In this episode of the Truth, Lies Alzheimer's podcast, host Lisa Skinner reviews a March 18, 2024 BigThink article by Ross Pomeroy that critiques the newly approved Alzheimer’s antibodies lecanemab and the still‑pending donanemab. She frames the discussion with a COVID‑era analogy, warning listeners that medical information has often been presented without full transparency. Skinner outlines the trial results: lecanemab slowed cognitive decline by about 27% (≈0.45 points on an 18‑point scale) and donanemab by about 35% (≈3 points on a 144‑point combined scale). Both drugs effectively cleared amyloid plaques in two‑thirds to over 80% of participants, yet patients continued to decline, suggesting amyloid removal alone is insufficient. She details safety concerns—brain inflammation, micro‑bleeds, and three deaths in the donanemab trial—as well as the steep financial burden (≈$109,000 per patient per year for lecanemab, with similar projected costs for donanemab) and the extensive monitoring required (PET scans, genetic testing, regular infusions). Expert commentary is presented, ranging from skepticism about the amyloid hypothesis (Derek Lowe, Josh Bloom) to arguments that hope itself can be therapeutic (Chuck Dinerstein). The episode then pivots to prevention, citing Lancet data that roughly 40% of dementia cases could be delayed or prevented through lifestyle changes such as blood‑pressure control, reduced air‑pollution exposure, moderate alcohol use, learning a second language, and playing a musical instrument. Skinner concludes with practical advice for caregivers on how to discuss these treatments with clinicians, emphasizing informed questioning and the potential greater public‑health impact of preventive measures. She also promotes her Minding Dementia support group for ongoing caregiver support.
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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.
Hey everybody. Welcome to a brand new episode of The Truth, Lies Alzheimer's Show. I'm Lisa Skinner, your host. And as promised many times, I came across another new article about lecanumab and donanumab. And I promised everybody that I would keep you updated on every bit of information I can share with you. And one of the reasons why I feel so strongly about keeping you informed is if we all can kind of reflect back on COVID and all of the information that we received during the years that before the vaccinations came out. And it just seemed that to me anyway, and this is my personal opinion, that we were being told what they wanted us to know and what they wanted us to hear. Regardless of whether or not it was accurate information or not. I personally would have preferred that if they didn't know something, they should have just been straight with us and transparent and said, you know, we don't have all the information about this, but, you know, we are feverishly working on it. But that never happened. It's like they were just making stuff up as, as they went along. And I think a lot of the information that we got during that period of time was not always very accurate. And I don't want that to be the case for all of you on these— what they're calling game changer medications, because every time I read a new update on it, it seems like the efficacy and the status of these drugs are changing significantly. So I'm sharing this with you today because I know some of you have loved ones out there who are on these medications going through the infusions. And I want you to be informed on everything new that comes out about it so you can talk to your doctors about the information that comes out. All right. So this was written March 18th, 2024, and it's an article on BigThink.com. And the title of this article to me, and this is what caught my eye, compelling. Don't buy the hype on new breakthrough Alzheimer's treatments. That's the title of this article. Here we go. The sober reality behind the effectiveness of two new drugs touted as Alzheimer's breakthroughs, Lecanemab and Donanemab. These are the key takeaways. Like beacons of light in the dark, and I'm quoting, two drugs have emerged over the past two years as the first disease-modifying treatments for Alzheimer's disease. However, these drugs are expensive, complicated to administer, because we know now they do not penetrate the blood-brain barrier. Brain barrier and cause— can cause dangerous side effects. Most importantly, numerous researchers think the drug's benefits will be imperceptible to patients and their families. So rather than grasping for a nebulous medical solution, many experts say it's better to focus on prevention. Roughly 40% of dementia cases could be delayed or prevented by addressing lifestyle and environmental factors. This was written by Ross Pomeroy, and he goes on to say the quest to find effective treatments for Alzheimer's disease has historically been a lost cause. We know this. A field littered with failed drugs and dashed hopes. According to a recent systematic review between 2003 and 2022, researchers have tested 100 compounds against the devastating cognitive disease in Phase 1 and 3 trials. Only 2 drugs made it through the rigorous gambit of pharmaceutical science. Their beneficial effects were too small to make a meaningful difference to patients. Then, like beacons of light in the dark, 2 drugs emerged from Phase 