Can Alzheimer's Be Prevented? The Neuroscience of Aging and Memory Loss

Inside your head lies the most complex structure in the world, the human brain. It weighs just about three pounds, yet it's home to some 86 billion neurons. The brain forms a memory. Even remembering your name is something that has caused by an underlying biological protein change in my brain. But what happens when the vast networks that hold our memories begin to fade away? For many, this is the first sign of Alzheimer's disease. And it fundamentally affects not just how you feel and think and your memory, but also can affect your motor skills and your ability to move and to function as a physical being in the world. The symptoms are all too plain to see, but their origins are still largely a mystery. The brain is one of the most complicated human organs, and it's very hard to study. It's famously called the black box because it's inside your skull and you can't put a needle in it to do a brain biopsy while you're alive. Here in the United States, more than 7 million Americans are living with Alzheimer's disease. By 2050, that number is projected to rise to nearly 13 million. There are 47 million Americans today in the United States that have the pathology of Alzheimer's starting silently in their brain before symptoms. That's why scientists are racing to detect the But as soon as someone detects memory changes, they should go to their doctor for the earliest diagnosis and potential for the earliest treat. It's a small organ, but it runs everything. And when one thing goes wrong, it starts to change and unravel. I'm David Rubinstein. For nearly a decade, I've interviewed some of the most interesting and powerful people in the world. Presidents, athletes, CEOs, entrepreneurs. I talk to them about their careers and their lives. Inevitably, we almost always end up talking about how they're living and how much they think about trying to live better. We're all trying to make sense of the mountain of new information available and the ambitious efforts underway to tackle the biggest health obstacles. Well, Longevity come with me as I talk with the leading experts in science and medicine and ask them the questions we all have, how to be healthier and ultimately, how to live longer. The brain gets its power from billions of neurons, tiny cells that help us read, remember, even move. Each one connects through countless synapses, building trillions of pathways. It's like a city that never sleeps. Electrical signals racing down invisible highways, lighting up with every thought, memory and emotion. At any moment, the mind is juggling countless tasks, spotting a face in the crowd, solving a problem, recalling a memory and sending instructions throughout the body. But like any other organ, the brain can break down. What is the difference between Alzheimer's and dementia? Alzheimer's is a very specific type of dementia. Dementia is really an umbrella term. It's like using the term cancer. And then you really have to drill down into what type, especially when you want to know about treatment options and Alzheimer's is no different. It is one of the several types of dementia and underlying causes are really important in understanding the lifetime risks, the how you're going to live with Alzheimer's and the potential for treatment. The most popular one that people hear about is Alzheimer's. It is also the one that is the most prevalent. Others are vascular dementia, temporal dementia, dementia with Lewy bodies. There are other types of dementia that are even sort of smaller in number, probably over 30 types of dementia. What exactly is Alzheimer's? That's the million billion dollar question. Alzheimer's disease is a neurodegenerative disease. It's a brain disorder where the brain ages rapidly and the brain declines over time. And there are certain proteins, pathologic proteins, something called amyloid. It's a sticky plaque and tau, these tau proteins that get tangled. And these proteins build up in the brain. The brain ages more quickly than we'd like and the brain shrinks. When someone develops Alzheimer's, the brain's nerve cells, those neurons, start losing their ability to connect with each other. The chemical messengers that help those cells communicate also begin to dwindle. Without them, learning new information becomes harder. And over time, the connections that already exist start to break down and the memory stored there slowly fade away. So what are the early signs that people have of Alzheimer's? So Alzheimer's is a brain disease that doesn't just always focus on memory loss, changes in thinking skills, but also it's a neuropsychiatric disease. People's behavior can change. They can be more fearful. I have Alzheimer's disease, early onset. They can even be more paranoid. I am not leaving my flat. Depression is a risk factor also for Alzheimer's disease. I don't know what's happening anymore. A person's sleep can be disjointed and changed. So since Alzheimer's is a brain disease, many different symptoms can occur, not just short-term memory loss. Sometimes people may miss certain signs of Alzheimer's. Is there a good indicator for the average person who doesn't have access to you? What should they think about whether they are doing something or are they forgetting something that might be a good early sign of Alzheimer's? So if someone has always been absent-minded, if someone has always had trouble remembering names, that's different. If someone was sharp, was on it, and then over time, over years, became less sharp, repeating stories, losing their keys, misplacing their cell