Hope on the Horizon: A Special Report on Alzheimer Research

Are you caring for a loved one with dementia? You don't have to figure this out all on your own. Welcome to Truth, Lies Alzheimer's, the show that helps you reimagine a new relationship with your loved one, a relationship a little more free of stress and anxiety. Join host Lisa Skinner and her 30-plus years of experience as she guides you on a new path to a better relationship with those you care for. Here's Lisa.

Hi everybody. Welcome to a brand new episode of The Truth, Lies Alzheimer's Show. I'm Lisa Skinner, your host, and I am so excited with the information that I have to share with you today. I actually had planned on presenting a different topic, but my AARP bulletin came yesterday, and I saw the title, which is a special report, The Future of Alzheimer's: Why Doctors Have New Hope About the Disease and What It Means for Us. So I started reading it, and I think I feel more encouraged about the future of Alzheimer's disease than I have ever. 30 years of doing this professionally, 50 years since my grandmother was diagnosed with Alzheimer's disease, and I pick up this story, this special report, and I feel so hopeful and so encouraged that we finally are on a positive track to be able to kick this disease where it counts. We're not there yet. This is ba— still baby steps, but at least they are steps in a positive direction. I saw the light at the end of the tunnel when I finished reading this. So I am going to share this information with all of you, and I hope you feel the encouragement and the hope that I'm feeling now. So here we go. Alzheimer's: New Learnings, Rising Hope. Since its discovery 117 years ago, the brain disease has stymied researchers. Isn't that the absolute truth? But that has begun to change, and for the first time ever, ways to prevent, slow, and even treat the disease are emerging. Leonard Chirez called his partner in a panic. I card machine at the gas station, so I drove to 3, says Chirez, a retired floral designer in Phoenix. I kept forgetting things. Well, that was in 2018. One year later, Chirez, 58, was diagnosed with mild cognitive impairment. And shortly thereafter, he was diagnosed with Alzheimer's disease. Since June of 2023, he has received twice-monthly infusions of Lecanemab, or also known as Leqembi, the headline-grabbing medication approved last year by the FDA that removes Alzheimer's hallmark plaques from the brain and slows down the memory loss. I think I'll have more days of happiness, Shirez says. It is a measure of how bleak the outlook for patients was that lecanemab garnered so much attention and hope. It isn't a miracle drug. It doesn't stop, reverse, or cure this mind-robbing disorder. And on average, It can slow mental decline by a mere 5 months over an 18-month treatment period, the research is telling us. It comes with dangers of its own, including the risk of brain swelling and bleeding. Studies are ongoing, but despite all these drawbacks, it represents a huge breakthrough. A foundation on which the medical community can finally begin to build. Neurologist and Alzheimer's research Dr. Randall Bateman puts it this way: This is the beginning of the ability to treat and change the course of Alzheimer's disease. The first little victory. Only patients with early-stage symptomatic Alzheimer's disease and confirmed high levels of amyloid protein in the brain are candidates for Lecanemab. In a 2023 community-based Mayo Clinic study, it's showing only 8 to 17% of those were eligible based on the trial criteria. And it costs an estimated $6,636 annually, even with Medicare coverage. And people are finding this to be prohibitively expensive for them. Yet, after more than 40 years of studies, tens of billions of dollars spent in research funding, at least 146 failed drugs, and plenty of public controversy and private despair amongst Scientists, the approval of Lecanemab marks a major turning point in the fight against Alzheimer's. Woo-hoo! It's the first disease-modifying drug for Alzheimer's to receive traditional FDA approval and win standard Medicare coverage. Most significantly, Lecanemab is one of, in a handful, of recent advances expected to at last transform how the medical community diagnoses, treats, and eventually prevents one of America's most feared diseases. I've been doing this for 45 years, says geriatrician and neuroscientist Howard Phillett, MD, co-founder and chief science officer of the Alzheimer's Drug Discovery Foundation. This is truly a watershed time. Over the next 5 years, scientists anticipate more breakthroughs, convenient blood tests to diagnose Alzheimer's in your doctor's office, a variety of drugs that can attack the disease on many different fronts, a customized research-proven lifestyle strategies that will likely become New standards of care. Within 10 years, scientists say Alzheimer's may be handled in your doctor's office the way heart disease and diabetes are handled now, diagnosed via blood tests and treated with a combination of drugs and lifestyle strategies. The dream of patients, doctors, researchers, and society. Instead of just being known as a terminal disease, Alzheimer's could become treatable, preventable, and OMG, even reversible. There's no time to waste. It's a race against time. By 2030, 8.5 million older Americans are projected to have Alzheimer's disease. A half million of us will develop it just this year. Once it begins, there is no way to halt it. As brain cells die, connections between them wither, and the brain itself shrinks. Memory worsens, thinking skills