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What Modifiable Factors Decide Who Gets Alzheimer’s?

By | November 8th, 2017

November 8, 2017

Why do some people get Alzheimer’s and others don’t? Many researchers are trying to answer that question by studying how risk of dementia increases alongside the development of other diseases, like heart disease and diabetes. Laura Baker, Ph.D., associate professor of gerontology and geriatric medicine at Wake Forest, is tracking patients to see if how we can change the trajectory of an Alzheimer’s diagnosis. 

  • Studying people who don’t progress to Alzheimer’s is just as important as studying those who do
  • The National Institutes on Aging funds several centers across the country to pool Alzheimer’s data
  • Analyzing this data includes looking at how different diseases like diabetes and even prediabetes affect risk of Alzheimer’s

Being Patient: First, tell me a little bit about your practice.

Laura Baker: My background is in neuroscience, psychology and clinical trials. I’ve been conducting clinical trials for almost 20 years now. In the context of that, I see patients: research participants who are coming to our clinic for an assessment to determine whether they’re eligible for one of our clinical research studies. We do a thorough evaluation, like many specialized clinics, to determine the nature of their memory impairment or cognitive impairment and see if they are a good fit for the study we’re trying to conduct.

In the context of evaluating the results, we also provide feedback to the families. So I’ll sit with the families, tell them what we see, talk to them about their concerns, what have they noticed. I’ve been doing this for quite some time, so I’ve gotten exposure to hundreds of different kinds of people with different kind of concerns at different stages along the disease.

Being Patient: So are you trying to track the symptoms and how are they relevant?

Laura Baker: Yes. We’re looking for folks who are at different stages of the disease. Some studies, we want only people who are not starting to show cognitive symptoms yet. Those are cognitive asymptomatic folks. We need to make sure they are not in an impaired range on any of their tests. But often times they’re at high risk, because we study the contributions of metabolic disease and cardiovascular disease to Alzheimer’s disease. A lot of our folks don’t have memory impairments yet, but they have borderline medical conditions that do increase their risk. We’re trying to identify those folks who are at higher risk who have modifiable risk factors and put them in a study to see if we can change their trajectory and impact the health of that individual.

Being Patient: So how do you track?

Laura Baker: In our Alzheimer’s center, we have what’s called a clinical core, like all National Institute on Aging funded centers across the United States. It’s an observational study where we can do full evaluations on individuals at various stages of disease, from asymptomatic to full Alzheimer’s dementia. We do full characterization on brain imaging, lumbar punctures, collect cerebral spinal fluid and blood, and track cognition. And we watch the trajectory over time. We’re using this information to help us predict who’s going to follow what path. Those who are asymptomatic now, for example: some of them will progress to dementia, some won’t. This longitudinal perspective study that we’re doing at all Alzheimer centers will help us understand the very early risks that predict who may one day progress to dementia out of the people with no cognitive symptoms now. And a question that’s just as important: Who doesn’t progress to Alzheimer’s? What’s different about those people and can we use that information to help us develop new interventions?

Being Patient: Can you give a sense of what stage you’re at right now?

Laura Baker: So there are 32 or 33 NIA-funded Alzheimer centers across United States. Every center has a clinical core and each clinical core across the United States has four to five hundred people that they’re following. We’re a brand-new center, so we have about 250. Our contribution is many of our people in the southeastern part of the United States have more severe cardiovascular and metabolic disease. Other parts of the country may not have that kind of prevalence so this helps the group study the contributions of cardiovascular disease and metabolic disease in this trajectory process. Each center is expected to bring a unique contribution that helps us understand the bigger picture and the critical factors that determine who’s going to follow what pathway.

Being Patient: It’s like how other diseases relate to Alzheimer’s, like cancer and diabetes. Can we say that we know people with other ailments are at a higher risk for Alzheimer’s?

Laura Baker: Yes. We know that people who have cardiovascular disease are at higher risk for developing dementia. I think there is still some controversy about whether it’s Alzheimer’s dementia, but there’s a strong contingent of scientists who say, “Absolutely. It’s Alzheimer’s-type dementia.”

Being Patient: What do we know about how those two are related?

Laura Baker: So there are a few papers that have been published over the last five years actually showing those who have cardiovascular risks or cardiovascular events [like heart attacks] or brain imaging showing more white matter, stiffer veins, have a higher incidence and prevalence of Alzheimer’s disease or related dementia.

These risks are true risks for development of dementia, so how can we intervene? The Mayo produced a finding years ago that shows that people who have metabolic disease like insulin resistance, pre-diabetes, their risk of developing Alzheimer’s disease is significantly increased.

If you have Type 2 diabetes, your risk of developing Alzheimer’s disease is 65% greater. Usually when I say this in the community, you can hear people gasp. Most of the time in my community, half of the people in the room have either Type 2 diabetes or a family member has Type 2 diabetes. This is a scary statistic. This is not just Type 2 diabetes; if you have pre-diabetes, if you’re heading down the road to Type 2 diabetes, you are going to score worse on cognitive tests and your risk is still higher.

Being Patient: What’s the connection between metabolic disease and the brain?

Laura Baker: This is a topic of much research going on right now. It’s something that our laboratory has been studying quite a bit. Susanne Kraft, whom I work with closely, has looked at the link between insulin resistance and Alzheimer’s disease. She’s now actually testing a new treatment that helps restore metabolic health to the brain specifically, not to below the neck but to the brain so it’s inhaling insulin to restore deficit in the brain that’s caused or is related to the insulin resistance. Her preliminary results say this is working. This is a brand new, novel intervention that does not involve a drug, doesn’t necessarily focus specifically on amyloid but we’re trying to correct a metabolic disease and we’re seeing improvements in memory of people with Alzheimer’s disease. Not just people at risk but people with disease.

This interview has been edited for length and clarity. 

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