Spotting signs of dementia early

People everywhere are living longer. But the downside of this is that we’re also succumbing in increasing numbers to diseases of old age, like Alzheimer’s. And, often, by the time we make the diagnosis, it’s likely too late to intervene with treatments to slow down or reverse the condition, or enrol people into trials to test potential therapies. But if we can detect who is going to develop these conditions well in advance, we have a much better chance of intervening and keeping a person healthier for longer, or finding the breakthrough drug that can do that. And that’s what Cambridge University’s Tim Rittman is trying to do, by looking for indicators of diseases like Alzheimer’s that are manifest nearly a decade before the disease becomes apparent…

Tim - What we really wanted to see was what was the earliest that we could pick up some of the subtle symptoms of Alzheimer's disease and other types of wear and tear disease to the brain. What we did was went to this incredible study called the UK Biobank and that has invited half a million people from around the country to come and have various tests, so memory and thinking tests and questionnaires about their day to day function. So we were able to look at the people from those half a million who went on to get these various types of dementia and other similar diseases and look back at how they had performed. Five to ten years before they'd got a diagnosis.

Chris - What did you find? Did you find there were some good indicators in there?

Tim - Yeah, we did particularly for, for Alzheimer's disease. So there's the largest number of people with Alzheimer's disease, about 2,700 people had developed that over the course of the study. And when we went back to their baseline first visit, people did worse on test of memories you might expect. They did worse on tests of what we call cognitive flexibility, sort of logic type tests and they did worse on things like reaction times. And this was specific to certain diseases. So there's another slightly rarer type of dementia called progressive supranuclear palsy and that has very poor balance. We found that people with this PSP disease were falling two to three times more than their healthy peers long before they had the diagnosis.

Chris - Why do these things manifest in that decade before the disease is overtly diagnosed?

Tim - We've always suspected this has been the case. Because if you look at brain scans for example, there's some types of dementia where we know people are going to get the disease and those are the types of dementia where people carry a gene for it. And in those genetic forms of dementia, we've seen changes in the brain 10 years beforehand. We've always suspected this has been the case in much more common types of dementia. But until now we haven't been able to look back in time and this study's been enabled us to be able to do that.

Chris - Are these sorts of predictors sufficiently specific though? Because falling over is a pretty common thing to happen. Many older people do that. They become weaker, their muscles are not as strong, so they are more prone to falls, for example. It doesn't mean they're at risk of progressive supranuclear palsy or Parkinson's or something. They might be, but they might equally not be. So is there not a danger we're going to drag in lots of the wrong people with these sorts of markers? Or do you think they are sufficiently specific that you think you can point the finger at someone and say, "with this constellation you are an x percent higher risk of Alzheimer's, so we're going to study you?"

Tim - Yeah, it's not that specific enough to say, yes, you're definitely going to get this disease in a few years’ time. But what we, what we can hopefully do is identify a group of people who are high risk so that we can enroll them into clinical trials. Because we suspect that if drugs are going to work for these diseases, they're going to work at the very earliest stages. So if you give these tests to a whole load of people, some people are going to do well, some people are going to do poorly. That doesn't necessarily mean that those people who do poorly are going to get dementia. But we know that they're at a higher risk and those are the people that we want to invite into trials for preventive studies and for new treatments.

Chris - So many of the people we're studying in trials at the moment, it's a bit late because they've already manifested the disease and we really gonna struggle to change the course of the disease or stop them deteriorating much beyond where they currently are. Whereas if you come in before it becomes much more overt, your argument will be you're heading it off before it worsens, so that their quality of life and ability to function is retained for longer.

Tim - Exactly. We suspect that the disease gathers pace as it progresses. So by the time you've had a diagnosis and you've got really obvious symptoms, it's very obvious on the brain scan that you've lost brain cells for example. We can't get those back, but if we can catch people at the very earliest stages, we have the best chance then of maintaining that function. That gives a real a window of opportunity to try and intervene early.

Chris - And just briefly, do you have any candidates or do we have drugs yet that might be able to do that so a company can come to you and go, "Thanks very much for showing us who we need to enroll in our trial now we're gonna do it."

Tim - To be honest, it's a really exciting time to be in this kind of research because there are lots of trials which are ongoing. There was an announcement by a company a couple of weeks ago about a drug called Lecaneamab, which potentially slows down the disease. I think we need a bit more information to know that for certain. But yeah, these trials are happening, so it's an exciting time.