Lifespan is how long you live. Healthspan is how long you stay well. Brain span is how long your mind still works: memory, judgment, language, the ability to stay yourself.

That is the number I care about as a clinical neurophysiologist. And it is not a 70-year-old number.

Alzheimer’s pathology can start between 45 and 65, years to decades before anyone forgets a name. Average age at diagnosis is 72. By then the window where you could have changed the trajectory has been open, and mostly ignored, for twenty years.

For women, that window has a name. It is midlife. It is the menopause transition. Lisa Mosconi’s March 2026 review in the Journal of Clinical Investigation calls it what it is: the front line of Alzheimer prevention

.

Nearly two-thirds of people with Alzheimer’s are women. A 45-year-old woman’s lifetime risk is about 1 in 5, twice that of a man the same age.

Longevity does not fully explain that gap!!

Alzheimer’s is a midlife disease that shows up late

We keep treating Alzheimer’s as a disease of old age because that is when we diagnose it. The plaques, the tangles, the drop in the brain’s glucose metabolism: those are already moving in the years around menopause.

Mosconi’s imaging synthesis is blunt. Postmenopausal women, and to a lesser extent perimenopausal women, carry a heavier Alzheimer’s biomarker load than premenopausal women and than men of the same age: more amyloid, more tau, lower brain glucose use, less gray matter in the regions Alzheimer’s hits first. Those differences survived age adjustment. Mosconi still flags that postmenopausal women are typically older, so residual aging cannot be ruled out. Endocrine change is the leading explanation, not a closed case.

If you are in your 40s or 50s and your brain feels different (words slower, sleep lighter, a sharpness that used to be automatic), that is not a personality flaw and it is not “just stress.” Mosconi reports that subjective cognitive decline shows up in 34% to 62% of peri- and postmenopausal women. It is also one of the earliest clinical flags we have that the brain is under strain. Say it out loud. Ask for a neurological frame, not only a mood label.

Earlier menopause is not a gynecology footnote

A paper in npj Aging, published 31 July 2026, looked at resting-state brain activity in 90 postmenopausal women from the Human Connectome Project-Aging dataset. The authors split them into three equal groups of 30 by age at menopause. Age at the scan did not differ across groups.

This is not the clinical definition of early menopause (before 45). It is a relative split of the sample. The earlier group reached menopause at a mean of 45.5 years (SD 3.5; range 38.0 to 49.2). The later group reached it at a mean of 54.0 years (SD 1.4; range 51.7 to 56.4). Both groups were scanned around age 58 to 60.

Women in the earlier group had weaker global brain activity and weaker coupling between that activity and cerebrospinal fluid (CSF) flow. The difference sat in higher-order regions: default mode and frontoparietal networks. In the earlier group, weaker activation of those waves tracked with poorer episodic memory. The same link was not there in women who reached menopause later.

CSF flow is not a trivia fact. Liu and colleagues treat this coupling as a noninvasive marker of how global brain activity lines up with fluid movement, a system previously tied to sleep and to waste clearance. Weaker coupling is a plausible bridge between “my periods stopped earlier than my peers” and “my memory is not what it was.”

Mosconi’s review of the clinical literature already pointed this way. She cites a meta-analysis of 22 studies and nearly 5 million women in which later menopause (after 55) was associated with a 33% lower Alzheimer’s risk. Early menopause and premature ovarian insufficiency tracked with higher dementia risk. Surgical menopause is worse. Multiple studies have reported nearly double the long-term dementia risk after both ovaries are removed.

If you had your ovaries out, or you hit menopause before 45, that belongs in your medical history the same way a parent with Alzheimer’s does. Most charts still file it under gynecology.

What I will not do in this letter

I will not tell you to start hormone therapy for Alzheimer’s prevention.

Mosconi is explicit. Current guidelines do not recommend menopause hormone therapy to prevent cognitive decline or dementia in the general population. They do support starting estrogen near menopause to help preserve cognition in women with early menopause, especially after oophorectomy. Observational data hint at benefit when therapy starts close to menopause, and harm or no benefit when it starts in the late 60s and 70s. Those are not the same brain. Timing, formulation, route, APOE genotype, and healthy-user bias still sit on the table. There is no Level 1 trial showing that midlife hormone therapy prevents late-life Alzheimer’s.

The conversation you have at 48 is not the conversation at 68. Same molecule. Different brain. Bring a clinician who has read the 2026 data. I am not that prescriber.

What you can do this week

Mosconi notes that current population models put modifiable factors at up to 45% of global Alzheimer’s cases. Those models are sex-aggregated. They still barely count female-specific biology. You do not have to wait for the model to catch up.

1. Write down your reproductive timeline. Age at first period, pregnancies, age at last period, ovaries yes or no, tamoxifen or aromatase inhibitors if those were you. Put it in your phone. Take it to your next appointment. This is the history most Alzheimer’s workups still skip.

2. Treat nighttime hot flashes as brain data. Mosconi reviews a study of 226 midlife women in which more frequent, objectively monitored vasomotor symptoms during sleep, but not in the daytime, tracked with greater white-matter hyperintensity volume, a marker of possible cerebrovascular injury. A follow-up in the same cohort linked sleep-related flashes to a more amyloid-like blood signature. If you are waking hot, that is a sleep and a vascular problem, not an inconvenience. Tell the person who manages your hormones. Ask what they will do about the nights, not just the days.

3. Protect the sleep that moves fluid. Liu’s group measures global brain activity that is stronger during light sleep and coupled to CSF flow. That coupling is the signal they found weaker after earlier menopause. This week: no phone in bed, same lights-out time, caffeine off the table in the evening. Boring. Measurable.

4. Train the body that feeds the brain. Mosconi lists cardiovascular health, metabolic health, and physical activity among the modifiable risks that current models already count. This week: two resistance sessions, or a timed walk you can repeat. You are not training for a race. You are keeping the vascular and metabolic line to memory open.

5. Stop outsourcing the “is this normal?” question. If word-finding, sleep, or mood shifted with your cycle or with menopause, say so out loud to a clinician. Mosconi notes that women keep a verbal-memory advantage even after an Alzheimer’s diagnosis, which can mask earlier pathogenesis. You are allowed to ask for a neurological frame. You are allowed to ask about APOE. You are allowed to ask whether hormone therapy is even on the table for you, especially if menopause came early or your ovaries are gone.

None of that requires a biohacker stack. It requires treating midlife as the prevention window it actually is.

Brain span is the metric

I am done letting Alzheimer’s live in the someday folder. Brain span is the years your mind stays fully online. For women, the slope of that line is set, in part, while you are still running a company, raising people, and being told the fog is hormones and the hormones are not neurological.

They are.

By 2050, Mosconi notes, more than 1.2 billion women worldwide will be in or approaching menopause. The prevention window is not 72. It is now.

Next Neuro Experience episode goes out Tuesday, 8 September.

I’m Louisa Nicola, clinical neurophysiologist.

This is Neuro Athletics.

Sources

Mosconi L. Women’s midlife: the front line of Alzheimer prevention. J Clin Invest. 2026;136(6):e199832. https://doi.org/10.1172/JCI199832

Liu X, Luo L, Pritschet L, Mao Y, Han F, Proctor DN, Liu X. Early menopause is associated with reduced global brain activity. npj Aging. 2026. https://doi.org/10.1038/s41514-026-00450-1

Jim Kwik was called “the boy with the broken brain” by a teacher, out loud, when he was nine. A brain injury at five left him years behind. He’s now the brain coach Hollywood actors and CEOs hire to think faster. So when he talks about what a brain can rebuild, I listen.

We met to talk about AI. But the thing I keep coming back to is simpler, and it’s the most useful way to think about your brain I’ve heard in a long time.

He calls cognitive reserve a savings account.

It’s real neuroscience, and it’s why two people can have the same Alzheimer’s pathology in their brains while one loses their memory and the other stays sharp at 90. The reserve is the buffer. You spend a lifetime building the balance, and it’s what protects you when things start to go wrong underneath.

Every day, you either make a deposit or take a withdrawal.

The withdrawals are the ones you already suspect: bad sleep, chronic stress, sitting all day, processed food. But Jim named a new one. Every time you let a machine do your thinking, that’s a withdrawal. He pointed to an MIT study where people wrote essays with ChatGPT, with Google, or with just their heads. The AI group had the least brain engagement and barely remembered what they’d written. His line: you don’t go to the gym and have someone lift the weights for you. But that’s what we’re doing with our minds all day.

The deposits are small, free, and completely in your hands. This is the part your evening is made of:

• Read the actual book, not the AI summary.

• Do the tip math in your head. Kill the calculator for small stuff.

• Sit in a boring moment instead of grabbing your phone. Jim’s point: boredom is where your best thinking happens, and we’ve deleted it.

• Learn something slightly too hard. If it’s easy, you’re not getting stronger, in the gym or the mind.

• Have the real conversation. Social connection is one of the biggest deposits there is.

None of that costs money or needs a supplement. It just needs you to keep doing your own thinking, on purpose, while the world builds very convenient machines to do it for you.

Jim’s image for it: getting through your day is like being on a plane. You can be the passenger, thrown around by everything that hits you, or you can move into the cockpit and fly it. Cognitive reserve is just you, every day, choosing to stay the pilot.

There’s a lot more in this one, including how he rebuilt a brain everyone wrote off. Full episode out now.

Listen on YouTube, Apple, and Spotify.

TOPICS DISCUSSED
00:00 Are We Raising the Dumbest Generation Because of AI?
01:06 What Happens When Technology Thinks for Us?
02:03 The ChatGPT Study: What Happened to Memory and Recall
03:00 Cognitive Offloading vs Cognitive Surrender
05:01 Brain Rot, Doomscrolling, and the Attention Crisis
08:19 Why Reading Is Training for Your Brain
09:30 Neuroplasticity and the London Taxi Driver Study
12:20 “Natural Intelligence Is Becoming Artificial”
13:06 Why Asking Good Questions Matters More Than Ever
16:50 How Weak Critical Thinking Makes You Easier to Manipulate
19:31 Cognitive Reserve: Your Brain’s Savings Account
22:52 Cognitive Antifragility: Why the Brain Needs Challenge
25:34 How to Stay Human in the Age of AI
29:15 Metacognition: Thinking About Your Thinking
34:46 Why High Performers Protect Their Attention
40:46 Jim Kwik’s Childhood Brain Injury
45:27 Five Years of Severe Sleep Apnea
49:48 What You Do First Thing in the Morning Matters
52:47 Jim’s 3 + 3 Morning Exercise
54:00 “Mind Before Media”
57:22 Where AI Is Going Next
58:31 Artificial Intelligence vs Augmented Intelligence
60:19 The AI Risk Nobody Talks About: Losing Purpose
62:15 Be the Pilot of Your Brain, Not the Passenger

I just spent an hour with Keith Rabois, and I have not stopped thinking about how he lives.

If you don’t know the name, he’s one of the most successful investors of the last twenty years, an early force behind PayPal, Square, and DoorDash. He has more money than he could spend in a lifetime. And he treats his own body with the seriousness of a professional athlete in season. He has not missed more than a handful of workouts in seven years, and the ones he did miss still visibly bother him. He tracks every session. He treats training like brushing his teeth, non-negotiable, not up for debate on any given morning, because he’s figured out that the moment it becomes optional once, it becomes optional forever.

Here’s the thing I’ve noticed, and Keith is just the latest example. The most successful people I meet, the investors, the founders, the ones operating at the very top of brutally competitive fields, almost all treat their bodies like elite athletes treat theirs. It’s one of the most consistent patterns I’ve seen in this work, and I don’t think it’s a coincidence.

I want to talk about why, because it changes how you might think about your own health.

They stopped separating the body from the mind

For most of us, health lives in one box and work lives in another. You go to the gym to look better or to feel less guilty, and then you go do your actual job, which happens in your head.

The people at the top don’t think that way. They’ve collapsed the two. They train their bodies because it’s how they protect their minds, their focus, their decision-making, their stamina over a very long career. Keith said something that stuck with me: staying relevant as a VC as the decades pass is genuinely hard, and one of the ways he does it is by keeping his body and brain young, sharp, and curious. The fitness isn’t separate from the career. It’s infrastructure for it.

And there’s real biology under that instinct. When you train, especially when you lift and when you push your heart rate up, you’re not just building muscle. You’re driving the release of molecules that cross into the brain and support the growth and survival of neurons. Exercise is one of the only things we know of that reliably protects the aging brain. These high performers may have arrived at it through obsession and self-experiment, but the science agrees with them.

They measure

The second pattern: they don’t guess. They measure.

Keith has trends on his own blood work going back to 2003. He knows his numbers, tracks them year over year, and can tell instantly when something is off because he has two decades of his own baseline to compare against. This is the opposite of how most people do health, which is to wait until something hurts and then react.

One number he’s fixated on is VO2 max, essentially the size of your engine, the maximum amount of oxygen your body can use when you’re working hard. He asks everyone their VO2 max. Founders, friends, his own partners. And if it’s low for their age, he tells them, bluntly, to fix it.

At first that sounds like a fit guy’s quirk. Then you look at the research. In a study of over 122,000 people, the least fit had roughly five times the risk of dying compared to the fittest, and being in that bottom group was a worse bet on your life than smoking, than diabetes, than high blood pressure. We’ve built entire public health campaigns around cigarettes. This beat all of them and almost nobody talks about it.

