Maria Shriver and Dr Richard Isaacson Talk Prevention of Alzheimer Disease

Richard S. Isaacson, MD


September 16, 2016

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Editor’s Note: Medscape contributor Dr Richard Isaacson recently spoke with journalist and Alzheimer’s advocate Maria Shriver about the latest data on preventing dementia through lifestyle interventions.

Richard S. Isaacson, MD: Hi. I am Richard Isaacson, director of the Alzheimer's Prevention Clinic at New York Presbyterian/Weill Cornell Medicine in New York City. It is my great pleasure to be here with Maria Shriver, who is inspiring change not only throughout the United States and the world, but also in neurology waiting rooms all over the country. She is on the cover of the August/September 2016 issue of Neurology Now, a publication of the American Academy of Neurology.

Maria, tell me about all the amazing things you are doing, and how and why you are inspiring change.

Maria Shriver: I am happy to be featured in Neurology Now and that it is available to patients in so many waiting rooms, because I am trying to get people to focus on their brains. I am trying to learn why women develop Alzheimer disease (AD) at twice the rate of men—it is not only because women live longer. And I am trying to get researchers, doctors, and the public at large to focus on preventing AD, understanding AD, funding research into AD, and joining clinical trials. I am doing this because having seen AD up close—watching my father, a man who had such a brilliant mind, lose it—has made me want to try to prevent other families from having that experience.

But I am particularly interested in why women's brains seem to be afflicted with AD at such a higher rate. Is it hormonal? Is it stress-related? Does it have anything to do with childbirth? Does it have to do with depression?

Every time I have asked these questions, people say, "I don't know, I don't know," and that is not acceptable to me anymore. I have been working with a variety of doctors, humanitarians, and social-change agents to get people focused on funding gender-based research into this question. I know you have been doing a lot of research at the Alzheimer's Prevention Clinic. What are the newest data?

Dr Isaacson: Our group at the Alzheimer's Prevention Clinic recently published our first paper.[1] It included an initial study of the first 36 people we have tracked longitudinally. In brief, in the Alzheimer's Prevention Clinic, we see people who are normal, with no cognitive impairment, but who have a family history of AD.

Ms Shriver: Yes. I participated in this.

Dr Isaacson: At intake, we conduct a comprehensive neurologic history. We take a thorough family history, and try to learn everything about the person.

We then do cognitive testing. We set a cognitive baseline, which is extremely important. We use the National Institutes of Health toolbox (a set of brief tests that assess cognitive, emotional, motor, and sensory function, developed under the auspices of the National Institutes of Health) and a variety of other very sensitive validated tests.

Then we perform a comprehensive precision medicine panel, looking at lipid function, the particle size of the lipids, inflammatory markers, and metabolic markers—not only A1c and fasting glucose, for example, but a variety of other things, such as adiponectin. We look at nutritional markers.

We look at many things, and we "digest" the results, taking the person's genetics and everything else into consideration. From this, we devise a very specific, five- to six-page personalized approach to preventing AD. Then we track compliance over time, and 6 months later we see how people did.

In this first analysis of this small group of 36 patients, we were able to show not only stabilization, but also improvements in cognitive function.

Ms Shriver: That is very important. We should pause on that, because "improvement" is a big word—improvements in cognitive functioning. You know many people—most people, even just a year or two ago—thought that would be impossible.

Dr Isaacson: When we started the program 3 years ago, even I was not sure this was possible.

Ms Shriver: So that is huge.

Dr Isaacson: I am very excited about it. That initial study included 36 patients, but at the upcoming Lancet Neurology preclinical neurodegenerative disease conference in October (the first-ever conference focused only on preclinical disease) and the Clinical Trials on Alzheimer's Disease Conference in December, we will be presenting the next round of our pre- and postdata on 166 patients followed over 6 months.

For now, our initial published study showed that individualized dietary and lifestyle interventions can result in robust and significant improvements in executive function and processing speed. We were not able to move memory much at all, however; we found no change in memory during the 6 months.

These are normal people without cognitive impairment at baseline. We were not expecting to see improvements; ideally, we expected to see stabilization. We know these were not practice effects, because we use a variety of tests that are somewhat resistant to practice effects (although it cannot be entirely excluded). Our patients are improving their brain health over time.

We are also learning which biomarkers correlate with each of these changes. For example, if you want a targeted approach to improve someone's executive function and that person has problems with high cholesterol—not just high low-density lipoprotein (LDL) cholesterol, but inflammatory particles, such as small dense LDL particles or apolipoprotein B—we can adjust the patient's diet in specific ways.

But it is complicated. We have help from preventive cardiologists, nutritionists, and neurologists, and we try to take a very comprehensive approach to treat these risk factors. And now, for the first time, we have shown improvements in brain function.

Ms Shriver: Improvements in executive processing and overall brain processing. How important are the data on games, and on learning new skills?

Dr Isaacson: A new study[2] that looked at a program called "Brain HQ" was presented at the 2016 Alzheimer's Association International Conference in Toronto.

Ms Shriver: I just did a story on this for the Today Show.

Dr Isaacson: I have no commercial interest in this program, which you have to purchase, but it was a fascinating study. Ten years ago, investigators randomly assigned participants to different types of brain activities, including classroom-based memory strategies, classroom-based reasoning strategies, computer-based speed-of-processing training, or a noncontact control group. They participated for 5 weeks. The study showed that 10 years after this 5-week program finished, people who completed the processing-speed games had a lower incidence of cognitive impairment than people who participated in the other activities.

Ms Shriver: That is super-exciting.

Dr Isaacson: It also showed that those who completed the processing-speed games had fewer car crashes and a variety of other things.

Ms Shriver: I thought that was fascinating, because the processing-speed games actually make you broaden your sight—broaden the things that you look at in the game. I believe all of this research is exciting because it tells all of us that our brains can continue to grow, and there are things that we can do each and every day to strengthen our brains.

Dr Isaacson: In medical school, I was taught that you could not do anything about treating AD, much less preventing it. But it is a new decade. The new frontier of AD treatment and prevention is precision medicine. I am quite excited about where our field is going.

Ms Shriver: It is important to remember that AD is developing in the brain for 20-30 years before you have symptoms, so it is important to get involved in this when you are young. That is one of the things I like to talk about—inspiring changes so that young people will think about what they can do today, so they will not end up with AD "tomorrow." This is a very important new approach.

Dr Isaacson: You cannot take a single vitamin or a supplement or a cholesterol medicine, anything like that, to prevent AD. There is no one-size-fits-all approach. This is not an algorithm. I wish it was. The textbook on AD prevention has not yet been written, but we are making progress. AD prevention studies are ongoing. I believe we have reached a new frontier in AD prevention.

Ms Shriver: And you are part of it.

Dr Isaacson: Two thumbs up. I have four family members with this disease, so, like you, I understand that we have to do something now.

Ms Shriver: We want to inspire change now.

Maria Shriver has disclosed no relevant financial relationships.


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