Print This PostBefore I started working in dementia research, the word biomarker was pretty vague to me – like, a scientific term I generally understood from context but didn’t fully recognise the significance of, almost synonymising it with ‘symptom’. Now, having worked in clinical trials, I’ve come to understand just how central biomarkers are to what we do. And, more importantly, what they might mean for the future of dementia care.
The clue is in the name: bio means biological, and marker means indicator. Biomarkers are detected through tests. For example, in pregnancy, even supermarket tests look for one of the most well-known biomarkers: human chorionic gonadotropin (hCG) – a hormone produced by the placenta, a biomarker which shows a person is pregnant.
When we consider biomarkers in dementia, it’s important to acknowledge the bigger picture – with over 100 forms of dementia, each individual dementia will have an individual set of biomarkers which we need to identify in order to help us diagnose them. However, most of these dementias are exceptionally rare – the vast majority of people will have one of four dementias, or a combination of these: Alzheimer’s disease; vascular dementia; dementia with Lewy bodies; or frontotemporal dementia.
For the sake of simplicity, I’m going to narrow down to Alzheimer’s disease for this blog. Alzheimer’s is the most common type of dementia and is diagnosed by assessing reported symptoms and experiences of change in a person’s day-to-day life, using cognitive assessments and scans of the brain. Another test we can do to more specifically diagnose a dementia subtype as Alzheimer’s is a lumbar puncture, where we use the cerebrospinal fluid to identify proteins in the brain – these proteins are biomarkers of Alzheimer’s.
So, if we have biomarkers already to diagnose Alzheimer’s, why is there still a need for biomarker research? The problem is that our current methods for assessing dementia are not very accurate and usually only allow us to make a diagnosis once the disease has already progressed to a mild or moderate stage. Dementia is a progressive condition – it gets worse over time. Most people book an appointment with their doctor once they notice that something is wrong and not improving. By that point, the disease has already been developing for some time.
MRI helps detect early signs of Alzheimer’s by showing shrinkage in brain regions linked to memory, such as the hippocampus.
Currently, diagnosis often happens by tracking decline with tests of memory and thinking, and perhaps with some brain imaging, like CT scans or MRIs. A person might be tested and not meet the criteria for a diagnosis initially, but if they return with ongoing or worsening symptoms, a follow-up test may show that their scores have dropped and their condition has declined. This evidence of progression often leads to a diagnosis. However, this system is not particularly precise.
But hold up – what about the proteins in the brain? The biomarker for Alzheimer’s that we already know about. Unfortunately (in my opinion), at the moment, it is not common practice in the United Kingdom to use lumbar punctures or amyloid PET scans (another way to detect the proteins) to confirm a diagnosis of Alzheimer’s. Lumbar punctures are invasive. Lumbar punctures and amyloid PET scans are expensive. And because of this, most clinicians will use just the standard tests and assessments to support a diagnosis.
Realistically, because the currently available treatments for Alzheimer’s are not hugely effective, the results of the lumbar puncture or PET scan might not significantly change how the condition is managed. Because of this, currently, if Alzheimer’s is suspected, drugs will generally be prescribed, and then the person’s reaction to them will decide whether or not they continue to take them. However, with new Alzheimer’s treatments becoming available, this approach may need to change – we need to be more sure of our diagnosis before prescribing new treatments – and having more accessible and less invasive biomarkers is therefore becoming even more important.
This is where biomarkers can make a real difference for people undergoing dementia assessments.
Better and more accessible biomarkers would allow us to detect diseases like Alzheimer’s earlier and with greater accuracy, and perhaps before more difficult symptoms appear. It will also mean that any prescribed Alzheimer’s treatments are given with more confidence.
And this leads us on to research. In research, we need to be sure of our diagnosis; otherwise, how can we know that what we are looking for is actually there? Or, how can we ensure that what we are trialling to help is working on the right disease? For example, if someone is misdiagnosed with Alzheimer’s, but instead has frontotemporal dementia, and we are trialling a drug with them, if they show no improvement, then that just means that the drug isn’t working with frontotemporal dementia. But the information, we gather from this person will suggest that the drug doesn’t help Alzheimer’s, because they have been misdiagnosed. For this reason, it is extremely important we have the correct diagnosis in research.
Although there are new anti-amyloid drugs (although it is unclear if these are better than our current medications, and they are not presently available on the NHS), research to date has not found a way to cure Alzheimer’s – or any other dementia. This being said, we also haven’t ever been able to do research into interventions with people who are in the early or premorbid stages of the disease, because if people are not diagnosed until mild to moderate stages, we don’t know who the people with early/premorbid Alzheimer’s are, to include them in research.
And this is another reason why biomarker research is so valuable – because biomarker research hopes to allow us to detect change earlier, and to answer the questions: Could an intervention at an early stage extend a person’s ability to remain independent? Could an intervention at an early stage prevent progression? And maybe once we have these answers, can we find a cure?
Biomarkers are promising, but they’re not perfect.
They aren’t necessarily going to tell us how or why, but they may help point us in the right direction for finding that out, later down the line. And while biomarkers are essential to the science, they can be challenging for participants. In my role, I support participants through the entire trial process and have seen first-hand the burden that participants take on to further research. A lumbar puncture, for example, is a lot to ask of someone. And yet so many say yes, because they want to help. Research also takes a long time. If we are wanting to see changes over time and we don’t know how early we need to look, it’s not uncommon for people to be involved in biomarker studies for months, if not years. It’s a big ask, and I’m always so grateful and impressed at the resilience and willingness of our volunteers to get involved and remain proactive in our studies, despite the demand.
So, while biomarkers may not offer all the answers, they bring us closer to asking the right questions, sooner. It offers us the potential to move from reacting to symptoms, to proactively identifying change, perhaps before it’s noticed. That shift could change everything – from how and when we intervene, to the kinds of treatments that we’re able to offer people at risk. It’s not a perfect science, and it demands a lot from those who take part. But thanks to the generosity and spirit of research participants, we’re slowly building a clearer picture of what’s happening in the brain and the body, earlier. And with that knowledge, we move closer to a future where dementia might be detected sooner, managed better, and one day – hopefully – even prevented.
With thanks to Dr.P. for sharing her expertise and knowledge.
Marian Montanha
Author
Marian Montanha is a Clinical Studies Office in the NHS – Neuroprogressive and Dementia Network in Scotland. With a background in Psychology and a keen interest in Neuropsychology, Marian plays a vital role in clinical research, coordinating and managing clinical trials, ensuring smooth operations, and maintaining accurate records, while also promoting research and collaborating with clinical teams. Passionate about patient care, she is driven to help people maintain dignity, independence, and quality of life. Marian’s top tip for ECRs? “You don’t know what you don’t know”.
NIHR
Dr Emma Law
Great Blog!