If you keep up with research on Alzheimer’s prevention, you may have heard about rapamycin, a transplant drug now being studied for its potential to slow aging, which boosted blood flow to the brain in people at risk for Alzheimer’s, especially women.
With a long maternal history of Alzheimer’s, when a study says especially women and at risk, it’s talking about me. Maybe it’s talking about you too.
Ultimately, blood flow to the brain is important for everyone. So I dug in.
The study, in plain English
Rapamycin has been around for decades, mostly to keep transplant patients from rejecting a new organ. It works by blocking mTOR, a master switch inside cells that tell them to grow and build.
When mTOR stays switched on too much, as it tends to with age and possibly more so in APOE4 carriers, cells spend less time on repair and cleanup, including the cells that line your blood vessels.
Blocking it shifts them back toward maintenance, which is why longevity researchers are interested in rapamycin, and why Dr. Lin wanted to know whether it could restore blood flow to the brain.
Dr. Ai-Ling Lin at the University of Missouri spent years showing that rapamycin restored blood flow to the brain in mice carrying APOE4, the strongest genetic risk factor for Alzheimer’s.
Then she tested it in people. The full study was published in September 2026 in the Journal of Cerebral Blood Flow & Metabolism.
Twenty-three healthy adults, ages 45 to 65, took a low dose of rapamycin every day for four weeks. Nine of them carried APOE4. Those nine saw blood flow to the brain rise by more than 15%, and the gains came mostly from the women, whose blood flow rose by roughly 30% in the memory area and 35% across the whole brain. The men with APOE4 barely responded.
No one knows why yet, but women APOE4 carriers likely start with more room to improve, for reasons I'll explain below. The people without APOE4 saw no real change, likely because their blood flow had little room to improve. Both groups were considered healthy at the time of the study. Things change if you have insulin resistance, high blood pressure, or sleep apnea, which reduce blood flow with or without the gene.
The researchers hope that restoring blood flow early, years before symptoms, might delay or prevent Alzheimer's altogether.
My honest take
I’m glad this research exists, and I’m glad women carriers responded well, since we make up nearly two-thirds of everyone diagnosed.
But nine people. Four weeks. No placebo group. No measure of memory. And a drug that suppresses the immune system, with no long-term data on using it for prevention. The bigger trials are still years away.
Most of us don’t want to wait for the next study, the next drug, the next headline, especially when the thing this study is measuring can already be changing in the brain.
Why blood flow matters so much
Whether or not you carry APOE4, and whether you're a woman or a man, your brain needs optimal blood flow to work at its best. Every minute of every day, your blood carries oxygen and nutrients to your brain.
Glucose and ketones for fuel, B vitamins, omega-3s, amino acids your brain uses to make neurotransmitters, all of it arrives through your bloodstream. Your brain has almost no reserves of its own, so it relies on a constant, steady supply.
Oxygen shows just how much your brain depends on that supply. Your brain is about 2% of your body weight and uses roughly 20% of your oxygen, and blood flow is the only way oxygen reaches it.
This is also why supplements can only do so much on their own. You can take every brain-supporting supplement on your shelf, but if blood flow to your brain is impaired, less of what you’re taking reaches the cells that need it.
The most common reasons blood flow slows:
High blood sugar and insulin resistance, which stiffen and damage blood vessels
Blood pressure that runs too high, or too low
Sitting most of the day
Sleep apnea, which drops oxygen to your brain over and over through the night
Blood flow problems are among the earliest changes researchers can see on brain scans in Alzheimer's, often showing up before amyloid buildup or brain shrinkage.
The vessel lining that keeps your coronary arteries healthy also keeps the tiny vessels in your brain open, so damage to one tends to show up in the other. That's why heart disease, atrial fibrillation, and high blood pressure all raise the risk of dementia, and why Dr. Bredesen counts vascular problems as one of the core drivers of Alzheimer's.
There’s good news here.
Blood flow to your brain is one of the fastest things in your body to respond.
It can change in weeks, sometimes hours, and the same steps that improve it also protect the barrier. The most reliable ones are already within your control.
What actually gets more blood to your brain
Nitric Oxide. Your blood vessels make their own medicine. Nitric oxide is a gas your blood vessel lining makes, and it tells the muscle in your vessel walls to relax so the vessels widen and more blood flows through.
