COMMENTARY

Targeting Alzheimer Disease Risk Reduction to Each Patient

Richard S. Isaacson, MD

Disclosures

June 15, 2017

Hi. My name is Richard Isaacson. I'm director of the Alzheimer's Prevention Clinic at Weill Cornell Medicine and NewYork-Presbyterian.

In a recent profile on Medscape, there was a nice overview about the approach to the management of an Alzheimer's prevention patient. This article generated a lot of discussion. I wanted to take a deeper dive into exactly what we do in the Alzheimer's Prevention Clinic and how any clinician may be able to approach reducing a person's risk for Alzheimer disease and giving very specific targeted approaches.

In that profile, there was a picture of me with my hands forming a triangle. This really underscores how every piece of data, when it comes to Alzheimer's prevention, needs to be triangulated. What does this mean? The ABCs of Alzheimer's prevention are like the three points of a triangle. "A" stands for anthropometrics or body composition. "B" stands for blood biomarkers. That can include genetics. It can also include lipids, metabolism markers, nutritional markers, and inflammation. "C" stands for cognition or cognitive measures.

The key take-home point with this is, in an effort to assess a person, just like you have the triangle and the three points, there are two ways of communication. The patient sitting on one side gives the clinical history. Once the doctor hears the clinical history and interprets the A, B, and C, only then can a physician give back a personalized or precision-based medicine approach to Alzheimer's prevention.

In the next couple of minutes, let's try to go into more detail. First "A": anthropometrics or body composition. In body composition, we use a biometric scale. We look at percentage of body fat. We look at lean, dry muscle mass. In this sense, we can then understand not only whether a person is overweight based on their BMI, but where the fat is and what we can we do to help a person to reduce that fat. Is it metabolically an active fat? Problems with metabolism increase insulin resistance. That's one way to fast-forward the button on Alzheimer's disease and really increase amyloid deposition in the brain.

The "B" of the triangle is blood biomarkers. General laboratory results that we look at include lipids. We look at metabolism markers, inflammatory markers, and nutritional markers as well. We also look at genetics. When it comes to cholesterol, we want to optimize cholesterol. We want to look at metabolism. When it comes to hemoglobin A1c, fasting insulin, as well as fasting blood sugar, those are the things we want to make sure are in adequate control. What is adequate for brain health? That's a little tricky. We try to reduce metabolic and cardiovascular risk factors, [since doing so], in our clinical experience, can have a positive effect on brain health.

When it comes to cholesterol biomarkers, increased cholesterol usually equals decreased executive function on an executive function task. When it comes to increased metabolic markers, that usually correlates with impaired memory function or suboptimal memory function on a cognitive task. These are the types of focused target interventions that we do in our clinic for Alzheimer's prevention and risk reduction.

When it comes to nutritional markers, we look at omega-3 fatty acid levels. We look at a variety of other markers as well. Finally, we do look at genetics. I don't think most practitioners out there are ready to go down this road, but, for example, APOE4-positive versus -negative patients may need different interventions. That is our blood biomarker overview, although there are more details that we can go into.

When we talk about cognitive function [the "C" of the triangle], we, in our clinic, use computer-based cognitive testing. We use the NIH Toolbox. Practically speaking, using computer-based testing may be more sensitive in a population that does not have cognitive decline. We also use more traditional measures like the Trail Making Test, animal naming, and the Mini-mental State Exam and paragraph recall. We do use a variety of tools out there to try to set a baseline and then determine where to intervene when it comes to overall risk.

Finally, we have to take into consideration what the patient tells you. The clinical history is as important as any of these three points of the triangle. The clinical history starts with knowing where the person is from, understanding their demographic and background history, and understanding their cognitive trajectory. How they performed in high school, where did they go for college and what was their GPA? What were their standardized test scores?

This is a really helpful tidbit that we've learned in the program. Where there is an increasing cognitive trajectory, meaning someone who improves over time, there is often an element or neurodevelopmental diversity. This may even predict a person's APOE4 status. For example, people who are born with an APOE4 gene tend to have smaller brains, even in infancy.

We then ask a variety of different questions about exercise patterns. How much cardio? How much weight training? Sleep patterns-not just how many hours, but a variety of other detailed questions. Any changes over time? We ask about mood. We ask about cognitive activities. Do they play a musical instrument? Do they take adult education classes? Finally, stress mitigation. We take all of this into consideration along with past medical history and current medications, which may either have a protective or harmful effect on brain health over time. Only then can we put together a comprehensive plan.

Hopefully, in the future, the book on Alzheimer's risk reduction and intervention will be written. Currently, I think we are only just about at the first chapter. I do think that clinicians out there can make targeted interventions based on all of this data in an effort to reduce someone's risk based on the best available evidence. Thanks so much.

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