Steven Bartlett with Louisa Nicola
Louisa Nicola argues that while 60 million people worldwide suffer from Alzheimer’s, 95% of these cases are preventable. She clarifies that Alzheimer’s is a disease of midlife that begins developing in the brain during a person’s 30s, even though symptoms may not manifest until their 60s. While genes like APOE4 increase susceptibility, the disease is primarily driven by lifestyle factors such as sedentary behavior, poor sleep, and diet. Nicola emphasizes that women are disproportionately affected, representing 70% of all Alzheimer's cases, not merely because they live longer, but because the physiological drop in estrogen during menopause creates a metabolic crisis in the female brain.
The concept of "cognitive reserve" explains why some individuals can have a brain full of Alzheimer’s pathology (amyloid plaques) yet show no outward symptoms of dementia. Nicola explains that this reserve is built through the complexity and density of neuronal connections; the more connections you have, the more you can afford to lose without losing function. Activities like reading and handwriting help, but physical exercise is the most potent builder of this reserve. A person with high cognitive reserve has a brain that is resilient to stress, aging, and pathology, effectively masking the disease's impact until the very end.
Nicola advocates for heavy resistance training (lifting at 80% of one-rep max) as a non-negotiable intervention for brain health. When muscles contract under heavy load, they release "myokines" (specifically Irisin and IL-6) which cross the blood-brain barrier. These chemical messengers instruct the brain to release BDNF (Brain-Derived Neurotrophic Factor), which triggers the growth of new neurons in the hippocampus, the memory center of the brain. She highlights that leg strength is directly correlated with brain volume and cognitive preservation, specifically recommending the deadlift as the single most effective exercise for neuroprotection.
Cardiovascular health is inextricably linked to brain health because the brain is the body’s most vascular-rich organ. Nicola cites a landmark study by Dr. Ben Levine which showed that two years of consistent exercise could reverse the aging of the heart by 20 years, provided the intervention begins before age 65. To achieve this, she recommends the "Norwegian 4x4" protocol: four minutes at 90-95% max heart rate, followed by three minutes of active recovery, repeated four times. This high-intensity interval training increases VO2 max and maintains the elasticity of the heart's ventricles, ensuring efficient delivery of oxygen and nutrients to the brain.
Sleep is described not just as rest, but as a cleaning cycle for the brain. Nicola details the function of the "glymphatic system," which activates primarily during deep sleep to wash away metabolic waste, including amyloid-beta plaques. Just one night of sleep deprivation can increase amyloid accumulation by 5%, which compounds over years to cause significant neuronal damage. For those struggling with sleep, she suggests viewing sleep hygiene as "training," utilizing tools like temperature regulation, glycine supplementation, and ensuring darkness to facilitate this critical waste-clearance process.
For women, the transition through perimenopause and menopause represents a critical window of vulnerability for the brain. As estrogen levels plummet, the female brain experiences a 30% reduction in glucose metabolism, effectively starving brain cells of their primary energy source. This energy deficit can trigger "brain fog" and accelerate neurodegeneration. Nicola suggests that during this phase, women may benefit from a ketogenic diet to provide the brain with an alternative fuel source (ketones) and speaks candidly about the potential neuroprotective benefits of Hormone Replacement Therapy (HRT) to mitigate this metabolic drop-off.
Nicola positions creatine not merely as a muscle builder, but as a vital brain supplement. The brain consumes 20% of the body's energy, and creatine acts as a rapid fuel source for ATP production in brain cells. She notes research suggesting that high doses of creatine can help mitigate the cognitive effects of sleep deprivation, protect against concussion damage, and improve mood. Unlike the standard 5g dose used for muscle maintenance, Nicola discusses higher loading phases (up to 20g) to fully saturate the brain's energy stores, emphasizing that it is safe and effective for both men and women across the lifespan.
The interview concludes with a discussion on the Anterior Mid-Cingulate Cortex (AMCC), a brain region scientists now view as the seat of the "will to live." This area physically grows when a person engages in tasks they find difficult or do not want to do. Conversely, it atrophies in those who live sedentary, comfortable lives. Nicola argues that doing hard things—whether it is intense exercise, cold plunges, or complex learning—is necessary not just for discipline, but to structurally reinforce the part of the brain responsible for resilience and longevity.