Richard S. Isaacson, M.D., serves as Director of the Alzheimer’s Prevention Clinic, Weill Cornell Memory Disorders Program, and Director of the Neurology Residency Training Program at Weill Cornell Medicine/NewYork-Presbyterian Hospital.

Dr. Isaacson specializes in Alzheimer’s disease (AD) risk reduction and treatment, mild cognitive impairment due to AD and pre-clinical AD. His research focuses on nutrition and the implementation of dietary and lifestyle interventions for AD management.

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**Jed Levine (JL):** Richard, thank you for taking the time to talk with us. Let’s start by talking about how you became interested in Alzheimer’s, dementia and cognitive health.

Dr. Richard Isaacson (RI): When I was in high school, my Uncle Bob was diagnosed with Alzheimer’s. Back then it was called senility or senile dementia. We didn’t know what it was, but he definitely changed. Initially, it was little things we blamed on age. Then, as he got worse, it wasn’t just his memory, it was behavior and personality. That was the first time I saw Alzheimer’s disease.

Throughout medical school, I was interested in the brain and planning to do neurology, which was the most challenging subject for me. Also, my brother is a neurologist who specializes in Parkinson’s, so maybe there’s something in my DNA.

I’ve had four family members with Alzheimer’s disease, so I’ve seen it from very early to late stage, when people go into institutional care. I got most involved with a cousin when she was diagnosed with memory issues. After I talked to her primary care doctor, I was certain I made the right choice to specialize in Alzheimer’s disease.

JL: You definitely have a deep personal interest in this. Can you tell us about your work at Weill Cornell Medicine/NewYork-Presbyterian Hospital?

RI: In 2005, I finished my training and in 2009, I saw an Alzheimer’s patient whose son was a doctor. After the diagnosis, he asked, “So, Isaacson, I know you have several family members with this disease. What do you do to try to prevent it?” In 2009, I also saw my first patient referred for Alzheimer’s risk reduction. Over the next several years, about 20 percent of my practice was focused on family members of patients with Alzheimer’s to determine if they could do anything to reduce their risk.

In 2013, I was recruited by Weill Cornell Medicine to continue that work on a full-time basis. Now, 20 percent of my work is treatment that includes mild cognitive impairment due to Alzheimer’s as well as Alzheimer’s disease dementia. In 2013, we also opened up the Alzheimer’s Prevention Clinic, which takes a deep dive into a person’s risk. We try to identify their modifiable risks versus their non-modifiable risks, and then put together a personalized plan, based on genetics and multiple other factors. The term for this process is “clinical precision medicine.” The term “precision medicine” was coined at Cornell.

Clinical precision medicine is the best term because there is no one-size-fits-all approach when it comes to Alzheimer’s treatment, Alzheimer’s risk reduction, or the path towards Alzheimer’s prevention.

JL: Were you concerned about the name being misleading or leading people to believe that there is actually more than you can deliver?

RI: I’ve been extraordinarily careful about using the word prevention. If you look on our flyers, we say, “A new approach to brain health,” or we say, “A personalized approach to cognitive health.” In our verbiage, we don’t use the terms “Alzheimer’s” and “prevention” in the same sentence frequently.

But, with our stake in the ground, we finally decided to be courageous and controversial and put the words “Alzheimer’s” and “prevention” in the same sentence and we added the word “clinic.”

The key here is that, in 2016, we can use these terms together similar to the way we do with other diseases. For example, when I say you can prevent a heart attack or you can prevent a stroke, I have to ask, can you really prevent a heart attack or stroke? Maybe, but you can’t prevent all heart attacks and strokes.

Based on our hypothesis, supported by the data and our observations, a subset of patients who are at risk of Alzheimer’s disease can prevent Alzheimer’s, or at least delay it long enough for the development of a blockbuster drug. In other words, through lifestyle and other medical changes, they can effectively prevent Alzheimer’s disease.

The term “Alzheimer’s prevention” is still controversial, but with Alzheimer’s prevention trials going on now, people see me when they are over 65 to see if they qualify for an Alzheimer’s prevention trial.

The A4 study has just changed the way the whole field will look at Alzheimer’s disease and, hopefully, make the largest impact on Alzheimer’s disease. That being said, we have five years or more until we see any data, and we don’t have a blockbuster drug on the horizon yet.

In a clinical setting, we put people on an evidence-based, relatively low-risk, personalized, and clinically precise intervention plan to reduce risk. This is not something where someone says, “Okay, exercise and eat better.” This is, “Well let’s see, the evidence on nutrition is X, but your nutritional biomarkers are Y, Z, A, D, E, and K, so let’s tell you to eat the following...” It’s a customized plan that is so customized that, right now, we’re one of only three Alzheimer’s prevention type clinics in the United States.

JL: Where are the other two?

RI: The Alzheimer's Prevention Program at Cedars Sinai in Los Angeles and at the University of Alabama at Birmingham. Their title of the clinic is The UAB Alzheimer’s Disease Risk Assessment and Intervention Clinic, which is, I would say, a more accurate term and a more careful term. Actually, it may be the best title. Dr. David Geldmacher was too cautious to put the words Alzheimer’s and prevention together. I have always felt okay about it because if I have an Alzheimer’s prevention clinical trial, that legitimizes it in some way.

When it comes down to it, we are applying the best evidence in terms of the randomized control trials. We are also applying our best epidemiological evidence to reduce someone’s risk for Alzheimer’s. Similar to heart disease or stroke, we are trying to reduce risk or delay onset. The problem is if someone thinks Alzheimer’s is inevitable, the default is to do nothing proactively to protect themselves or reduce their risk. The number one reason patients in my clinic are not proactive is fear of the worst disease on Earth.

JL: There are things that are particularly terrifying about Alzheimer’s.

RI: When people get the notion that there’s nothing they can do and they keep eating a certain way, don’t see their primary care doctor, don’t take their blood pressure medicines or fight their diabetes, they haven’t addressed easy modifiable risk factors that can protect brain function. We now have enough evidence to say that.

JL: That’s an important distinction. Controlling things that you can control to maintain health and, as a byproduct, maintaining brain health is relevant. Even in the face of a difficult disease, the hope is that you’re going to improve the quality of life and the outcome for the individual.

RI: Our team collectively spends up to seven hours for every patient to give that individualized “What can you do to reduce your risk?” Each patient has to fill out a 45-minute survey and take a 45-minute online course about the genetics, the risk factors, and the stages of Alzheimer’s. I see each patient for an hour and a half. We do an hour and a half of cognitive testing, body measurements and cognitive games on the computer. These are followed by a team discussion conference that takes 20 to 30 minutes per patient.

The field is in its infancy, so we literally learn every day. What we’re seeing now, and we have recently published some preliminary data on this, is that if people take control of their brain health and listen to the things that we tell them to do, there are certain areas of their cognition that will improve. As an example, processing speed will improve. Executive function will improve and this is not just “practice effect.” This is six months later, validated data in multiple domains. We’re improving cognitive function.

JL: Are you improving memory?

RI: We’re not improving memory as robustly. Memory has been about the same. Improving memory is the hardest thing. But executive function, processing speed and overall cognitive function are absolutely improving in people that are the most compliant.

Biomarkers are also improving. Cholesterol and omega-3 fatty acid levels in the blood may improve. Homocysteine may come down and B vitamin levels may come up. Low vitamin D has been corrected. If we can hit this disease from a metabolic perspective before the amyloid gets there, then we can delay amyloid from depositing. That’s what we are looking for.

Read more of the interview with Dr. Richard Isaacson in the Fall 2016 newsletter.

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