杏吧原创

Margaret Lock takes a holistic view of Alzheimer鈥檚. She warns that it鈥檚 here to stay and explains why it鈥檚 time to rethink one of our greatest health woes

How did an anthropologist come to study Alzheimer鈥檚 disease?
Initially, I became interested in people鈥檚 responses to genetic testing for the risk of late-onset Alzheimer鈥檚. 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鈥檚 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鈥檚. 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.

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 鈥� nearly all of whom were highly educated 鈥� didn鈥檛 even remember what their gene variant was called or really understand the risk estimates they鈥檇 been given.

Everyone had been taught that having the risky e4 variant didn鈥檛 mean they would necessarily develop Alzheimer鈥檚 鈥� 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鈥檚?
In retrospect, I realised I鈥檇 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鈥檙e 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鈥檚 it isn鈥檛 that simple. I had to do research to address this complexity. I needed to tackle the bigger picture. That鈥檚 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鈥檚 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鈥檚 are numerous and still far from being fully understood. What鈥檚 more, knowing about them will never result in a simple cure.

What is wrong with our current framework for understanding Alzheimer鈥檚?
There is no tight correlation between the manifestation of dementia 鈥� particularly memory loss and disorientation 鈥� 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鈥檚 pathology, but show no signs of dementia in neuropsychological testing. This mismatch is very troubling.

What is the prevailing theory about what causes Alzheimer鈥檚?
There are several theories, but many researchers continue to subscribe to the 鈥渁myloid cascade鈥� 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 鈥� long before any clinical symptoms appear.

This hypothesis is probably appropriate for rare early-onset Alzheimer鈥檚. But given what we know today, even its creator, molecular biologist , has expressed doubts about its validity for the more common late-onset Alzheimer鈥檚.

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鈥檚 because, to begin with, there are competing ideas about what contributes to Alzheimer鈥檚. And an increasing number of researchers believe that numerous subtypes probably exist: 鈥渕ixed dementia鈥� 鈥� a combination of symptoms of vascular dementia and Alzheimer鈥檚-type dementia 鈥� may be the most common form. Also, research has shown that it is extremely difficult, if not impossible, to separate out late-onset Alzheimer鈥檚 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鈥檚 really just the way some people age?
This is an ontological problem that has been at the heart of this Alzheimer鈥檚 endeavour all the time, and we still don鈥檛 have the answer.

The majority of researchers think that as we get very old, if we don鈥檛 die of something else first, all of us will probably become demented when the brain no longer functions well. Obviously, some people鈥檚 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鈥檚 vascular system compound the picture hugely. We鈥檝e long had Alzheimer鈥檚 pegged as a problem of neuropathology to be cured with drugs. Now, finally, people are adding Alzheimer鈥檚 and dementia to the list of conditions impacted by lifestyle. We鈥檙e realising it isn鈥檛 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鈥檚 should be managed as a public health issue in the same way as conditions such as HIV infection 鈥� using education, preventive measures and research into treatments.

鈥淲e have to recognise that becoming demented is a lifelong process鈥�

In 2012, US president . But we need to understand that we cannot set deadlines for eradication or declare war on this disease. It鈥檚 not like wiping out smallpox. You can鈥檛 wipe out ageing brains.

This article appeared in print under the headline 鈥淲hen anthropology tackles Alzheimer鈥檚鈥