The challenges of measuring dementia

Oxford Brain Diagnostic’s Dr Steven Chance explains the importance of early detection of dementia for treatment and research, and why new measurements of neurodegeneration are needed.

Though the prevalence of dementia is increasing every year, knowledge about the disease and how to treat it has not yet enabled us to slow it down. Part of this is due to the difficulties in analysing the brain to detect the signs of dementia.

“We usually need to look at the brain post-mortem to be certain of what has changed in that patient,” explains Dr Steven Chance, CEO of Oxford Brain Diagnostics (OBD). “Until then it’s a probable diagnosis.”

He adds: “You can glean lots of information about the fine structure of the brain by looking at it through a microscope – such as information about the synapses, dendrites, axons, and the cell bodies and their organisation – but that’s only possible in post mortem material, which is no help to the patient in their lifetime.

“MRI scans can be used during a patient’s lifetime but are mostly limited to volume measurements. That doesn’t accurately reflect the fine-scale changes that are happening, which are often more subtle in the early stages of dementia.”

The focus of Chance’s work at OBD is to bridge this gap between the information gleaned from a microscope and from MRI scans, by developing new measurements in MRI that can analyse the fine microscopic structure of the brain, enabling researchers to quantify changes in the brain at a more detailed level.

He explains: “There are two cardinal markers of Alzheimer’s disease that are traditionally investigated and are actively studied – amyloid plaques in the brain and how tangled the tau proteins are. That is used to provide a diagnostic scoring.

“What is often overlooked is that you can have a buildup of these toxic proteins without having cognitive decline. What we really need to know is how badly damaged the brain structure is by this disease process. That determines how affected somebody is. Our measurements are all about understanding that missing third element, the neurodegeneration itself.”

“The brain can often seem like a rather mysterious organ. I’d like to help to demystify it”

A key goal for the team at OBD is to ensure that these measurements are useful at the early stages of the diseases as well as later on in its progression.

“In the earlier stages it’s difficult for a clinician to be sure whether or not a person has dementia, and it is difficult to differentiate between different kinds of dementias,” Chance says.

“On the one hand, clinicians have people who come in concerned that they have memory loss, but often they don’t actually have the early stages of the disease. It’s very hard for a clinician to be sure one way or the other, so the patients tend to become part of the system and have ongoing checkups. It would be very helpful for clinicians to be able to reassure those people that they actually have a healthy brain.

“On the other hand, there are people who come in with very mild changes, and clinicians can’t be sure how badly affected they are. Some of those people can decline very rapidly, even before their next appointment. This can result in serious consequences as they can end up having to go to A&E because they become confused and lost.”

This adds a huge burden to the health service, he says, as well as exacerbating the patient’s suffering.

Being able to accurately test for dementia earlier in the disease progression will also make it easier to quantify the effect a drug intervention will have.

“The current drugs and treatment options are often trialled with patients for several months before they can determine which is best,” says Chance.

“What we’d like to do is help to refine the information to identify those people who will respond best to the current medications. This can also help tell researchers what to look for when testing new interventions, which could potentially be disease-altering treatments that improve the underlying condition.”

The intention is to develop measurements that are agnostic to the mechanism of the disease and can be applied to whatever new models for dementia might arise in the future.

“The point of convergence of all the different hypotheses of dementia is that the underlying fine structure of the brain becomes damaged and breaks down,” says Chance. “That’s the aspect that we measure, so our method is sensitive whichever approach you take.”

The importance of prevention

While earlier detection of dementia is key for improving outcomes in the disease, Chance notes that it’s equally important to move from the “firefighting” attitude of much of modern healthcare towards disease prevention and screening.

“This would allow people to adapt their lifestyles over a much greater timeframe, which will effectively delay the onset of disease, even in some cases without the benefit of new drugs.

“There are several promising new methods of screening, as well as new technologies, apps, and ways to examine clinical or demographic data, all of which can help to stratify people that might need screening. Genetics will be another key tool for this.”

He adds he would like to see a broader focus on “brain health” and associated lifestyle changes amongst the public.

“The brain can often seem like a rather mysterious organ. I’d like to help to demystify it so that people are better informed and have a sense of not just their blood pressure and their heart health, but also their brain health.

“There are plenty of products in the supermarket that say they are good for heart health. I’d like us to be able to generate more information for people so that we increasingly see packaging that says something is good for your brain health as well.”

Despite the high-profile failures in dementia research, Steven says he is still optimistic for the space.

“I don’t think it’s blind optimism. Certainly, the challenges in the disease are not going away. If anything, they are becoming more acute. But that is going to focus minds. I think that all science progresses through a series of tests and failures as it gradually converges on the correct answer. There are plenty of new ideas out there.

“I think there’s optimism that biotechs and other smaller ventures are bringing some dynamism to the marketplace and to the science. The failures of some of the big pharmaceutical trials have cast a bit of a shadow over current scientific ideas, but this is the moment for new ideas to come to the forefront.”

About the interviewee

Dr Steven Chance is the CEO and co-founder of Oxford Brain Diagnostics. Previously he was associate professor in neuroscience at the University of Oxford, with 20 years’ experience researching the microscopic basis of brain disease, particularly Alzheimer’s disease.