Personalizing Cognitive Impairment Risk Assessment Before Symptoms Start

Individuals vary in their resilience or vulnerability to Alzheimer’s disease — resilience may offer protection in the face of a poor environment, whereas vulnerability may be buffered by modifying environmental risk factors.

In this exclusive MedPage Today video, James E. Galvin, MD, the director of the Center for Brain Health at Miami University Miller School of Medicine, takes us through the assessment tools his team has developed to measure such resilience and vulnerability, and how they plan to make them available to clinicians everywhere.

Following is a transcript of his remarks:

Our research has really been interested in understanding why people might develop Alzheimer’s disease. So the Alzheimer’s Association puts out statistics that roughly at age 80, 85, about 40% of people will have dementia. But I like to think about it the other way. That means that 60% of people will not develop dementia. And so our research group has been really interested in trying to figure out what makes these people different. What could explain why some people develop disease and other people don’t? And so this allowed us to begin to think about this concept of resilience and vulnerability.

The Lancet Commission recently published a paper talking about various risk factors that occur over the course of a lifetime. And this is similar to some of the work that’s been done by many investigators, including our group, by trying to identify factors that are potentially modifiable.

And what we know is that about 60% of the attributable risk of Alzheimer’s disease are things that we can’t control: age, sex, genetics, family history. But about 40% of the attributable risk are things that we have at least some control over. Our group spent a lot of time thinking a lot about how we could measure this. So we went into our database of really well-characterized individuals, and we created a number of tools.

One of the first tools we created was a very brief test of cognitive performance called the Number Symbol Coding Task. And what this essentially is, is it’s a test of executive attention abilities.

The next thing we set about is trying to understand this resilience. And so we created something called the “Resilience Index,” and this is composed of six factors. The first is cognitive reserve. So understanding how a person’s lifelong occupational and educational attainment may help protect their brain. So we created a tool called the cognitive reserve unit scale, which is a fancy formula for looking at their highest educational attainment with their highest occupational attainment, with occupation trumping education. So for example, you could have a high school education but start your own company. That’s a better measure of your true cognitive reserve than how far you went in school, because not all educational opportunities are equal. So that was one domain.

Then we developed a tool that could look at physical activity where we could actually create a dose of how much activity someone does on a daily basis. We created a tool that can do the same thing for cognitive activity. We created a tool that allows us to look at social engagement, and then we adapted tools looking at diet, using the MIND diet as the basis for this. And mindfulness, which is essentially a way of not letting the weight of the world bear down on you and having some self-reflection and de-centering. So again, you can look at things objectively. And so these built into this resilience index.

Then we turned our attention to vulnerability, and we did the same thing. We identified using machine-learning techniques; we identified 12 factors that could help explain what puts someone at a higher vulnerability to develop a brain disease. Four are not modifiable — age, sex, race, and education. And eight of them are modifiable, like heart disease, stroke, high cholesterol, high blood pressure, obesity, frailty, depression. And so we can put in the context of what makes us vulnerable, things that we can’t modify but we need to understand, and things that we can modify.

So now that we have a measure of cognitive performance, we have a measure of resilience (resistance to disease) and vulnerability (the risk of disease). We could put these all together into a brain health platform. And this allows us then to, in three-dimensional space, to be able to plot how healthy a person’s brain is the very first time we meet them. And does their brain look like someone who has a healthy brain and is likely to stay healthy, or does their brain look like it’s at risk? And if it’s at risk, what domains are putting them at the highest risk? This then allows us to take sort of a precision medicine-like approach to develop personalized prevention.

We’re in the process of building that platform. And then hopefully try to make it available for clinicians so that you could practice brain health, whether you’re in Miami or in Paducah, Kentucky, it doesn’t matter. No, no knock against Paducah, it’s a lovely town. But the idea is that you may not have the resources to do all the fancy biomarkers that we do here. But since all of this is validated biologically, we can take that platform and make it available to clinicians anywhere.