You walk into a room and forget why you came in. You laugh it off. Then the worry finds you at 2am.
Neurologist and #1 New York Times bestselling author Dr. David Perlmutter joins me to talk about his new book, Brain Defenders, and the immune cells inside your brain that can protect it or work against it.
We cover what menopause does to your brain’s connections, the labs to ask for, why ApoE4 is a predisposition and not a prediction, where hormone therapy fits, and why love may be brain food.
In This Episode
Gorgeous, let me ask you something.
When was the last time you stood in the middle of your kitchen with no idea why you walked in there?
On a recent live call, I asked the women in my Magic Menopause community about memory. About 70 percent said memory and dementia worry them.
Seventy percent.
So I called in someone I trust on the brain. I first heard Dr. David Perlmutter speak in 2009, at an Institute for Functional Medicine conference in Florida. He was connecting cortisol, your stress hormone, to what happens inside the brain, and so many pieces clicked into place for me.
He’s a board-certified neurologist and the author of Grain Brain and Brain Maker, and he has been years ahead of the curve ever since.
I want you to hear this one start to finish. Here’s what stayed with me.
Meet Your Brain’s Defenders
Neurons, your nerve cells, make up only about half the cells in your brain. I didn’t know that until he said it.
About 10 percent are immune cells called microglia. Think of them as your brain’s own security and maintenance crew.
Dr. Perlmutter explains them with a firehouse, and I love it. Firefighters don’t sit around waiting for a fire. Between calls, they check the hoses and keep the engine ready.
On a good day, your microglia work the same way. They nurture your neurons, help build synapses (the connections between nerve cells), and keep the blood-brain barrier, your brain’s protective filter, in good repair.
But microglia can switch sides.
He calls it the “evil twin.” When microglia flip, they stop supporting your brain and start breaking down the very connections it depends on.
And what flips them is largely metabolic. That’s the part that made me sit up. High blood sugar. Inflammation from anywhere in your body, including a leaky gut, when your gut lining lets through things it shouldn’t.
Your daily choices are talking to these cells all day long.
Why Your Brain Feels Menopause Too
Two out of three people living with Alzheimer’s in America are women.
Dr. Perlmutter was clear that living longer doesn’t explain that gap. Timing matters, and the signs tend to show up after menopause.
Here’s the biology in plain English. When estradiol, your main form of estrogen, drops in perimenopause and menopause, some synapses get tagged with a protein called complement. That tag works like a “remove me” sign. Your microglia see it and clear those connections away.
Then he closed the loop for me. Your mitochondria, the energy factories inside your cells, are also where cholesterol starts its conversion into pregnenolone. Pregnenolone is the raw material your body uses to make testosterone, and from testosterone, estrogen.
Estrogen, in turn, helps your mitochondria repair and renew, and it helps keep microglia in their supportive mode.
Mitochondria support estrogen. Estrogen supports mitochondria.
So when estrogen falls fast, your whole system feels it. That’s why your metabolism deserves even more of your attention in midlife.
Blood Sugar Is the Biggest Lever
If Dr. Perlmutter could get one message across, it would be this one.
Blood sugar matters for your brain.
He shared that type 2 diabetes is associated with almost three times the risk of Alzheimer’s and an 85 percent higher risk of Parkinson’s.
He also talked about a recent Cochrane review, a large independent analysis of the research, on drugs designed to clear beta amyloid from the brain. Beta amyloid is the protein long blamed for Alzheimer’s.
In his view, the benefit was small, and the risks were serious. So he puts his focus upstream, on metabolism, years before memory changes start.
His ideal window is your thirties and forties. That’s when he wants your blood sugar, weight, blood pressure, vitamin D, and homocysteine in a healthy range.
Past that window? Today is a beautiful day to start.
The Labs Dr. Perlmutter Wants You to Know
He pointed out that many labs now let you order these tests yourself, no prescription required (this varies by state). For fasting insulin and blood sugar, walk in fasted.
Hemoglobin A1C, your average blood sugar over roughly three months. He likes to see 5.2 to 5.4. A 5.8 might get you a pat on the back, but he wants an A plus, not a C plus.
Fasting insulin, which shows how hard your body is working to manage blood sugar.
Homocysteine, a marker tied to brain and heart health and to methylation, your body’s way of using B vitamins. He likes about 8 or lower. I like to see 6 to 8.
Vitamin D, and he wants it optimal.
pTau217, a blood marker linked to Alzheimer’s risk. He’d like it under about 0.1.
ApoE genotype, so you know your genetic starting point.
Waist-to-hip ratio and sleep quality. No lab required.
If you carry an MTHFR variant, a common gene change that affects methylation, you’re in good company. Dr. Perlmutter has one too. In his experience, methylated B vitamins, including methylated B12, followed by a recheck in three to four months, often help bring homocysteine into a healthy range.
These are Dr. Perlmutter’s optimal targets, shared for education. Your own doctor can help you read your numbers and decide what’s right for you.
Everyday Medications Worth a Conversation
As an OB/GYN, I had to ask him about anticholinergic bladder medications, the ones often prescribed for urgency and leaking. In my world, bladder urgency is often a conversation about tissue-level hormones and the urinary and vaginal microbiome first.
He explained that acetylcholine, a key brain messenger, runs low in the Alzheimer’s brain, so medications that block it raise a real concern. He also named acid blockers (proton pump inhibitors), NSAID pain relievers, and antibiotic overuse, largely because of how they affect your microbiome.