It also keeps the lining smooth, which helps prevent inflammation and clots. Your body breaks it down within seconds, so it has to keep making it all day long, and it makes less every decade, starting approximately in men in their 40s and women in their 50s.
Healthy blood vessel linings make plenty of nitric oxide, and nitric oxide keeps them healthy.
The following impair blood vessel lining health:
High blood sugar and insulin resistance
High blood pressure
Chronic inflammation
Oxidized LDL and high ApoB
High homocysteine
Air pollution
Heavy metals like lead and cadmium
Inactivity
Poor sleep and sleep apnea
Chronic stress
Excess alcohol
Loss of estrogen after menopause
Aging
All of these and more come up as topics in my Direct Access community and on our group Zoom calls. Click to learn more.
A supplement that can help increase nitric oxide is N1O1, a lozenge developed by Dr. Nathan Bryan, who has spent over 25 years researching nitric oxide. It dissolves in your mouth and delivers nitric oxide’s building blocks directly, so it doesn’t depend on the bacteria in your mouth the way beets and greens do.
The human research comes from Dr. Bryan’s earlier lozenge formulation. In a placebo-controlled trial of adults over 40 with several cardiovascular risk factors, one month of the lozenge raised nitric oxide markers in the blood.
In another trial, a single lozenge lowered blood pressure within an hour in people with hypertension.
No one has measured brain blood flow with it yet, but early trials show it improves how your blood vessels behave, and your brain depends on those same vessels.
You should talk with your doctor before using it, because the effects can stack. The studies were done in people who weren’t on medication. Skip it if you take nitroglycerin or erectile dysfunction medication.
N101: https://n1o1.com/product/n1o1-nitric-oxide-lozenges/
N.O. Beetz: https://n1o1.com/product/n-o-beetz/
Now, on to the ways your lifestyle habits can improve your blood flow.
Walk outside every day. Exercise is the most proven way to increase blood flow to the brain, including the memory center area.
Do it outside when you can, since sunlight on your skin converts stored nitrogen compounds into nitric oxide, which moves into your bloodstream and helps relax blood vessels.. Twenty to thirty minutes of brisk walking, fast enough that your breathing picks up, gets you both. If you can do more, then do more.
Pickleball counts. Studies in middle-aged and older players show it reaches moderate intensity, with bursts of harder effort, which is the range that increases blood flow and nitric oxide production. It adds two things a solo walk doesn’t: quick decisions and hand-eye coordination, which challenge the brain, and social connection, which on its own is linked to lower dementia risk.
The trade-off is injury, so be careful out there.
Rethink your mouthwash. Some of the nitric oxide your body uses depends on bacteria living on your tongue. They convert the nitrates in leafy greens and beets into a form your body turns into nitric oxide.
Antiseptic mouthwash wipes those bacteria out. In one study, healthy adults who used an antiseptic mouthwash twice a day for a week saw their blood pressure rise, and larger studies have linked twice-daily use to a higher risk of high blood pressure and prediabetes.
I keep refusing the travel bottles of Listerine I’m offered twice a year after a dental cleaning. And I do so by saying: Thanks, but that will decrease my nitric oxide : ). I get a confused look, but never a question.
If you use one every day, switch to a gentle, non-antiseptic option, and keep your mouth healthy with brushing and flossing.
I like Dentalcidin Rinse, it’s good for your oral microbiome and won’t interfere with nitric oxide. If you’ve opted in for my Fullscript discount, the links above will take you to it when you are signed in. You’ll save $7 every time you purchase. The corresponding toothpaste is also available and excellent.
Most people are saving well over $40/month on their supplements, so opting in makes sense.
I'll write more about the oral microbiome soon. For now, it's enough to know it matters for your brain as much as your heart.
Eat a big salad of greens. Arugula is one of the richest nitrate sources there is, followed by spinach, Swiss chard, and celery, and your body turns those nitrates into nitric oxide.
The conversion depends on bacteria on your tongue, and daily antiseptic mouthwash kills them, so switch to a non-antiseptic option. Long-term acid-blocking medications can blunt the same pathway, which is worth raising with your doctor.
Check your blood pressure, high and low. High blood pressure in midlife damages the small vessels in your brain, and better control has been shown to lower the risk of mild cognitive impairment.
Low blood pressure is often ignored, even though it’s common in lean, active women. If you get lightheaded when you stand, your brain may be getting shortchanged several times a day.
Where I’d start this week, along with a couple of easy to self-order blood tests is next: