Becoming Alzheimer’s

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

There has been a lot of first-lady discussion recently, some centered on the new film, Melania, and others recommending the earlier book and film, Becoming, about Michelle Obama. No matter what your political views are, however, the recent question raised by multiple groups — “When does it become Alzheimer’s?” is an important one that is likely to impact most of us directly or indirectly.

This issue goes back more than a century to when Alois Alzheimer himself described the pathology that is associated with what is now recognized as the most common form of dementia. But just as for diabetes, cancer, and other chronic illnesses, research over the years pushed the recognition of the start date of the pathophysiology earlier and earlier, until now we realize that the pathology characteristic of Alzheimer’s begins 20 years or even more before the dementia. This has led to two completely different uses of the “A word,” Alzheimer’s disease: one for the pathology (which is present in many of us with no symptoms, and in fact it is now routine to avoid the dementia when precision medicine treatment is started at this presymptomatic phase), and one for the dementia. Unfortunately, these are often used interchangeably, creating confusion and often fear about what is actually meant. 

So in 2024 the Alzheimer’s Association convened a working group that included industry representatives from Novartis, Takeda, Lundbeck, and others, as well as individuals previously affiliated with Eli Lilly and Acumen Pharmaceuticals, and some academicians. The idea was to have broad representation. The group recommended that the pathological description be adopted, which would mean that, even in those without symptoms, if the blood shows a high value for p-tau 217 (or similar markers in spinal fluid or on PET scan), a diagnosis of Alzheimer’s would be made. OK, that recommendation could actually help to detect very early changes and avoid dementia in the vast majority of people, just as identifying early insulin resistance can help us to avoid the many complications of diabetes. So far so good, right?

But then the group did something completely irrational, which revealed the transparent primary goal of the meeting: it was recommended that those without symptoms not be tested for Alzheimer’s pathology until ongoing trials of anti-amyloid antibodies — yes, the same ones that have shown minimal efficacy and maximal cost, accompanied by significant side effects — show success! Frankly, I am shocked that trials of these antibodies have been approved for those without symptoms — this is like having your doctor tell you, “Your cholesterol came back a bit high, so I’ve scheduled you for bypass surgery tomorrow — you may die, but we are trying to find out if surgery is helpful at this early stage.” WTF?! (Can you imagine going before the human experimentation committee for approval and saying, “Yes, we know that there are already excellent preventive measures that are inexpensive, effective, and without negative side effects, and yes, we know that we could make asymptomatic people symptomatic, cause brain atrophy, and deplete the life savings of many — but do you realize what the market potential is?!?”)

But it gets even more absurd — of course the obvious reason for all of us without symptoms to find out where we stand with respect to p-tau and related biomarkers is because of the vast literature on successful prevention — from exercise to plant-rich ketogenic diets like KetoFLEX 12/3 to brain stimulation like BrainHQ or photobiomodulation to the PreCODE and ReCODE protocols, as well as others — and then follow the biomarkers to ensure that we are going in the right direction. Instead of pointing out the successful publications on these and recommending them for anyone with biomarker evidence of presymptomatic Alzheimer’s pathology … well, I’ll let you read their recommendation for yourself: “Disease-targeted therapies have not yet been approved for cognitively unimpaired individuals. For this reason, the work group currently recommends against diagnostic testing in cognitively unimpaired individuals outside the context of observational or therapeutic research studies.” So we are supposed to await trials so that we can start on a drug with less efficacy at far more cost and far worse side effects — not much of a sales pitch!

Meanwhile, the International Working Group (IWG) responded by cautioning against early biomarker testing, which is like recommending that you wait to test your lipids until you have chest pain. Now of course that would make sense if the treatment involved a drug with significant side effects and poor efficacy, but since treatment at the presymptomatic stage with personalized protocols like ReCODE or PreCODE is effective, and actually improves health (in our recent trial, there were significant improvements in systolic blood pressure, diastolic blood pressure, weight, blood glucose, lipids, and methylation) — as we’ve seen for years now — there is no need to await symptoms, and in fact there are clear advantages to starting early.  If a junior medical student made recommendations like the ones from these groups, you would give him or her a failing grade. Apparently, one’s belief in when it “becomes Alzheimer’s” depends on whether you are trying to increase drug sales or you haven’t read the published literature on precision medicine for reversing cognitive decline. Thankfully, following multiple clinical trials and experience with thousands of individuals, we can offer a much better path forward:

• Alzheimer’s is defined as a pathology (as Alzheimer himself described it), with amyloid plaques and neurofibrillary tangles (with p-tau), so any of us may harbor that pathology, whether we have symptoms or not. Now that we have early detection and effective treatment, there is no reason to wait until dementia develops to find out where you stand.
• The symptoms that accompany the Alzheimer’s pathology occur in four phases: (1) presymptomatic; (2) SCI (subjective cognitive impairment); (3) MCI (mild cognitive impairment); and (4) dementia. These symptoms may be mistaken for “normal aging”, so it is best not to wait for evaluation.
• The most sensitive p-tau test is offered by Neurocode and is available at getabrainscan.com. 
• If your biomarkers turn out to be high, please don’t worry — we’ve repeatedly seen improvements in both biomarkers and cognition while on the ReCODE protocol.

Adopting these guidelines should help each of us to reduce our chance of developing dementia dramatically.