A routine physical at the doctor’s office includes checking your heart rate and blood pressure, but what if you could also get a measure of how much inflammation there is in your brain in order to gauge whether you’re at risk for Alzheimer’s?
Rudy Tanzi, a professor of neurology at Harvard University, explores this question in his research. Tanzi says the future of Alzheimer’s prevention could look like this: You will get a brain scan around age 50. If your inflammation levels indicate that beta-amyloid—the toxic protein that accumulates into plaques in Alzheimer’s patients’ brains—is higher than normal, you would take a drug to lower beta-amyloid levels, just as you take medication to lower your cholesterol and prevent cardiovascular disease. Tanzi, who is currently working on a drug that will target beta-amyloid, is hopeful this process will be as efficient as it is effective.
But that kind of assessment isn’t available yet—so what can we do to lower Alzheimer’s risk in the meantime? Tanzi said making lifestyle changes related to sleep, exercise and diet will not only lower your risk of developing Alzheimer’s, but could also slow down the progression of the disease. His research shows that by changing your habits, including practicing meditation or making dietary changes, you can chemically modify your DNA by controlling your genes’ activity. According to Tanzi, these changes could ward off the neuroinflammation that leads to Alzheimer’s.
Being Patient spoke to Tanzi about how lifestyle changes can help those with copies of ApoE4—the gene most associated with Alzheimer’s—prevent cognitive decline and how changing your day-to-day habits could keep your brain healthy. This is part two of a two-part series on Being Patient’s discussion with Tanzi on Alzheimer’s research and prevention. Read part one here.
Being Patient: Many people who have been impacted by Alzheimer’s care about lifestyle factors, especially those who have one or two copies of the ApoE4 gene, which could increase your chances of developing Alzheimer’s. You’ve written several books with Deepak Chopra on brain health. For people with those genes, is making lifestyle changes to protect their brain worth it?
Dr. Tanzi: Yes, it’s worth it. These rare mutations in the early-onset genes that we found—like amyloid precursor protein (APP)—guarantee that someone will get the disease by 60 years old. My colleagues and I are working on a drug that will hopefully go into Phase 1 trials next year and could help people with these mutations.
However, the most common Alzheimer’s gene is ApoE4. If you have one or two copies of this gene, your risk of developing Alzheimer’s increases, but you’re not guaranteed to get the disease. Only a small percentage of mutations in Alzheimer’s are guaranteed to give you the disease. If you have an ApoE4 gene, lifestyle changes are not only worth it, but it’s obligatory to make every lifestyle change you can to stave off the disease.
We also know that ApoE4 works together with other genes. We now know 35 other Alzheimer’s genes that work together with ApoE4 to determine whether or not you’re at risk of developing Alzheimer’s. Our knowledge of genetics is much more sophisticated than it was years ago. I run the Cure Alzheimer’s Fund Alzheimer’s Genome Project (AGP) and we’re looking beyond ApoE and the first familial onset genes. We’re looking at three dozen genes, so there’s much more than ApoE4, and E4 is not insurmountable.
That’s why in the books I wrote with Deepak Chopra, Super Brain, Super Gene and The Healing Self, we provide lifestyle guidelines to help maintain brain health and stave off the disease. At Massachusetts General, we also started a new center: the McCance Center for Brain Health. We’re strictly studying what we can do in our lifestyle to promote brain health and stave off diseases like Alzheimer’s. We’re doing the hardcore science on these lifestyle changes.
Being Patient: You have coined the acronym SHIELD, which includes action steps people can take to keep the brain healthy. Can you tell us more about SHIELD?
Dr. Tanzi: I was thinking about an easy way to describe how you can shield your brain from Alzheimer’s. The six parts of SHIELD are the following:
It’s never been more important to get eight hours of sleep. You don’t have to get eight hours of consistent sleep. You want to go into a dream cycle like REM, but when you come out, you’ll go into the deepest sleep—slow-wave sleep. That’s when the ‘scrubbing bubbles’ (the microglia, or the janitors of our brain) hit; they eat up debris in the brain. Some of the debris get forced out of the brain into the spinal fluid. I like to call this kind of sleep ‘mental floss,’ because that’s when you clean your brain. You have to allow yourself to sleep enough during the day and to go in and out of enough dream cycles so that you go into this rinse cycle several times. If you only slept for five or six hours, take an hour-long nap and a second hour-long nap. If you don’t get eight hours of sleep, you will accumulate more debris that will cause more inflammation in the brain.
This term relates to FOMO (fear of missing out). If you don’t get back to someone with a text or email right away and vice versa, don’t flip out. Don’t have too many expectations of yourself and others. Expectation is a big cause of stress. Just let things go. Envision what you would like to happen, but don’t force it or stress out.
You can also meditate. We published a study that shows meditation helps change gene expression in Alzheimer’s pathology against inflammation. It was the first true quantification of how meditation affects your entire set of genes, or genome.
