After almost 3 years of preparation and work on the Evanthea Randomized Clinical Trial
we have reached a major milestone!
The preprint of the EVANTHEA Dementia Reversal Trial has been formally released and
here is the link. Preprints are a formal draft that has not undergone peer review yet. If offers authors the
ability to share critical data. The peer reviewed journal article will be submitted to the
Journal of Alzheimer’s and Dementia next month and will likely be out in public in the
spring.
The major insight is that precision medicine works dramatically! It improves cognitive
outcomes rather than just slowing decline. The randomized controlled trial had stronger
effects than the original pilot study in 2022. The size of the effect is more than 700%
higher than the pharmaceutical standard, lequembi.
Key Takeaways
- Who was eligible? Mild cognitive impairment in subjects 50-75 defined as MOCA 19-25, or multiple deficits below 50 th percentile on CNS Vital signs. Subjects with major acute illnesses e.g., cancer, heart failure were not eligible. Needed a partner to help with implementation.
- What was the intervention? A precision medicine approach that identified the known root causes of early Alzheimer’s and addressed those root causes. There was a core intervention common to all patients in improvement in diet, sleep, exercise, brain exercises, stress management and evaluation of environmental toxicants. There was significant discretion of timing and selection of specific interventions by investigator, e.g., no one uniform protocol but rather a precision personalized medical approach.
- Design of the trial: Randomized clinical trial, there were six centers located in Marin CA, Walnut Creek CA, Sacramento CA, Nashville TN, Cleveland OH, and Hollywood FL (Rezilir Health). Group A patients received the intervention and Group B patients received “usual care” with the opportunity to get the intervention after 9 months.
- What were the results? There was a significant improvement of more than a standard deviation in cognitive scores as measured by CNSVS. (Exhibit 1). For example, the CNS-VS neurocognitive index improved by more than 18 points in Group A compared to Group B (15 points is a standard deviation).
- How does it compare to pharma? There was more than a 700% improvement in cognition compared to Lecanamab (Lequembi) , a commonly used monoclonal antibody that is approved by Medicare for early Alzheimer’s.
- Was there a variance in outcomes by center? There has been significant variance in outcomes by anonymized center. The slide below was shared by Dr. Dale Bredesen in a presentation in summer 2025 at the CIRS X conference. Further detail on center specific outcomes will be publicly reported in the peer reviewed literature and conferences at upcoming months.
Upcoming Series
Over the next few months, I will be writing a weekly document that shares some of the lessons that the Rezilir team and I have learned. Some of these insights will be:
- What exactly is a precision medicine approach? How does that compare to conventional medicine?
- What are the usual success of this approach in the study? What does a standard deviation of cognitive improvement mean for an individual? What is the change in quality of life as a result of this improvement?
- What type of differences have we seen in the implementation of a precision medicine approach? What does the data from published research show? What can we see as a participating center? How can we optimize improvement for patients?
- Why is team based care critical for the success of precision medicine?
- How do we set up a personalized N of 1 approach?
- What is the impact of intensive neuromodulatory therapy?
- What drives a set back or decline in this approach?
- What is the pace of change that can be achieved?
- What is the sequence of treatment?
- What are negative prognostic factors?
Feel free to send us questions and we will address them in our ongoing discussion with you.
