the drug has some effect on slowing the rate of progression.
A word whispered at meetings is “heterogeneity” – that we should think of this not so much as Alzheimer’s, but as Alzheimer’s. diseasesI think a very plausible future is that there will be drug forms, not so drug forms and potentially untreatable forms of Alzheimer’s. The stories of multiple sclerosis tell us that; the stories of many cancers tell us that.
The implication is that we really need to think about how we will live with this disease. We are not going to drug ourselves out of the problem. Banking on a cure for all causes of debilitating cognitive impairment later in life is like planning your retirement with lottery tickets: You can win and win big, but chances are you won’t.
George: Given the many dimensions of Alzheimer’s, what should we pay attention to now?
Karlawish: We are beginning to see a tremendous irony in the field of Alzheimer’s disease. The reason Alzheimer’s is a disease is because of its relentless attack on our autonomy and self-determination. Alzheimer’s disease prevents people from living their lives the way they want to live. That’s what makes it a disease, complete, complete – along with amyloid, tau, and neurodegeneration.
The irony is that biomarker transformation threatens the same autonomy we try to preserve. We can tackle those threats, but for that we have to organize ourselves as a society.
Our approach to coping with this disease should emphasize helping people living with it maintain their autonomy and identity, even when cognitive impairment is hampered.
That must be the way we shape our strategy as a country in terms of the support we provide to people, the way we talk about the disease and the language and images we use.