That’s why he asks. He’s not showing off. He understands that this one number is one of the clearest signals we have of how long and how well a person is going to live. It’s the kind of thing the people at the top know and most people have never been told.

They make it impossible to skip

The third pattern is the one I think you can actually steal, whatever your budget or schedule.

They remove the decision. Keith keeps red light at home because if it’s convenient, there’s no excuse not to do it. He trains no matter what because “no days off” isn’t about being a machine, it’s about never letting the door open to the excuse. He even double-books his workouts with friends so that seeing people he cares about and training happen at the same time, and neither gets sacrificed to a busy week.

None of that requires being a billionaire. It requires designing your life so the healthy thing is the easy thing. That’s the actual transferable lesson hiding underneath all the cryotherapy and the blood panels.

What this means for you

You’re not going to pull twenty-two vials of blood or do cryotherapy every morning, and you don’t need to. Most of what these people do at the extreme is time and money that ordinary life doesn’t hand you, and I’m not going to pretend otherwise.

But the mindset underneath it is free, and it’s the part worth taking.

Treat your body as the thing your whole life runs on, not a vanity project you get to when there’s time. Know a few of your own numbers instead of waiting for something to break. And build your days so the good choices don’t require willpower, because willpower runs out and systems don’t.

The most successful people in the world figured out that the body and the career are the same project. You don’t need their money to apply the same idea. You just need to stop treating your health like it’s optional, the same way they never let themselves treat their training like it’s optional.

My full conversation with Keith Rabois is out now, on YouTube, Apple, and Spotify.

I am speaking in Nashville September 12. Secure your tickets here!

I want to tell you about a group of people who, by the rules we thought we understood, should not exist.

They lived past 100. When they died and their brains were examined, they were full of amyloid plaques and tau tangles, the physical hallmarks of Alzheimer’s disease. The same wreckage found in the brains of people who lost everything to this dis…

Read more

I just sat down with one of the most accomplished neurosurgeons alive.

He runs one of the top brain institutes in the world. He takes the cases no other surgeon will touch. He has clipped over 5,000 brain aneurysms and performed more than 10,000 operations. He works with Neuralink, putting chips into the brains of paralyzed patients and watching them move a cursor with a thought. He has held living, thinking human brain tissue in his hands more times than almost anyone on earth.

So near the end, I asked him the question I most wanted answered.

What do you do to protect your brain?

Here is exactly what he said.

“I don’t take a single supplement. I don’t do any of that.”

Let that land for a second. The man who has seen more of the human brain than you or I ever will, who could take anything, who has access to everything, takes nothing from a bottle.

What he does instead is almost boring.

He sleeps seven hours, without fail, every night. He exercises first thing every morning, before the day can steal the time. He is careful about what he eats. And he protects the people and relationships around him.

That is it. Sleep, movement, food, connection. The four things you already know, done by the one person who has the most authority on earth to tell you they are not enough. And he is telling you they are.

I have been saying a version of this for years, and it still hits differently coming from a man with his hands inside people’s skulls three days a week. There is no secret. There is no supplement he knows about that you don’t. The people with the most knowledge are doing the simplest things, relentlessly.

He also said something that stopped me.

He believes that in twenty years, we will look at alcohol the way we started looking at cigarettes in the 1960s. Something we all did socially, without much thought, that turns out to be quietly damaging the organ we most want to protect. Coming from him, that is not a wellness opinion. That is a warning from someone who sees the damage up close.

And then there is the part that sounds like science fiction and is already real. He walked me through the patients who cannot move their arms or legs, who now control a computer with their thoughts alone. One of them races a cursor across a screen faster than a healthy person can. He thinks we are at the beginning of treating things we never thought neurosurgery could touch. Depression. Addiction. One day, maybe, Alzheimer’s.

This was one of the most remarkable conversations I have had on the show. It moved between the far future and the simplest possible truth, and both were coming from the same pair of hands.

If you want the future of the brain and the four things the best in the world actually does to protect his, this is the episode.

TOPICS DISCUSSED
00:00 Intro: The Brain Surgeon at Neuralink's First Hospital
00:39 The Guy Who Does the Cases Nobody Else Wants
02:17 A Day in the Life: 5:30am Starts and Three Surgeries
03:20 "Game Tape": Reviewing Every Operation Like an Athlete
04:24 The Surgeon Athlete and Why Surgery Is a Physical Skill
05:32 Fifty Years From Now: What Happens to Neurosurgery
06:11 The ROSA Robot and Mapping a Seizure Focus
08:16 Deep Brain Stimulation and Hitting an Exact Target
08:52 Will We All Be Operated On by Robots?
10:02 The Brain AVM: The One Case a Robot Can't Take
11:18 Why Bleeding Breaks a Robot: The Waymo Problem
13:15 What a Brain-Computer Interface Actually Does
14:49 The Hand Knob: 108 Electrodes in One Small Spot
15:50 Cursor Control at World Record Speed
16:31 Inside the Implant: Threads a Tenth the Width of a Hair
17:27 "No, the Chip Cannot Read Your Thoughts"
17:58 What the Device Really Reads: A Train of Spikes
19:18 From Movement to Sensation: What Comes Next
19:48 Why Restoring Sight Is So Much Harder
20:58 The 1943 Paper That Predicted All of This
22:37 Elon, Telepathy, and What's Actually Possible
23:00 Boosting Creativity and Intelligence in 50 Years
25:10 "When I Retire, We'll Be Treating Depression and Addiction"
26:04 Alzheimer's: Light Therapy and the Blood-Brain Barrier
27:11 Treating the Disease vs Preventing It
28:25 10,000 Operations: How He Feels About Robots Taking Over
29:54 Neuroplasticity: How Nolan's Brain Learned the Device
31:34 What Actually Changes at the Neuron Level
32:04 Patient Two and the Robotic Arm
32:42 5,500 Aneurysms: The Cases That Stay With Him
33:16 Cardiac Standstill: Cooling a Brain to 15 Degrees
35:46 What Separates a Great Surgeon From an Average One
36:17 Traits of Greatness: The Formula Nobody Has Cracked
37:21 The Phone Call in the Middle of a 16-Hour Surgery
39:35 "I Must Have Been Born for This"
41:26 Can You Tell How Old a Brain Is Just by Looking?
43:12 Why Alzheimer's Is Invisible in a Living Brain
44:14 What a Neurosurgeon Does to Protect His Own Brain
44:40 "Alcohol Will Be Viewed Like Cigarettes in the 60s"
45:13 Peptides, Injectables, and Zero Supplements
46:52 The Last Generation to Operate With Open Hands
48:10 How Louisa Found Him on Twitter in 2021
48:53 The Six Mysteries of the Mind
49:14 Which One Gets Solved First, and Which May Never
50:03 Is Consciousness in the Tissue?
51:39 Memory: The Circuitry We Still Can't Explain
53:18 Why Consciousness Is Harder Than Memory
55:12 Louisa's Father's Stroke
56:02 Advice for Anyone Watching a Parent Decline
56:21 His Sister's Brain Tumor and How He Carries It
57:38 A World Where Stroke Is an Outpatient Repair
58:40 Forty Years On, Finally at the Dawn

This newsletter is brought to you by Function Health

Real question: When was the last time you looked beyond how you feel and measured what is actually happening inside your body?

Feeling healthy matters. It simply does not tell you everything.

Cardiovascular, metabolic, and kidney risks can develop for years without obvious symptoms. A routine panel is valuable, yet it may leave important questions unanswered.

That is where broader biomarker testing becomes useful.

LDL particle number, non-HDL cholesterol, and triglycerides can provide additional context on cardiovascular risk.

Urine albumin and creatinine-based eGFR help assess kidney health, while ferritin, iron saturation, and methylmalonic acid offer insight into iron stores and vitamin B12 status.

GGT, bilirubin, and albumin add context to liver health and function.

No single result tells the whole story. The real value comes from reviewing these markers together, tracking them over time, and discussing meaningful changes with a qualified clinician.

That is why I like Function Health.

Function includes 160+ lab tests annually, repeat testing, and clinician-reviewed results in one place. It gives you a more complete view of your health and better information for decisions around nutrition, training, recovery, and long-term care.

The goal is not to collect more data.

It is to identify meaningful changes early enough to respond intelligently.

You cannot improve what you never measure.

If you are serious about performance, longevity, and taking a more proactive role in your health, check out Function Health and sign up using my code below.

GET TESTED HERE

Here is the claim I am willing to defend.

Menopause is a neurological event that happens to involve the ovaries. Not the other way around.

The brain is the first organ affected by falling estrogen, not the last. And the medical system is still treating it as a gynecological problem with some annoying cognitive side effects, which is why a 44-year-old woman describing brain fog is far more likely to leave her appointment with an antidepressant than a neurological workup.

I made this episode because of one number that reframes the entire debate: women who started hormone therapy within five years of menopause had substantially lower Alzheimer’s risk. Women who started after 65 had higher risk. Same therapy. Opposite outcomes. The only variable was when they began.

That is not a nuance. That is a fork in the road, and most women are being walked past it without being told it exists.

TOPICS DISCUSSED
00:00 – Cold open: bold claims & who is Sam Bertram
00:51 – Why vertical farms collapse (Bowery) & how OnePointOne survived
05:49 – The number that started it all: 1.1 billion malnourished
07:30 – Why micronutrient deficiency is the real killer
08:21 – What OnePointOne actually is: "a box that grows plants"
10:03 – Training plants with light & water to boost nutrients
11:00 – Closing the loop: food matched to your body's data
12:28 – The plan for 1,000 farms & the AutoStore partnership
15:46 – Plant biology 101: growing with no soil, no sun
18:11 – The robots — and why humans are still essential
21:27 – Pesticides, washing produce & disease clusters
23:53 – Beet greens for cancer patients & the Whole Foods deal
24:42 – A 13-person company run on AI
25:15 – The 15-day crop & cracking the cost code
27:11 – Biology vs. software: what really makes it work
28:01 – Humanoid robots, ~5 years away
30:27 – Why raise $80M and not $500M
33:56 – What they do to a plant that nature never would
36:28 – Expanding crops: strawberries, cannabis, mushrooms
38:05 – Growing food & materials in space (Elon, text back)
39:38 – Personalized food grown from your blood test
40:24 – Food as medicine & the truth about Western medicine
41:11 – Sam's mystery illness: 8 years without exercise
44:23 – Plants as medicine — who "fed and dosed" the world?
49:32 – Manufacturing pharmaceutical molecules inside plants
50:18 – Replicating $30–40k drugs cheaply (Rituximab, Lecanemab)
54:21 – Why the Middle East may beat the US, RFK Jr & MAHA
55:11 – Genetics, cancer & the healthy 80–90%
57:35 – Taste: beating junk food at its own game
58:27 – Why good food got so expensive (money printing)
59:14 – A world without hunger — how far away?
1:00:24 – Tasting the farm: microgreens, bok choy, mizuna & kale
The estrogen shield

Most women are taught that estrogen is a reproductive hormone. It is also the most important neuroprotective molecule in the female brain, and it does four things nothing else does: it drives mitochondrial energy production in neurons, it pushes amyloid processing down the clean pathway instead of the toxic one, it upregulates antioxidant defense, and it maintains white matter integrity.

Then, over the menopause transition, it drops by roughly 80%.

Mosconi’s 2021 imaging work in Scientific Reports found menopause status was a stronger predictor of Alzheimer’s brain changes in women than age or family history. That is the finding that should have changed clinical practice and has not.

The twenty-year head start

The silent phase of Alzheimer’s begins two to three decades before symptoms. In women, that window overlaps almost exactly with perimenopause.

Which means the brain fog you are dismissing as burnout is happening at the same moment the pathology is forming. Not causally identical, but not unrelated either.

The part that makes me angry is the diagnostic gap. Women presenting with cognitive symptoms are more likely to be assessed for depression than investigated neurologically. By the time anyone looks properly, years have passed.

The hormone window

A meta-analysis presented at the 2025 American Neurological Association meeting found HRT initiated within five years of menopause was associated with up to 32% lower Alzheimer’s risk. Initiated after 65: 38% higher.

The mechanism explains the timing. During perimenopause and early postmenopause the brain’s estrogen receptors are still functional. Reintroduce estrogen and the signaling machinery responds. Wait a decade and neurons that have been starved of that signal do not respond the same way.

And in the EPAD cohort, women carrying APOE4, the ones at highest genetic risk, showed the largest benefit from early initiation.

I am not a prescribing physician and I am not telling you to take anything. I am telling you that the conversation you have at 42 is a different conversation than the one you have at 68, and that a lot of clinicians are still working from the 2002 WHI framing that has since been reanalyzed. If your doctor has not read anything published after 2002, find one who has.

The honest caveat: this is observational and conference-presented, not a completed randomized trial in perimenopausal women. The timing hypothesis is well supported. It is not settled. Anyone selling you certainty here is selling you something.

The rest

Three more layers in the full episode: why resistance training produces the irisin-BDNF cascade without the cortisol cost, why the glymphatic system only clears amyloid during deep slow-wave sleep and why perimenopausal women lose that stage disproportionately, and why cortisol is the thread running through every other mechanism.