You’re stuck with the DNA you inherited, so you won’t change that. However, a real geneticist looks at the genome the way a captain or a sailor looks at the ocean: You respect it, and just when you think you know it, it’s going to take you out if you try to control it. But there’s something called epigenetics, which looks at how your lifestyle and habits control your genes’ activity. The DNA is the same, but genes (those making proteins or RNA) can be turned up or down. A gene making a certain protein can make a lot or a little of that protein. Then, picture 22,000 genes all making different proteins and RNAs, and turning the dial for each one. That creates programs, so you could have thousands of genes adjusting themselves up and down because you just changed your diet from eating junk food every day to organic healthy food.
The beautiful thing about epigenetics is that when those gene expression patterns change for the good, the DNA itself gets chemically modified, so those expression programs stick and stay with you. If you want to change a habit and do something consistently for 60 or 70 days, like staying away from junk food and processed food, your gene expression profiles change. Chemical modifications hit the DNA and lock it in until you take on a new habit. Those genes will make you only want good food. Epigenetics and neuroplasticity in the brain are adaptable to your lifestyle. The brain and those genes go on autopilot to make sure you stay with a routine without trying.
Interaction means staying social and going out of your way to see family and friends. The brain is a very social organ. It needs to know it’s connected to the hive. Right now, connectivity has never been higher, like with social media. However, social media is a double-edged sword because it also causes stress. Nevertheless, interacting and staying social is important. People who are lonely are at a higher risk for Alzheimer’s. That doesn’t necessarily mean people who are living alone. If you’re living alone and you’re happy about it, and you interact with people when you wish, that’s fine. But living alone and stressing out about it is called loneliness and that’s a risk factor for Alzheimer’s.
We have a new paper coming out in a couple months in the journal Science that was funded by the Cure Alzheimer’s Fund. We show how exercise causes the birth of new nerve cells in the hippocampus, the brain’s short-term memory area that gets inundated and attacked by Alzheimer’s. In Alzheimer’s mice, we showed that if you grow new nerve cells in the hippocampus, induced by exercise, you can make cognitively impaired mice better. The new nerve cells helped their brain. It’s kind of like growing your own stem cells without having to inject stem cells into the brain, which we still can’t do very well yet.
Exercise keeps your heart healthy. A lot of the attack on the brain as we get older is neurovascular, including strokes and mini strokes. Exercise helps keep the heart healthy. It reduces inflammation in the brain and turns on enzymes in the brain to clear the amyloid plaque. It’s never been more true that what’s good for the heart is good for the brain.
Learn New Things
This concept relates to making new synapses. You have one hundred billion neurons in your brain and trillions of connections, or synapses as they’re called, that make up the neural network. Every time you experience something new, your neural network changes. That’s called neuroplasticity. Alzheimer’s is caused by plaques and tangles in the brain, neuroinflammation and cell death. With Alzheimer’s, everything that happens in the brain leads to the loss of synapses. The more synapses you make in life, the more you can lose. We tell people about their synaptic reserve, which is especially important as they age. When you learn new things, you make new synapses. You also strengthen the synapses and pathways you already have because learning is always based on association. Anything new has to be connected to what you already know, so when you make new synapses, you connect them with the old synapses and strengthen those.
I tell people that when they’re going to retire, they shouldn’t just think about their financial reserve, but also their synaptic reserve—so they can enjoy their money. I play the piano and keyboards professionally and even though I’ve been playing since I was a kid, just the other day on the piano, I noticed my left hand was doing new things. It’s great to have both sides of the brain firing. When looking at functional MRIs, you can see that folks who have the most connectivity between the left and right brain age better. Your brain loves doing anything new, which is why you should force yourself to brush your teeth with your left hand instead of your right hand, put on your pants with the other leg first or take a different commute to work. These shifts really nurture the brain. Combine them with exercise, which makes you sleep better, interacting more with people and dealing with stress. These are all key.
Diet is immensely important. You are what you eat. For heart and brain health, there’s nothing better than a plant-based diet. I know there are trendy books that say we should just eat tons of red meat like cavemen did, but I remind people that we died at 25 years old back then when people followed the paleo diet. The Mediterraneans have been doing it right for thousands of years. The Mediterranean diet is better than anything.
I’m vegetarian, so I get my protein from other sources, but the Mediterranean diet says we should cut out red meat, eat more fish and lots of plant-based foods, nuts and fiber. Tomatoes and mushrooms are very good for you. Nothing’s been shown to be better than a Mediterranean diet and in the epidemiological studies.
There are also supplements. There’s a lot of stuff out there about brain supplements, but most of it is not scientifically tested. Most brain pills shove 40 ingredients into a small pill. Even though some of those ingredients are good for you, there’s no way in a pill that small that any of those ingredients will do anything, so you’re wasting $50 to $100 on nothing. But some of them that concentrate on one ingredient that can be good.
