Running from Alzheimer’s disease

Seniors_Walking_The_Beach_4146426The last time Sam Wang and I wrote about the value of exercise for the aging brain, we got a comment that made us laugh out loud. A video gamer dismissed us as “jocks” who didn’t understand the lifestyles of nerds. To the contrary, we’re both nerds in good standing who have never been described as jocks by anyone who’d met us. I don’t like to exercise all that much, but I keep encouraging everyone to do it anyway. And I take my own advice.

The reason that I do is because those of us who exercise have better brain function than sedentary people from preschool through old age. Exercising regularly from middle age reduces the risk of developing Alzheimer’s disease in your 70s by a factor of three. Starting to exercise as late as your 60s can still reduce the risk by as much as half. Now a new study reports that exercise reduces the buildup of an Alzheimer’s disease-associated protein called amyloid in the brain, particularly in people with a genetic susceptibility to the disease.

Among the genes identified as risk or protective factors, one has a stronger effect than all the rest put together. People with two copies of the risky allele of the ApoE gene, ApoE4, get Alzheimer’s fifteen years earlier than people with the protective allele, on average. The risky allele also speeds the cognitive decline associated with ordinary aging. Even cognitively normal people with the ApoE4 allele have more amyloid in their brains than people without the allele, as shown by PET imaging with a radioactive tracer. In long-term studies, people with a lot of amyloid revealed by this type of imaging are more likely to develop Alzheimer’s later on.

Previous studies have suggested that exercise has extra cognitive benefits for people with the ApoE4 genotype, and the new study provides a clue to why that might happen. Participants who met the American Heart Association recommendation of 30 minutes of moderate exercise on five days per week were considered to be exercisers, while people who did less (many did nothing) were categorized as sedentary.

downloadAs expected, people with at least one copy of ApoE4 had more brain amyloid than people without the allele, and exercisers had less amyloid than non-exercisers. The effects of exercise on amyloid were especially strong for people with the ApoE4 genotype, suggesting that they are particularly vulnerable to the bad effects of a sedentary lifestyle on the brain. As the figure shows, people with ApoE4 who exercised had less brain amyloid than people without the risky allele who were sedentary. This study shows that regular exercise eliminates the excess risk of brain amyloid accumulation associated with the ApoE4 genotype — and suggests that it may greatly reduce the risk of Alzheimer’s disease in people with this genetic susceptibility.

There’s one important caveat to the exercise recommendation: people with the ApoE4 gene variant have an increased risk of brain damage following head injury, so they should avoid playing contact sports. A disease called chronic traumatic encephalopathy or CTE has symptoms resembling those of Alzheimer’s disease, Parkinson’s disease, or Lou Gehrig’s disease. (Researchers now suspect that the famous baseball player had CTE, misdiagnosed as the disease that was named after him.) Professional soccer players in Italy are more likely to be diagnosed with Lou Gehrig’s disease than the general population. Professional football players in the US have a higher than average incidence of depression and memory problems, which may be due to CTE, as reported in an extensive series in The New York Times(Teenagers have a particularly high risk of brain damage from contact sports.)

Given these concerns, those of us who manage to exercise despite our lack of enthusiasm might be better off than the real jocks in some ways. But there’s no question that both groups can look forward to a sharper old age than most sedentary people.

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