The woman I worry about most in clinical work is the one doing everything right. Running a business, training hard five days a week, sleeping six hours, skipping meals. She is elevating cortisol in every domain simultaneously and she thinks she is being healthy.

Full episode out now.

This newsletter is brought to you by Function Health

Real question.

When was the last time you looked beyond how you feel and actually measured your health?

Not guessed. Not assumed. Measured.

Many of the biological changes that increase the risk of cardiovascular disease, metabolic dysfunction, and other chronic conditions begin years before symptoms appear.

That’s why biomarkers matter.

Apolipoprotein B (ApoB), non-HDL cholesterol, and Lipoprotein(a) [Lp(a)] provide a more comprehensive picture of atherosclerotic cardiovascular risk than LDL cholesterol alone in many people.

Fasting glucose, HbA1c, fasting insulin, and the triglyceride-to-HDL ratio can help assess glucose regulation, insulin sensitivity, and overall metabolic health.

High-sensitivity C-reactive protein (hs-CRP), creatinine, estimated glomerular filtration rate (eGFR), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and the urine albumin-to-creatinine ratio (UACR) offer valuable insight into systemic inflammation, kidney health, liver function, and early vascular damage.

No single biomarker tells the whole story. Together, they help establish a baseline, monitor trends over time, and identify opportunities for earlier intervention.

That’s one reason I like Function Health.

With 160+ lab tests annually, it provides a broad snapshot of key physiological systems, helping you make more informed decisions about nutrition, exercise, recovery, and long-term health.

You can’t optimize what you don’t measure.

If you’re serious about improving your healthspan, reducing preventable risk, and making decisions based on data instead of guesswork, Function Health is a great place to start.

Check it out and use my code below.

GET TESTED HERE

If you have any questions, feel free to email me directly at sponsor@drlouisanicola.com

Example Mid Roll Ads

tl;dr

• #1 Podcast in Medicine, #12 in Health

• 250,000+ downloads per episode — one of the largest brain health audiences in the world

• 22.4% are founders or C-suite executives, 18.6% are physicians or healthcare professionals, 31.2% are high-performance professionals (finance, law, tech), 15.8% are researchers or academics (potentially overlapping).

• 34.7% earn over $250,000 annually.

• 800,000+ Instagram followers — the largest clinical neuroscience brand on social media.

• The only brain science podcast hosted by a clinical neuroscientist — credibility that cannot be replicated Audience spans high-performing executives, elite athletes, clinicians, and health-obsessed consumers — people who spend aggressively on brain health, performance, and longevity

An Overview

The Neuro Experience is not a general wellness podcast. It is the only show at the intersection of clinical neuroscience, brain health, neurotechnology, and human performance — hosted by a credentialed neuroscientist who advises Fortune 500 executives and professional athletes. Our audience does not passively consume content. They act on it. They buy the supplements, book the tests, invest in the devices, and upgrade their protocols. They are the highest-intent brain health audience available to advertisers.

Audience Profile

Our audience is a mix of high-performing professionals and health-obsessed consumers — united by one thing: they take their brain seriously.

Example Episodes;

Over The Last Quarter

Substack

Instagram

Louisa Nicola

Louisa’s has been interviewed on the biggest podcasts in the world and her reach is continuing to rise.

Why sponsors win on TNE

TNE is not a CPM play.

It is a trust play.

Our audience trusts Louisa's clinical credentials. When she recommends a product, it carries the weight of a doctor's recommendation — not an influencer's. This is why TNE sponsors see conversion rates far above podcast industry averages. What makes

TNE different for sponsors:

Clinical credibility — host-read integrations carry the authority of a neuroscientist, not a lifestyle influencer High purchase intent — this audience is already spending on brain health; they are looking for what to buy next Visual production — YouTube and social integrations mean your brand is seen, not just heard Category ownership — exclusive positioning means you own your vertical on the show

Partnership Structure

We partner on a quarterly basis.

Each quarterly partnership includes:

Mid-rolls on all episodes that quarter (~12 episodes): Custom-scripted, host-read integrations with visual overlays on YouTube.

This also includes a feature in the newsletter sent with each episode (60K+ subscribers).

Category exclusivity:

Only one partner per vertical for the duration of the partnership. If you are our sleep technology partner, no other sleep company appears on the show.

Social media integration:

Your brand featured across Instagram (800K+ followers), YouTube, and clip distribution — not just audio.

Custom activation:

We work with you to design an activation that makes sense — whether that is a live event, a cobranded research initiative, or exclusive listener offers. Ideal Sponsor Categories.

We work with companies solving real problems in brain health, performance, and longevity. Our sponsors are category leaders.

*Presenting Sponsorship

Each quarter, one presenting sponsorship is available. This option gives your brand prominent visibility across the show and its platforms.

The package includes:

• First sponsor placement in each episode

• A short mention within the first ~5 minutes of the episode, before the main content begins

• Placement of the presenting sponsor’s logo on all episode pages for that quarter across major podcast platforms

• Placement of the presenting sponsor’s logo on the Neuro Experience website and homepage during the sponsorship period

Thank you so much for considering a sponsorship with us! If you have any questions, please email me at sponsor@drlouisanicola.com

I did not go to Arizona to talk about lettuce.

I went because of one exchange I knew we would eventually get to, and when we got there it was the most important five minutes of the conversation.

The Alzheimer’s drugs that exist right now, lecanemab and donanemab, are monoclonal antibodies. They clear amyloid from the brain. They are also expensive, they are administered by infusion, and they carry a real risk of brain swelling and microhemorrhage. Most people who could theoretically benefit from them will never receive one, and the reason is not scientific. The reason is that monoclonal antibodies are grown in mammalian cell culture, and mammalian cell culture is extraordinarily expensive.

I have written before about what I call the cognitive class war: the growing gap between people who can buy access to brain health and people who cannot. Drug manufacturing cost is one of the load-bearing walls of that gap.

Sam Bertram claims he can knock that wall down by growing the molecules inside plants.

He is not a pharmacologist. He is a mechanical engineer from Victoria, Australia who co-founded OnePointOne with his brother John in 2017, after reading that 1.1 billion people began this millennium malnourished. The company nearly died. Several of its better-funded competitors did die. What survived is a farm built inside a warehouse robotics system, growing greens for every Whole Foods in Arizona, harvest-ready in fifteen days.

And in partnership with UC Davis, they have already grown rituximab, a monoclonal antibody used in non-Hodgkin’s lymphoma, inside their plants.

This is not as exotic as it sounds. Plant-made pharmaceuticals are already real. Taliglucerase alfa, approved by the FDA in 2012 for Gaucher disease, is produced in carrot cell culture. The experimental Ebola therapy ZMapp was grown in tobacco plants. The science exists. What has not existed is the manufacturing scale.

So the question I brought to Arizona was simple. If the molecule can be grown in a plant, and the plant can be grown in a box next to a distribution center, what happens to the price of a brain?

Leave a comment

TOPICS DISCUSSED
00:00 – Cold open: bold claims & who is Sam Bertram
00:51 – Why vertical farms collapse (Bowery) & how OnePointOne survived
05:49 – The number that started it all: 1.1 billion malnourished
07:30 – Why micronutrient deficiency is the real killer
08:21 – What OnePointOne actually is: "a box that grows plants"
10:03 – Training plants with light & water to boost nutrients
11:00 – Closing the loop: food matched to your body's data
12:28 – The plan for 1,000 farms & the AutoStore partnership
15:46 – Plant biology 101: growing with no soil, no sun
18:11 – The robots — and why humans are still essential
21:27 – Pesticides, washing produce & disease clusters
23:53 – Beet greens for cancer patients & the Whole Foods deal
24:42 – A 13-person company run on AI
25:15 – The 15-day crop & cracking the cost code
27:11 – Biology vs. software: what really makes it work
28:01 – Humanoid robots, ~5 years away
30:27 – Why raise $80M and not $500M
33:56 – What they do to a plant that nature never would
36:28 – Expanding crops: strawberries, cannabis, mushrooms
38:05 – Growing food & materials in space (Elon, text back)
39:38 – Personalized food grown from your blood test
40:24 – Food as medicine & the truth about Western medicine
41:11 – Sam's mystery illness: 8 years without exercise
44:23 – Plants as medicine — who "fed and dosed" the world?
49:32 – Manufacturing pharmaceutical molecules inside plants
50:18 – Replicating $30–40k drugs cheaply (Rituximab, Lecanemab)
54:21 – Why the Middle East may beat the US, RFK Jr & MAHA
55:11 – Genetics, cancer & the healthy 80–90%
57:35 – Taste: beating junk food at its own game
58:27 – Why good food got so expensive (money printing)
59:14 – A world without hunger — how far away?
1:00:24 – Tasting the farm: microgreens, bok choy, mizuna & kale

Thank you for listening.

Louisa

Here is my position, and it will cost me.

The supplement list is the least important part of supplementing for your brain. The order matters more than the contents. And two of the five most-recommended brain supplements have a headline number attached to them that does not survive contact with the randomized trials.

I will show you all of it. Including the part where I take my own products off the list.

Where This Started for Me

When I began my academic career, I was sifting through enormous amounts of data trying to answer one question: what makes a brain grow?

It was a naive question. It was also the right one. Because if you can work out what builds a brain, you can work out what defends one.

So I went to first principles. Not “what supplement is trending.” Not “what does the market sell.” Just: what is the brain physically made of?

That question led me straight into the literature on EPA and DHA.

The brain is roughly 60% fat by dry weight, and DHA is the omega-3 fatty acid selectively concentrated in the membranes of your neurons. It is not a nutrient that supports the brain from the outside. It is a nutrient the brain is structurally built from.

I expected the trials to be overwhelming. Give people the substrate their brain is made of, and the brain should hold up better.

The trials were not overwhelming. Many of them failed.

That failure is the most interesting thing in this entire field, and understanding why is what separates people who take supplements from people whose supplements work.

Why the Trials Failed

In 2010, a randomized controlled trial called VITACOG gave high-dose B vitamins to older adults with mild cognitive impairment. It lowered homocysteine and slowed brain atrophy (Smith et al., PLoS One, 2010). Brain imaging showed the treatment specifically reduced gray matter loss in the regions Alzheimer’s attacks first (Douaud et al., PNAS, 2013).

Then the researchers split participants by omega-3 status.

The B vitamins worked in people who already had adequate omega-3. In people with low omega-3, the B vitamins did close to nothing (Jernerén et al., American Journal of Clinical Nutrition, 2015).

Read that again. The intervention did not fail. The intervention failed in the people missing a different nutrient.

Now the same pattern from the other direction. Researchers in the Framingham Offspring cohort counted how many of three nutrients a person was suboptimal in: omega-3, homocysteine (a functional marker of B-vitamin status), and vitamin D. Each additional suboptimal nutrient was associated with roughly 50% higher dementia risk. People suboptimal in all three carried close to four to five times the risk of people suboptimal in none (Alzheimer’s & Dementia, 2024).

Your brain does not read your supplement list. It runs these nutrients as an interacting system, and a gap in one blunts the benefit of the others.

This is the answer to the question I started my career with. The brain is not built from a hierarchy of nutrients where you take the best one. It is built from a system, and systems fail at their weakest point.

Which means the entire framing of “the top five supplements” is wrong. You do not want the five best supplements. You want no weak links. And you cannot know where your weak links are by reading a list. You can only know by measuring.

That is not a satisfying thing to sell. It is what the evidence says.

Leave a comment

Why 35, Not 65

Because the silent phase of Alzheimer’s begins roughly 15 to 20 years before symptoms appear. The pathology builds while you feel entirely fine.

For women, the window is sharper. Across the menopause transition, Mosconi and colleagues showed perimenopause itself brings reduced brain glucose metabolism, gray matter changes, and increased amyloid deposition, with peri- and post-menopausal APOE-ε4 carriers accumulating more amyloid than age-matched ε4 men (Mosconi et al., Scientific Reports, 2021). Two-thirds of people with Alzheimer’s are women. This is a large part of why.

The conversation you are told to have at 65 should be starting now. Nutrient status is one of the few levers available to you for that entire twenty-year window, and it is one of the only ones you can measure.

What I Am Going to Do Behind This Paywall

I am going to give you the five, with the trial doses and an honest evidence grade for each, separating what has randomized support from what rests only on observational data.

I am going to tell you why the famous vitamin D number circulating right now is observational, and what happened when it was tested properly.

I am going to flag two safety problems in the standard B-vitamin protocol that almost nobody mentions, one of which can cause nerve damage at doses currently sold on shelves.

And I am going to take two ingredients off this list that I have a commercial interest in selling you, and explain exactly why the evidence does not justify them.

That last one is the reason this newsletter exists. You do not have a shortage of people telling you what to take. You have a shortage of people whose incentive is to tell you what not to.

🔒 For paid members, the rest of this letter covers:

• The three blood tests to run before you spend a dollar. Omega-3 index, homocysteine, 25(OH)D, with the target ranges I use and why the standard lab “normal” for homocysteine is far too permissive.

• The five, with trial doses and an honest evidence grade. Which are backed by randomized trials, which are observational only, and why that distinction decides what you should expect.

