“One more question,” is now a regular parting shot from the son or daughter of a patient I have just diagnosed with dementia. It is dropped in just as they are about to leave – almost an afterthought.
Typically, we have spent the last hour painting a picture of the road ahead for the family: the trauma of shifting from the role of a grownup child to one of a carer, a succession of losses, and ultimately the fading of the person they had once known.
In the past, the stunned family may have silently filed out, deep in thought. But now we tend to stand by the door, opening a new conversation. “What can I do to not get this?”
It is difficult to overstate the opportunity for dementia research that is contained within this repeated question. Researchers have long recognised the value of treating dementia in its “pre-clinical” phase. But it is difficult to conduct clinical studies in people with few or no symptoms. To do so, you need reliable tests to detect pre-clinical dementia and you need to monitor the effects of the treatments being tested.
Perhaps the most fundamental challenge, however, remains the scarcity of research and clinical infrastructure to detect, track and investigate disease progression from its earliest stages. Even healthcare systems that are highly centralised, such as the UK’s NHS, are simply not geared up to detect, let alone treat, pre-symptomatic dementia.
Research registers or trial-ready cohorts, such as the Great Minds registry, that we at Dementias Platform UK have developed, have tried to address this gap. These registers use genetics and data relevant to dementia risk – such as diabetes and hypertension – collected over many years for reaching out to people most likely to benefit from treatments targeting pre-clinical dementia.
Yet the volunteers that make up these registers are not representative of those that develop the disease. And the registers are way too small for the task. We need to think bigger and broader.
Enter the adult children of my patients, people in late midlife who are used to being active in managing their physical health through seeking relevant research information and maintaining a healthy lifestyle. Typically, they are well-versed in using digital technologies such as smartphones and wearable devices to track their risk factors. They know how to sift through the latest research and are used to challenging their doctor on the rationale for starting a new treatment.
It is only natural that they wonder why, if they can look after their physical health, they should not be able to look after their brain health. And if it is possible for brain health, would they not be the ideal partners in our challenge to prove the effectiveness of potential treatments for pre-clinical disease?
I believe that four key developments over the past decade make this alliance now a realistic option:
1. Improved understanding of risk factors. The accumulation of evidence through high-quality studies has given us a firm understanding of the risk factors of dementia. Combining these risk factors can be very useful in identifying those at high risk of being in pre-clinical dementia, giving us the ability to detect the “right patient”.
In a recent study, we discovered the point that marks a rapid escalation in the build-up of Alzheimer’s disease proteins, giving us the precise timeframe for action. Combining this knowledge could help us tell people if and when they might develop dementia – something currently unavailable.
2. Rapid development of digital technologies. We have seen a rapid expansion of digital technologies that can characterise cognition and memory in great detail, including using smartphones and other digital devices to conduct memory tests.
Tracking the passive use of these devices – how quickly we find words when texting, how quickly we read articles, characteristics of speech during phone calls – could help us characterise cognition over long periods. This has the dual benefits of both identifying those on the cusp of being symptomatic and also of reducing the number of people needed by clinical studies by using long-term data to uncover beneficial effects of any new treatments being tested. Effects that might otherwise have been lost to noise.
Further developments go beyond simply tracking cognition and put the user in control of their modifiable risk factors with coaching support. The advances of these digital technologies, when combined with the fact that more and more people across society and age groups have access to these devices, provide a major opportunity to track memory ability and help people manage their brain health by making lifestyle changes directed at their risk factors for dementia. Crucially, this would introduce diversity to research, democratising access to the latest opportunities beyond the unrepresentative group of typical research volunteers.
3. The blood biomarkers boom. What was science fiction ten years ago is now rapidly becoming a reality. We can now spot the beginnings of dementia and differentiate the causes with a simple blood test. The test has the benefit of being both highly specific (the ability of the test to determine whether a person does not have the disease) and non-invasive.
4. Linking and sharing data. The last component is recognising the importance of linked data and rapid data access to researchers to accelerate research through projects such as Dementias Platform UK Data Portal and Alzheimer’s Disease Data Initiative Workbench. This technology enables a combination of research and clinical data to uncover the hidden indicators of pre-clinical dementia on the scale required.
The above advances provide a unique opportunity to establish the research infrastructure needed to tackle pre-clinical dementia. And so we come back to the critical component in all this – the force behind the question of my patients’ sons and daughters. This is the time for them to make their mark on dementia research, and it is our duty as doctors and scientists to help them achieve it.