Emerging research suggests a very small difference in a single gene affects the rate at which men’s intellectual function drops with advancing age.
Investigators at the Stanford University School of Medicine and the Veterans Affairs Palo Alto Health Care System say changes in the coding pattern of a particular gene appear to cause the variations.
In the study, researchers tested the skills of experienced airplane pilots and found that having one version of the gene versus the other version doubled the rate at which the participants’ performance declined over time.
The study is published online in the journal Translational Psychiatry.
The particular genetic variation, or polymorphism, implicated in the study has been linked in previous studies to several psychiatric disorders.
However, this is the first acknowledgment that the genetic variation influences skilled task performance in the healthy, aging brain said the study’s senior author, Ahmad Salehi, M.D., Ph.D.
The study also showed a significant age-related decline in the size of a key brain region called the hippocampus, which is crucial to memory and spatial reasoning, in pilots carrying this polymorphism.
“This gene-associated difference may apply not only to pilots but also to the general public, for example in the ability to operate complex machinery,” said Salehi.
The gene influences a protein called brain-derived neurotropic factor, or BDNF, which is critical to the development and maintenance of the central nervous system.
As BDNF levels decline gradually with age even in healthy individuals; researchers such as Salehi have suspected that this decline may be linked with age-related losses of mental function.
In the current study, researchers reviewed the effects of a small variation or polymorphism that occurs when one protein component is substituted for another. This alternative version has been linked to higher likelihood of depression, stroke, anorexia nervosa, anxiety-related disorders, suicidal behavior and schizophrenia.
Accordingly, Salehi and his colleagues reviewed whether this polymorphism actually affected human cognitive function.
To do this, they followed 144 pilots, all healthy Caucasian males over the age of 40, who showed up for three visits, spaced a year apart, spanning a two-year period.
During each visit, participants – recreational pilots, certified flight instructors or civilian air-transport pilots – underwent an exam on a Federal Aviation Administration-approved flight simulator for pilots.
This test session employs a setup that simulates flying a small, single-engine aircraft.
Inevitably, performance dropped in both groups. But the rate of decline in the “met” group was much steeper.
“We saw a doubling of the rate of decline in performance on the exam among participants carrying the mildly altered gene during the first two years of follow-up,” said Salehi.
About one-third of the pilots also underwent at least one round of magnetic resonance imaging over the course of a few years, allowing the scientists to measure the size of their hippocampi.
“Although we found no significant correlation between age and hippocampal size in the non-met carriers, we did detect a significant inverse relationship between age and hippocampal size in the met carriers,” Salehi said.
Salehi cautioned that the research covered only two years and that the findings need to be confirmed by following participants over a multiyear period. This is now being done, he added.
No known drugs exist that mimic the genes action in the brain, but there is one well-established way to get around that: Stay active.
“The one clearly established way to ensure increased BDNF levels in your brain is physical activity,” Salehi said.