• The vitamin D problem. Where the “40% lower dementia risk” figure comes from, and what the randomized trials found instead.

• Two safety issues in the B-vitamin protocol, including one that causes peripheral neuropathy at commonly sold doses.

• What I refuse to recommend, including my own ingredients, and the well-marketed supplement that was tested head-to-head in a major trial and did nothing.

Read more

There is a group of 80-year-olds that researchers have started calling super movers.

Their brains are aging on a different track from everyone else in the room.

And it has almost nothing to do with luck.

Let me start with what the study found, then walk you through the biology, then tell you what I would do with it.

I have spent more than a decade looking at human brains, in operating rooms alongside a neurosurgery team and in Alzheimer’s research. The fact that pulled me into this work and has never let go is this: two-thirds of the people living with Alzheimer’s are women, and the window where the disease is most preventable opens decades before the first symptom appears.

So when a study lands that tells us who keeps their mind into their late 80s, and why, I read every word of it. This one is worth yours.

It published in Neurology last month.

What Is a Super Mover?

The study is titled “Cognitive Aging and Brain Health: A Comparison of Super Movers vs Nonsuper Movers,” by Jayakody and colleagues, published in Neurology in 2026.

The researchers followed nearly 4,000 older adults in a long-term aging study. Every participant took a timed walking test. The fastest 9%, those whose walking speed sat at least 1.5 standard deviations above the average for their exact age group, were labeled super movers.

Then they looked at what happened to those people’s minds over time.

Super movers were about 50% less likely to develop cognitive decline than their same-age peers who walked slower.

Not 50% less likely to have a stiff knee. 50% less likely to lose their memory, their reasoning, their independence.

The single fastest thing you can measure about an aging body, how quickly it walks across a room, tracked one of the most important things about an aging brain.

Why Would Walking Speed Predict Brain Health?

Because walking is not a leg activity. It is a whole-brain, whole-body activity that happens to use your legs.

Walking well requires balance, coordination, sequencing, spatial navigation, and the muscle to execute all of it at once. When any of those systems begins to fail, gait slows first, often years before a memory test catches anything.

But there is a deeper reason, and it is the part of this I find most compelling, because it sits at the center of my own research: the muscle-brain axis.

Muscle is not inert scaffolding. It is an endocrine organ. When it contracts, it releases signaling molecules called myokines into the bloodstream, and some of them act directly on the brain.

The clearest example: in 2013, Wrann and colleagues showed in Cell Metabolism that exercise drives a muscle protein called FNDC5, which is cleaved into a hormone called irisin, and that this pathway increases BDNF in the hippocampus. BDNF, brain-derived neurotrophic factor, is one of the most important molecules for keeping neurons alive and building new connections.

Working muscle sends a chemical signal that tells the memory center of the brain to grow.

This is not only mechanism on paper. In 2011, Erickson and colleagues published a randomized controlled trial in PNAS showing that one year of aerobic exercise increased the volume of the anterior hippocampus by 2% in older adults, reversing one to two years of normal age-related shrinkage, and that the growth tracked with rising blood BDNF.

The super mover study fits this precisely. The fast walkers did not just have better legs. They held on to hippocampal volume as they aged.

Fast walking does not protect the brain by accident. It is a visible readout of a body that is chemically feeding its own brain.

The Finding That Should Stop You

Here is the result I have not been able to put down.

Some of the super movers had brain plaques and tangles, the abnormal proteins that define Alzheimer’s disease, and showed no cognitive symptoms at all.

Read that again. Their brains carried the pathology. Their minds did not carry the disease.

There is a name for this. It is called cognitive resilience: the brain’s capacity to keep functioning normally while damage accumulates underneath. This study points to physical capability as one of the things that builds it.

That reframes the entire prevention conversation. For a long time we treated Alzheimer’s pathology as destiny. This is evidence that how you live can help decide whether the pathology in your brain ever becomes the disease you experience.

It also fits the larger picture. In 2024, the Lancet Commission (Livingston and colleagues, The Lancet) reported that around 45% of dementia cases are potentially preventable by addressing 14 modifiable risk factors, and physical inactivity is one of them.

This matters most for women, who carry two-thirds of the Alzheimer’s burden, and it matters most in the years around menopause, when the brain’s protective signaling shifts.

So Here Is the Real Question

That is what the study found. Fast walkers keep their minds. Muscle feeds the brain. And physical capability appears strong enough to hold the disease at bay even when the pathology is already present.

Which leaves the only question that actually changes your life: how fast is fast enough, how do you measure it, and can you build it if you are not there yet?

That is where the rest of this goes.

🔒 For paid members, the rest of this letter covers:

• The exact walking speed that qualified as a super mover, and the 10-second test to measure yours at home this week

• Why the plaques-without-symptoms finding may be the single most important result in the paper, and what specifically builds cognitive resilience

• The three training variables that raise gait speed after 60 (it is not “walk more”)

• What this means for women inside the perimenopause window, and why the prevention clock starts earlier than most are told

• The exact resistance and power training protocol I would program to move someone toward super mover status

If your brain is worth protecting, this is where the work starts.

Read more

Subscribe now

Team,

There is a substance that’s been classified alongside heroin for over 50 years. It has no accepted medical use according to the federal government. And it just outperformed the best antidepressant we have — in two doses. In this solo episode, I walk you through exactly what psilocybin does to your neurons, why it works where antidepressants fail, the real risks nobody should ignore, and why the President of the United States signed an executive order in April 2026 to accelerate psychedelic therapy review.

This is the most research-dense episode I’ve ever recorded. I cover the default mode network and why its hyperactivity is the neurological substrate of depression, the imaging data showing structural brain changes within 24 hours of a single dose, the head-to-head NEJM trial against escitalopram, the 80% smoking cessation rate from Johns Hopkins, and why the quality of the subjective experience predicts clinical outcomes better than the pharmacology alone. If you or someone you love has ever struggled with depression, addiction, or treatment resistance — this one matters.

TOPICS DISCUSSED
00:00 Intro: A Schedule I Drug That's Making Neuroscientists Rethink the Brain
00:39 The Default Mode Network and Your Sense of Self
02:49 How Depression Locks the Brain Into a Rigid Loop
03:23 Where SSRIs Stop Short of the Problem
04:44 The Brain Imaging Data: "Massive" DMN Disruption and Reorganization
06:58 Confirming It in Drug-Naive Brains
08:04 The Rewiring: How Psilocybin Changes Neural Architecture
08:35 Dendritic Spines and Synaptic Density
09:39 How Chronic Stress Shrinks Your Neural Connections
10:16 One Dose, More Connections in 24 Hours (Neuron 2021)
11:02 BDNF, TRKB, and a Signal 300x Stronger Than Antidepressants
13:21 Psilocybin vs the Gold-Standard SSRI
14:37 Double the Remission Rate: The Numbers That Matter
15:53 Side Effects, Durability, and Treatment-Resistant Depression
16:39 The Addiction Breaker: 80% Smoking Abstinence at Six Months
17:36 Alcohol, Opioids, and the Shared Architecture of Addiction
19:10 The Dark Side: Real Risks and Hard Contraindications
22:35 The Policy Earthquake: Executive Orders and FDA Breakthrough Status
24:37 Why It Actually Works: Set, Setting, and the Mystical Experience
26:57 Bringing It All Together

Why I Recorded This Episode

I’ve spent the last several years inside clinical neuroscience research on some of the most complex questions in brain health. I study neurodegeneration. I study what breaks. I study what protects.

When I look at the psilocybin research that has come out of Johns Hopkins, Imperial College London, and now multiple phase 3 trials — I’m genuinely stunned. Not because it’s trendy. Because the mechanism is unlike anything else in psychiatry.

Every antidepressant we have works by adjusting the chemical environment around your neurons. SSRIs increase serotonin in the synapse. The neurons themselves — their physical structure, their connections — remain essentially unchanged. The grooves in the record are still there. The medication turns down the volume.

Psilocybin doesn’t turn down the volume. It takes the record off the turntable entirely.

What the Imaging Shows

The default mode network is the brain’s self-referential system. It’s the network responsible for your inner monologue, your sense of self, your ability to imagine the future. In a healthy brain, it activates and deactivates in a balanced rhythm.

In depression, it becomes hyperactive and rigid. It fires constantly. The brain gets stuck in a loop of inward self-critical thought that becomes increasingly negative and increasingly narrow. This isn’t a metaphor. It’s measurable on fMRI.

A 2024 study published in Nature used precision functional mapping and found that psilocybin produced — their word — “massive” disruptions to this network. The rigid pattern collapsed. And in its place, the brain reorganized. Regions that had never communicated before started firing together.

A separate 2022 Nature Medicine study showed these connectivity changes persisted at 3 weeks. The patients who showed the strongest disruption during dosing were the most likely to be in remission afterward.

The disruption wasn’t a side effect. It was the mechanism.

The Number That Changed My Mind

Here’s the data point that made me record this episode.

Researchers gave mice a single dose of psilocybin and watched their prefrontal cortex under a two-photon microscope. Within 24 hours, dendritic spine density increased by 10%. New physical connections between neurons — visible, measurable, structural. At one month, 60% of those new spines were still there.

Then came the receptor data. The active metabolite of psilocybin binds to the TrkB receptor — the receptor that tells neurons to grow — with 300 times the affinity of conventional antidepressants.

That’s not a marginal improvement. That’s a fundamentally different signal strength.

The Head-to-Head Trial

In 2021, the New England Journal of Medicine published a randomized controlled trial comparing psilocybin directly against escitalopram — the gold standard SSRI — in moderate to severe depression.

Two doses of psilocybin. Six weeks of escitalopram. Same patient population.

The headlines said “no significant difference.” The secondary outcomes told a different story: 57% remission with psilocybin versus 28% with escitalopram. The psilocybin group showed improvement within one week. The escitalopram group was still building to therapeutic effect at week six. And at six months, the psilocybin group maintained their gains significantly better.

Two doses. Faster onset. Double the remission rate. Better durability. Fewer side effects.

80% Quit Rate

The addiction data is equally striking. Johns Hopkins enrolled lifelong smokers — 19 cigarettes a day for 31 years, average of six previous quit attempts — and gave them two to three psilocybin sessions with cognitive behavioral therapy.

At six months: 80% biologically confirmed abstinent. The best pharmacological treatment we have produces 35%.

A 2022 JAMA Psychiatry RCT showed similar results in alcohol use disorder. The mechanism appears to affect the underlying architecture of addiction itself — the rigid neural patterns carved by decades of repetition.

The Risks Are Real

I want to be clear about this. Psilocybin is not for everyone.

Every clinical trial excluded patients with a personal or family history of psychosis, schizophrenia, or bipolar I. Cardiovascular disease requires screening. HPPD is rare but documented. And critically — unsupervised recreational use produces a completely different risk profile from supervised clinical use.

The therapeutic context is not optional. The drug alone is not the treatment. The drug plus the therapeutic container is the treatment. Patients who report a stronger subjective experience — measured by the Johns Hopkins Mystical Experience Questionnaire — have significantly better clinical outcomes. Same drug, same biology, but the quality of the experience predicts the result.

Set and setting aren’t just supportive elements. They may be active ingredients.

Where This Is Going

On April 18, 2026, the President signed an executive order accelerating federal review of psychedelic therapies. The Compass Pathways NDA submission is expected in late 2026. Oregon already has a licensed psilocybin services framework. Australia has been prescribing it for treatment-resistant depression since August 2023.

The evidence threshold for clinical use has been crossed. The question is no longer whether psilocybin works. It’s how to deliver it at scale without stripping out the elements that make it work.

I’m Louisa Nicola — clinical neurophysiologist — Alzheimer’s prevention specialist — founder of Neuro Athletics.

My mission is to translate cutting-edge neuroscience into actionable strategies for cognitive longevity, peak performance, and brain disease prevention. If you’re committed to optimizing your brain — reducing Alzheimer’s risk — and staying mentally sharp for life, you’re in the right place.

This newsletter is brought to you by Function Health

Most people wait until something feels wrong before paying attention to their health.

The challenge is that many chronic diseases begin years before symptoms appear.

That is why biomarkers matter.

They provide objective information about the biological systems that influence long-term health and performance.

ApoB and Lipoprotein(a) [Lp(a)] help assess cardiovascular risk beyond a standard cholesterol panel. Fasting insulin, HOMA IR, fasting glucose, and HbA1c provide insight into insulin sensitivity and blood sugar regulation. hs CRP reflects systemic inflammation, while eGFR, creatinine, ALT, AST, TSH, and Free T4 help evaluate kidney, liver, and thyroid function.

No single test predicts your future. The value comes from measuring these biomarkers over time, identifying meaningful trends, and using that information to guide conversations with your healthcare provider.

That is why I recommend Function Health.

With more than 160+ lab tests annually, Function Health gives you a comprehensive view of your cardiovascular, metabolic, hormonal, liver, kidney, and immune health, helping you make more informed decisions about nutrition, exercise, recovery, and long-term wellness.

The goal is not to look for disease.

The goal is to understand your biology before symptoms appear.

If you’re serious about optimizing your health and performance, measuring is a far better strategy than guessing.

Check out Function Health and use my code below to get started.

ORDER HERE

I saw something the other day that genuinely terrified me.

