By Dale Bredesen, M.D., Chief Science Officer for Apollo Health

When I was a little boy, a friend told me that there was no Easter Bunny. Seeing the disappointment on my face, he immediately followed up with, “But Santa Claus is real.” That put a quick but transitory halt to the hemorrhage of my youthful innocence — I realized that, if the Easter Bunny was a hoax, wasn’t it likely that Santa Claus was also a parental concoction?

You may have seen the latest version of the Easter Bunny: over the past few weeks, the New York Times, the Wall Street Journal, the BBC, ABC, WIRED, and numerous other news outlets have all reported that there is a new, “promising,” “historic breakthrough” drug candidate — “the beginning of the end of Alzheimer’s” — called lecanemab. In a clinical trial, this drug candidate did not improve cognition, nor did it prevent decline, but it had a modest effect to slow decline — by 27%. Now imagine that Elon Musk announced that all of the SpaceX rockets explode and the astronauts perish, but in a SpaceX breakthrough, the rockets now explode 27% later than before — would that be a breakthrough? Of course not.

When it comes to treating Alzheimer’s successfully, it is critical to distinguish between three different effects: (1) slowing of decline; (2) population improvement; and (3) practical improvement. Of course we all want to see people improve, and sustain their improvement, as we’ve now seen for over a decade. 

Most of the anti-amyloid antibodies, such as bapineuzumab, solanezumab, crenezumab, and gantenerumab, have no effect on Alzheimer’s, but three have shown a modest effect, when started early, during mild cognitive impairment or early dementia, to slow the decline, by 22% (aducanumab in one trial), 27% (lecanemab), or 32% (donanemab). Unfortunately, this is accompanied by frequent brain swelling or hemorrhage (40% in one study), and in some cases, death.   

In contrast, some treatments actually improve cognition, but only when evaluated in a population. In other words, if 100 people went on a treatment that improved only a few of them, it would not be a practical solution, but statistically would be considered a “success.” An example is exercise, which alone improves cognition in a group, but leaves many without much noticeable improvement, simply because, alone, it does not address all of the potential contributors to cognitive decline.

What is needed is a treatment that gives each individual a high chance of sustained improvement, which is what we observed in our clinical trial, in which 84% of patients improved their cognitive scores. 

So the next time you hear about a “historic breakthrough” for a drug that makes no one better, has frequent side effects, and costs a fortune, you might want to ask whether the drug comes with an Easter basket and furry ears.

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