Margaret Lock takes a holistic view of Alzheimer’s. She warns that it’s here to stay and explains why it’s time to rethink one of our greatest health woes
How did an anthropologist come to study Alzheimer’s disease?
Initially, I became interested in people’s responses to genetic testing for the risk of late-onset Alzheimer’s. The uncertainties are enormous and even the experts cannot give you much information upon which to make decisions. Around that time I met Robert Green, a specialist in the genetics of Alzheimer’s now at Harvard Medical School. He was starting a .
What was the focus of the trial?
The e4 variant of the apolipoprotein E (APOE) gene is associated with increased risk for late-onset Alzheimer’s. The trial participants were tested to see which variant they carried and then followed up for a year with structured questionnaires. My research group then carried out open-ended interviews with more than 70 of the people who were tested.
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What did you learn about how people understand their genetic risk?
It was extraordinarily interesting, because it was clear that a lot of the participants – nearly all of whom were highly educated – didn’t even remember what their gene variant was called or really understand the risk estimates they’d been given.
Everyone had been taught that having the risky e4 variant didn’t mean they would necessarily develop Alzheimer’s – about 50 per cent of people who have it never do. Even those few in the trial who learned they were at increased risk were not too concerned. Everyone was middle-aged, many caring for ailing parents, and most had busy working lives. The last thing to worry about was this gene that might cause trouble 20 years later.
How did the interviews influence your view of our approach to Alzheimer’s?
In retrospect, I realised I’d come at the research rather naively. When I started looking into it, I suppose I swallowed much of the genetic hype of the day. We’re sold the story that so many cures will be found once we understand more about genetics. But it quickly became clear to me that with Alzheimer’s it isn’t that simple. I had to do research to address this complexity. I needed to tackle the bigger picture. That’s where anthropologists can help.
What can you do as an anthropologist to change how we think about the disease?
Researchers working at the molecular level, and clinicians seeing patients every day, tend to become somewhat myopic. It is important for someone to step back and consider the whole complex Alzheimer’s picture, with its many unknowns and uncertainties. There are no quick or simple answers, and the public needs to be made aware of the magnitude of this problem as societies age around the world.
The genes associated with risk for late-onset Alzheimer’s are numerous and still far from being fully understood. What’s more, knowing about them will never result in a simple cure.
What is wrong with our current framework for understanding Alzheimer’s?
There is no tight correlation between the manifestation of dementia – particularly memory loss and disorientation – and the demonstration of plaques and protein tangles in the brain at autopsy, which is the gold standard for diagnosis. From brain-imaging studies it is estimated that about appear to be walking around with considerable amounts of so-called Alzheimer’s pathology, but show no signs of dementia in neuropsychological testing. This mismatch is very troubling.
What is the prevailing theory about what causes Alzheimer’s?
There are several theories, but many researchers continue to subscribe to the “amyloid cascade” hypothesis, introduced more than 20 years ago. It holds that once abnormal amyloid protein builds up in the brain, it sets off a cascade of changes in which amyloid plaques are formed, followed by tau protein tangles and cell loss that eventually results in profound dementia. Proponents of the theory are promoting biomarker research to detect the first signs of this cascade in order to develop drugs to prevent it – long before any clinical symptoms appear.
This hypothesis is probably appropriate for rare early-onset Alzheimer’s. But given what we know today, even its creator, molecular biologist , has expressed doubts about its validity for the more common late-onset Alzheimer’s.
Why are there doubts about this approach?
In the past decade or so billions of dollars have been spent on developing drugs, with very limited success. And researchers have long known that, even if they did develop a drug to combat symptoms of advanced disease, once enough damage has been done it cannot be reversed. So since about 2007, the primary focus has become prevention through the detection of biomarkers.
But in private conversations with a good number of neurologists and epidemiologists, scepticism is rampant. That’s because, to begin with, there are competing ideas about what contributes to Alzheimer’s. And an increasing number of researchers believe that numerous subtypes probably exist: “mixed dementia” – a combination of symptoms of vascular dementia and Alzheimer’s-type dementia – may be the most common form. Also, research has shown that it is extremely difficult, if not impossible, to separate out late-onset Alzheimer’s from the unavoidable processes of ageing. They are so entangled that we cannot hope to distinguish between them, particularly among people aged 75 and older.
So is late-onset Alzheimer’s really just the way some people age?
This is an ontological problem that has been at the heart of this Alzheimer’s endeavour all the time, and we still don’t have the answer.
The majority of researchers think that as we get very old, if we don’t die of something else first, all of us will probably become demented when the brain no longer functions well. Obviously, some people’s brains will tire out much sooner than others.
Can we influence when our brains wear out?
It is increasingly apparent that diabetes, obesity and the state of one’s vascular system compound the picture hugely. We’ve long had Alzheimer’s pegged as a problem of neuropathology to be cured with drugs. Now, finally, people are adding Alzheimer’s and dementia to the list of conditions impacted by lifestyle. We’re realising it isn’t something that suddenly pops up when you get old.
What should our strategy be now?
We have to recognise that becoming demented is a lifelong process. It is a cumulation of environment and behaviour affecting our biology, beginning before we are born and extending throughout our lives. Alzheimer’s should be managed as a public health issue in the same way as conditions such as HIV infection – using education, preventive measures and research into treatments.
“We have to recognise that becoming demented is a lifelong process”
In 2012, US president . But we need to understand that we cannot set deadlines for eradication or declare war on this disease. It’s not like wiping out smallpox. You can’t wipe out ageing brains.
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Margaret Lock is an anthropologist who specialises in medicine and biotechnology at McGill University in Montreal, Canada. She is the author of The Alzheimer Conundrum (Princeton University Press, 2013)
This article appeared in print under the headline “When anthropology tackles Alzheimer’s”
