Why do we need biomarkers for Alzheimer’s disease?
This blog was written by Professor Simon Lovestone, Professor of Translational Neuroscience at the University of Oxford and was originally featured on the NIHR website.
There is an increasing focus on finding biomarkers, or tests, for dementia. Whether in the contents pages of journals, or in conference programmes, biomarker research seems to be the order of the day. This work is really exciting, and for me, one of the take-homes from a large international conference on dementia this summer was that new imaging methods to ‘see’ Alzheimer’s disease pathology in the brain are making real advances. This is in both early detection and also in our understanding of disease processes. I’m sure that there will be lots more biomarker work from brain imaging to blood tests, and beyond, presented at the conference next year in London.
So why do we need biomarkers? And how might they be used?
Perhaps it’s easiest to think first about why we don’t need biomarkers. Most importantly, in my opinion, we don’t need them to screen populations. Screening tests to detect early disease are important in other areas of medicine. I have my cholesterol measured and not so long ago I was screened for bowel cancer. I shall spare readers the details, but I was pleased to pass both tests and am persuaded by the evidence that the benefits of screening to detect diseases like bowel cancer that can be treated outweigh any downsides of having screening.
This however wouldn’t be true for a dementia test because we don’t yet have any treatments for the diseases that cause dementia. The downsides of such a test would be the anxiety it would cause and it’s hard to see what the benefits would be. However, I don’t think anyone in the field is really suggesting that biomarkers should be used in general population screening.
Our work to find biomarkers is directed at a different outcome. We want to find markers for use in clinical trials, and in particular clinical trials to find drugs that prevent dementia. As Alzheimer’s and other dementias have a long period where the disease affects the brain but doesn’t cause symptoms, a treatment for the disease that worked in this phase would be a real breakthrough. Many of us think that such an approach is not only possible but is also more likely to succeed than a treatment given to people with established disease. The field is electrified by this prospect, but there is a real difficulty associated – how do you choose who should enter such a trial? And then how do you know if the drug is working?
The answer of course is a biomarker. A test that would help to select people with early signs of the disease but no symptoms, and a test to measure change in this phase – called preclinical disease – would be enormously useful. This is what we are looking for in the recently announced NIHR/MRC funded Deep and Frequent Phenotyping study. Using brain imaging, tests of synaptic function in the brain, eye tests, monitoring of gait, blood and spinal fluid tests and more, we hope to be able to find a marker that would be indicative of a positive drug effect in a clinical trial.
We won’t know for years whether people with one test result compared to another do in fact go on to get clinical symptoms, but the outcomes of this research are really important. I don’t think it’s an exaggeration to say that future success in the search for a prevention of Alzheimer’s depends on this and similar studies.
In the meantime there is an intermediate situation that is really difficult to address. What about people who sense that something is wrong but they don’t have dementia? I am often asked by people with memory problems such as mild cognitive impairment, ‘can I have a test to see if I have Alzheimer’s?’ The answer for now is ‘no’ – but someday, and maybe not so far in the future tests to achieve this may be approved. This is going to be a really difficult area ethically whilst there is no treatment available. It is going to take a lot of thought from experts in ethics as well as public and patient representatives to get the answer right. It would be a good idea to start this discussion soon.
So we don’t want, and aren’t looking for a test to screen the general population. We do desperately need, and are now actively researching, a test to make clinical trials for new treatments possible.
The views and opinions expressed in this blog are those of the authors and do not necessarily reflect those of the NIHR, NHS, Department of Health or Join Dementia Research.
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