decline, and navigating everyday life becomes less and less possible. At least a third of people with early-stage Alzheimer's slip into a more severe stage in about 3 years, putting Lecanemab and possibly other early-stage treatments out of reach. Because heredity plays a role, many of us with a family history— that would be me— of Alzheimer's disease have long looked to the future with dread. Rochelle Long, age 67, of Shaker Heights, Ohio, cares for her 86-year-old mother with advanced Alzheimer's disease while still working a full-time job. Her father, grandmother, 4 aunts, and an uncle all had this disorder. So far she's okay, but optimism comes hard. Drug companies have spent how many billions of dollars through the years, and this is where we are? Lon says it's disheartening. Even the most optimistic experts agree that lecanemab itself won't turn the tide, but it could become part of an arsenal that can. For the first time, we can bend the curve of cognitive decline, says Harvard Medical School neurologist Risa Sperling, MD, and director of the Center for Alzheimer's Research and Treatment at Brigham and Women's Hospital in Boston. Sperling is heading a new study looking at lecanemab to prevent Alzheimer's in people at risk. As a neurologist who takes care of patients and sometimes— and someone whose father and grandfather also died of the disease, I think an extra 5 to 6 months of relative stability and independence is worth it, she says. But it's still not good enough. We need a home run. And at last, the medical community may be getting its turn at bat. But why is this so difficult? Across the pharmaceutical industry, up to 90% of all experimental medicines that research clinical trials don't make it to the market, either because they don't work or they have bad side effects. Alzheimer's drug research has an even higher failure rate. From 2004 to the mid-2021, 98 experimental Alzheimer's drugs failed in later-stage human studies. More were abandoned in labs or early human trials. Listen to this. Not a single new drug for Alzheimer's was approved by the FDA for nearly 18 years. Among the research community, people were despondent. It was like a clinical depression across the field, Bateman says. One major obstacle has been the historical difficulty of diagnosing Alzheimer's. Brain scans have shown that 17 to 22% of participants in Alzheimer's studies in the recent past did not have amyloid plaque and may not have actually had the disease. And 36% of failed Phase 3 drug trials from 2004 to 2021 did not even test participants for the presence of amyloid plaques or tau tangles. Meaning their cognitive problems could have been due to something else. You're never going to get a positive result when you've got the wrong people in the trial, says Catherine Mummery, head of clinical trials at University College London's Dementia Research Center. Another major issue: researchers may have been too narrowly focused on one culprit. One quarter of the failed drugs were aimed at these amyloid plaques, globs of protein in the brain that were first spotted 117 years ago by German psychiatrist Alois Alzheimer in the brain of a woman with severe dementia. Since these sticky blobs were the defining feature of the disease, it made sense that they were the primary target of researchers. The reason we've been so focused on plaques for so long is that they really stand out as soon as you look at the brains of people with Alzheimer's disease, says Kyle Travaglia, a scientist at the Allen Institute for Brain Science in Seattle, where he's a part of a team creating an atlas cataloging how thousands of different types of brain cells are changed in Alzheimer's disease. You see these giant ugly balls all over the brain. It wasn't unreasonable to look at them initially, yet drug after drug developed to target these amyloid plaques, most notably aducanumab, An earlier drug similar to lecanemab that was recently discontinued failed to show any clear impact on the cognitive decline of patients. Lecanemab is the first to show even modest success. Donanemab, which also clears amyloid plaques and slows disease progression, is expected to receive full FDA approval this year. And researchers are beginning to look at using focused ultrasound to open the blood-brain barrier and amp up the effectiveness of anti-amyloid drugs. In January, a West Virginia University study of 3 people that combined focused ultrasound with drug infusions removed more amyloid than the drug did alone. So these are the new approaches and our new hope. Other theories about what triggers Alzheimer's are getting more and more attention, and drugs that target culprits other than amyloid are rare— are moving into the early and late-stage human trials. In 2016, 50% of disease-modifying Alzheimer's drugs in human studies were aimed at amyloid plaque. By 2023, of 141 treatments in human trials, 84% of them were not for amyloid. Phyllis says the intensity and variety of research and lessons learned during years of frustration should lead to faster progress. Targeting amyloid is significant, he says, but it's not the whole story. There's a growing consensus that several factors might work together to cause the disease. Researchers continue to study amyloid plaques, but other human trials are underway on drugs designed to reduce brain inflammation, protect synapses, which are parts of the brain cells that communicate with one another, and improve aspects of brain metabolism, such as processing blood sugar, the brain's preferred fuel. In particular, researchers take— are taking a harder look at tau