phone, having trouble with technology, those are things that are more telltale signs. Now the person who discovered Alzheimer's, or at least gets the credit for it, is Dr. Alzheimer, who had a patient, as I understand it, and when he ultimately did an autopsy on that patient, he saw in the patient's brain some amyloid plaque. So to have Alzheimer's, do you automatically have to have this amyloid plaque? So that is a great question. And Dr. Alzheimer, in 1906, did publish a very short article in which he described his patient, Augusta D., and her brain tissue that he analyzed at autopsy. And in that brain tissue, he did describe two things, amyloid plaques and tau tangles. So he actually described both. And since then, the definition of Alzheimer's biologically is that you have to have the presence of both. So how do you know if you're likely to get Alzheimer's? Can you get it without having a genetic predisposition? Our primary answer to that is that if you have a first-degree relative who's been diagnosed with Alzheimer's, you're likely at an elevated risk. However, risk is very complicated. There is no guarantee that a person will have Alzheimer's unless they have a very specific autosomally dominant mutation, and that's very unique. It's very specific. And generally, those families know who they are because that type of autosomal dominant Alzheimer's is fully penetrant and generally also early in onset, anywhere between 40 to 60. A first-degree relative does increase your risk. There are some genes that can increase your risk. The most common one is ApoE4 in particular, which increases risk of Alzheimer's but is not a guarantee. There are people who live very healthily and aging into their 90s with ApoE4. Right now in the United States, we have roughly 330, 340 million people. What percentage of these people do you think have Alzheimer's or dementia? There are 47 million Americans today in the United States that have the pathology of Alzheimer's starting silently in their brain before symptoms. Our goal is to try to develop what we colloquially call the cholesterol test for the brain. Just like you go to your doctor and you get your cholesterol and you get your total cholesterol, your HDL, your LDL, which is the bad cholesterol, and triglycerides, one day, one day soon, and honestly today, we can check for different proteins, different markers, different names, but similar theory where we can check if a person is at risk for developing dementia or cognitive decline due to Alzheimer's disease. Now, I've often heard that if you want to prevent yourself from getting Alzheimer's or dementia, you can start doing crossword puzzles, you can learn a foreign language, take up a musical instrument. Is there any evidence that any of this works? You can do all the Sudoku you want, but you're just going to get better at Sudoku. When it comes to learning something new, a musical instrument, a language, absolutely. Even learning how to play a musical instrument midlife onward has been shown to reduce the chances of developing cognitive decline, dementia. Staying engaged, keeping the brain active, adult education classes. The more you do, the more you learn as we age, the more protected your brain will be. What should I do to kind of prevent Alzheimer's from coming, assuming there's not a predetermined genetic predisposition that's going to bring it to me? What should I do for a lifestyle? The first thing to note is that we're all at risk because we have a brain and the brain ages, just like the rest of our bodies. It's an organ that ages just the same. So we're all at risk, and we should all think about protecting our brain and our brain health and our cognition as we age. The Alzheimer's Association recently conducted a clinical trial testing whether healthy habits can protect the brain. The study found that older adults who maintain several healthy lifestyle habits at once saw a boost in brain function. That included staying active, eating a brain healthy diet, staying socially and mentally engaged, and keeping up with routine checkups. Researchers followed two groups over two years. One group received general health education and occasional check-ins, but the second group received more structured support, including in-person sessions focused on exercise, diet, mental stimulation, social connection, and health monitoring. The findings were promising. The structured group that had more intense attention was significantly improved in terms of cognitive memory. Conservatively speaking, they were one to two years cognitively younger. That is amazing, and that's only with aging. Now it is with a group of individuals that was at risk for dementia. The participants weren't elite athletes. Many were overweight, had chronic conditions like diabetes or high blood pressure, and yet their brain function still improved. The more we can protect it, the better we can be prepared for any onslaught that might come as we age associated with disease. Resilience is the key for aging in cognition. Coming up, sorting through Alzheimer's risk factors. One that specifically affects women during midlife. During the perimenopause transition, when women's estrogen drops rapidly in a certain woman with a certain specific set of genes, their increased risk of Alzheimer's during that transition. In 2023, the average life expectancy in the United States ranges from the late 70s to the early 80s. But with longer lives come challenging questions. Do our brains simply wear down with age, leading to Alzheimer's or other forms of dementia? Age is the number one risk factor for Alzheimer's