I often feel that as aggressive longevity and health extension people, dementia/AD (and cancer) are less under our control than metabolic, cardiovascular and other vital organ related diseases and hence found some of the perspectives in this new Newsweek piece interesting
When Aisen started, Alzheimer’s disease was thought to begin with the onset of observable cognitive and functional decline and, after progressing for seven years or so, result in death. But the onset of early dementia, we now know, is in fact just the final phase in a far longer progression that takes place over roughly 25 years. It begins with the accumulation of amyloid-beta at least 18 years before any behavioral changes are detectable to most future patients or their loved ones.
“For all of history, people have been afflicted by senility and dementia, and for thousands of years, you couldn’t do anything about it,” says Bateman. “Even in recent history, you could only diagnose people after they died. Now a single blood sample can with 95 percent accuracy identify Alzheimer’s. And in just six to 18 months, we can remove plaques from the brain that have built up over 20 years. We can for the first time change the course of how fast the disease progresses. To me, it’s just absolutely incredible. It’s really profound.”
Reiman, in fact, believes these side effects might be less of an issue for those in an earlier phase of the disease. In the late stages, he says, “you’re having to pull amyloid plaque out of the brain, but also off of blood vessels, which is the main reason for the side effects,” such as bleeding and swelling, he says. In the brains of those who are at earlier stages of the disease, the plaques “haven’t been there as long. So, they’re less adherent, and you may have fewer side effects as well.”
Interesting perspectives here on how very early action via the new FDA drug(s) (and others in the pipeline) could
(a) perhaps have a big impact on preventing AD and
(b) perhaps also have a much better safety profile in those early stages such that early intervention might make sense
The next 5-10 years may be quite exciting and interesting here:
In the hopes of further arresting this systemic collapse, Aisen is co-leading the AHEAD trial, which is in the midst of recruiting “presymptomatic” patients to participate in a four-year study of lecanemab. The new cohort will consist entirely of people who are, for the most part, cognitively and functionally asymptomatic but have abnormal levels of amyloid in their brains. The idea is to capture people in years one through 10 of the progression. A later phase of the trial, he says, will target a cohort who is “even closer to year one.”
At the same time, the TRAILBLAZER study, co-led by Banner Institute’s Reiman, is taking a similar approach, but using donanemab, the new drug from Eli Lilly that is expected soon to win FDA approval, to target those in earlier stages of the disease.
It will take five years before AHEAD yields results, estimates Aisen, and 10 years before we have a real handle on how to prevent the disease. Reiman is slightly more optimistic but agrees many more steps are needed.
Still, both see a bright future ahead.
“Lecanemab is a real landmark. Having a fully approved drug [that] slows the disease is significant. But we’ve got to move on and increase the benefit,” Aisen says. “I’m very optimistic. We’re just going to build on this success. Things will get better and better until the entire population is routinely screened for risk and the risk is fixed before the disease starts.”