Capturing cognition

Typically, until quite recently, we’ve thought of Alzheimer’s disease being a disease of older people, people live with the dementia phase of the illness. And the earlier stages of disease haven’t really been picked up, or recognised, or managed effectively in clinical practise. And when you get to those late stages of disease, we tend to define it, not necessarily on biological changes or biomarkers, but on two critical areas, cognition and function. And when cognition is affected, we tend to drill down on memory testing. It’s typically thought of that dementia is a memory disorder. And then one looks at the diagnostic criteria for Alzheimer’s dementia, another area of cognition, like planning, judgement, organising, may be affected.

And to have a diagnosis of dementia, this has to then have an impact on day-to-day function. So these are, in a way, quite sort of loose, vague criteria. And the way we assess whether or not somebody has actually got cognitive impairment to the degree that one would see in dementia, we use, to be fair, quite blunt instruments. For instance, the test asks for things like what the date is, where you are right now, what is this called, what are these called? And you can imagine, or you can see, that being able to answer those questions is reasonably straightforward, until you’re at quite a significant degree of disease and quite advanced in that process.

Now, if we want to go earlier in the course of disease, those tests have got no value. They’re too global. They’re too general. We have to think about what parts of the brain are affected early in disease. And how can we test those? So we’re here in the Pentland Hills, about five or six miles to the south of Edinburgh. And if you remember, we were talking earlier about an area of the brain called the hippocampus, which we pointed to in the video we showed the brain imaging scan. Now, that area of the brain is really, really important in terms of Alzheimer’s disease, because we know that it’s affected very early by amyloid and tau pathology, which we’ve discussed previously.

And there’s particular parts of the hippocampus, subfields of the hippocampus, small areas within it, which, again, have been identified as being a very early target for the Alzheimer’s pathology. Now, what does that part of the brain do? Well, it’s involved in what’s called visuospatial memory. And there’s two types of visuospatial memory called allocentric and egocentric visuospatial memory. Now, egocentric is, if you imagine, if you’re inside a scene like we are today, in the mountains themselves, and we’re wandering around, trying to navigate our route. We use egocentric visuospatial memory to find our way around. It’s like trying to find your car in the car park after you’ve been shopping.

Allocentric visuospatial memory is where if you’re outside of a scene, and you’re trying to look into it to try to work out, from a different direction, whether or not it’s the same scene, the same environment. Now we have tests for those things, which we’ve shown to be really, really sensitive to changes early in the course of disease in people at high risk of disease. And the two tests we use are the supermarket trolley test for egocentric visuospatial memory, and what we call the four mountains test for allocentric visuospatial memory. In the last clip, you saw, over my right shoulder a hill called Allermuir. And that hill there is the same hill.

But what we’ve done is we’ve changed perspective on it. And when we’re testing allocentric visuospatial memory, what we do is use a test developed between UCL and Cambridge called the four mountains test. Now, in this test, which you can see in front of you now, we show you one image of a scene which has four mountains in it, with lighting and clouds in a certain way. And what we do in the test is ask you to try and remember that. Because what we do in a few seconds is show you four different scenes, only one of which is the same scene, but from a different perspective.

So which one of those four do you think is the same scene you saw earlier?

So you can see how more challenging, more difficult that test is of visuospatial memory than the global tests that we were talking about earlier, where one is asked what is the date? Where are you? What are these called? And that’s why the tests like the four mountains tests and the supermarket trolley test are much more sensitive tests of early changes that one may see in early Alzheimer’s disease.