Introduction to Alzheimer's Disease Louisa, a clinician and academic, focuses on Alzheimer's disease (AD) which typically starts in our 30s but shows first symptoms in late 60s, 70s and beyond. Approximately 60 million people worldwide have AD, a number projected to triple by 2050, with 110 million women affected. 70% of AD patients are women, who are often underrepresented, lied to, and downplay their symptoms. AD is a preventable disease, but once diagnosed, there is no cure; it's like end-stage cancer. The brain fully develops around 25-30 years old, after which decline can begin without proper care. Factors like sleep deprivation, poor diet, lack of physical activity, and environmental toxins slowly erode brain function. One night of sleep deprivation increases the risk of amyloid beta buildup by 4%, a hallmark of AD. 95% of AD cases are preventable, as it is primarily a disease of lifestyle, not genetics. Only ~3% are driven by specific genetic mutations like Presenilin 1, Presenilin 2, and Amyloid Precursor Protein. Dementia is an umbrella term, with Alzheimer's disease being one form. Comparing brain scans shows a healthy, thick, voluminous brain versus an atrophied brain with thinner cortex and larger ventricles. Building Cognitive Reserve Cognitive reserve is the brain's ability to withstand stresses and insults, similar to physical V2 max. The brain has 87 billion neurons with 5,000-10,000 connections each; the cerebellum's Purkinje cells have up to 50,000 connections. Every time you have a thought, you build a new connection; novelty and engagement enrich the brain. Connections fail if not utilized, leading to reduced thinking and processing speed. Ways to build cognitive reserve include handwriting, reading, and consistent exercise. Scrolling on social media is detrimental, relying on short dopamine hits and hindering sustained focus. The Power of Exercise: Resistance & Aerobic Training Exercise is the most potent stimulus for brain health and Alzheimer's prevention, yet 80% of the US population don't exercise 30 minutes a week. Physical activity guidelines: 150-300 minutes of moderate to rigorous activity per week. Resistance training provides the biggest return on investment for brain health. The SMART trial showed that resistance training 2-3 times per week in patients with mild cognitive impairment preserved cognitive functions, enhanced processing speed and fluid intelligence, and slowed gray matter atrophy. For brain benefits, one should lift heavy (around 80% of one-repetition max). Heavy lifting releases myokines (e.g., irisin, IL-6) which cross the blood-brain barrier. Irisin helps BDNF (brain-derived neurotrophic factor) express itself, promoting new neuron growth in the hippocampus (the first area affected by AD). IL-6 acts as an anti-inflammatory cytokine, reducing brain inflammation and downregulating tumor cell growth, offering anti-cancer effects. Strong legs are the most important tool for AD prevention, as demonstrated by an identical twin study where stronger legs correlated with a larger brain and preserved cognitive function. If you could only do one exercise, it would be the deadlift, as it engages almost every muscle and requires significant neural drive. Sedentary lifestyle is a disease; a Cleveland Clinic study found "active sedentary" individuals (exercising 30-60 min but sitting 10+ hours) still face increased cardiovascular risk. Performing 10 air squats every hour can compensate for a sedentary lifestyle and help lower glucose spikes. For women, prioritizing Zone 5 (high-intensity aerobic activity) over Zone 2 is recommended, followed by resistance training, then Zone 2 if time allows, as women get less return from Zone 2. Zone 5 training remodels the heart's chambers, while also shunting blood and myokines to the brain. Dr. Ben Levine's landmark study showed that 4 hours/week of moderate-rigorous exercise (including high-intensity) for 2 years remodeled the heart by 20 years in sedentary middle-aged males, effectively turning 50-year-old hearts into 30-year-old ones. The heart retains its plasticity for remodeling until around age 65, making midlife the crucial window of opportunity. The **Norwegian 4x4** (4 minutes at 90-95% max heart rate, 4 minutes off, repeated 4 times, 1-2 times/week) is the gold standard for increasing V2 max, which is the strongest predictor of all-cause mortality. Running outdoors