disease and dementia. And, you know, the way that we live our lives, high blood pressure, high cholesterol, diabetes, the foods that we eat, a sedentary lifestyle, not being physically active. There are many different reasons why we think Alzheimer's disease is more common today. But age is the number one risk factor. Women, for example, are at higher risk of Alzheimer's than men during the perimenopause transition, when women's estrogen drops rapidly in a certain woman with a certain specific set of genes, their increased risk of Alzheimer's during that transition. In the U.S., millions are living with dementia. And this year alone, the cost of dementia has soared to 781 billion dollars. There's enormous costs for treating dementia, and that's because of the intense, in part because of the intense care that these people with dementia need. It's not just patients who are affected. There's formal caregiving, others, partners may have to give up their time and take time off to work to care for their loved ones. So that all adds up to a tremendous cost. Many caregivers reduce their work hours or leave their jobs, leading to eight billion dollars in lost earnings every year. For those living with dementia, the loss in quality of life is estimated at 302 billion dollars annually. To calculate these figures, researchers at USC Schaeffer Center developed a model drawing data from individuals' health, work status, family care arrangements, and personal finances, and tracked how these evolve over time. As research advances in the field, pharmaceutical companies are investing heavily in Alzheimer's treatments. It's one of the biggest kind of really untapped, you know, markets left for drug companies. You know, about seven million people in the U.S. have Alzheimer's disease. That's supposed to grow significantly as the population ages. There's fewer competitors. So there's many, many reasons for drug companies to want to get in. In 2023, the FDA approved the first drug to slow the progression of Alzheimer's disease. Last year it approved another. Both drugs target and help remove toxic amyloid plaques from the brain, though they only modestly slow the disease. But there is a cost. There are serious side effects from these drugs. There's something called amyloid-related imaging abnormalities. That is basically a polite name for brain swelling or brain bleeding. Now, most of the time the side effects, you know, are mild or even asymptomatic. But sometimes it can get quite serious, and there have been deaths associated in patients from the brain bleeding and brain swelling. How can you determine short of an autopsy if you have amyloid in your brain? So in the past, when I was in medical school, eons ago, that was the only way. Today, it's a simple blood test. Through the vein, through a finger prick, we can detect amyloid and tau. And in our lab, we detect hundreds of proteins, hundreds of brain proteins, just from the blood. If you would have asked me about blood five years ago, I would have said it was a pipe dream. Today, science has moved so far forward that we can rely, in fact, on blood tests. You can imagine that in the future, near future, this could be a part of your primary care's annual workup of your blood test. That is a complete game changer and transformational for our field in terms of detection. Now, many drug companies are experimenting on developing drugs that will deal with Alzheimer's. Is there any likely you would have a wonder drug coming along that will ensure that you can't get or won't get Alzheimer's? Is that likely? We already have so many drugs, so many interventions to get people off the road to Alzheimer's. Whether you think about lifestyle choices and exercise, whether you think about treating a risk factor, you've heard about the Ozempics, the Wegovys, the Mangiaros, the Zetbound, a category of drugs called GLP-1 drugs. I believe in the right dose, in the right patient, and for the right duration of time, these drugs can also be protective on brain health. Along with studies on prevention and risk reduction, researchers are also exploring vaccines and antibody-based therapies as possible game changers. Our current treatments are monoclonal antibodies against amyloid beta in particular, and that is a passive vaccination approach, because you're injecting an already created monoclonal antibody into the body. A vaccine is creating a piece of that protein itself so that your body creates the antibodies. You're not giving the antibody, you're actually asking the body to create an antibody. And we're actually moving earlier and earlier, and there are trials that we'll be reading out within the next two to three years that potentially, with these monoclonal antibodies, so it's passive vaccination, can tell us if we can stop this disease in its tracks or even slow it down earlier and prevent people from cognitive decline in stage three and four, which is mild cognitive impairment. Are there active vaccines in the pipeline? Yes, there are. Are they potentially exciting? Absolutely. No stone can be left unturned, because this disease is in such a strong trajectory that this is the time to study more, to do more, accelerate our research so that we can in fact get to that asymptomatic stage and slow or stop this disease. But scientists at University College London say new drugs alone aren't enough. They're calling for big changes in health care and public policy around the world so these treatments can truly make a difference. Coming up, new hope in the fight against Alzheimer's. Scientists say we may soon detect the disease before