Louisa Nicola: Most Replayed Moment: Alzheimer's Starts 20 Years Before Symptoms! How To Protect Your Brain Now

The host asks for the single most compelling study showing that exercise is central to Alzheimer's prevention and brain health. The guest says that across the data, "the biggest amount of return on investment is from resistance training," which they confirm means strength training. The study they point to is the SMART trial, in which people with mild cognitive impairment did resistance training two to three times per week. According to the guest, participants not only preserved their cognitive functions but also improved processing speed and fluid intelligence, and showed "slowing of the gray matter". The guest does not say what exactly slowed, and gives no effect sizes, participant numbers or trial duration.

Asked what gray matter is, the guest explains that the brain has both gray and white matter. Gray matter is made of cell bodies on the outer portions of the brain. White matter sits deep within the brain, where the myelinated neurons are, and small lesions can build up in it over time.

The guest brings up a common fear. People tell them their mother had Alzheimer's and ask whether they will get it too. That leads to a genetic risk factor the conversation hadn't covered yet: APOE4, the gene for apolipoprotein E. The guest calls it one of the strongest risk factors for Alzheimer's disease but stresses that "it is not a foregone conclusion that you're going to get it." As an example, they say Chris Hemsworth was tested and has two copies. Everyone inherits two copies of the gene, one from each parent, and it comes in three main variants: APOE2, APOE3 and APOE4.

The guest has been tested and is a 3-3 carrier, which they describe as the general-population profile. It neither raises nor lowers their risk. A copy of APOE2 is described as protective against the disease.

The risk figures as the guest gives them: one copy of APOE4 raises risk by two to three times; two copies raise it by 10 times, which the guest restates as the figure for a male; a female with one copy is described as having double the risk of her male counterpart, about sixfold; a female with two copies faces about 15-fold risk. The guest says APOE4 status can be checked with a doctor through a simple blood test.

The numbers don't line up perfectly. Doubling a two- to threefold risk fits "about sixfold" for one copy, but 15-fold for two copies is not double the 10-fold male figure. The transcript also runs together two statements: "If you have two copies of the gene, it raises your risk by 10 times. If you are a male, it raises your risk by 10 times." The guest calls the sex difference "the devastating thing" but cites no source for any of these estimates.

Having strong legs is by far the most important tool in your toolbox for the prevention of Alzheimer's disease.

The guest says they became convinced of this after reading a study of identical twins, who share the exact same genetic profile. The twins were followed for 10 years with cognitive tests and MRIs. As the guest describes it, the twin with the greatest strength and the most leg power had a bigger brain and larger gray matter volume, preserved their cognitive functions, and did better on different cognitive tests. The study isn't named, and the description is associational. It reports which twin did better, not that leg training caused the difference.

When the host asks why resistance training would increase brain size, the guest first sets a threshold. They say all of the studies show that to produce the neural effects of resistance training, "you need to be lifting at around 80% of your one repetition max", which they acknowledge is quite heavy.

The guest separates this from the social-media argument over heavy versus light lifting. For hypertrophy alone, meaning gains in muscle mass and muscle cell size, they say men and women can get there either with light weights and high reps or heavy weights and low reps, depending on who you are and how much time you have. For the brain specifically, they say you want to lift heavy, for several reasons.