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 very short period of time, we had a revolutionary redefinition of what we talk about when we talk about Alzheimer’s,” said Karlawish in an interview with MedPage Today. “This is really possible due to 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. The battle lines are drawn on healing versus care. More than six million Americans live with Alzheimer’s and many more provide free care to patients. And decades after scientists realized they could clear the brain of amyloid plaques – a hallmark of the disease, along with tangles of tau – people with Alzheimer’s have no effective treatments.
This is the backdrop for the new Karlawish book, The problem of Alzheimer’s disease: how science, culture and politics transformed a rare disease into a crisis and what can we do about it. MedPage Today Judy George, senior staff writer, spoke with Karlawish to learn more about the complexity of Alzheimer’s in today’s society.
George: Let’s start with the biomarker revolution. Now we can imagine amyloid and tau in people’s brains, and blood tests for Alzheimer’s are on the horizon.
Karlawish: When I started, patients must have dementia to be diagnosed with Alzheimer’s. It was a kind of Gothic horror story; I couldn’t say what was wrong with you until 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 to push the diagnosis of Alzheimer’s into states of being milder and milder and even intact – people who have no disabilities or, at most, have mild cognitive disabilities.
This certainly creates opportunities for early diagnosis and treatment. But it presents real challenges for people in terms of 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 types of stigma in Alzheimer’s disease. There is self-stigma – the stigma that an individual feels when he is unable to do things. There is public stigma – the world around them thinks less of them. And there is the stigma that people around the patient or family can feel, a distance from others.
I quote a story in the book about Ronald Reagan. His ambassador to the White House and the United Kingdom, 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 simply “out of his mind”. He was basically saying, “I am staying away from Ronald Reagan, I am distancing myself from him”, which meant he was also distancing himself from Nancy Reagan, I presume. For me, this is a very poignant example of stigma.
Ground zero of stigma expression in Alzheimer’s disease is what I call the word “z” – that is, that we cultivate this rhetoric of death before death or of the undead, that people become zombies.
George: You mentioned that the Alzheimer’s field has a “strange opposition between care and cure”. How did this come about?
Karlawish: He is involved in several events. The Alzheimer’s field struggled to gain legitimacy, and focusing on topics other than “let’s find 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 has been recognized for centuries. There was no debate that cardiovascular disease was a disease. Still, in 1980, there was great ignorance about the legitimacy of Alzheimer’s as a disease.
We support research to find a cure, but we don’t agree on how to care for people with Alzheimer’s disease. Care was involved in contentious political debates around the role of the state in long-term care services and in ideological and supportive battles over the role of the family.
In the 1990s, a party in America said absolutely no tax increases, no expansion of federal programs beyond defense and a few related things, and was deeply skeptical about feminism and creating equal opportunities for women. While none of these positions were articulated to specifically harm or injure people living with dementia or their caregivers, they did so 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 for diagnosis and treatment. I consider the basic infrastructure that allows the American family to function, such as roads and traffic lights: we do not question this 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 history of amyloid, which is interesting. Around the turn of the century, the first studies appeared using a very new method that eliminated amyloid in transgenic mice. The researchers thought that they might need to find a new line of work because Alzheimer’s would be resolved.
Well, here we are 21 years later and it is not resolved, and at best we have a treatment that is controversial. Even the most optimistic approach to aducanumab is that the drug has some effect in slowing the rate of progression.
One word that is whispered at meetings is “heterogeneity” – that we really should think about it not so much as Alzheimer’s disease, but as Alzheimer’s disease illnesses. I think a very plausible future is that there will be druggable, not so druggable, and potentially untreatable forms of Alzheimer’s. The multiple sclerosis stories tell us that; the stories of many cancers tell us that.
The implication is that we really need to think about how we are going to live with this disease. We will not be able to get out of the drug problem. Betting on curing all causes of disabling cognitive impairments at the end of life is like planning your retirement with lottery tickets: you can win and win big, but you probably won’t.
George: Given the many dimensions of Alzheimer’s, what do we need to pay attention to next?
Karlawish: We are beginning to face enormous irony in the field of Alzheimer’s. The reason why Alzheimer’s is a disease is because of its relentless attack on our autonomy and self-determination. Alzheimer’s disease prevents people from living the way they want to. This is what makes it a disease, completely, completely – along with amyloid, tau and neurodegeneration.
The irony is that the transformation of the biomarker poses threats to the same autonomy that we are trying to preserve. We can face these threats, but we have to organize ourselves as a society to do this.
Our approach to dealing with this disease needs to emphasize helping people living with it to maintain autonomy and identity, even in the face of disabling cognitive disabilities.
That must be the way we structure our strategy as a country in terms of the support we offer people, the way we talk about the disease and the language and the images we use.