New Alzheimer’s Trial: Personalized
The Evanthea Trial is an ambitious attempt to test a different idea - that Alzheimer’s care may work best when we look for and address multiple drivers of decline, not just amyloid.
Few words are as fraught with hyperbole as the word breakthrough, yet we hear it used all too often in reporting on Alzheimer’s trials. The problem is, exciting results don’t always hold up in larger trials, and treatments that help in the lab don’t always help in the real world.
That’s why a newly posted preprint from Apollo Health is worth a close look, but with a level head. The study reports that a precision-medicine program improved cognition in people with mild cognitive impairment (MCI) or early dementia, while standard-of-care treatment did not.
While the study is not yet peer-reviewed, it suggests that Alzheimer’s treatment could potentially be more effective if it becomes more personalized.
What does Evanthea mean by “personalized”?
The Evanthea Trial was a randomized, multicenter, controlled clinical trial comparing the efficacy of a precision medicine protocol to the standard of care for treatment of Alzheimer’s. It was conducted at six sites across the United States with participants aged 45 to 76 who were treated at the MCI or early dementia stage (similar to the stage treated in trials for anti-amyloid drugs like Leqembi and Kisunla)
The interesting thing is the “precision” part of the trial. Instead of targeting one pathway, the “precision medicine” protocol, based on Apollo Health’s ReCODE/Bredesen approach, started with an in-depth, individualized workup to identify each participant’s main drivers of cognitive decline. These included metabolic and vascular risk factors, inflammation, sleep and lifestyle patterns, and contributors like biotoxins, oral microbiome issues, or tick-borne illnesses.
Treatment was then personalized through a coordinated program of medical interventions and lifestyle modification (nutrition, exercise, sleep, and coaching). A far cry from the usual one-size-fits-all use of drugs.
What did the trial find?
According to Apollo Health’s summary and the preprint, trial participants who received the precision-medicine protocol showed statistically significant improvements in several cognitive domains, including overall cognition, memory, executive function, and processing speed.
Apollo also reported that symptoms improved in ways noticed by both patients and their partners. That matters because test scores alone are less important than better day-to-day cognitive functioning.
The study also reported statistically significant improvements in multiple overall health measures, including blood pressure, body mass index, insulin sensitivity and hemoglobin A1c, lipid profiles (“cholesterol”) and methylation markers.
This is important because it’s increasingly clear that brain function is affected by more than plaques and tangles. Vascular health, inflammation, and metabolic health all appear to shape cognitive resilience over time.
273% more effective than Kisunla?
One of the most striking claims made by Apollo Health is that the overall effect of its protocol was greater than any other treatment for cognitive decline. In fact, the company claims that the protocol was 273% more effective [TS1] than the most effective of the three common Alzheimer’s treatments it compared, earning a 1.12 on the Cohen Efficacy Scale vs 0.3 for Kisunla, and lower scores for Leqembi and the US Pointer study’s structured lifestyle interventions.
That’s a bold claim that deserves our attention - but also our skepticism.
Comparing effect sizes across different trials is difficult because different studies include different patients, different testing methods, different timeframes, and different outcome measures. So while the Evanthea results may be promising, it’s too early to treat 273% better as a settled conclusion.
Still, the improvement described in the study is large enough that it should be taken seriously.
What happened to people on standard-of-care?
Apollo Health also highlighted that some patients whose health had been on the decline for 9 months despite adhering to the standard-of-care actually improved their cognitive scores after 6 months on the precision-medicine protocol.
As with the previous finding, this is notable but not proof. Once a study switches groups into a new treatment, it becomes harder to interpret cause and effect. Larger trials would be needed to provide real proof.
Bottom line
The Evanthea Trial is an ambitious attempt to test a different idea—that Alzheimer’s care may work best when we look for and address multiple drivers of decline, not just amyloid.
The early findings are encouraging. They highlight statistically significant improvements in several cognitive measures, plus improvements in broader health markers that matter for brain function. But this is still early evidence. The results are currently posted as a preprint, and peer review is still in progress.
My advice is, watch this closely, ask hard questions, and hope the findings hold up as larger studies are undertaken.
[TS1]Guy, this is from the table on What is the Evanthea Trial? - Apollo Health , improvement