I thought it was just another headline about teen mental health, but when I looked at the actual data, the neurophysiologist in me hit the panic button.

It was a study showing that giving a 12-year-old a smartphone doesn’t just make them sadder. It fundamentally alters their sleep architecture during the most critical window of brain development.

Now, before we go any further in this letter, which is going to be about why we are accidentally seeding an Alzheimer’s epidemic 40 years from now, I want to give you organically what rolled off my metaphorical tongue into a post I made after reading that study:

“Stop Worrying About Teen Angst. Start Worrying About Teen Tau.” (Mini Rant)

I’m about to say what a lot of neuroscientists want to say, but might not have the words for.

Let’s start with an observation. I’m sure I’m not the only one who has noticed the pattern:

Every time a new study comes out about teens and screens, the conversation immediately pivots to mental health. Depression. Anxiety. Self-esteem. Cyberbullying.

They mock the “tech bros” who won’t let their own kids use iPads, appeal to their ability to diagnose mood disorders, or cheer on vulgar attacks against social media CEOs — all while conveniently sidestepping the actual neurological data.

They know who they are.

And more importantly, you do too.

I don’t know about you but this keeps me going back to the mental health crisis is just the canary in the coal mine. The real crisis is structural. It’s biological. It’s happening in the interstitial spaces of the brain while your teenager is staring at a screen at 1:00 AM.

This is a different sort of letter — an insider’s look not into how to limit screen time today, but into the larger neurological forces that shape the brain we ultimately end up with at age 65.

If you value nuance, intellectual honesty, and learning how to think more clearly about science and medicine, I think you’ll find this one both unique and worthwhile.

What do you think?

Leave a comment

Anyway, that study clearly hit a nerve.

The reason why is simple.

I spend my life looking at the brains of 60-year-olds, trying to figure out where things went wrong. Trying to trace the pathology backward. Trying to answer the question that haunts every Alzheimer’s researcher: When did this actually start?

Here is what I know to be true about Alzheimer’s disease: it does not start when you forget your keys at age 65. The pathology—the accumulation of amyloid plaques and tau tangles inside the brain—begins decades before the first symptom appears.

It is a slow, silent buildup that happens when the brain’s waste clearance system fails to do its job over and over and over again.

And the only time that waste clearance system fully operates is during deep sleep.

The Glymphatic System

This is the glymphatic system. During deep, slow-wave sleep, the brain’s interstitial spaces expand by up to 60%, allowing cerebrospinal fluid to flush through neural tissue and carry away metabolic waste—including amyloid-beta and tau.

When you don’t get enough deep sleep, the system doesn’t run. The waste accumulates. Night after night after night.

Now look at what we are doing to adolescent sleep.

The Pew Research Center data from December 2024 shows that 46% of American teenagers are online “almost constantly.” That number has doubled in the past decade.

Then came the Pediatrics study. Published in January 2026, it analyzed data from over 10,500 children. The researchers found that smartphone ownership before age 12 was significantly associated with depression, obesity, and insufficient sleep.

The younger the child was when they got the phone, the worse the outcomes.

But here is what struck me most. The researchers also looked at a subset of children who hadn’t received a phone by age 12. Among those kids, the ones who then acquired a smartphone showed more harmful mental health symptoms and worse sleep than those who continued without one.

Getting the phone changed them.

“A kid at age 12 is very, very different than a kid at age 16. It’s not like an adult at age 42 versus 46,” said Dr. Ran Barzilay, the lead author.

He’s right.

The adolescent brain is not a smaller version of an adult brain. It is a fundamentally different organ. The prefrontal cortex—the region responsible for impulse control, long-term planning, and executive function—doesn’t finish myelinating until approximately age 25.

The glymphatic system is clearing waste from a brain that is still under active construction.

This is the window we are disrupting. Not with a single bad night. With years of chronic, low-grade sleep deprivation during the exact developmental period when the brain is most vulnerable to accumulating the proteins that cause neurodegeneration.

We are not just looking at a mental health crisis. We are looking at a generation that may be seeding the conditions for Alzheimer’s disease four decades from now.

But is there actual evidence for this in young, healthy people?

And how much tau can really accumulate from just a little bit of lost sleep?

The answer is more terrifying than I expected.

Psst — The Good Stuff Is Below

Upgrading to paid is basically the cheat code for your brain health. For less than the price of a fancy coffee, you get the neuroscience insights I don’t put anywhere else on the internet:

• The 17.2% Spike: The exact biological mechanism linking teen sleep loss to tau accumulation (with the specific study data)

• The fMRI Evidence: How social media physically alters the adolescent prefrontal cortex

• The 3-Step Protocol: How to protect your teenager’s developing brain from neurodegeneration

• The Vault: The entire archive of every paid post I’ve ever written, instantly unlocked

The full breakdown is below for paid subscribers — including the specific study showing what happens to Alzheimer’s biomarkers in young people after just one night of lost sleep.

Read more

Subscribe now

Team,

He carries two copies of ApoE4 — the highest genetic risk factor for Alzheimer’s disease. He went through medical school at Harvard knowing exactly what that meant. His LDL sits at 700. Every guideline in medicine says he should be on aggressive lipid-lowering therapy. Every cardiologist he’s consulted has told him he’s a dead man walking.

He got a coronary CT angiogram. Then he waited seven years. Then he got another one.

Zero plaque.

Nick Norwitz is a physician-scientist who decided the consensus was wrong, ran the experiment on himself, and then published the case report so the rest of us could argue about it. He is either the most reckless doctor in America or the most honest one. Possibly both.

In this conversation, we go deep on the ApoE4 paradox — why carriers burn through DHA faster than everyone else, why standard fish oil supplements fail them, and why the phospholipid form of omega-3 reaches the brain through a completely different transport system. Nick explains the Mfsd2a transporter, why it matters more than dose, and what he personally takes.

Then we get into what I think is the most underappreciated target in Alzheimer’s research today: GSK-3 beta. This is the enzyme that phosphorylates tau. Nick lays out the lithium orotate data — the same data that sold out supplement shelves worldwide after he posted about it — and explains why low-dose lithium may be doing something fundamentally different from what psychiatrists use it for.

The second half of the conversation is where it gets controversial. Nick makes the case that metabolically healthy individuals with elevated LDL may not benefit from statins. He walks through the EZPAVE trial — the one that made headlines — and explains why the data doesn’t say what the headlines claimed. We talk about what actually causes heart disease in someone who is insulin-sensitive, exercises, and has no metabolic dysfunction. And he explains what GLP-1 agonists are doing inside the brain completely independent of weight loss — targeting amyloid and tau through mechanisms that have nothing to do with appetite.

We also cover: the sardine diet experiment and omega-3 thermogenesis, ketones as misfolded protein clearance agents, creatine for depression, BPC-157 risks, retatrutide and PCSK9, the glymphatic system and 40Hz devices, and why Nick believes CRISPR prime editing will make ApoE4 a treatable condition within the next decade.

Watch this episode with Nick Norwitz to find out.

TOPICS DISCUSSED
00:00 Intro: The ApoE4 Paradox and the Case Report That Broke the Internet
00:57 Why Standard Omega-3 Supplements Fail and What to Take Instead
05:13 DHA and the Phospholipid Carrier: How It Crosses the Blood-Brain Barrier
10:19 ApoE4 Explained: Risk, Genetics, and Why Nick Is Optimistic
17:38 Why ApoE4 Carriers Burn Through DHA Faster and Need More
20:31 Women, Omega-3s, Menopause, and Brain Insulin Resistance
21:41 Statins, Sex Differences, and the DHA-Blood Sugar Connection
26:01 Statins and Dementia: What the Data Actually Say
32:24 Tau, GSK-3 Beta, Lithium Orotate, and Targeting Alzheimer's Pathology
42:19 The Glymphatic System, 40Hz Devices, and Sleep as Brain Clearance
45:21 Gene Editing, Prime Editing, and the Future of ApoE4 Therapy
49:33 Nick's Case Report: 700 LDL, Zero Plaque, and Seven Years of Data
55:10 The EZPAVE Trial: Why the Headlines Don't Hold Up
01:00:33 KetoneIQ: Ketones for Brain Energy and Focus
01:01:29 Cheers Health: Supporting Liver Function and Cognitive Recovery
01:03:54 If Not LDL, What Causes Heart Disease in Metabolically Healthy People?
01:12:05 The Oreo Experiment and the Sardine Diet: Self-Experiments in Metabolism
01:19:10 Ketones, Women's Brains, and Clearing Misfolded Proteins
01:21:08 The Full Brain Health Protocol: Omega-3s, Creatine, NAD, Lithium, and More
01:24:01 GLP-1s for the Brain: Independent of Weight, Targeting Amyloid and Tau
01:25:28 Peptides: BPC-157 Risks, Retatrutide, MOTS-c, and What's Worth Watching
01:29:02 Why Nick Is Controversial And Why He Doesn't Mind

This newsletter is brought to you by Function Health

When was the last time you measured your health instead of assuming it?

Many of the processes that contribute to cardiovascular disease, metabolic dysfunction, and other chronic conditions can develop for years before symptoms appear.

That is why biomarkers matter.

ApoB and Lipoprotein(a) [Lp(a)] can provide important insight into cardiovascular risk.

Fasting insulin, HOMA-IR, fasting glucose, and HbA1c help assess blood sugar regulation and metabolic health.

hs-CRP, eGFR, creatinine, ALT, AST, TSH, and Free T4 provide information about inflammation, kidney function, liver health, and thyroid function.

The goal is not simply to detect disease. It is to understand your health status early enough to make informed decisions.

That is why I like Function Health.

Their comprehensive testing platform measures 100+ lab tests annually, giving you a broader view of your health and helping guide decisions around nutrition, exercise, recovery, and long-term wellness.

You cannot manage what you do not measure.

If you are serious about performance, longevity, and preventive health, check it out and sign up using my code below.

ORDER HERE

I didn’t expect a single comment on a podcast to go viral.

When I sat down with Shawn Ryan recently, we covered a lot of ground regarding brain health, performance, and longevity. But the moment that caught fire online was when I stated, unequivocally, that I do not believe BPC-157 is entirely safe.

The pushback was immediate. BPC-157 is the darling of the biohacking and fitness communities. It is touted as a miracle healing compound, capable of repairing torn tendons, soothing inflamed guts, and accelerating recovery from almost any injury. People swear by it. They inject it, they take it orally, and they defend it fiercely.

But as a neurophysiologist, I don’t deal in anecdotes. I deal in data. And when you look closely at the data, the narrative around BPC-157 starts to unravel.

The reason I spoke out on the podcast was simple: the data suggests that BPC-157, when injected, doesn’t know the difference between a cancer cell and a normal cell. When it provides vascularization to heal a torn muscle, it could just as easily be vascularizing an undetected tumor.

But that is only half the story.

What I didn’t say on the podcast—what I’ve been thinking about since—is what this peptide does to the brain.

The mechanisms that make BPC-157 effective at healing a torn rotator cuff are the same mechanisms implicated in the pathophysiology of Alzheimer’s disease. And I’m not the only one raising this concern. A 2025 peer-reviewed reply in Pharmaceuticals by Józwiak and colleagues explicitly flagged BPC-157’s pro-angiogenic and nitric oxide-related activities as warranting serious investigation regarding neurodegenerative disease .

People are injecting a gray-market compound for “longevity” and “brain health,” unaware that they may be chronically stimulating the very pathways associated with blood-brain barrier breakdown and pathological tau accumulation.

The BPC-157 Paradox

BPC-157 (Body Protection Compound-157) is a synthetic peptide sequence based on a protective compound found in human gastric juice. In animal models, it has shown remarkable abilities to accelerate the healing of tendons, muscles, and the nervous system .

The mechanism behind this healing is angiogenesis—the physiological process through which new blood vessels form from pre-existing vessels. BPC-157 enhances VEGFR2 activity and stimulates the Akt-eNOS pathway, driving nitric oxide production and new blood vessel formation.

I actually did a podcast all about peptides here-

If you have a torn rotator cuff, you want angiogenesis. You want new blood vessels delivering oxygen and nutrients to the damaged tissue to accelerate repair. This is why athletes and biohackers report such rapid recovery times.

But here is the paradox: angiogenesis is also the paramount way that tumors grow and metastasize.

Pathologic angiogenesis is heavily implicated in the proliferation of tumor cells . A tumor cannot grow beyond a few millimeters without establishing its own blood supply. It needs vascularization to survive and spread.

The concern is not that BPC-157 causes cancer. There is no evidence that it is mutagenic or carcinogenic in the conventional sense. The concern is that if you have an existing, undetected micro-tumor—which many healthy adults do—injecting a potent, systemic angiogenic agent like BPC-157 could provide that tumor with the blood supply it needs to rapidly expand.

As I said on the podcast: BPC-157 doesn’t know the difference between a cancer cell and a normal cell. It just builds blood vessels.

But as a neurophysiologist, the cancer risk isn’t even what concerns me most.

What concerns me is what happens when you chronically stimulate these pathways in the brain. Because the same two systems BPC-157 activates—VEGF signaling and nitric oxide production—are now being directly implicated in the progression of Alzheimer’s disease in middle-aged adults. And the data on this is is in favour of everything I am proclaiming.

Read more

I spend most of my time in search of meaning for Alzheimer’s disease.

I read the papers. I interview the researchers. I try to understand what is happening inside the brain when it begins to lose itself — the tau tangles, the amyloid plaques, the synaptic silence. That is the work of this show. That is what I care about most deeply.

But I can no longer ignore AI.

Not because it’s trendy. Because the entire architecture of artificial intelligence — every neural network, every transformer model, ChatGPT, Claude, Gemini — was built by a neurophysiologist. A man named Warren McCulloch. He studied the electrical activity of the brain. He asked the same question I ask: how does a physical organ made of neurons produce the experience of understanding?

In 1943, McCulloch and a 19-year-old homeless runaway named Walter Pitts co-authored a paper that proved biological neurons could be modeled as logical units. That paper is the direct ancestor of every AI system running today.

I recorded this solo episode because the story of McCulloch and Pitts is not just a history of technology. It is a story about the brain. It is a story about what kind of cognitive environment produces extraordinary minds — and what happens when that environment is dismantled at the exact moment the machines those minds invented are scaling to govern human history.

The cognitive class war is not just about who gets Alzheimer’s disease. It is about who will be capable of directing the most powerful technology ever built. And it was founded by a neurophysiologist who wanted to understand how brains think.

That’s my world. I couldn’t stay silent on this one.

TOPICS DISCUSSED
00:00 Intro: The 1943 Paper Behind Every AI Model Today
02:53 Walter Pitts Childhood in Depression-Era Detroit
03:17 Hiding From Bullies, He Finds Principia Mathematica
03:40 A 12-Year-Old Writes to Correct Bertrand Russell
06:35 Walter Pitts Meets Warren McCulloch in 1942
08:32 Inside the 1943 Paper That Founded Neural Networks
11:17 From the Perceptron to ChatGPT and Claude
13:43 Norbert Wiener, MIT, and the Macy Conferences
15:05 The 1952 Lie That Destroyed Walter Pitts
19:11 Pitts Dies Alone in a Boarding House, 1969
21:46 Five Conditions That Made a Genius Possible
24:16 Why Those Conditions No Longer Exist Today
33:53 The Cognitive Class War and Who Will Govern AI

The Boy in the Library

Walter Pitts was born in Detroit in 1923. His father was a boilermaker. Prohibition-era Detroit was a rough place, and the Pitts household was rougher than most. By the time Walter was 12, he was being beaten regularly by his father and bullied in the streets.

In the autumn of 1935, a group of neighborhood boys chased him. He ducked into the local public library to hide. The library closed for the evening, but he didn’t want to risk going home. So he hid in the stacks and stayed.

Alone that night, he wandered through the books. He pulled down a three-volume work he had never seen before: Principia Mathematica by Bertrand Russell and Alfred North Whitehead. Its goal was to derive all of mathematics from pure logic.

He started reading it. He stayed in the library for three days.

Then he wrote a letter to Bertrand Russell at Cambridge University. The letter pointed out what Pitts believed were errors in the first volume. He was 12 years old. Russell wrote back and encouraged him to come to Cambridge. But Pitts couldn’t go. He was 12, his family was poor, and his father would not have allowed it.

He spent the next three years teaching himself Greek, Latin, German, and increasingly advanced mathematics — in the same library, often hiding from his father. At age 15, he ran away from home. He never went back. He never spoke to his family again.

He made his way to Chicago, where he heard that Bertrand Russell was giving lectures at the University of Chicago. Pitts was homeless. He had nothing. He attended Russell’s lectures by sneaking into the auditorium. After one of the lectures, he approached Russell directly. Russell remembered the boy who had corrected his book and introduced him to Rudolph Carnap, the great logician.

A few weeks later, Pitts showed up at Carnap’s office with Carnap’s own book covered in margin annotations identifying further errors.

Pitts began attending graduate seminars in mathematics and logic — unenrolled, without a high school diploma. He was 15 years old, living on the streets of Chicago, sitting in graduate philosophy seminars at one of the best universities in the world.

The 1943 Breakthrough

In 1942, at age 18, Pitts was introduced to Warren McCulloch. McCulloch was in almost every respect his opposite: 45 years old, born into a well-to-do East Coast family, educated at Haverford, Yale, and Columbia. He was a senior researcher studying the electrical activity of the brain.

But McCulloch was a philosopher at heart. His central question was not how the brain works mechanically. It was what it means to know. How does a physical organ made of meat produce the experience of understanding?

When they met, they talked for hours. McCulloch invited Pitts to come live with his family. Walter Pitts, now 18, moved into the McCulloch home and stayed for years. He became effectively an adopted son.

And in that home, over the next year, they did something together that no one else had ever done before. They wrote a paper called A Logical Calculus of the Ideas Immanent in Nervous Activity. It was published in 1943 in the Bulletin of Mathematical Biophysics.

The paper made a single audacious claim: neurons in the brain could be modeled as logical units. Each neuron either fires or it doesn’t. That binary behavior could be treated as a logical operation — true or false, one or zero. And if you connected enough of these binary logical units together in the right configuration, you could implement any computable function.

Brains, they were saying, are computers. Not metaphorically. Mathematically.

From 1943 to ChatGPT

In 1958, Frank Rosenblatt used the McCulloch-Pitts framework to build the perceptron — the first practical artificial neural network. In the 1980s, Geoffrey Hinton extended this with backpropagation. In 2012, Alex Krizhevsky used backpropagation on a deep neural network to win ImageNet. In 2017, Google published “Attention Is All You Need” — the transformer architecture underneath every large language model today.

Every single one of those breakthroughs traces back in an unbroken intellectual line to the 1943 paper that Walter Pitts co-authored when he was 19.

The boy who taught himself Greek and Latin in a public library to escape an abusive father is a foundational reason the AI industry even exists.

The Betrayal

The success of the paper brought Pitts to MIT, where Norbert Wiener — the founder of cybernetics, a child prodigy who had finished his PhD at Harvard at 18 — invited him to join his group. Pitts quickly became the intellectual center of the cybernetics movement. At the Macy Conferences, he was treated as a peer by John von Neumann, Margaret Mead, Claude Shannon.

Then in 1952, Wiener’s wife Margaret fabricated a lie — that Pitts and several other men had seduced her teenage daughter Barbara. It wasn’t true. But Wiener believed her. He cut off all contact with Pitts and McCulloch without explanation.

This destroyed Pitts. He had built his intellectual life around two father figures. Now one had cast him out. He began to drink. He burned the manuscript he had been working on — a major paper extending the 1943 framework to three-dimensional neural networks. He burned his notes. He stopped publishing.

On May 14, 1969, Walter Pitts died alone in a boarding house in Cambridge of bleeding esophageal varices. He was 46 years old. Four months later, Warren McCulloch died. The partnership that founded computational neuroscience ended within a single season.

The Cognitive Ecology

The standard story of Walter Pitts is a tragedy. A brilliant mind destroyed by a single malicious lie. That story is true. It is also incomplete.

The interesting question is not why Pitts fell. The interesting question is how he ever rose in the first place.

The answer is that the conditions of his rise were as specific and contingent as the conditions of his fall:

There was a free public library in Detroit in 1935 that stocked Principia Mathematica. It had no entrance requirements, no membership fees, no algorithmic curation telling the boy what to read.

There was Bertrand Russell, who took the time to read and reply to a letter from a 12-year-old stranger.

There was an intellectual culture that took prodigies and autodidacts seriously without demanding credentials.

There was Warren McCulloch, who saw a mind worth saving and opened his door — without filing paperwork or consulting human resources.

There was a small intellectual community where a 19-year-old could be evaluated for what he could do, not what degrees he held.

Each of these conditions is gone or substantially diminished.

The Cognitive Class War

The artificial neural networks that descend from the 1943 paper are now trained on clusters of tens of thousands of GPUs costing hundreds of billions of dollars. The models have hundreds of billions of parameters. They are growing in capability at a rate that has surprised even the people building them.

Meanwhile, the biological neural networks — the human minds that produced the original insights — are facing pressures the cybernetics generation never faced. The capacity for sustained, deep, solitary engagement with difficult material is harder to develop in the current environment than it was a generation ago.

We have machines that compute more than ever. We have humans whose capacity to think deeply about what those machines are doing is, by several measures, harder to develop than it was a generation ago.

The cognitive class war is not just about who gets Alzheimer’s disease. It’s about who in the coming decades will be capable of evaluating, governing, and directing the artificial intelligence systems that descend from Walter Pitts’s 1943 paper.

If we want another Walter Pitts — and we will need another one, and another, and another — we will have to rebuild some of what we have dismantled. The libraries. The willingness to take prodigies seriously. The space for deep solitary reading. The intellectual communities small enough to recognize unusual talent.

These aren’t nostalgic asks. They are infrastructural requirements for a future in which human beings remain capable of directing the technologies we’ve built.

In 1935, a 12-year-old boy hid from the neighborhood bullies in a public library. He pulled a book off a shelf. He read it for three days. He wrote a letter to its author. Eight years later, he co-authored the paper that founded modern artificial intelligence.

I don’t know if we still produce minds like that. But I think it’s worth asking.

This newsletter is brought to you by Timeline Nutrition

Your body relies on mitochondria to convert nutrients into the energy that powers movement, recovery, and everyday performance.

As we age, mitochondrial function gradually declines. This reduction in cellular efficiency has been associated with lower energy production, reduced muscle function, and slower recovery.

Mitopure® by Timeline Nutrition contains Urolithin A, a postbiotic compound that has been investigated in clinical research for its effects on mitochondrial health. It is the first Urolithin A ingredient studied in multiple human clinical trials and has been shown to support:

• Mitochondrial function
• Muscle strength and endurance
• Cellular energy production

Clinical studies have found that daily supplementation with Mitopure can improve muscle strength by up to 12% over four months, even without changes to exercise habits.

Think of it as supporting your body’s cellular renewal systems, helping mitochondria maintain healthy function so your muscles and cells can perform more efficiently over time.

Support your cellular energy and mitochondrial health with Mitopure® today.

GET 20% OFF

Summary

Who was Walter Pitts?

Walter Pitts was a self-taught mathematical prodigy and logician who co-authored the foundational paper of modern artificial intelligence. Born in Detroit in 1923, Pitts ran away from an abusive home at age 15. Despite having no high school diploma, his brilliance in formal logic led him to collaborate with neurophysiologist Warren McCulloch. In 1943, at age 19, Pitts and McCulloch published “A Logical Calculus of the Ideas Immanent in Nervous Activity,” which provided the first mathematical model of how biological neurons could implement logical computation.

What was the McCulloch-Pitts 1943 paper?

The 1943 paper “A Logical Calculus of the Ideas Immanent in Nervous Activity” by Warren McCulloch and Walter Pitts is considered the foundational document of computational neuroscience and artificial intelligence. The paper demonstrated that the binary behavior of neurons (firing or not firing) could be modeled as logical operations (true or false). They proved that a network of these binary logical units could implement any computable function, establishing the theoretical basis for all modern artificial neural networks, including deep learning and transformer architectures.

What happened to Walter Pitts?

Despite his foundational contributions to cybernetics and artificial intelligence at MIT, Walter Pitts’s career ended in tragedy. In 1952, a fabricated rumor caused his mentor, Norbert Wiener, to abruptly cut off all contact with Pitts and McCulloch. Devastated by the loss of his intellectual father figures, Pitts burned his unpublished manuscripts, withdrew from academia, and struggled with severe alcoholism. He died alone in 1969 at the age of 46 from bleeding esophageal varices.

What is the cognitive class war?

The “cognitive class war” refers to the growing asymmetry between the rapidly scaling capabilities of artificial intelligence systems and the depleting cognitive ecology of the human population. While AI models are trained on massive computational clusters, the environmental conditions that historically produced deep, sustained human cognition—such as uninterrupted solitary reading, accessible public intellectual resources, and non-credentialed mentorship—are being systematically dismantled by the attention economy. This concentrates the capacity to govern AI in increasingly fewer hands.

Someone sent me a paper recently — Cell Death & Disease (Yu et al., 2024) — that got attention for showing stress hormones can drive the “spread” of Alzheimer’s pathology through the brain.

The reaction wrote itself: so that’s it, then? Stress is the enemy? Should we all quit our high-pressure jobs tomorrow?

No. And the fact that this is the question everyone jumps to is exactly the problem.

Because the disease was never going to announce itself with a stressful week. It works on a longer clock than that — the damage begins building ten, fifteen, twenty years before a single symptom shows up, in people who feel completely fine. By the time the forgetting starts, the part you could have changed already happened, in silence, during the years you assumed there was nothing to worry about.

So the real question isn’t whether to escape your job. It’s whether you’re going to keep ignoring the one window where any of this can actually be changed.

The person who kept pressing this question was correctly pointing out that the study showed a direct mechanism between glucocorticoids (stress hormones) and the secretion of toxic tau proteins. And by this surface-level reading, any amount of stress is the worst thing you could subject your brain to.

Now, of course, you could look closer at the methodology.

Notice that the people who panic over these headlines often misunderstand what tau actually is, and how stress interacts with it. We tend to conflate “feeling stressed” with “achieving biological neurodegeneration.” I’m not denying that chronic, unmanaged stress accelerates cognitive decline. I’m simply pointing out that the way we currently talk about stress and Alzheimer’s is fundamentally disconnected from the actual molecular biology happening inside your neurons.