tangles, which are globs of protein that form inside the brain cells themselves. One medicine attracting a lot of attention is called B2b080. In a trial led by Mumery at the University College in London, it was the first anti-tau drug to successfully remove these damaging protein tangles from brain cells in a human study. Tau tangles in the brain seem to mirror much closer to the cognitive symptoms that people actually have, Bateman says. A lot of us think that's a clue. If we could neutralize tau, people's symptoms could be better managed. At the University of California, San Francisco, a study called the Alzheimer's Tau Platform form recently won a $151 million grant from the National Institutes of Health to test two anti-Tau drugs plus an anti-amyloid drug that will be given together to 900 people with early-stage disease. At a certain point with amyloid accumulation, Tau gets sparked like a forest fire that really starts to do damage, Mummery says. On a different front, Finnish researchers launched a study that combines brain-healthy lifestyle steps with metformin, a diabetes drug that might improve blood sugar processing in the brain. The study will look at the effects of lifestyle plus the medication in people at risk for Alzheimer's and dementia who do not have thinking and memory problems. The brain is only 3% of our body weight but uses 20 to 25% of the body's energy, mostly from glucose, Philip explains. Trouble absorbing blood sugar, called insulin resistance, does increase with age. If the brain is deprived of energy, the neurons can die, says Philip, whose foundation helps the study. We want to see if the combination would have more benefits than either one alone. Having drugs against these various factors, Philip says, means that within 10 years, customized multi-drug treatments will likely be described based on a simple blood test. And then in parentheses it says, an analogy would be our approach to treating heart disease, which might involve cholesterol medications, blood pressure pills, blood sugar controls, dietary changes, or a combination of treatments. We are starting to give combination drugs in trials, Mumrey says. I believe that in 10 years' time, we will have blood biomarkers that give a fingerprint of what your disease looks like. We'll be able to use that to define an individualized treatment regime. We'll be thinking about brain health in terms of prevention more than just dementia symptoms. I'm an optimist, she adds. We have a foundation. Once you have that foundation, the research can be accelerated. Is your brain on fire? I've always been intrigued by inflammation, says Linda Van Eldick, director of the Sanders Brown Center on Aging and the Alzheimer's Disease Research Center at the University of Kentucky in Lexington. She says chronic inflammation may be one of the primary drivers of Alzheimer's. On a separate note, we are hearing this more and more and more. Van Eldik studies microglia, immune cells that patrol the brain by the tens of billions. Normally they work like trash trucks gobbling up little scraps of amyloid protein waste before it can cause trouble. But when overwhelmed by inflammation, microglia pump out a torrent of inflammatory chemicals called cytokines. Cytokines damage nerve cells or neurons and synapses, reducing communication between the cells, she explains. It's a vicious cycle. When cells are damaged by cytokines, microglia start producing more inflammation. Well, you then get more damage. Then you get more inflammation, Van Eldik says. This may explain why aging, head injuries, stroke, and other brain insults increase risk for Alzheimer's and other dementia, she says. Then Eldik's NIH, National Institutes of Health, funded research includes versions of an anti-inflammation drug candidate that blocks microglia from overproducing inflammatory compounds without stopping their normal trash collection duty, she says, in Phase 1 clinical studies. The drug was found to be safe in healthy adults. It is currently being tested in people who had strokes caused by brain bleeding and with brain cancers treated by radiation. Now, if successful, Van Eldik expects the drug will be tested next in people who have Alzheimer's disease. She also expects it to be used in other cell-damaging brain conditions in which abnormal inflammation plays a role. This drug has the potential to be a first-in-class disease-modifying therapy for Alzheimer's disease and related dementia, Van Eldik says. Controlling neuroinflammation is at the forefront of new treatment ideas for Alzheimer's, Philip agrees. In 2023, there were more drugs in human trials for inflammation than for any other Alzheimer's disease-modifying factor. And Phillips says inflammation drugs could be among the first Alzheimer's compounds to win FDA approval in the next 3 to 5 years. Well, the battle on the home front continues. The difficulty in diagnosing Alzheimer's accurately has long hindered scientists' ability to study this disease. Historically, it could be confirmed only by examining the brain after death. Today, researchers can make a firm diagnosis of Alzheimer's by spotting amyloid plaque via positron emission tomography, or also known as the PET scan, or by testing for its presence with a lumbar puncture, says Ronald Petersen, MD, who is a Mayo Clinic neurologist and Alzheimer's researcher. But the first one is expensive. And the second one is invasive, so they're not routinely used. On a side note, a lot of insurance companies are not covering PET scans, and they are primarily being used in clinical trials right now. New and