HeraSphere #26: Alzheimer's starts in midlife

Hi friends,

At the YPO Women's Wellness Summit, neurophysiologist Dr. Louisa Nicola surprised me with the statement that "Alzheimer’s is a disease of midlife."

I've never thought much about protecting my brain. Even though it is the organ that controls everything I do, the clarity of my thoughts, my ability to remember my children's faces, I take it for granted.

I have seen too many friends struggle with caring for parents with dementia. As a society, we've accepted it as inevitable—just part of getting older. But according to Dr. Nicola, who has spent over 13 years studying the brain, 95% of Alzheimer's cases could have been prevented.

This week, I’m sharing Dr. Nicola’s teachings. This disease starts in our 30s and 40s, decades before the first symptom appears. The choices we make right now—in midlife—determine whether our brains stay sharp later in life.

TL;DR: What You Need to Know

• Alzheimer's begins in your 30s-40s, but symptoms show up 20-30 years later

• Up to 95% of cases are preventable—only 3-5% are purely genetic

• Women face 70% of all Alzheimer's diagnoses (110 million women globally by 2050)

• One night of poor sleep raises amyloid beta (Alzheimer's hallmark) by 4%

• Three pillars of brain protection: Exercise, Sleep, Anti-inflammatory Nutrition

• Start prevention today - your 80 year old brain will thank you

What Is Dementia and What Are the Different Kinds?

• Alzheimer's disease sits underneath the Dementia umbrella and accounts for 60-80% of all dementia cases. It's characterized by two troublemakers in the brain: amyloid plaques (sticky protein clumps) and tau tangles (twisted protein fibers). These accumulate and slowly strangle neurons, leading to memory loss, confusion, and difficulty with language.

• Vascular dementia happens when blood flow to the brain gets reduced, usually after strokes. Lewy body dementia involves different protein deposits and causes visual hallucinations and movement problems. Frontotemporal dementia—what Bruce Willis has—attacks the frontal and temporal lobes and shows up as personality changes rather than memory loss.

• Dementia and Alzheimer's are pathological diseases, not the natural consequence of getting older. And Alzheimer's is the type we can most directly influence through how we live.

Women Face 70% of all Alzheimer’s Cases

• By 2050, 110 million women globally will have Alzheimer's disease. For decades, the assumption was simple: women get Alzheimer's more because we live longer.

• We now have substantial evidence showing that is not the full picture. Being a woman is an independent risk factor for Alzheimer's disease, because estrogen is like premium fuel for your brain. It helps your brain metabolize glucose, which is essentially brain gasoline.

• During perimenopause and menopause, estrogen levels drop—and when they do, your brain experiences a 30% reduction in glucose metabolism. Your brain suddenly can't use its primary fuel source efficiently. Imagine trying to run your car on watered-down gas. Your brain starts breaking down white matter—the wiring that connects different brain regions—to use as an alternative fuel source.

• That brain fog you're experiencing during perimenopause? Your brain is shooting up a flare saying, "We have a fuel crisis down here." Brain fog is a warning sign that your brain is experiencing metabolic stress and an opportunity to intervene (HRT, lifestyle changes) to protect long-term brain health.
  Brain fog itself doesn't cause Alzheimer's, but ignoring the underlying metabolic crisis increases risk.

The Perimenopause Brain Health Crisis

• When estrogen levels become dysregulated during menopause, the hypothalamus, the part of your brain that controls temperature regulation, loses the ability to properly monitor your body temperature.

• In a normal brain with adequate estrogen, the hypothalamus would make a minor adjustment. But without proper estrogen signaling, your hypothalamus doesn't know what to do. So it panics. It signals "I'm super hot!" and cranks your temperature way up—that's a hot flash. Then it crashes it back down. Then up again. Then down.

• Around 60-65% of women in menopause report having hot flashes or night sweats. They're waking you up at night, and fragmented sleep means you never get into deep sleep. Deep sleep is when your brain activates the glymphatic system—the cleaning crew that flushes out amyloid beta and tau proteins.

• No deep sleep = no cleanup = toxic protein accumulation = accelerated path to Alzheimer's. One night of sleep deprivation raises amyloid beta by 4%. Now imagine months or years of disrupted sleep from hot flashes and night sweats. The compounding effect is devastating.

Don't Suffer Through Sleep Disruption

• Hot flashes and night sweats are warning signals that your brain is in metabolic crisis, and your sleep architecture is being destroyed. Too many women think hot flashes and night sweats are just something to endure. Something to "tough out."

