The biomarker revolution has changed the way people look at Alzheimer’s disease — and that has its downsides, says Jason Karlawish, MD, co-director of the Penn Memory Center at the University of Pennsylvania in Philadelphia.
“Over a fairly short period of time, we’ve had a revolutionary redefinition about what we talk about when we talk about Alzheimer’s,” Karlawish said 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 collides with politics. Battle lines are drawn over cure versus care. More than six million Americans live with Alzheimer’s, and many more provide unpaid care for 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 have no effective treatments.
This is the backdrop for Karlawish’s new book, The Problem of Alzheimer’s: How Science, Culture, and Politics Turned a Rare Disease Into a Crisis and What We Can Do About It. MedPage Today senior staff writer Judy George spoke with Karlawish to learn more about the complexity of Alzheimer’s disease in today’s society.
George: Let’s start with the biomarker revolution. We now can image amyloid and tau in people’s brains, and blood tests for Alzheimer’s are on the horizon.
Karlawish: When I started out, patients had to have dementia to be diagnosed with Alzheimer’s. It was a sort of 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 what was invisible visible. But the biomarker revolution will not be without challenges. One is the pushing of the Alzheimer’s diagnosis into milder and milder and even unimpaired states of being — persons who are not impaired, or at most are mildly cognitively impaired.
This certainly creates opportunities for early diagnosis and treatment. But it presents real challenges to people in terms of their identity, autonomy, and threats that come from stigma and the need for monitoring and therefore intrusion into their privacy.
George: What kind of stigma?
Karlawish: There are three kinds of stigma with Alzheimer’s disease. There’s self stigma — the stigma an individual feels when they can’t do things. There’s public stigma — the world around them thinks less of them. And there’s stigma that people around the patient or family members may feel, a distancing from others.
I cite a story in the book about Ronald Reagan. His ambassador to the White House and the U.K., Walter Annenberg, was quoted as saying that he preferred to remember Reagan as a vigorous fellow. He didn’t want to see him with Alzheimer’s because he was just “out of it.” He was essentially saying, “I’m staying away from Ronald Reagan, I’m distancing myself from him,” which meant he was distancing himself from Nancy Reagan as well, I assume. To me, that is a very poignant example of stigma.
The ground zero of stigma expression in Alzheimer’s disease is what I call the “z” word — namely, that we cultivate this rhetoric of death before death or the living dead, that people become zombies.
George: You’ve mentioned the Alzheimer’s field has an “odd pitting of care versus cure.” How did this emerge?
Karlawish: It’s wrapped up in a number of events. The Alzheimer’s field struggled to gain legitimacy, and focusing on topics other than “let’s figure out how to diagnose and cure this disease” was perceived as a distraction from that mission.
When the Alzheimer’s Association was founded in 1980, there was no debate that cancer was a disease; cancer had been recognized for centuries. There was no debate that cardiovascular disease was a disease. Yet in 1980, there was vast ignorance about the legitimacy of Alzheimer’s as a disease.
We support research to discover a cure, but we don’t agree on how to care for people with Alzheimer’s disease. Care has become caught up in contentious political debates around the role of the state for long-term care services and support and ideological battles about the role of the family.
In the 1990s, one party in America said absolutely no increases in taxes, no expansion of federal programs beyond defense and some related things, and had a deep skepticism about feminism and creating equal opportunity for women. While none of those positions were articulated to specifically harm or otherwise hurt persons living with dementia or their caregivers, they did just that because they thwarted a coherent national conversation about how we should provide care.
You have to build infrastructure for care — for long-term services and support, not just diagnosis and treatment. I consider it basic infrastructure that allows the American family to function, like roads and traffic lights: we don’t question those as being what we need.
George: The FDA will decide the fate of aducanumab soon. What can we expect from drugs like aducanumab?
Karlawish: Aducanumab is part of the story of amyloid, which is interesting. Right around the turn of the century, studies first appeared using a very novel method that cleared transgenic mice of amyloid. Researchers were thinking they might have to find a new line of work because Alzheimer’s would be solved.
Well, here we are 21 years later and it’s not solved, and at best we have a treatment that’s controversial. Even the most optimistic take on aducanumab is that the drug has some effect on slowing the rate of progression.
A word that’s whispered at meetings is “heterogeneity” — that we really should think of this not so much as Alzheimer’s disease, but Alzheimer’s diseases. I think a very plausible future is that there will be druggable forms, not so-druggable 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 we really need to think about how we’re going to live with this disease. We’re not going to drug our way out of the problem. Banking on a cure for all causes of late-life disabling cognitive impairments is like planning your retirement with lottery tickets: you may win and win big, but odds are you’re not going to.
George: Given Alzheimer’s many dimensions, what do we need to pay attention to next?
Karlawish: We’re beginning to face an enormous irony in the field of Alzheimer’s. The reason why Alzheimer’s is a disease is because of its relentless assault on our autonomy and self-determination. Alzheimer’s keeps people from living their life the way they want to live their life. That’s what makes it a disease, fully, completely — along with amyloid, tau, and neurodegeneration.
The irony is that the biomarker transformation poses threats to the very same autonomy we’re trying to preserve. We can address those threats, but we have to organize ourselves as a society to do that.
Our approach to dealing with this disease needs to emphasize helping persons living with it to maintain autonomy and identity, even in the face of disabling cognitive impairments.
That needs to be the way we frame our strategy as a country in terms of the support we provide people, the way we talk about the disease, and the language and images we use.