3 clinical trials as the first disease-modifying treatments for Alzheimer's disease. Isai and Biogen's lecanemab burst onto the scene first, with data suggesting that it slowed cognitive decline by 27%. Eli Lilly's donanemab followed with a more impressive result—slowly decline by 35%. Scientists and journalists use words like breakthrough and revolutionary to describe these findings. Both drugs were given to older adults in the very early stages of Alzheimer's in trials lasting 18 months. A disease-modifying treatment is one that delays, slows, or reverses the progression of a disease by targeting its underlying cause. Until Lecanemab and Donanemab treatments for Alzheimer's only lessen the debilitating symptoms, which include memory loss, paranoia, difficulty focusing, etc. These two drugs, however, slowed the disease's progression while removing aggregated clumps of misfolded beta amyloid proteins. Such plaques have long been theorized as a potential cause of Alzheimer's as they are highly prevalent in 3/4 of sufferers' brains, first developing in areas that deal with memory and other cognitive functions. Just over 2/3 of participants receiving lecanemab actually had their brains effectively cleared of amyloid plaques. More than 80% of those given donanemab did as well. But this is where the drugs start to lose their sheen. So listen to this. Lecanemab and Donanemab removed the amyloid plaques, yet the Alzheimer's patients in the trials continued to decline. Remember, the drugs only slowed the disease. They did not stop it. This suggests that beta amyloid buildup is likely not the primary cause of Alzheimer's disease, hinting that the drug's overall effectiveness will be limited over the long term. Derek Lowe has worked on drug discovery for over 3 decades, including on candidate treatments for Alzheimer's. He writes Science's In the Pipeline blog covering the pharmaceutical industry. Amyloid is going to be, has to be a part of the Alzheimer's story, but it is not, cannot be a simple amyloid causes Alzheimer's, stop the amyloid and stop the disease, he told Big Think. Lo is just one of many commentators who has also noted that the drug's beneficial effects would likely be imperceptible to family and friends. Data from the trials back those dour opinions. Although the effect of the drug will be described as being about a third, it consists on average of a difference of about 3 points on a 144-point combined scale of thinking and daily activities. Professor Parish Malhotra, head of the Division of Neurology at Imperial College in London, said of Donanemab. What's more, Lecanemab only improved scores by 0.45 points on an 18-point scale assessing patients' ability to think, remember, and perform daily tasks. According to him, that's a minimal difference. And people are unlikely to perceive any real alteration in cognitive functioning. That's a quote from Alberto Espé, a professor of neurology at the University of Cincinnati College of Medicine, as he told KFF Health News. At the same time, these potentially invisible benefits come with the risk of visible side effects. Both drugs caused users' brains to shrink slightly. Moreover, as many as a quarter of the participants suffered inflammation and brain bleeds, and some very severely. 3 people in the Donanemab trial actually died due to treatment-related side effects. And then there's the steep cost with limited benefits. The time and costs associated with actually administering the drugs. Before taking, one prospective patient must receive a PET scan to look for amyloid plaques. They also must undergo genetic testing to confirm they don't have specific genes that would make them more susceptible to side effects. And once they start the treatments, patients require regular injections. Every 2 weeks for lecanemab and every 4 weeks for donanemab in a clinical setting. They also require frequent scans to watch for brain inflammation and bleeding. All of this takes time and money. The Institute for Clinical and Economic Review tabulated the annual cost for lecanemab, which is FDA-approved, by the way, They came to roughly $109,000 per patient per year. Included were the $26,500 list price as well as costs for actually administering the treatment. These are done through infusion. Also convened a panel of 15 experts and asked them to assess the treatment's value for the money. All 15 voted that the value is low. Donanemab has yet to receive FDA approval, but it should arrive this year. When it does, experts expect the value to be similarly unimpressive. Medicare and Medicaid patients will comprise most of the market for the new treatments for Alzheimer's. So taxpayers and other beneficiaries will end up footing the sizable bill. But should a cold cost-benefit analysis be the only way to analyze lecanemab and donanemab? In written comments to Big Think, Chuck Dinerstein, medical director at the American Council on Science and Health, presented a different perspective. While much has changed over the last few decades with respect to medicine's tools, at some point, medical options are exhausted, and the physician can only offer one of our older tools, which is hope. The importance of hope should not be underestimated. For those of a scientific bent, consider hope like a placebo, which works 30% of the time. These novel treatments undeniably constitute Alzheimer's