In our Alzheimer’s in a dish, we screened for natural products that might hit the plaques, tangles and neuroinflammation in the brain. There are a few supplements and ingredients that can be helpful, but people should check with their doctor before taking them. There’s cat’s claw, which is a vine from Peru. I started a company with a friend, Dr. Allan Snow, that offers a supplement called Percepta. This is cat’s claw mixed with MemorTea from the mountains of China. The cat’s claw hit the plaques and tangles and helped quell the neuroinflammation in our dish. The tea is meant to be an antioxidant to stop the free radicals from inflammation.
A lot of people take nicotinamide riboside, which is also called Niagen. A company called Crominex makes something called Tru Niagen, which is just nicotinamide riboside. That adds cellular energy. If a cell has enough energy, it’s less likely to make a tangle. If a microglial cell that’s normally good at housekeeping and cleaning up amyloid has enough energy, it’s less likely to become inflammatory and start killing nerve cells.
The third one is Ashwagandha. That has been shown to help export the plaque out of the brain. It can make some people sleep, so people generally take that one at night. The Ashwagandha has to come from the root, so I use the Ashwagandha that comes from a company called Douglas Labs.
In our center for brain health, we want to start doing trials on these supplements to see if we can stave off Alzheimer’s and promote brain health. There are very few supplements that I actually believe in; most of them are snake oil, but there are a few that can really help you.
Being Patient: Is it ever too late to practice SHIELD? What if you’ve already been diagnosed with dementia?
Dr. Tanzi: Absolutely not. The older you are, the more you should practice it. If you’ve already been diagnosed, we can’t say that SHIELD will cure you, but the hope is that it will slow down the disease. We’ve already tested the effect of meditation on your genes, so now, we’re going to take all the parts of SHIELD and do clinical trials that pharmaceutical companies will never do on lifestyle intervention and quantify their positive effects, looking at biomarkers, imaging and cognitive testing.
My colleagues and I also invented a device that tracks eye and head-eye movement as an indicator of inflammation in the brain. We’re using it to detect concussions in football. Rather than just having a neurologist swing his finger around, this device would track eye movement as an indicator of how much synaptic dysfunction and inflammation there is in the brain. Even though this device is being made for concussions, we think this could become like a blood pressure cuff for the brain. You test the baseline and do this test with movement to track inflammation in the brain. We want to combine everything to create a brain health index (BHI): biomarkers, blood tests and imaging. When you go to the doctors, you learn your heart rate and blood pressure, but this could allow you to also know your BHI.
Being Patient: If we know that plaques appear in our brain up to 20 years before we see symptoms of Alzheimer’s, should there be more studies on Alzheimer’s prevention and lifestyle factors? What should researchers focus on to change what people know about maintaining healthy brains?
Dr. Tanzi: This is very analogous to what we’ve done with heart disease and cancer. We now live our lives in a way that helps us avoid carcinogens. We keep track of what causes cancer. We keep track of our cholesterol to keep our hearts healthy. But we don’t diagnose Alzheimer’s disease until you have symptoms and enough damage in the brain that you’re already suffering from the early stages of dementia. Imagine if we did the same thing with cancer and said, “Oh, now you have a large tumor, pain and organ failure.” If we waited for symptoms before we treated cancer, then said, “OK, now we’re going to give you a tumor suppressor,” it wouldn’t work. If you wait until someone has a heart attack and say, “OK, now you should start taking medication to lower your cholesterol,” that wouldn’t work either. But that’s what we’ve been doing with Alzheimer’s. We have to change that.
Prevention against plaques will be treatment. If you start treating the pathology two decades before symptoms occur, you may never get the symptoms. Prevention may be what causes the plaques. Maybe if we find certain viruses or microbes that trigger the plaques, primary prevention could be antivirals, antimicrobials or vaccination against the microbes that trigger the plaques. We have to hit these pathologies way before symptoms appear, but we can’t wait for symptoms to treat this disease.
With that said, even for those who already have symptoms, if you hit the neuroinflammation and quell that—which is what we’re trying to do with some of these new therapies—there’s a chance we can help patients who already have the disease. But you have to hit the plaques and tangles early.
I’m working with my colleague, Steve Wagner, Ph.D., at UCSD on a drug called a gamma secretase modulator (GSM) that we invented 20 years ago. It’s finally coming to fruition with the help of the Cure Alzheimer’s Fund and the NIH’s Blueprint program. We’re hoping to get it into a Phase 1 clinical trial. That drug will hit the amyloid, even in people who have these early-onset familial mutations that guarantee the disease by age 60. This drug still works against those mutations in the dish in the mice. Our goal is to get this into trials. Then maybe someday, that drug will become the statin of Alzheimer’s; you keep your cholesterol down with those medications, but if you want to keep your amyloid down 20 years before symptoms occur, you could get a brain scan at age 50, see that your amyloid is higher than it should be and take this drug to get your amyloid down, just like for cholesterol medication. I think that’s how we’re going to nip this disease in the bud.
This interview has been edited for length and clarity.