Going in early: Researching prevention

So to understand more about Alzheimer’s disease, how to manage it, how to detect it, we need to do research. And one of the most important types of research that we do is what’s called cohort studies. Now, traditionally, when Alzheimer’s disease and the dementia that came from it was typically thought of as a disease of older people, we could only learn so much from doing cohort studies or doing trials, investigations in people over the age of 65. As we’ve learned that the disease starts in, at least, mid-life, we have to start exploring what changes are taking place in the brains of people in that age band, and what risk factors might be driving it.

So cohort studies work by recruiting, sometimes, several hundred, if not thousands of people, into a study where they all follow a very similar protocol of investigations that will often include brain imaging, sampling of blood, of spinal fluid, doing cognitive evaluations, doing questionnaires to talk about their lifestyle and other risk factors. And then critically important is to follow these people up over time. If it’s done cross-sectionally, and you had one assessment of an individual, there’s only so much you can learn about what we call direction of causality. Did this thing happen before an event later on down the line? If you only do one tiny point, you can make a distinction between which came first.

You just have a single look at that individual. And because this disease that is, if you like, a very long period of development, over many years, these cohort studies, necessarily, have to last for several years, if not even decades. And two studies that we actually are fortunate enough to run from here within the UK, within Scotland, European Prevention of Alzheimer’s Dementia Project, which is across the whole of Europe, and Prevent Dementia Project, which is in the UK and Ireland, are examples of taking individuals, or working with individuals, I should say, in that age group, sort of over 40 up to about the age of 60 or 70, and doing all this very, very detailed assessment.

And of course, in designing these studies and undertaking these studies, it’s critically important, in fact, it’s essential, that we work very closely with the participants in the project to make sure that what we are doing is relevant for them, because these may well be the people who are at risk of dementia because of family history. But also to make sure that what we are we’re undertaking is, if you like, acceptable, it doesn’t cause too much distress or is burdensome. Alzheimer’s disease and other neurodegenerative diseases, of course, are not uniquely European, or in the UK, or in Ireland. These are global.

There are global concerns in people with dementia and Alzheimer’s disease all over the world, in every part of the world, in fact. And one of the things we have to make sure we do is if we’re generating these data, these ideas, these answers, they have to be applicable to everybody in the world. And there may be subtle differences between people who come from different parts of the world. There’s more similarities between us than there are differences. But subtle differences may be very important.

And that’s why there’s a lot of initiatives right now of looking at ways of taking cohort studies from different parts of the world and bringing those data together, those findings, those experiences, as well, together, to be able to then analyse these data. Not just in the 2,000 people in the EPAD project, or the 700 people in the Prevent study, but the 4,000 people who are in a study in India, and the 3,000 people in a study in Australia. And these initiatives are led by people like Bill Gates, through something called the Alzheimer’s Disease Data Interoperability platform, here in the UK, by Dementias Platform UK.

And these huge infrastructure projects are really helping us to unlock some of the mysteries, if you like, about why people develop Alzheimer’s disease, and therefore, what we can do to prevent it in the future. And of course, one thing that’s critically important is making all the effort and taking all the steps to address health inequalities. The way we design these studies, we’ve tended, in the past, to involve people who are from a certain racial background, certain socioeconomic backgrounds, who live, dare say it, near university towns and cities. And in some ways, that will mean that the data that we generate and the conclusions that we form may not be necessarily applicable to everybody all over the world.

And I think, in doing global studies, we can address some of those concerns. But even in local studies, at national level, we need to make sure that there are mechanisms to ensure that the population in these studies reflects the background population of that country. And this is also really important to think about, well, if we are to detect disease early, if we are to have tests that we can use, or interventions that we can, maybe, affect the course of disease, these also have to be accessible at a global level.

There’s no point to designing a study that means that having a PET amyloid scan is absolutely crucial for detecting early disease, because PET amyloid scans aren’t available all over the world and never will be. And to the same point, there’s no point in running interventional studies which are very expensive interventions, be they pharmacological or non-pharmacological if, from an economic perspective, they’re out of reach of 90% of the world’s population. So these are things at a design level we have to give consideration to, before we even start a cohort study.