S1 Episode 56: Genetics, Metabolism, and Alzheimer’s Disease

One in three cases of Alzheimer’s disease may be preventable, but some cases are quite predictable. Dr. Richard Isaacson, Director of the Alzheimer’s Prevention Clinic at Weill Cornell Medicine, explains how scientists look at genetics, lifestyle, and medical history to evaluate an individual’s risk of developing the disease.

Dr. Phil Stieg: This is Dr. Phil Stieg. Thanks for making this show one of Apple’s top 25 life sciences podcasts. It is an achievement we are very proud of. I also want to thank my guests, the many fascinating medical experts and neuroscientists who joined me each episode to share their insights and scientific discoveries, the patients who share their inspiring stories, our executive producer, Licia Hahn, our musical producer, Karen Driscoll, and the production team at The Podcast Authority for producing the show. Stay tuned for more episodes of This Is Your Brain in 2021. Happy New Year and wishing you all good brain health.

Dr. Stieg: Happy to have Dr. Richard Isaacson back with me today. He is a director of Weill Cornell’s Alzheimer’s prevention clinic and memory disorders program. And one of the leading authorities on Alzheimer’s disease. Richard, welcome. What are some of the common misconceptions about Alzheimer’s disease?

Dr. Richard Isaacson: The major misconception about Alzheimer’s disease is that there is nothing you can do that. There is nothing a person can do to to protect their brains and reduce risk. And I hear this all the time. My mom did everything right, and still got Alzheimer’s. And I get that. One of the three cases of Alzheimer’s may be preventable. The other two out of three cases, unfortunately are not, and maybe we can delay it by a year, two years or five years.

Dr. Stieg: What age do you suggest people start thinking about this?

Dr. Isaacson: That’s a good question. I’m not sure we know the answer to this yet. And I would say my answer has changed. I mean, we started the Alzheimer’s prevention clinic at Weill Cornell Medicine in New York Presbyterian back in 2013. And I can tell you that this field has exploded and I have learned so much, I’m learning so much every day in about more than half of the things I recommend to patients today, I didn’t even know about in 2013 and that wasn’t that long ago. So I think if I would’ve had to answer to this question a long time ago, I would have said probably 40 is a good baseline.

I don’t agree with that anymore. We see patients age 25 and above, and you know, I’ve seen people in their late twenties that have some degree of something and I can’t exactly put my finger on it, but something’s going on. I think for the vast majority of people, thirties and forties is reasonable. I think if you ask most Alzheimer’s experts out there, they’ll probably say fifties or sixties, I think some will say 65. And that’s just a round number that I don’t agree with in any way, shape or form, because again, this disease starts decades before symptoms. I think it depends on family history.

I think it depends on risk, but twenties, thirties, or forties is probably a decent time

Dr. Stieg: Given the healthcare financing climate. Do you think that the insurance companies are going to say, we’re not going to pay for all of this neuropsychological stuff? If you’re that worried about having Alzheimer’s go get the definitive tests, number one. Number two, is there the definitive test.

Dr. Isaacson: Great question. And unfortunately, our medical system is really good at paying a lot of money when people get sick. But unfortunately our medical system is not so good at investing money in preventative healthcare and reimbursing for preventative healthcare. So, you know, simply put, some third-party payers in the government just won’t pay for preventative care to get that cognitive baseline. So it’s unfortunate, but I hope the climate will change. You know, we’re now really studying the cost effectiveness of our care in putting in grants so that we can specifically research this.

What I would say is we don’t have a perfect, definitive Alzheimer’s test that someone can take right now, especially on the broad scale that’s cost-effective, easy to obtain, that can definitively say, do, does this person have Alzheimer’s or not? That being said, there were really fancy tests out there. There are PET scans, amyloid PET scans. Amyloid is the bad protein. It’s a protein that gets gunked up in the brains of people with Alzheimer’s. And they’re now the union, since the 2012 on the FDA has approved tracers or brain scan studies where they inject something that labels or binds to this amyloid, and you can see the pictures light up.

