The biomarker revolution has changed the way people look at Alzheimer’s disease – and it has its drawbacks, says Jason Karlawish, MD, co-director of the Penn Memory Center at the University of Pennsylvania in Philadelphia.
“Over a relatively short period of time, we have had a revolutionary redefinition of 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 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 over healing versus care. More than six million Americans live with Alzheimer’s, and many more offer unpaid care to patients. And decades after scientists first realized they could clear the brain of amyloid plaques – a hallmark of the disease, coupled with a confusing pressure – people with Alzheimer’s have no effective treatment.
This is the background for Karlawish’s new book, The problem of Alzheimer’s: how science, culture and politics have turned a rare disease into a crisis and what can we do about it. MedPage Today senior author Judy George spoke to Karlawish to learn more about the complexities of Alzheimer’s disease in contemporary society.
George: Let’s start with the biomarker revolution. We can now see amyloid and tau in people’s brains, and blood tests for Alzheimer’s are imminent.
Karlawish: When I started, patients had to have dementia to be diagnosed with Alzheimer’s. It was a kind of Gothic horror story; I could not tell you what was wrong with you before you died, and until then it was at most a probable diagnosis.
Biomarkers made what was invisible visible. But the biomarker revolution will not be without challenges. One is pushing the Alzheimer’s diagnosis into lighter and lighter and even more unfavorable conditions of being – persons who are not disabled, or at most mildly cognitive.
It certainly creates opportunities for early diagnosis and treatment. But it presents real challenges for people in terms of their identity, autonomy and threats arising from stigma and the need for monitoring and thus the intrusion of their privacy.
George: What kind of stigma?
Karlawish: There are three types of stigma associated with Alzheimer’s disease. There is self-stigma – the stigma that an individual feels when they cannot do things. There is public stigma – the world around them thinks less about it. And there is stigma that people around the patient or family members may experience, a distance from others.
I mention 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 man. He did not want to see him with Alzheimer’s because he was just out of it. He essentially said, “I stay away from Ronald Reagan, I distance myself from him,” which means he also distances himself from Nancy Reagan, I suppose. To me, this 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 said that the Alzheimer’s field has a “strange pit of care versus healing”. How did it come about?
Karlawish: It has been featured in a number of occasions. The field of Alzheimer’s has struggled to gain legitimacy, and the focus on topics other than ‘let’s determine how to diagnose and cure this disease’ is seen as a distraction from the mission.
When the Alzheimer’s Association was founded in 1980, there was no debate that cancer was a disease; cancer has been recognized for centuries. There was no debate that cardiovascular disease was a disease. Yet in 1980 there was great ignorance about the legality of Alzheimer’s as a disease.
We support research to discover a cure, but we do not agree on caring for people with Alzheimer’s disease. Care has become entangled in controversial political debates over the role of the state in long-term care services and support and ideological battles over the role of the family.
In the 1990s, one party in America said absolutely no increases in taxes, no expansion of federal programs outside of defense and some related things, and had a deep skepticism about feminism and the creation of equal opportunities for women. Although none of these positions have been articulated to specifically harm or harm people living with dementia or their caregivers, they have done so only because they are thwarting a coherent national conversation about how we 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 makes the American family function, like roads and traffic lights: we do not question it as we need to.
George: The FDA will soon decide the fate of aducanumab. What can we expect from drugs like aducanumab?
Karlawish: Aducanumab is part of the story of amyloid, which is interesting. By the turn of the century, studies first appeared using a very new method that purified transgenic mice of amyloid. Researchers thought 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 has not been resolved, and we have a controversial treatment at best. Even the optimistic view of aducanumab is that the drug has an effect on the rate of progression.
A word that is whispered during meetings is “heterogeneity” – that we should not only think of this as Alzheimer’s disease, but Alzheimer’s illnesses. I think a very plausible future is that there will be intoxicating forms, not so intoxicating forms, and possibly incurable forms of Alzheimer’s. The stories of multiple sclerosis tell us this; the stories of many cancers tell us this.
The implication is that we really need to think about how we are going to live with this disease. We are not going to get our drug out of the problem. Helping prevent cognitive impairment at the end of life is like planning your retirement with lottery tickets: you can win and win, but the chances are likely not to go.
George: Given Alzheimer’s many dimensions, what should we pay attention to next?
Karlawish: We are beginning to face an enormous amount of irony in the field of Alzheimer’s. The reason why Alzheimer’s disease is a disease is the relentless onslaught on our autonomy and self-determination. Alzheimer’s prevent people from living their lives the way they want to. This is what makes it a disease, complete, complete – along with amyloid, tau and neurodegeneration.
The irony is that the transformation of biomarkers poses threats to the same autonomy we seek to preserve. We can address the threats, but we need to organize ourselves as a society to do so.
Our approach to dealing with this disease should emphasize helping people who live with it to maintain autonomy and identity, even if they are cognitive impairments.
It should be the way we set up 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.