• If you're experiencing hot flashes, night sweats, or sleep disruption during perimenopause or menopause, talk to your doctor. Replacing estrogen during menopause can reduce your risk of Alzheimer's disease by up to 30%—not because estrogen alone prevents Alzheimer's, but because it helps with the hot flashes and night sweats, which allows you to sleep, which allows your brain to clear toxic proteins.

• Estrogen is also anabolic to muscle, meaning it helps with muscle protein synthesis. It supports bone mineral density. Both muscle and bone are critical for brain health and longevity as we age. When you replace estrogen during menopause, you're addressing multiple aging risk factors simultaneously.

• The window of opportunity matters. Research suggests that starting HRT during perimenopause or early menopause—when the brain still retains flexibility to respond—may be more effective than waiting until later for Alzheimer’s prevention. This is a conversation to have with your doctor, ideally starting around age 40.

The Genetic Lottery

• The latest research indicates that only 3-5% of Alzheimer's cases are driven by genetic mutations you inherit from your parents. The rest is lifestyle.

• The APOE gene is related to Alzheimer’s risk. There are three variants: APOE2 is protective (you won the lottery), APOE3 is neutral (most common), and APOE4 increases your risk—3x with one copy, 12x with two copies. But even with APOE4, Alzheimer's is largely preventable.

• Think of genetics as loading the gun. Lifestyle is what pulls the trigger. You can get tested through your doctor if you want to know your status.

The #1 Way to Protect Your Brain is Exercise

• When you exercise—especially when you push yourself hard, your muscles start releasing proteins called myokines. Think of myokines as text messages from your muscles to your brain. These molecules travel through your bloodstream, cross the blood-brain barrier, and basically tell your brain, "Hey, grow some new neurons. Strengthen those connections. Stay sharp."

• The key players have names like BDNF (which grows new neurons in your hippocampus, your memory center), irisin (which supports brain plasticity), and cathepsin B (which enhances memory and learning). Studies show people who strength train have larger hippocampal volumes. That means their memory centers are bigger and work better.

• A 10-year twin study followed over 300 pairs of female twins and found that leg strength in midlife predicted cognitive aging and brain structure a decade later. Between identical twins—same DNA, same upbringing—the twin with stronger legs showed better memory, reasoning, and cognitive performance over time. Brain scans revealed larger gray matter volume and healthier brain structure in the stronger twin.

• Your legs house the largest muscles in your body. When you train them, you're pumping more blood and oxygen to your brain, triggering the release of those protective myokines, and literally growing your cognitive reserve. Higher muscle mass is associated with a 12% reduction in Alzheimer's risk, and leg strength appears to be one of the strongest predictors.

Dr. Nicola’s Brain Health Exercise Tips

• Air Squats Every Hour: Sitting is a disease. Research shows that doing 10 air squats every hour can compensate for sedentary lifestyle damage. Set a timer on your phone. When it goes off, stand up, do ten bodyweight squats, sit back down. This keeps blood flowing, activates your largest muscle groups, and triggers those protective myokine messages throughout the day.

• The Norwegian 4x4 is a 35-minute weekly protocol that improves VO2 max (the strongest predictor of how long you'll live), remodels your heart by up to 20 years, and pumps protective myokines to your brain—delivering longevity benefits for your heart and brain in one brutal workout. Warm up for 10 minutes. Then do four rounds of 4-minute high-intensity intervals at 85-95% of your max heart rate. Between each round, you get 3 minutes of active recovery at 60-70% max heart rate. Cool down for 5 minutes. Learn more here.

• Strength training is non-negotiable. Muscle is an anti-aging organ. It produces myokines, regulates glucose, fights inflammation, and supports bone density. Aim for 2-3 sessions per week. Focus on compound movements—squats, deadlifts, rows, presses. These work multiple muscle groups at once, which means more myokine production.

• Creatine helps fuel the brain. Your brain uses about 20% of your total calories. Creatine helps your brain produce ATP, which is cellular energy currency. When glucose metabolism is impaired during perimenopause, creatine becomes even more critical. Research shows creatine can protect your brain from sleep deprivation, shield against concussion and stroke damage, and reduce stress-related cognitive decline. In Alzheimer's patients, creatine supplementation preserved cognitive function, increased energy, and improved exercise capacity.

