Lifelong brain activity more powerful than genetics when it comes to Alzheimer’s

A new study looked at people who do — or do not — carry a gene called APOE-eta-4 associated with increased risk of developing Alzheimer’s disease (AD). The study findings illustrate again that genetics are not destiny.

Researchers in this study started out with 393 men and women ages 70 to 89 years old without dementia who were enrolled in the Mayo Clinic Study of Aging. Among them, 340 participants were clinically assessed as “normal” in terms of cognitive function and 53 had “mild cognitive impairment.”

Next, the researchers categorized the participants into two groups. The first group had education levels of 14 years or more — just two years beyond high school. The second group had education levels of less than 14 years. (This was obviously a generation where not everyone had to get college degrees, whether or not they are worth anything.)

Researchers used the median education level of each group. They also assessed mid-life physical activity. Third, the researchers obtained PET and MRI scan imaging data to look for amyloid plaque and neural degeneration.

Here’s what they found…

First, there was a strong, overall link between older men and women who carried the APOE-eta-4 gene and the presence of more amyloid in the brain. (Previous studies have also shown this association.)

However, they also turned up something even more interesting among the group of men and women who carried this gene. Highly educated gene carriers — who also engaged in higher cognitive activity during mid-life (ages 50 to 65 years) — showed lower amyloid levels in scans than gene carriers with less education. In general, gene carriers with higher education were protected against the genetic effects of the disease.

Plus, among those who didn’t carry the gene, higher cognitive activity during mid-life also showed better cognitive function. (Though the activity did not alter amyloid levels.)

Interestingly, mid-life physical activity showed no association with amyloid in any of the groups.

These findings highlight the important role of mental activity, especially among people genetically predisposed to Alzheimer’s. Lifelong intellectual enrichment is associated with lower amyloid, and higher education is associated with higher brain metabolism, in genetic carriers.

Most prior studies looked at the influence of lifestyle factors — such as higher education, mid-life cognitive activity, and physical activity — on cognitive status.

But this study looked at the influence of those lifestyle factors on biomarkers in the brain. From this highly technical evaluation, some consistent observations emerge.

Genetics isn’t destiny

First, genetic influences appear to have a role in AD. But it appears you can overcome the influence of genetics with lifelong intellectual activity. In other words, genetics is not destiny.

Second, not only aren’t genetics destiny…it turns out brain changes aren’t destiny either! In fact, as I recently pointed out, a big, new autopsy study found many older people with extensive pathologic changes in the brain showed no cognitive signs of dementia during their lifetimes. On the flip side, many older people who didn’t have these brain abnormalities still did have Alzheimer’s disease. Overall, there was a total disconnect between what experts saw in the brain upon autopsy and the patients’ actual cognitive function in life.

Third, all the influences that benefit the brain occur over many years. This finding highlights the importance of lifelong intellectual engagement — from educational attainment in younger life…to cognitive activity in mid-life and later life. Thus, as I often report, a few hours — or even a few hundred hours — of playing on-line computer “brain games” isn’t likely to help. But consistent intellectual and social engagement over many years does.

For example, a paper published in the New England Journal of Medicine more than a decade ago showed that men and women who participated in cognitive activities such as reading, playing board games, and playing musical instruments over an average period of five years had markedly lower dementia risks.

Although it has been a dozen years since this study came out (and others like it), the vast majority of researchers continue to bark up the wrong tree. They continue to focus on developing the wrong drugs, for the wrong targets.

And on a closing note, although this study did not find that physical activity lowered amyloid levels, we know moderate exercise benefits your heart tremendously. And exercising the heart is important for the brain as well. After all, the heart must supply blood and oxygen to the brain.

Speaking of keeping your brain healthy, stay tuned for my new Alzheimer’s prevention and reversal on-line learning protocol, coming out later this spring. Keeping your brain active and learning about how to avoid dementia will have a double benefit for your brain.


  1. “Effect of intellectual enrichment on AD biomarker trajectories,” Neurology ( 2/24/2016