And that means that if a person has amyloid in their brain and they have symptoms similar to Alzheimer’s, then it is Alzheimer’s disease.

Dr. Stieg: Specifically that if we see amyloid, which is the breakdown of proteins in the brain on one of these PET scans, that one, you have Alzheimer’s or two you’re at high risk for developing Alzheimer’s.

Dr. Isaacson: So if the person is symptomatic and the symptoms are consistent with Alzheimer’s-like symptoms like we discussed, then it’s pretty definitive than the person has Alzheimer’s. If a random person in the community gets a brain scan and they have amyloid, and it’s just a random scan, it is absolutely not definitive that that person will develop Alzheimer’s disease.

Dr. Stieg: So have they done the study that looks at a random population of patients and compare it to, to patients with Alzheimer’s and shown that there’s an equal proportion of patients positive with this PET scan, as there are patients that have all of these

Dr. Isaacson: So different studies show different things, but the take home message here is at about a third of people with amyloid in their brain that have no symptoms will not develop Alzheimer’s dementia. And this is tricky and this is one of the confusing aspects of the field. And, and that’s why I’m a clinician. I see patients, I talk to patients and I manage the patients sitting in front of me. And I try not to get too caught up with some of the fancy brain imaging in the fancy tests. And I try to just treat the patient as best I can.

Dr. Stieg: But again, for the person that’s worried about this, you know, there’s this, a lot of have heard about APOE4 gene. And whether you have one of those genes or two of those genes and how that is predictive for developing, and can patients go get that? Would you order it if somebody asks you to let them do it?

Dr. Isaacson: So APOE E is a gene and you get to a three or four from mom or dad. So you’ll either be a three-three or two, three or four, four, or whatever it is getting. One copy of the four gene does increase your risk. Somewhat. If you have two copies, it increases it more. If you get a two from mom or dad, that’s actually protective. And a three basically means you’re at neutral risk. So With the advance of commercial-based testing. Anyone can really spit in the little tube, send it away. And six weeks later understand what their APOE gene is.

Here’s the tricky thing about this. People can have the APOE4 gene and never get Alzheimer’s. People can also not have the gene and absolutely get Alzheimer’s. The APOE4 gene in my opinion, is not used and shouldn’t be used to be a diagnostic test. What I use the test for and where I think the field is going is precision medicine. And what that means is different people with different genes need different therapies. People with the APOE4 gene may need therapies, A, B, and C. People without the APOE4 gene may need therapies, X, Y, and Z.

And we’ve, we’ve published several studies now and several reports that really detail this. So from a personalization of therapy perspective, I do think the APOE4 gene is helpful. And I do test it on my patients. From a diagnostic perspective, we don’t use it for that.

Dr. Stieg: You have the worried 30 or 40 year old patient. They say, gosh, I want to do everything I can to prevent this. I’d like a PET scan. I’d like to get the, the APOE4 test and they’re positive for both. Would you recommend that? So that then they could start to try to do the things that you are preaching about preventing the disease progression, right?

Dr. Isaacson: Right. So we tend to not order amyloid PET scans, especially in people in their thirties and forties. Now we do have research protocols that look at people between the ages of 40 to 65, where we do get amyloid PET scans on everybody. We also get MRIs and other studies, we also get the gene tests, but someone in their thirties or twenties or thirties, I would tend not to order a PET scan because the likelihood of it being positive is pretty low. That being said, there are people out there that will do this. They will beg and want and plead and, and force a doctor out there to have to order the scans and have the genes.

But, but again, the problem is these tests are not entirely definitive. If someone has amyloid, or if someone has the gene, it doesn’t mean that they’re going to get the disease. So regardless, we use the best information possible. And we look at their risk factors. We look at their exercise levels. We look—

Dr. Stieg: What are the risk factors?

Dr. Isaacson: There’s so many risk factors for Alzheimer’s and we’ll talk about some of the highest yield ones. But I think it’s really important for people to know that one out of every three cases of Alzheimer’s disease may be preventable if that person does everything right. And the modifiable risk factors are these everything right choices that people need to do. So, first of all, we look at blood and we look at cholesterol levels. We look at nutrition markers. We look at inflammatory markers. When we look at metabolism like, like blood sugar, we look at what a person’s body fat is, where the body fat is.