We often talk about stress in this way that misunderstands how it actually damages the brain in our world. Our intuitions are primed by psychological data—people who report high stress have higher rates of dementia. We assume the damage is just general “wear and tear.”

But in the real world, stress damage is highly specific. It is the product of a precise biochemical cascade that targets the structural integrity of your neurons. Stress doesn’t just wear the brain down; it actively commands the brain to dismantle itself.

A mechanistic versus psychological level analysis is useful here. As we’ll discuss, a 2020 analysis from the Neurology journal found that in cognitively unimpaired adults who already had amyloid plaques, better stress coping was associated with lower tau burden. This is because the biological response to stress has massive spillover effects—the right coping mechanisms can halt the cascade before it forces tau to misfold and spread.

If you are a high performer, you have almost certainly been told that stress is killing your brain. You are probably experiencing some level of chronic stress right now.

The Railroad Tracks of the Mind

To understand why stress is so destructive, you first have to understand what it destroys.

Inside every neuron in your brain, there is a complex transport system. Think of it like a microscopic railroad network. Nutrients, mitochondria, and signaling molecules must travel down the long axon of the neuron to reach the synapse. If this transport system fails, the synapse starves, communication stops, and the neuron eventually dies.

The “railroad tracks” are made of structures called microtubules. And the “ties” that hold these tracks together—keeping them stable and straight—are made of a protein called tau.

In a healthy brain, tau is essential. It binds to the microtubules, ensuring the tracks remain intact so the neuron can function.

But tau is highly sensitive to its chemical environment. Specifically, it is sensitive to enzymes called kinases, which add phosphate groups to the tau protein. This process is called phosphorylation.

When tau becomes hyperphosphorylated—when too many phosphate groups are added—it changes shape. It loses its grip on the microtubule. The railroad ties pop off, and the tracks collapse.

Without the tracks, the neuron’s transport system disintegrates. But it gets worse. The detached tau proteins don’t just float away harmlessly. They begin to clump together, forming toxic aggregates known as neurofibrillary tangles. These tangles choke the neuron from the inside out.

This is the hallmark pathology of Alzheimer’s disease.

But what triggers this hyperphosphorylation in the first place? Why does tau suddenly let go?

AND, can we take anything to stop this? turns out, we actually can.

Read more

I filed this week’s episode under food. Halfway through recording it, I realized I was making a brain episode.

My guest is Nick Green, co-founder and CEO of Thrive Market. He built it into 1.7 million members and close to a billion dollars in sales on a premise that every venture investor he pitched rejected: that ordinary Americans want to eat well and can’t, because the system is arranged so they can’t. Price, geography, and a regulatory setup that quietly works against them.

A few things from the conversation I have not been able to put down.

The FDA lets companies certify their own additives as safe. The mechanism is called GRAS, generally recognized as safe, and many of those ingredients have not been re-reviewed in decades. The EU bans thousands of additives the US still permits. On this one, we are the control group.

One thing spikes blood sugar harder than sugar does, and it is high-fructose corn syrup, used at a scale almost nowhere else on earth allows. Nick’s one-word account of why: lobby.

And the line I keep coming back to: if you cannot outsource your trust to the government, you end up outsourcing it to whoever did the hard work instead.

Here is why this sits on my desk and not just a food writer’s. Metabolic dysfunction is not adjacent to the three diseases most likely to end your life. It is upstream of them, cardiovascular disease, cancer, and Alzheimer’s alike. The Framingham Heart Study cohort, published in the Journal of Prevention of Alzheimer’s Disease in 2025, found that in midlife, every single daily serving of ultra-processed food raised Alzheimer’s risk by 13 percent. The effect showed up in people under 68 and vanished above it, which means the damage is being laid down in the exact years most people assume they have nothing to worry about. For women, that window overlaps with the menopausal drop in estrogen, when the brain is already shedding a layer of protection.

So no, this is not a willpower story, and it is not only a food story. What goes in the cart in your forties is a variable in what your brain looks like in your seventies.

The full conversation with Nick is out now.
TOPICS DISCUSSED
00:00 Intro: The Ultra Processed Food Crisis Nobody Is Talking About Honestly
01:06 Nick Green and the Mission Behind Thrive Market
01:27 Growing Up in Minnesota: How a Mom's Grocery Struggle Built a Billion-Dollar Insight
07:24 70% of Kids' Diets Are Ultra Processed — and It's Not a Willpower Problem
08:38 The Membership Model: How Thrive Makes Organic Cheaper Than Conventional
09:31 AI-Personalized Grocery Shopping: Building Your Cart Around Your Health Goals
13:47 The Food System Is Rigged: MAHA, the FDA, and the GRAS Loophole
16:13 Synthetic Dyes, Preservatives, and Why the EU Bans What America Allows
20:43 The Most Unregulated Food Category: Supplements and Ultra Processed Crossover
22:04 How Thrive Vets Every Product: Auditing Manufacturers Up the Supply Chain
23:13 Thrive's Own Brand: 25% of Sales and a Mission-Driven Private Label Model
25:09 Gives Memberships, Free Access, and Building a Community Around the Mission
27:25 The Regulatory Gap and Its Cost: Metabolic Syndrome, Diabetes, and Chronic Disease
29:44 GLP-1s Are Not Enough: Why Pharmacology Alone Can't Fix the Food System
32:41 Thrive vs. Whole Foods: The Key Structural Differences
35:43 Alzheimer's Risk, Ultra Processed Food, and the Framingham Heart Study
36:48 Why the Healthcare System Was Built for Infectious Disease — Not Chronic Prevention
38:05 Metabolism Is Upstream of Everything: Cancer, Heart Disease, Alzheimer's
40:03 MAHA, Government Regulation, and Why Consumer Empowerment Is the Real Solution
45:58 1.7 Million Members and Less Than 1.5% Market Penetration: The Scale of What's Left
47:23 The Un-Everything Store: Curation as a Competitive Advantage
49:16 What Keeps Nick Going: Mission as Decision Filter
51:31 Why Authenticity Always Wins — and What Thrive Wants to Prove to Every Founder

This newsletter is brought to you by Function Health

Real question. When was the last time you actually looked under the hood of your health?

Not guessed. Not assumed. Measured.

Most people wait for symptoms before paying attention to their health. The problem is that many of the biggest risk factors develop quietly for years before you ever feel them.

That’s where biomarkers matter.

ApoB and Lipoprotein(a) [Lp(a)] can provide a deeper understanding of cardiovascular risk than a standard cholesterol panel alone.

Fasting insulin, HOMA-IR, fasting glucose, and HbA1c help reveal how well your body is managing blood sugar and metabolic health.

hs-CRP, eGFR, creatinine, ALT, AST, TSH, and Free T4 offer valuable insight into inflammation, kidney function, liver health, and thyroid function.

The goal isn’t to find problems. It’s to identify trends early enough to do something about them.

That is why I like Function Health.

With 160+ lab tests each year, you get a more complete picture of your health so you can make better decisions around nutrition, training, recovery, and long-term wellness.

You can’t optimize what you don’t measure.

If you’re serious about performance, longevity, and taking a more proactive approach to your health, this is a great place to start.

Check it out and sign up using my code below.

GET TESTED HERE

I had an interesting discussion recently. Someone sent me a new study from The Journal of Prevention of Alzheimer’s Disease (Liao et al., 2026) that made headlines for claiming omega-3 supplementation actually accelerates cognitive decline in older adults.

Okay, they said, then by that logic, shouldn’t we all stop taking fish oil immediately?

To be clear, the researchers who ran this study are obviously very competent. But when you think of effective Alzheimer’s prevention, you don’t think of giving standard fish oil to people who already have cognitive impairment and expecting a miracle.

The person who kept pressing this question was correctly pointing out that the study showed a correlation between omega-3 use and faster decline in MMSE and ADAS-Cog scores. And by this surface-level reading, fish oil is the worst thing you could take for your brain.

Now, of course, you could look closer at the methodology.

Notice that the people in this study were not a healthy prevention cohort. They included individuals with memory concerns, Mild Cognitive Impairment (MCI), and Alzheimer’s dementia. The “supplement use” was entirely self-reported—meaning we have no idea about the dose, the adherence, the quality, the formulation, or the duration.

We tend to conflate “taking a supplement” with “achieving biological accumulation.” I’m not denying that the people in this study who took fish oil declined faster. I’m simply pointing out that the way standard fish oil is currently formulated (as triglycerides or ethyl esters) is not that strongly correlated with actual brain DHA enrichment, especially in sick populations.

We often talk about omega-3s in this way that misunderstands how they are actually delivered to the brain in our world. Our intuitions are primed by epidemiological data—populations that eat a lot of fish have lower rates of Alzheimer’s. We assume taking a pill isolates and rewards that same biological mechanism.

But in the real world, getting DHA into the brain is more the product of having the right molecular “authority and trust” to cross the blood-brain barrier, rather than just swallowing a massive dose of standard fish oil. Standard fish oil is not effective because the molecule, considered in isolation, is the most effective optimization engine. It fails because the brain’s highly selective barrier does not give it the authority to enter.

A formulation versus population level analysis is useful here. As we discussed last week, a 2023 analysis from this exact same cohort found that long-term omega-3 use was associated with lower Alzheimer’s risk. This is because the form of the omega-3 has massive spillover effects—the right form can cross the barrier, reduce inflammation, and coordinate to build structural integrity in neurons.

If you are an APOE4 carrier, you have almost certainly been told to take a fish oil supplement. You are probably taking one right now.

Here is the uncomfortable truth: If you are taking standard fish oil, it is likely not reaching your brain.

And if you carry the APOE4 gene, the problem is significantly worse than anyone has told you!

The Paradox of Fish Oil

For decades, the epidemiological data has been clear: populations that eat a lot of fish have lower rates of Alzheimer’s disease and better cognitive longevity. The assumption was simple. Fish contains high levels of docosahexaenoic acid (DHA), an omega-3 fatty acid that makes up a massive percentage of the brain’s structural fat. Therefore, taking DHA in a pill should protect the brain.

But when researchers actually ran the clinical trials, the results were disappointing. Standard omega-3 supplements consistently failed to show meaningful cognitive benefits in large-scale studies.

How could eating fish be so protective, while taking the exact compound found in fish did almost nothing?

The answer comes down to the delivery mechanism.

When you consume standard fish oil supplements, the DHA is typically in the form of free fatty acids, ethyl esters, or triglycerides. When these forms enter your bloodstream, they are readily absorbed by your heart, your liver, and your adipose (fat) tissue.

But your brain is protected by the blood-brain barrier (BBB). And the BBB is highly selective.

Standard forms of DHA cannot easily cross the BBB. They rely on passive diffusion, which is inefficient. Taking standard fish oil to increase brain DHA is like sending a letter without a zip code—it might eventually get there, but most of it will end up somewhere else.

The Express Courier

The brain has a specific, dedicated transporter designed exclusively to pull DHA across the blood-brain barrier. It is called Mfsd2a.

But Mfsd2a is picky. It will not accept free DHA or triglyceride-DHA. It only accepts DHA when it is bound to a specific phospholipid—specifically, lysophosphatidylcholine (LPC).

When you consume DHA in the LPC form (LPC-DHA), it doesn’t have to rely on passive diffusion. It binds directly to the Mfsd2a transporter and is actively pulled across the blood-brain barrier and straight into the neurons. It is the express courier.

This is why eating fish works better than standard supplements. Fish contains DHA in phospholipid forms, which can be converted into LPC-DHA and transported efficiently into the brain.

This mechanism alone explains why so many clinical trials failed. We were giving people the right molecule in the wrong package.

But if you are an APOE4 carrier, the story doesn’t end there.

The Part That Made Me Stop

When I first read about the Mfsd2a transporter, I thought we had the answer. Switch from standard fish oil to a phospholipid form, and the problem is solved.

Then I started looking at the data specifically for APOE4 carriers.

We know that APOE4 disrupts the tight junctions of the blood-brain barrier. This breakdown makes the barrier “leaky” to toxins, but paradoxically, it also impairs the passive diffusion of nutrients like free DHA.

Dr. Rhonda Patrick published a foundational paper in the FASEB Journal in 2019 outlining this exact problem. She proposed that because APOE4 carriers have impaired passive transport of free DHA, they are entirely dependent on the Mfsd2a transporter and LPC-DHA to get omega-3s into their brains.

So, the logical conclusion is that APOE4 carriers just need to take LPC-DHA, right?

That’s what I thought. Until I read a pair of papers from the same research group — one published in 2025, and a follow-up in 2026 — investigating this exact mechanism in APOE3 and APOE4 mice.

What they found completely upended my understanding of how we should be supplementing.

For APOE4 carriers, even the express courier might be failing.

Read more

Subscribe now

New episode with Brad Schoenfeld: the science of muscle hypertrophy, why training to failure is a myth, and how resistance training acts as a longevity intervention.

Brad Schoenfeld is a Professor of Exercise Science at Lehman College and one of the most highly published researchers in the field of muscle growth, with nearly 400 peer-reviewed papers. He is the author of Science and Development of Muscle Hypertrophy.

