APOE4: is every memory lapse a warning sign?

Hi Phoenix friend,

Once you learn your APOE4 status, every forgotten name can start to feel like a warning.

Would another test give you peace of mind? Or just another number to worry about?

I put that tension to Dr. Gayatri Devi, a neurologist and psychiatrist who directs Park Avenue Neurology in New York.

Her starting point was not to watch your memory more closely. It was to get a useful baseline, then stop treating each lapse as a fresh verdict.

APOE4 is a risk factor, not a diagnosis.

Prefer to watch? The full interview is here:

What would a useful baseline tell you?

Dr. Devi recommends a proper cognitive evaluation for people carrying two copies. Not just a score that says you passed.

She describes tests of language, different types of memory, visual-spatial skills and the ability to switch between tasks. The results need context: your age, your abilities and any earlier assessments.

Someone can score in the average range for their age and still be below their own earlier ability. Or that score may be normal for them.

One result cannot tell those stories apart.

A starting point gives a clinician something to compare with later.

Why checking again may tell you less

Dr. Devi tells her patients to leave at least a year between routine assessments. Repeating a test too often can make you better at taking it.

A higher score might reflect familiarity, not a change in memory.

That is her approach to routine retesting. It is not a reason to ignore new symptoms.

She also describes the trap of watching for every lapse:

At the end, she talks about multitasking and focused attention. Forgetting something while your attention is elsewhere is not, by itself, an answer to whether you have dementia.

(The goal is useful information. Not becoming your own full-time memory examiner.)

What about an Alzheimer's blood test?

Here is the distinction that matters: a positive p-tau217 result is not a forecast of dementia.

Dr. Devi describes a positive predictive value of about 30 to 35% in groups with no symptoms and low rates of amyloid. In plain language, that is the share of positive results that really correspond to amyloid being present.

It is not the chance that an APOE4 carrier will develop dementia. And it is not a figure you can apply to every carrier or every blood test.

In people with symptoms, she describes higher predictive values. Who gets tested, which test is used and where its cutoffs sit all matter.

A scan is not the same as daily life

Amyloid can be present without cognitive impairment. That is not a promise that symptoms will never develop.

Dr. Devi questions how amyloid findings should guide diagnosis and treatment. She also says she would consider testing and treatment earlier than the guidance she describes supports.

The limits: her case series is unpublished. She says her approach to treating before symptoms has not been proven in phase three trials. Her slower drug-dosing approach is not proof that it prevents brain swelling or bleeding.

Her broader priorities are less exotic: aerobic exercise, blood vessel health, sleep and reducing stress.

Turn this into a better appointment

Before adding another test, questions worth discussing with your clinician include:

• What would this test tell us, and what would it not tell us?

• How would you interpret it for someone with my symptoms, age and APOE4 status?

• What would change after a positive, negative or unclear result?

You do not need to watch the whole interview to use those questions.

Coming up next: the CEO of NewAmsterdam Pharma

My next conversation is with Dr. Michael Davidson, a cardiologist and lipidologist and the CEO of NewAmsterdam Pharma, the company that makes obicetrapib.

Obicetrapib is a once-daily pill developed to lower LDL cholesterol. It blocks CETP, a protein that moves cholesterol between particles in the blood.

In the BROADWAY heart trial (New England Journal of Medicine, 2025), 2,530 people with heart disease or familial hypercholesterolemia were already on maximum cholesterol-lowering treatment. On obicetrapib, their LDL fell 29.9% by day 84. On placebo, it rose 2.7%.

Why it matters for us: a planned substudy tracked p-tau217, the Alzheimer's blood marker I mentioned above, in 1,535 of those people for 12 months. In people with two copies, the placebo-adjusted difference was about 20%. Dr. Davidson is an author of both papers. The authors say a clinical benefit still has to be shown in dedicated prevention trials.

Obicetrapib is not approved for Alzheimer's, and this is not a recommendation to take it.

I explained obicetrapib and the BROADWAY result in a video and full write-up.

NewAmsterdam Pharma has also opened a phase 2 trial of obicetrapib in people aged 55 to 85 with preclinical Alzheimer's (brain changes before any symptoms). See it in our Clinical Trial Engine.

We are working with the NewAmsterdam Pharma team to explore clinical trial access for Phoenix members. I'll share more when there is more to share.

I record with him on Tuesday 17 November, and members' questions are already coming in.

The episode is free. So why join?

You are not paying to unlock a video. You are joining to bring your own questions and build your APOE4 protocol.

With Dr. Devi, the prepared member questions didn't make it on camera, though several of their concerns came up.

Inside Phoenix, you can put yours forward before future interviews. That gives you a way to help shape what I ask, not a promise that every question fits.

And the clinical trial access we're exploring with the NewAmsterdam Pharma team is for members.

What you're actually joining

Phoenix is an app and community of 750+ APOE4 carriers. You build your personal protocol, make a daily check-in (a quick note on what you did and how you feel), and use your monthly review to see what needs attention. You bring your own blood tests; Phoenix reads them against APOE4-specific ranges. You can bring questions to experts and join your pod, a small group of carriers with similar monthly goals, matched each month to help each other stay on track.

Not another Facebook thread that leaves you with a longer supplement list and more anxiety.

Know what to do next, and whether it's working.

Let's build your APOE4 protocol together.

For carriers who are serious about beating the odds.

Apply to join Phoenix

Cheers,

Kevin

P.S. I carry two copies of APOE4. I built Phoenix because I wanted to give myself the best chance of beating the odds. Now I'm building it for you too. Give it sixty days. If you don't feel Phoenix was worth it, tell me and I'll refund you myself.

Educational, not medical advice. Take this to your own clinician.