patients' best source of hope. Hope in decades. Patients and families will be pushing very hard to get this drug, and they are not going to be objective when it comes to determining its value. Maybe mom has a few better days a month and can recognize you and chat with you for a few minutes, Dinnerstein added. Roughly 6.5 million Americans suffer from Alzheimer's. Dementia today, and that population is projected to double by the year 2050. So you can bet that many of them and their family members will consider $100,000, a pittance, if it means slowing the disease even just for a few months. Will there come a time when treatments for Alzheimer's are clearly cost-effective? There are many who think that lecanemab and donanemab collectively represent a solid start down that path. The success of these drugs is likely to spawn and guide years of subsequent research, Yale neurologist Stephen Novella wrote at Science Based Medicine. But others aren't so sure. Again, these drugs target beta amyloid plaques. And they were very good at clearing them, yet the beneficial effects were comparatively paltry. Some researchers say that we just have to get patients these drugs earlier and clear the plaques more quickly before they grow widespread. The hope is that very early treatment will slow progression enough that people will not live at long enough to ever develop severe dementia, Novella wrote. This may lead to screening for Alzheimer's disease in asymptomatic individuals, especially if there is a family history. But Lowe is skeptical. That answer has been eroding as these trials have tried to catch people earlier and earlier in the disease progression. I honestly don't know what else you do. Give people the drugs before they're diagnosed with Alzheimer's? That's not going to be possible, he said. And what if the primary cause of Alzheimer's disease isn't beta amyloid? I think it's quite possible that the plaque hypothesis is backward, he says, that the plaques are a result of something that has already happened to affect the brain, not the cause of the disease. That was a statement that I quoted to you from Josh Bloom, who's the director of chemical and pharmaceutical sciences at ACSI, as he told Big Think. If this is true, then it doesn't much matter what antibody or drug is used to dissolve the plaques. It's already too late. It would be like trying to treat a wound by getting rid of the scab. Other theorized causes of Alzheimer's disease include tangles of another protein called tau, or possibly a viral infection. Unfortunately, I am not optimistic about any drug or antibody putting much of a dent in this horrible disease. This is just too much that doesn't make sense about what's really going on, Bloom said. So, prevention versus treatment. Rather than grasping for a nebulous medical solution, many experts say it's better to focus on prevention. Roughly 40% of dementia cases could be delayed or prevented by addressing lifestyle and environmental factors, according to a report published in The Lancet, and I actually, uh, read that report to you because I remember that statistic. Roughly 40% of dementia cases could be delayed or prevented by addressing lifestyle and environmental factors. These factors include exposure to air pollution and excessive alcohol consumption. Goes on to say, maintaining a healthy blood pressure might be the single best preventative measure. Researchers at Johns Hopkins have found that people using blood pressure medications lowered their risk by about one-third. Moreover, studies suggest that learning a second language could delay the onset of Alzheimer's symptoms by 5 years on average. That relates to the parts of the brain that are used when you're translating one language to another. So very, very powerful, um, brain activity and stimulation. Uh, the other thing I have researched is another— the other really powerful hobby you could take up that is as effective as learning a foreign language is learning a musical instrument. So in conclusion, while treatments for Alzheimer's aren't that effective yet, numerous preventive measures are. So there you have it. And again, I want you to be as absolutely informed on all the new information that's coming out on these drugs. So when, if and when you do have this conversation with your loved one's primary care physician, neurologist, whomever, and the topic of the lecanemab or donanemab infusions comes up, you'll be equipped to ask really good questions to see if it's the right decision for you or your loved one. So, I hope that this has been really helpful. I will keep you updated moving forward as often as I run across, uh, these updates on these medications. It seems like the fingers are pointing directly at lifestyle choices. So we can revisit that topic in upcoming episodes. I've done episodes on that in the past. I think maybe it's time to, to do a recap on that. Modifiable risk factors, non-modifiable risk factors, lifestyle choices. So we'll be— I'll be presenting that for you in the upcoming episodes so we can revisit that. I hope y'all have a great week and take good care of yourselves and your loved ones. And I will be back with another new episode of the Truth, Lies Alzheimer's Show with your host Lisa Skinner next week.
Bye-bye. Thank you for listening to Truth, Lies 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.