Watch on YouTube. Listen on Apple Podcasts, Spotify, or any other podcast app.

TOPICS DISCUSSED
00:00 Intro: The Belief Brad Held in the 90s That Science Has Since Overturned
01:08 Meet Dr. Brad Schoenfeld: 400 Papers and What We Still Don't Know About Muscle Growth
06:13 Light Weights vs. Heavy Weights: The Study That Changed Everything
09:10 Type I vs. Type II Muscle Fibers and Why Type II Atrophies With Age
11:43 Muscle, Brain Health, and the Two-Days-a-Week Resistance Training Protocol
17:26 Strength vs. Power: Why Explosive Training Matters More Than You Think
21:32 The Biggest Lie in Fitness: There Is No Single Best Way to Build Muscle
23:15 Two 30-Minute Sessions a Week Is Enough
27:01 Protein Requirements for Muscle Growth: Where the Research Actually Lands
31:18 GLP-1s and Muscle Loss: What the Evidence Says
38:36 Aerobic Training, Step Count, and Where Cardio Fits In
40:47 How Muscle Improves Every Organ System in Your Body
44:35 Research Gaps in Advanced Training Techniques
49:00 Mechanical Tension as the Primary Driver of Hypertrophy
53:37 Rest Intervals: How Long You Actually Need Between Sets
58:20 Lengthened Partials: The Training Insight That Surprised the Field
01:02:10 Electrostimulation and At-Home Resistance Technology: Does It Work?
01:05:41 Cold Plunges After Lifting: Why Brad Says Avoid Them
01:07:52 Sleep and Muscle Building: What the Evidence Does and Doesn't Show
01:11:30 The Third Edition: Evidence-Based Practice and How to Use Research

Dr. Brad Schoenfeld has spent his career dismantling the bro-science that dominates the fitness industry. As a Professor of Exercise Science at Lehman College and the author of the definitive textbook on muscle growth, he has published nearly 400 peer-reviewed papers on the topic. The following briefing shares his insights on the mechanisms of hypertrophy, the myths of training to failure, the role of muscle in longevity, and the optimal protocols for building and preserving lean mass.

For decades, the fitness industry operated on a simple, painful premise: if you aren’t training to absolute failure, you aren’t growing. Schoenfeld’s research has systematically dismantled this idea. The primary driver of muscle hypertrophy is mechanical tension, not the metabolic stress or muscle damage that causes the “burn.”

This shift in understanding changes the economics of training. If the goal is to accumulate mechanical tension over time, training to failure is an inefficient strategy. It creates a disproportionate amount of fatigue for a marginal, if any, increase in stimulus. “The cost-to-benefit ratio of training to failure on every set just doesn’t pencil out,” he noted. “You’re better off leaving one or two reps in the tank and accumulating more high-quality volume over the week.”

The dogma that heavy weights are required for muscle growth has also been overturned. Schoenfeld’s lab conducted some of the seminal research demonstrating that light weights can be just as effective as heavy weights for hypertrophy, provided the sets are taken close to failure.

This finding has profound implications for older adults or individuals with joint issues who cannot tolerate heavy loads. “It democratizes muscle growth,” he said. “You don’t need to put a heavy barbell on your back to build muscle. You just need to challenge the muscle sufficiently, regardless of the load.”

[Image Placeholder: Comparison of heavy vs light load training outcomes]

While much of the conversation around muscle focuses on aesthetics, Schoenfeld emphasizes its critical role in longevity. Sarcopenia, the age-related loss of muscle mass and function, is a primary driver of morbidity and mortality in older adults.

The loss of Type II (fast-twitch) muscle fibers is particularly concerning. These fibers are responsible for power and rapid force production—the exact qualities needed to catch yourself when you trip. “Resistance training is the only effective intervention we have to preserve Type II fibers,” he noted. “Aerobic exercise is great for cardiovascular health, but it does not prevent the loss of these critical muscle fibers.”

The rise of GLP-1 agonists for weight loss has introduced a new variable into the longevity equation. While these drugs are highly effective for fat loss, they also cause significant reductions in lean mass if not paired with resistance training.

“When you lose weight rapidly, a substantial portion of that weight is muscle,” Schoenfeld warned. “If you are taking a GLP-1 agonist and you are not resistance training, you are accelerating sarcopenia. You are losing the very tissue that protects you as you age.”

He emphasized that resistance training must be a non-negotiable component of any medically supervised weight loss program. “It’s not an optional add-on. It’s a requirement to ensure that the weight you lose is fat, not functional tissue.”

The recovery protocols popularized by athletes and influencers often conflict with the biological requirements for muscle growth. Cold plunges, in particular, have become ubiquitous, but Schoenfeld’s reading of the literature suggests they are counterproductive for hypertrophy.

While cold therapy may have benefits for systemic recovery or mental resilience, it actively interferes with the localized adaptations required for hypertrophy. “You are essentially putting out the fire that you just worked so hard to start,” he explained. “If you want to build muscle, heat is actually a better recovery modality than cold.”

As the field of exercise science has matured, “evidence-based practice” has become a buzzword. But Schoenfeld cautions against treating scientific studies as gospel without considering individual context.

“The most dangerous lie in fitness is the idea that there is a one-size-fits-all optimal program,” he said. “Science gives us the principles—mechanical tension, progressive overload, adequate protein—but the application of those principles must be individualized.”

He noted that the third edition of his textbook includes a new chapter specifically addressing the limitations of evidence-based practice. “We have to remember that studies report averages. But nobody is exactly average. You have to use the science as a starting point, and then adjust based on individual response, biomechanics, and lifestyle.”

This newsletter is brought to you by Function Health

Real question. When was the last time you actually looked under the hood of your health?

Not guessed. Not assumed. Measured.

Most people think disease appears suddenly.
It does not.

The body shifts quietly for years before symptoms ever show up. The problem is that standard checkups often miss the earliest signals.

That is why the right biomarkers matter.

ApoB is one of the strongest predictors of cardiovascular risk because it measures the number of atherogenic lipoprotein particles capable of entering arterial walls. You can have “normal” LDL cholesterol and still carry elevated cardiovascular risk if ApoB is high.

Lipoprotein(a), or Lp(a), is another major one. It is largely genetic, rarely included in routine panels, and strongly associated with premature cardiovascular disease and stroke. Millions of people have elevated levels without knowing it.

Then there is fasting insulin. Long before glucose rises into a diabetic range, insulin resistance is often already developing beneath the surface. Elevated fasting insulin is one of the earliest measurable signs of metabolic dysfunction.

Markers like hs-CRP provide insight into chronic low grade inflammation, which is deeply connected to cardiovascular disease, neurodegeneration, and metabolic decline. Triglyceride to HDL ratio adds another powerful signal for metabolic health and insulin sensitivity.

And for performance, recovery, and cognitive resilience, biomarkers such as vitamin D, omega 3 index, ferritin, and magnesium matter far more than most people realize. These directly influence immune regulation, mitochondrial energy production, sleep quality, muscle function, and brain performance.

This is not wellness hype.
These are clinically validated biomarkers supported by decades of cardiovascular, metabolic, and longevity research.

That is where Function Health changes the game.

You get access to 100+ biomarkers across cardiovascular, metabolic, hormonal, immune, and nutrient health. Not vague advice. Actual data that helps you adjust nutrition, training, recovery, and lifestyle with precision.

Because prevention is not about fear.
It is about visibility.

The earlier you detect dysfunction, the more leverage you have to change the trajectory before damage accumulates.

Waiting for symptoms is reactive medicine.
Understanding your biomarkers is proactive health.

If you care about performance, longevity, energy, and staying functional for decades, this is one of the smartest investments you can make in yourself.

Check it out and sign up using my code below.

ORDER HERE

Here’s something that should bother you.

In 2016, a team led by Elseline Hoekzema published a paper in Nature Neuroscience showing that pregnancy reduces gray matter volume across the brain. It’s been cited over 500 times!!! And the cultural interpretation was immediate and brutal: pregnancy makes you dumber.

“Mommy brain” became a medical fact. Women internalized it. Partners repeated it. Employers used it to justify six-week leave policies.

Except the paper never said that.

Hoekzema’s own conclusion was the opposite — that the reductions represented synaptic pruning. An adaptive process. The same mechanism that makes adolescent brains more efficient, not less. Her team explicitly noted: no cognitive deficits. The brain wasn’t degrading. It was reorganizing.

But nuance doesn’t make headlines. “Pregnancy Shrinks Your Brain” does.

So for a decade, millions of women believed something about their own biology that the science never actually claimed. And no one corrected it — because no one had the data to show what was really happening inside the postpartum brain, month by month, in real time.

Until this week.

What Happens When You Actually Watch the Brain Rebuild

A team at the University Hospital Aachen in Germany just published the most detailed longitudinal mapping of the postpartum brain ever attempted (Losse et al., Translational Psychiatry, May 22, 2026).

Here’s what they did: 24 women. Six MRI scans each. Within the first week after birth, then at weeks 3, 6, 9, 12, and 24. Every scan compared to 24 age-matched women who had never been pregnant.

Six snapshots of the same brain, over six months. No one had done this before at this resolution.

The result:

The maternal brain doesn’t recover. It grows. Continuously. For at least six months. And it was still growing when they stopped measuring.

Not a return to baseline. Not a slow crawl back. Active, measurable, sustained gray matter expansion — week after week after week. New tissue. New structure. New brain.

Three Systems. One Brain. A Layered Rebuild.

But the researchers didn’t just measure that the brain was growing. They mapped what was driving it — using a neuroimaging tool called JuSpace that overlays structural brain changes onto the known distribution of neurotransmitter and hormone receptors.

What they found is not a single mechanism. It’s three systems, layered:

The Engine (Weeks 0–24): GABA-A and Glutamate

From day one through month six — uninterrupted — brain growth co-localized with GABA-A and glutamate receptor distributions. The brain’s excitation-inhibition balance. The same system that controls neuroplasticity, mood, and sleep architecture. This is the continuous foundation. It never stops.

The Ignition (Weeks 0–6): Hormonal Crash

The most explosive growth happens in the first three weeks. During this window, brain changes additionally co-localize with cortisol, estradiol, and progesterone receptors. The moment you deliver, pregnancy hormones crash. Your brain reads that crash as a construction signal. Scaffolding down. Rebuilding begins.

The Second Wave (Weeks 12–24): Oxytocin

Three months in, a new signal emerges. Brain growth begins to co-localize with oxytocin receptor density. The bonding hormone. Released during breastfeeding, skin-to-skin, eye contact, positive touch.

Your baby’s face is building your brain. Literally. The spatial overlap between oxytocin receptor-rich regions and the areas showing the most growth in months 3-6 is striking.

The Paradox That Changes Everything

Now here’s where it gets uncomfortable.

Because the mothers in this study did have persistently smaller gray matter in certain regions compared to women who had never been pregnant. The amygdala. The hippocampus. The putamen. The supplementary motor area. These differences persisted across all six months.

The “shrinkage” was real.

So I thought: okay, the brain grows in some areas but stays damaged in others. Maybe “mommy brain” is partially true.

Then I read the behavioral data. And I had to put the paper down.

At 24 weeks postpartum, the researchers measured maternal attachment. The women with the smallest volumes in the left hippocampus, parahippocampal gyrus, and amygdala reported the lowest levels of hostility toward their infants.

I need you to sit with that for a moment.

The mothers with the most “shrinkage” had the strongest bond with their babies.

The brain isn’t shrinking. It’s pruning for purpose. Cutting unnecessary connections. Streamlining the mesocorticolimbic networks that drive caregiving. The same process we see in adolescence — where gray matter “loss” was misinterpreted for decades before we understood it was optimization.

The women with the “worst” brain scans were the best mothers. By the data.

The Part That Made Me Angry

Here’s where this stops being an interesting neuroscience paper and starts being a public health emergency.

Throughout the entire 24-week period, the continuous engine of brain growth — the GABA-A and glutamate system — is also the master regulator of mood.

Up to 55% of women experience postpartum mood instability (Chechko et al., 2024). This paper suggests why: the same system rebuilding your brain is the system most vulnerable to malfunction. When the E-I balance is disrupted during this window, it triggers postpartum depression and anxiety. Not as a psychological reaction. As a neurobiological event during active construction.

This is why brexanolone (Zulresso) and zuranolone (Zurzuvae) work — they’re GABA-A modulators. They target the exact system this paper shows is under maximum strain.

Now connect the dots:

The brain is actively remodeling for at least six months. The system driving that remodeling is the same system that controls mood. The process requires sleep — because GABA-A function is sleep-dependent. And we send women back to work at six weeks.

Six weeks. When the hormonal rebuild is barely winding down. When the oxytocin-driven second wave hasn’t even started. When the brain hasn’t begun its second act of growth.

We are interrupting the most significant period of adult neuroplasticity that exists — and calling it “recovery.”

Your brain isn’t declining. It’s undergoing the most dramatic remodeling event of your adult life. But it needs something specific from you during this window. And the system is designed to make sure you don’t get it.

For paid members of Neuro Athletics — what that “something specific” is, why the 9-to-12-week mark is the most dangerous window no one warns you about, and the protocol that changes everything about how we should be supporting postpartum women.

Read more