Please don’t stop anything on your own. Bring your list to your doctor and ask the question.
ApoE4 Is a Predisposition, Not a Prediction
About 25 to 30 percent of Americans carry at least one copy of ApoE4, the gene variant most linked to Alzheimer’s risk. For years, many neurologists didn’t even share those results with patients.
Dr. Perlmutter wants you to know yours.
He pointed to the POINTER study, published in JAMA. Adults around age 65 with blood sugar, weight, and blood pressure concerns followed a lifestyle program of diet, exercise, and brain training. Over two years, their cognitive scores went up instead of down. That included people who carried ApoE4.
In his view, if you carry ApoE4, lifestyle may matter even more.
He also framed chronic disease in a way I keep thinking about. Your genes are ancient. Your life is modern. Your body still expects morning light, dark nights, real food, daily movement, and real people around you.
Where Hormones Fit
Dr. Perlmutter didn’t hedge.
He believes the black box warning on hormone therapy grew out of flawed science and did women a disservice. In Brain Defenders, he says plainly that he supports hormone replacement therapy.
Timing matters to him. Waiting until memory changes begin is late. He mentioned Dr. Lisa Mosconi’s research on hormone therapy before menopause, and a study of women after hysterectomy who received estrogen and showed fewer Alzheimer’s-type changes in the brain.
His approach sounds a lot like mine. Personalized. Guided by labs. Estrogen, progesterone, and testosterone considered together, because that’s how they’ve always traveled in a woman’s body.
And metabolism comes first. It takes more than hormones to fix your hormones.
Your Cortisol Rhythm
Cortisol gets such a bad rap.
Dr. Perlmutter wants it high in the morning. That morning rise is what wakes you five minutes before your alarm, and a strong peak helps you meet the day.
What he doesn’t want is cortisol climbing at night. Over time, high evening cortisol is hard on your hippocampus, the memory center of your brain.
Here’s how he keeps the rhythm on track.
Move your body in the morning. It gives cortisol a healthy lift.
Skip the intense shows and the late-night scrolling.
Let cortisol settle so melatonin, your sleep hormone, can do its job.
And cold plunging? Fun fact. He said it mostly raises norepinephrine, an alertness messenger, and does very little for cortisol.
Love Is Brain Food
This is my favorite part.
Oxytocin, the hormone of love and connection, has receptors right on your microglia. When oxytocin shows up, it nudges those cells toward their loving, supportive side.
I call oxytocin the Queen Mother hormone. Now I have one more reason.
Dr. Perlmutter pointed to the Blue Zones, the places where people live the longest. Yes, they move and eat simply. They also stay connected. He sees isolation as one of the biggest threats to the aging brain.
So call your sister. Linger at dinner. Hug a little longer. ;)
Your Brain-Care Checklist
- Keep your blood sugar steady. It’s the biggest lever.
- Write down your labs, A1C, fasting insulin, homocysteine, and vitamin D. Then ask your doctor about pTau217 and ApoE.
Support your metabolism now, before memory changes begin.
Bring your medication list to your doctor. Don’t stop anything on your own.
Move in the morning. Wind down at night.
Protect your relationships. Connection feeds your brain.
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Frequently Asked Questions
What are microglia?
Microglia are your brain’s own immune cells, about 10 percent of the cells in your brain. In a healthy state, they help maintain neurons, support new connections between nerve cells, and keep the blood-brain barrier in good repair. Dr. Perlmutter explains that high blood sugar and inflammation can shift them into a destructive state he calls the “evil twin.”
How does menopause affect brain health?
According to Dr. Perlmutter, when estradiol drops during perimenopause and menopause, some synapses get tagged with a protein called complement, and microglia clear those connections away. Estrogen also supports mitochondria, the energy centers of your cells. That’s one reason he puts extra emphasis on metabolic health for women in midlife.
Why are women more affected by Alzheimer’s disease than men?
About two out of three people with Alzheimer’s in the United States are women. Dr. Perlmutter says longer life expectancy doesn’t explain the gap, and that symptoms tend to begin after menopause, so the drop in estradiol may play a role.
What labs does Dr. Perlmutter suggest for brain health?
He discusses hemoglobin A1C (he likes 5.2 to 5.4), fasting insulin, homocysteine (around 8 or lower), vitamin D, pTau217 (ideally under about 0.1), and knowing your ApoE status. Talk with your own doctor about which tests make sense for you.
If I carry ApoE4, will I develop Alzheimer’s?
Dr. Perlmutter calls ApoE4 a genetic predisposition, not a predetermination. He points to the POINTER study, where adults who followed a lifestyle program of diet, exercise, and brain training saw their cognitive scores improve over two years, including people who carried ApoE4.
What daily habits support healthy microglia?
In this episode, Dr. Perlmutter highlights steady blood sugar, quality sleep, morning movement, a calm evening wind-down, and close, loving connection. Oxytocin, the connection hormone, has receptors on microglia that help keep them in their supportive mode.
Why does Dr. Perlmutter want cortisol high in the morning?
He explains that a strong morning cortisol rise helps you wake up and meet the day, and that cortisol should then settle in the evening so melatonin can support sleep. Prolonged high cortisol is hard on the hippocampus, your brain’s memory center.
Resources Mentioned
Connect With Dr. David Perlmutter
Connect With Dr. Anna
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This article is for educational purposes and isn't a substitute for medical advice. Talk with your healthcare provider about your individual needs.
