Exercise, Estrogen, and Executive Function

Research in women suggests that lifestyle factors interact to protect the brain.

Regular physical activity has benefits for the brain. Many studies show that it can reduce stress and improve mood, particularly in people who are depressed.

More recent research suggests that exercise reduces the risk, or delays onset, of Alzheimer's disease and dementia. Physical activity also helps healthy adults stay mentally sharp as they age by preserving executive function (a cluster of mental attributes that includes working memory, planning, and the ability to juggle several tasks at once).

However, when it comes to women, the story becomes more complicated because estrogen also appears to play a role in cognitive function. After menopause, when levels of the sex hormone fall, some women find they don't think as clearly or remember things as well as they used to. It is not clear if these problems reflect normal age-related changes, hormonal effects on brain function, stress, other psychological issues, sleep disturbance due to hot flashes, or a combination of factors.

Researchers at the University of Illinois who reviewed the literature about brain effects of exercise found, while sifting through all the data, that studies that included large numbers of women reported more significant improvements in cognitive function as a result of exercise than the studies that included fewer women. Digging a little deeper in the literature, they found an animal study that suggested that exercise and estrogen replacement therapy were synergistic, boosting levels of a molecule associated with neuron function — at least in female rodents.

Studies report mixed results when evaluating the impact of hormone therapy on cognition in women. Early studies suggested that hormone therapy reduced cognitive decline and delayed the onset of dementia. But more recent research has concluded that this benefit is lost over time, and that extended hormone therapy may actually increase the risk of developing dementia.

Exercise and Hormones

Intrigued by the discrepancies, the University of Illinois researchers decided to investigate the interaction between duration of hormone therapy and aerobic fitness levels, theorizing that the long-term effects of hormone therapy may depend on overall physical fitness. They enrolled 54 postmenopausal women ages 58 to 80 and asked them whether, and for how long, they had ever taken hormone therapy. The researchers asked the women to take a treadmill exercise test to measure aerobic fitness and a standardized test to assess executive function. The women also underwent magnetic resonance imaging to measure brain volume and assess tissue changes.

Women who took hormone therapy for less than 10 years performed better on the executive function tests and showed less brain tissue loss when compared with women who took hormone therapy for 11 years or longer. But women who ranked highest on the test of physical fitness had lost less brain tissue, even when taking hormone therapy for a prolonged time, than women with the lowest fitness levels. Women with the highest fitness levels who never took hormone therapy were also protected against brain tissue loss associated with aging.

Lifestyle Choices Matter

Although the study was small and needs to be replicated, the authors conclude that it adds to the evidence that loss of brain tissue with age is not inevitable, and can be slowed in different ways. The study also suggests that lifestyle factors may interact to help preserve cognitive function.

A growing body of research now suggests that activities that keep the brain stimulated, such as reading and learning new skills, can also help to keep people mentally sharp as they age. Other research indicates that the same lifestyle choices that increase risk of cardiovascular disease may also contribute to cognitive impairment as people age — implying that exercising more, eating better, and adopting other healthy habits not only help the heart and body, but also benefit the brain.

Berchtold NC, et al. "Estrogen and Exercise Interact to Regulate Brain-Derived Neurotrophic Factor mRNA and Protein Expression in the Hippocampus," European Journal of Neuroscience (Dec. 2001): Vol. 14, No. 12, pp. 1992–2002.

Erickson KI, et al. "Interactive Effects of Fitness and Hormone Treatment on Brain Health in Postmenopausal Women," Neurobiology of Aging (Feb. 2007): Vol. 28, No. 2, pp. 179–85.

Larson EB, et al. "Exercise is Associated with Reduced Risk for Incident Dementia Among Persons 65 Years of Age and Older," Annals of Internal Medicine (Jan. 17, 2006): Vol. 144, No. 2, pp. 73–81.

For more references, please see www.health.harvard.edu/mentalextra.