As the belly size gets larger. The memory center in the brain gets smaller. And what most people don’t realize is that people think of Alzheimer’s as a brain disease. I think of Alzheimer’s disease as a medical disease and a medical condition that later affects the brain. So as the belly size gets larger, the person’s metabolism gets slower. The person’s blood sugar goes up, the person is more at risk for pre-diabetes and diabetes. People with diabetes have twice the risk of Alzheimer’s. People with metabolic problems and high blood sugars have memory problems, Metabolism and memory are connected.

And most people, again, just don’t realize this. But the notion that you can do nothing is false. There are so many things, of course—

Dr. Stieg: No. And I looked at the list of things that you say one can do. And again, it fits into the perspective of heart health, brain health. You know, make sure you don’t get diabetes, get regular exercise, lower cholesterol, you know, all those things that, that, that we preach in the American Heart and the American Stroke Association. But there is a suggestion that regular discussions and social interactions and intimate relationships are beneficial for prolonging cognitive function.

Dr. Isaacson: Oh, definitely staying engaged, having a sense of purpose, learning a new language, a new skill, a new hobby, learning how to play a musical instrument—

Dr. Stieg: How does learning a new language help? What is what’s going on there?

Dr. Isaacson: So the, the, the most general way to describe it as it creates a cognitive backup system, and it really creates, you know, extra pathways that can be relied upon later when the usual pathways start to burn out. So learning something new, keeping the brain engaged is just a great way to build something called cognitive reserve or this cognitive backup system.

Dr. Stieg: What you tell us is, is really hopeful. Where are we in terms of the status of a cure for Alzheimer’s disease?

Dr. Isaacson: So, unfortunately when someone already has dementia due to Alzheimer’s, they’ve had Alzheimer’s disease in their brain for decades and curing Alzheimer’s when someone already is symptomatic is fraught with challenges. However, prevention, in my opinion is a cure. If you can prevent the disease from happening, or if you can prevent a person with the disease from developing dementia, then in, in a sense that’s a cure in itself.

Dr. Stieg: So give me five easy steps to prevention.

Dr. Friedman: So number one, get educated, get informed. Listen to this. What’s your appetite, go online. Read about, Prevention read about how a person can protect the risk over time, get educated, get informed. Number two, exercise. There is no one single thing a person can do today that is more powerful for brain health than exercise. And I don’t just mean taking your 5,000 or 10,000 steps. I mean, doing something real and getting your heart rate up, going, doing weight training, doing cardiovascular training every every few days. At least 150 to 180 minutes a week at a minimum, in my opinion, based on the evidence is the best thing a person can do to fight Alzheimer’s disease and protect the brain.

Number three, know your numbers, know your cholesterol, your blood sugar, your blood pressure to people don’t even realize. But in 2019, there was a study that showed that just aggressive or comprehensive control of blood pressure—just blood pressure alone. Under the supervision of a physician can reduce the likelihood of someone developing pre dementia by 19%. That’s just blood pressure control from the 140s over 80s to 120s over 70s, just blood pressure control. Know your numbers, know your vascular risk factors. Super important.

The fourth thing is nutrition. You are what you eat when it comes to brain health, eating a Mediterranean style diet, eating less carbs, less is more when it comes to the bad carbs. Good carbs, great green leafy vegetables, no problem. Berries, no problem. It’s the processed foods and processed carbs that aren’t good for the brain or the body, and also fish. Fatty fish, lake trout, mackerel, herring, albacore, tuna, wild, wild salmon sardines, super high in omega-3 fatty acids. And the final thing is: take a deep breath.

Stress is a great way to fast-forward brain aging. Take a deep breath, mind your sleep. Take care of yourself.

Dr. Stieg: Richard, thanks so much for being with me today and giving us insight on the steps we can all take to help prevent Alzheimer’s disease. We all look forward to having you back to discuss the results of your groundbreaking clinical.