on-the-horizon blood tests that measure amyloid and tau in the brain aid researchers in tracking brain changes during studies. These blood tests are beginning to be used in doctors' offices. Sperling expects tests to be available in the next year, showing not just how much amyloid is in the brain, but whether it is triggering the explosion of tau that seems to torpedo our thinking and memory. This could help in the future determine risk in people who do not have Alzheimer's symptoms. We're going to do a much better job of predicting individual risk, she says, and that's significant, not just for treatment, but in terms of prevention as well. For all the deep science that surrounds the war on Alzheimer's, One of the most important weapons against the disease remains the simplest. Guess what that is, folks? Healthy living lifestyle choices. In that way, late-life Alzheimer's resembles heart disease, diabetes, and many other chronic conditions linked to aging. There is, however, a genetic component, yet so much of prevention is in our own hands. A 2022 University of Minnesota study found that an estimated 41% of Alzheimer's and related dementias were attributed to a dozen modifiable risk factors. Of which high blood pressure, obesity, and physical inactivity had the most impact. People need to know, what are my risk factors for Alzheimer's and other dementias? And are they things I can do something about? Says Christine Yaffe, MD, director of the Center for Population Brain Health at UCSF. Yaffe was the leader, was the lead researcher on a November 2023 study of 172 adults aged 70 to 89 who had 2 or more risk factors for dementia. Those who worked on one or more personally chosen risk factors for 2 years boosted their scores. On tests of thinking and memory and lowered their dementia risk more than those who simply received educational materials. Instead of a one-size-fits-all program, we wanted to see what would happen if we personalized it, Yaffe said. Strategies include taking care of high blood pressure, diabetes, and/or depression. Exercising, getting sound sleep, socializing, and quitting smoking. Dean Ornish, MD, founder of the nonprofit Preventive Medicine Research Institute and clinical professor of medicine at UCSF, is directing the first randomized controlled trial to determine if the same Lifestyle changes that he pioneered to reverse coronary heart disease might slow, stop, or even reverse the progression of mild cognitive impairment due to Alzheimer's disease. What's good for your heart is also good for your brain because they share many of the same underlying biological mechanisms, Ornish says. We're at a state of evidence with Alzheimer's similar to where we were 45 years ago with coronary artery disease. At that time, it was thought that heart disease could only get worse. We found that bigger lifestyle changes could often reverse the, the progression of heart disease. We are now studying if the same may be true for mild cognitive impairment due to Alzheimer's disease as well. One man shared, I have a sense of hope. Undo It, a book Ornish wrote with his wife Anne, describes his lifestyle medicine program for both heart disease and Alzheimer's. Prevention studies using drugs are gearing up. Researchers studying medications like lecanemab in people with early evidence of Alzheimer's brain changes who do not yet have life-changing thinking and memory problems. And in the future, Sperling says, drugs could be started before memory troubles appear, the way people with high cholesterol take statins. To lower their risk for heart attack, and those with diabetes who take blood sugar-lowering drugs to protect against complications such as kidney disease. This is the way forward, she says. It's exactly what we do in heart disease and diabetes. We lower cholesterol before somebody actually has a heart attack. And this is what we have to do in Alzheimer's disease. For the first time, she says, it is very feasible. So what does that tell us, folks? Get out of that chair and get walking, exercising. Next time you drive through a fast food restaurant and get a hamburger, think twice about shoveling it down your throat, and all the other things that I have talked about that are known risk factors for increasing your risk of developing Alzheimer's disease. And if you've listened to those episodes where I've shared those strategies, you already know that some of those risk factors are modifiable. Some are not. But the more that apply to you, the higher your risk becomes. So I hope this has been encouraging news for you today. I do see, um, a rainbow out there, a double rainbow for the first time in decades. As far as the future of being able to eradicate or even minimize the occurrence of developing Alzheimer's disease. So thanks for being here with us today, and I'll bring you a new episode next week. Oh, next week we have a special guest. Her name is Heather Thompson, and she's going to be here to talk to us about Hospice care. So make sure you tune in for that episode. Have a great week, everybody, and we'll see you again very soon. Thanks for being here. Bye-bye.

Thank you for listening to Truth, Lies, and Alzheimer's. We hope you found something in today's episode that helps. We understand that caring for a loved one with dementia can be the challenge of a lifetime. But you don't have to do it alone. If you're ready for exclusive access to even more great content and resources, head on over to Facebook and join Lisa Skinner's Minding Dementia support group. We're a community of like-minded caregivers, and we're here to help.