offers additional benefits like visual stimulation, dopamine release, and inflammation reduction, but Zone 5 training is superior for specific cognitive benefits. Managing Blood Pressure for Brain Health Hypertension (blood pressure over 135 systolic) damages tiny capillaries in the brain, leading to a "leaky brain" where the blood-brain barrier degrades. The Sprint trial showed that aggressive management of high blood pressure (e.g., pharmacologically with ACE inhibitors) preserved brain gray matter and cognitive functions. The recommended blood pressure is 120/80; daily monitoring with an automatic blood pressure cuff is advised. Beyond medication, reducing stress, managing cortisol, and engaging in exercise and adequate sleep can help normalize blood pressure. Cardiovascular disease is the #1 killer of women in the UK and Australia. Death from Alzheimer's typically occurs due to secondary effects like loss of swallow reflex or balance, not the disease itself. Dietary and Hormonal Interventions A **ketogenic diet** can provide an alternative fuel source (ketones) for the brain, especially crucial during the **metabolic crisis** that occurs in AD where the brain struggles to use glucose. For women in perimenopause, there is a **30% reduction in brain glucose metabolism** due to estrogen decline, contributing to brain fog and cognitive issues. Women going through perimenopause/menopause should consider adopting a ketogenic diet, as ketones are utilized more effectively by the brain than glucose. **Estrogen decline** is a significant risk factor for AD in women; hormone replacement therapy (HRT) can be a supportive measure. While not a direct cure, HRT can reduce AD risk by up to 30% by alleviating symptoms like hot flashes and night sweats, thereby improving sleep and reducing amyloid beta accumulation. Estrogen is also anabolic to muscle and aids bone mineral density, further supporting overall health. Women are advised to discuss HRT with their physician around age 40; studies no longer warrant the previous fear of HRT. Louisa plans to use an estrogen patch; vaginal estrogen cream can also offer cosmetic benefits for skin elasticity and collagen. Understanding Alzheimer's Pathophysiology The hallmarks of AD are two proteins: **amyloid beta (plaques)** and **tau protein (neurofibrillary tangles)**. Early theories demonized amyloid beta, but it's now understood as an antimicrobial peptide that protects brain cells. The problem is its accumulation due to poor clearance. During deep sleep, the glymphatic system activates, shrinking glial cells to wash out amyloid beta from the cerebrospinal fluid. Fragmented sleep, common in perimenopause due to hot flashes, disrupts this clearance, leading to amyloid buildup. **Tau protein stabilizes microtubules** in the axon; under stress or due to lack of estrogen, tau hyperphosphorylates, breaks off, and forms tangles, causing axon collapse and impaired information processing. **Estrogen blocks the enzyme responsible for tau phosphorylation**. **Sleep is the most underrated AD prevention tool**; one night of sleep deprivation increases amyloid beta by 4-5%. While you can't "make up for lost sleep" like a debt, banking sleep before anticipated deprivation (e.g., long flights) can help. Sleep Optimization Strategies For **trouble falling asleep** (racing mind): Supplement with **GABA** (gamma-aminobutyric acid), an inhibitory neurotransmitter that calms thoughts. **Backload carbohydrates** (starchy vegetables like sweet potatoes) at dinner. Implement an 8 PM "warm-down" routine: avoid emails, hard conversations, and intense content. For **trouble staying asleep** (waking up due to heat, stress): Ensure core body temperature drops at least 2 degrees (e.g., using a temperature-controlled mattress, sleeping with feet outside covers, cooling the room). Supplement with **glycine** to help with temperature regulation and potentially increase lifespan. Consider **adaptogens like Ashwagandha and Rhodiola** to manage stress and cortisol levels throughout the day. Mimic natural circadian rhythms: dim lights by 8 PM to encourage melatonin release; use red light bulbs and blue light blocking glasses. Essential Supplements: Omega-3, Vitamin D, Creatine **Omega-3 fatty acids** are crucial but must be chosen carefully: **95% of popular omega-3 supplements exceed normal oxidation levels**, becoming rancid if not stored properly (e.g., in heat). Look for **NSF-certified manufacturers** and **refrigerate omega-3 supplements immediately** upon purchase. Omega-3s enhance cell membrane fluidity for synaptic transmission and possess significant anti-inflammatory effects. Our brain is 60% fat, with 70% of that being DHA (derived from omega-3s), essential for blood-brain barrier health. **Vitamin D** is vital for brain health: Receptors are abundant in the hippocampus (memory centers). A study on female centenarians showed high vitamin D levels correlated with preserved cognitive functions and no AD. Vitamin D deficiency can increase all-cause dementia risk by 40%, while high levels (around 60 ng/dL) can lower AD risk by 80%. **Creatine** is a "phenomenal" and widely studied supplement: **Protects the brain against concussion, stroke, and stress**, and can help you "creatine your way out of sleep deprivation." A pilot study on AD patients given 20g of creatine per day preserved cognitive functions, increased energy, and improved exercise capacity. Naturally produced 2-3g/day is insufficient for brain benefits; higher doses are needed as muscles take priority for the standard 5g dose. For brain health, aim for 15-20g/day, split throughout the day. Creatine shows **anti-cancer effects**, with higher intake linked to a decreased risk of cancer, especially in adults over 50 (e.g., 0.36g/kg body weight). It helps with cell energy metabolism (ATP production), beneficial for low energy or brain fog. Concerns about kidney damage (creatinine) are largely unfounded; ask for a **Cystatin C test** for a more accurate kidney function assessment. A small study on perimenopausal women showed 1.5g/day creatine substantially increased mood and cognitive functions. Look for NSF-certified and "Creapure" (gold standard, gritty texture) creatine to ensure quality. Brain Training & Willpower The Stroop Test (reading color words vs. saying ink color) measures processing speed. **Tennis ball drills with an eye patch** are excellent for brain training: Engage visual cortex, processing speed, reaction time, and hand-eye coordination. Performing these drills (throwing/catching with one hand, alternating, then with an eye patch, and on one leg) builds cognitive reserve and new neural connections. The **Anterior Midcingulate Cortex (AMCC)**, often called the "willpower muscle," is a brain area that is larger in "superagers" (people who age well) and **grows when we do hard, challenging things**. The AMCC is considered the **seat of the will to live**; its size and activity predict survival after major setbacks. Conversely, the AMCC atrophies in those who live sedentary lives or avoid challenges. This highlights that growth occurs through resistance and effort, not just intent (e.g., forcing yourself to take an ice bath if you hate cold vs. if you enjoy it). The **"brain rot" associated with AI and mindless scrolling** stems from the brain getting small dopamine hits without effort, potentially hindering AMCC growth and cognitive function. While AI is incredible, its overuse can lead to a decline in our ability to think and use our cognition. Louisa's Personal Motivation & Philosophy Louisa's passion is driven by **anger and frustration at society's treatment of women** in health. She highlights women's underrepresentation in research, tendency to downplay symptoms, and fear of seeking medical advice. Her personal motivation stems from her grandmother, also named Louisa, who died of cancer after never asking for what she wanted or needed and hiding her symptoms. She believes in **free education and individual agency** over one's brain and body. Despite career costs (moving away from family, health sacrifices), she wouldn't change it due to the impact and the people she meets. Her deepest definition of success is "being able to control my brain states" – switching on focus when needed and knowing when to recover and switch off. She is hopeful for society's progress regarding Alzheimer's, believing social media provides a platform for education, but cautions against expecting easy solutions or external saviors. Louisa believes in God, finding that the complexity and precision of neural development and miraculous recoveries in neurosurgery point to a higher power beyond mere biology. She emphasizes the **heartbreaking reality of AD**: losing memories, identity, and the ability to recognize loved ones and oneself.