Women May Have More Youthful Brains Than Men

Women’s brains appeared about 3 years younger than men’s of the same age, a PET study of brain metabolism found.

Women had a persistently lower “metabolic brain age” relative to chronological age throughout their adult lifespan, reported Manu Goyal, MD, of Washington University School of Medicine in St. Louis, and colleagues in Proceedings of the National Academy of Sciences.

“We’re just starting to understand how various sex-related factors might affect the trajectory of brain aging and how that might influence the vulnerability of the brain to neurodegenerative diseases,” Goyal said in a statement. “Brain metabolism might help us understand some of the differences we see between men and women as they age.”

Some theorists have predicted that females might have more youthful brains compared with males, but findings supporting this idea have been contradictory. To test the hypothesis, Goyal and co-authors analyzed PET imaging of 205 cognitively normal men (n=84) and women (n=121) ranging from 20 to 82 years old.

The team assessed measurements of regional total glucose use, oxygen consumption, and cerebral blood flow, and calculated the fraction of sugar committed to aerobic glycolysis in various regions of the brain. More brain sugar is devoted to aerobic glycolysis in children and young adults, but the fraction drops steadily with age, leveling off at very low amounts by the time people are in their 60s, Goyal and co-authors noted.

They taught a computer algorithm to predict men’s ages based on brain metabolism data, then fed women’s metabolism data into the program. The algorithm estimated the women’s brains to be 3.8 years younger than their real ages (95% CI 1.0–6.6 years, P<0.010 t test), on average.

To confirm that the female–male difference in metabolic brain age was not specific to training on male data, the researchers flipped the process, training the algorithm on female data only. This time, the algorithm predicted metabolic brain age for men to be 2.4 years older than women (t test P<0.038).

This relationship continued throughout the adult life span: even among people in their 20s, female brains were more youthful than male brains, suggesting that sex differences during development may set the stage for brain-aging trajectories. The difference also was present in people who had brain amyloid.

“It’s not that men’s brains age faster,” said Goyal. “They start adulthood about 3 years older than women, and that persists throughout life.”

“I think this could mean that the reason women don’t experience as much cognitive decline in later years is because their brains are effectively younger, and we’re currently working on a study to confirm that,” he added.

The reasons for sex differences are unclear and further work is needed, the researchers noted: the study did not have sufficient data to assess menopausal status accurately and contained relatively few data points about middle-age individuals, the team pointed out.

And while metabolic brain age might be useful to predict the risk of cognitive decline or identify factors that potentially could improve or worsen the trajectory of brain aging, the findings need to be validated in other cohorts, the researchers added.