symptoms appear. I believe that in this decade we will be able to detect Alzheimer's changes in a silent phase of disease because that disease is there, very similar to cancer. This summer, Stanford researchers discovered that a younger brain, an immune system, can predict a longer life. But if a brain shows signs of aging, the risk of early death jumps by more than 180 percent. This Stanford study used a technique called proteomics that measures the levels of thousands of proteins in the blood and then they applied this to biological samples in a UK database from over 40,000 people. So this is sort of a statistical blood protein test that's searched in various organs for signs of aging and they found some signals in these tests that correlated to brain aging. It's these types of kind of brain aging tests and there have been a number of studies like this. But what you need to know is that they're not, at this point, they're not solid enough to be used at a level individual clinical diagnosis. They're really making statistical associations, searching for kind of like broad-based tests that might be used for signals of brain and other organ aging. So the best way to summarize to prevent getting Alzheimer's, if you can quote prevent it, would be to do what? The thing that I advocate for is to get educated and get informed. There are so many free resources out there. We did a randomized, controlled, NIH-funded trial. Through the comfort of your own cell phone, can do a risk assessment, can do a cognitive test, and then the software can tell the person what to do to reduce their risk. Sleep is critical. You know, you can exercise all you want, but if you're not and you're burning the candle at both ends and you're not sleeping, you can't get rid of that toxic protein, that amyloid protein that builds up in the brain of a person with Alzheimer's. So one way to think about it is exercise during the day, loosens up the protein, and adequate sleep during the night is when the trash gets taken out and that amyloid gets disposed of. So when I was growing up, people said, if you ate fish, that would help your brain. If you had carrots, that would help your eyesight. Is there any evidence that certain food will help your brain? So you are what you eat when it comes to brain health. The number one thing a person can do in terms of dietary approaches to staving off Alzheimer's disease is following a Mediterranean style diet. Green leafy vegetables, fatty fish like mackerel, lake trout, herring, albacore tuna, sardines, wild salmon a few times a week, dark cocoa powder, reducing wine, eating whole grains in moderation, eating a brain healthy diet. It's not just fats from fatty fish, but also olive oil, extra virgin olive oil, and avocados. There's brain healthy fats, there's proteins, and then there's antioxidants and vegetables that can really protect against Alzheimer's. We know that being physically active actually can help reduce our risk. We know that eating diets that are healthy can help reduce our risk. We know that strong relationships and social connection can also significantly reduce our risk of dementia. But just consider this, when people who are struggling with social disconnection, their increase in heart disease and stroke is around 30 percent, 30 percent increased risk. Their increased risk of dementia is around 50 percent. It's something that's essential that we need for survival. Just like when we don't have food and water, it can affect all of our systems and lead to illness, the same is true of our relationships as well. So for somebody that is watching now and says, okay, maybe I could have a predisposition to it, or maybe I might get it even if I don't have a predisposition, what should they do? Well, the first thing they should do is take a deep breath because Alzheimer's is scary and fear is paralyzing. I have four family members with this disease. I hate this disease. First, talk to your doctor. Manage risk factors. They should know their blood pressure. They should know their cholesterol. They should know their blood sugar. They should know their weight, their percent body fat, their muscle mass. As the belly size gets larger, the memory center in the brain gets smaller. I actually believe that Alzheimer's disease isn't a brain disease. I think it's a medical condition. And just like when someone has diabetes or high blood sugar for years and years and years, and it causes numbness in the toes and problems with their kidneys where they need dialysis, it's the same thing. If you control the medical risk factors that your doctor can help you with, that's when we can take someone off the road to Alzheimer's disease. So today, we cannot cure Alzheimer's. We can slow it down. That is more than we could say three years ago. However, I believe that in this decade, we will be able to detect Alzheimer's changes in a silent phase of disease because that disease is there. Very similar to cancer. We used to detect it in late stage. Is it possible to ever eliminate, in your view, Alzheimer's? Or because we're really dealing with aging, you're never going to eliminate it completely? In this decade, I do think there is incredible hope for us being able to go to our PCP, getting a blood test that tells us that there are some changes that should be addressed, getting medications and risk reduction strategies that will in fact slow or stop the disease in its tracks. What we see is that the future is turning Alzheimer's and perhaps even other dementia into a chronic disease. We can do that, but we will get there. I'm David Rubenstein. This is Bloomberg.