#2 Way to Protect Your Brain is Optimizing Your Sleep

• One night of sleep deprivation raises amyloid beta—a hallmark of Alzheimer's pathology—by 4%. Just one night. Think about new mothers, shift workers, anyone burning the candle at both ends. This compounds. Every poor night stacks on the last.

• When you sleep, your brain activates the glymphatic system. Think of it as the night shift janitorial crew for your brain. While you're unconscious, this system flushes out amyloid beta and tau proteins—the toxic waste that accumulates during the day. Chronic sleep deprivation means the cleaning crew never shows up. The trash piles up. Eventually, your neurons start drowning in it.

• For women in perimenopause and menopause, sleep disruption from hot flashes and night sweats creates a perfect storm for cognitive decline. If you're experiencing these symptoms, don't just accept them as part of aging. Talk to your doctor about solutions that can restore your sleep quality. Treat sleep like the medical intervention it is.

#3 Way to Protect Brain Health is to Reduce Inflammation in Your Diet

• Eat Omega-3 Fatty Acids: DHA and EPA. Your brain is literally 60% fat. The primary fat in your brain is DHA, an omega-3 fatty acid. DHA is like the mortar between the bricks of your brain cells. It keeps neuronal membranes flexible and functional. DHA reduces neuroinflammation (chronic irritation in the brain), promotes clearance of those sticky beta-amyloid plaques, increases hippocampal volume, and supports the growth of new brain cells. EPA, another omega-3, works alongside DHA to reduce inflammation and support mood.

• Studies show omega-3 supplementation is most effective in early stages of cognitive decline and particularly beneficial for postmenopausal women. Target 1,000-2,000 mg combined DHA + EPA daily. Get it from fatty fish like salmon, sardines, and mackerel, or take a high-quality fish oil supplement.

• The Mediterranean & MIND Diets (Mediterranean-DASH Intervention for Neurodegenerative Delay) have been associated with a 24-53% reduction in Alzheimer's risk. That's a massive risk reduction for doing something as simple as changing what's on your plate. These diets work by reducing chronic inflammation and oxidative stress—the two major arsonists setting fire to your neurons. Think of inflammation as a low-grade fire smoldering in your brain. Over decades, it burns through your cognitive reserve.

• What protects? Leafy greens like spinach, kale, and arugula. Berries, especially blueberries. Fatty fish. Nuts, particularly walnuts. Olive oil as your primary fat. Whole grains. Beans and legumes.

• What harms? Refined carbohydrates (white bread, pastries), sugary beverages, deep-fried foods, red and processed meats, and trans fats. These foods jack up inflammatory markers in your blood and brain, activating your brain's immune cells (microglia) and accelerating neuronal damage.

My Takeaway: This Is About Staying Myself

After hearing Dr. Nicola speak, I've reframed exercise. It used to be more about vanity. Now, I’m motivated to work out to stay sharp, engaged, and present in the future.

Here's what I’m doing:

• Creatine: 5 grams every morning (usually with my collagen peptide + goji berry concoction)

• Air squats: 10 reps every hour if I can - its imperfect, but progress over perfection!

• Norwegian 4x4: I just started doing this on my rowing machine, and its a great full body workout

• Resistance training: I’m aiming for 2x/week, with heavy emphasis on legs if I can’t get to every body part

• Omega-3s: 2,000 mg daily from fish oil

• Mediterranean-style eating: Greens with every meal, fatty fish 1-3x/week.

Alzheimer's begins in midlife, but 95% of cases are preventable through lifestyle. For women, the perimenopause window is critical—estrogen loss triggers a 30% reduction in brain glucose metabolism and sleep disruption from hot flashes accelerates cognitive decline.

Your brain is counting on you to move. Hard. Often. Starting now. Your brain at 80 depends on what you do at 40.

To your 80 year old brain,

Lilly

P.S. Know someone navigating perimenopause or watching a parent struggle with dementia? Forward this to them. Prevention starts now.

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Note: While I love diving deep into research and sharing what I've learned about women's health and wellness, I want to be crystal clear: I'm a passionate health advocate and researcher, not a medical professional. Think of me as your well-informed friend who does extensive homework – but not your doctor.

Everything I share in HeraSphere comes from careful research and personal experience, but it's meant to inform and inspire, not to diagnose or treat any medical conditions. Your body is uniquely yours, and what works for one person might not work for another. Always consult your healthcare provider before making significant changes to your diet, exercise routine, or wellness practices, especially if you have underlying health conditions or take medications.

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