Women’s waist-to-hip ratio linked to brain function in early menopause

A new study suggests that for women who have recently gone through menopause, having more fat stored around the midsection is associated with lower performance on certain thinking and memory tests. This research, published in Menopause, also found that this connection was not altered by the use of hormone therapy over a four-year period.

The time around menopause often involves significant biological changes for women, including a natural decline in the hormone estrogen and shifts in body composition. One common change is an increase in central adiposity, which is the accumulation of fat deep within the abdomen around the internal organs. This type of fat distribution is distinct from overall body weight and is known to be metabolically active, contributing to inflammation and reduced insulin sensitivity, which are risk factors for conditions like heart disease and diabetes.

Researchers have also been exploring how these metabolic changes might relate to brain health. The brain contains receptors for estrogen, particularly in regions responsible for higher-order cognitive processes like memory and executive function, which includes skills like planning and problem-solving.

A team of scientists from institutions across the United States, including the University of Wisconsin-Madison and the Mayo Clinic, hypothesized that the combination of declining estrogen and rising central adiposity could affect a woman’s cognitive abilities during this life stage. Their work is a secondary analysis of data from the Kronos Early Estrogen Preventive Study (KEEPS), a major clinical trial examining the effects of hormone therapy.

To investigate this relationship, the researchers analyzed data from more than 700 women between the ages of 42 and 58. All participants had gone through menopause within the previous three years and were specifically selected for being at low risk for cardiovascular disease. The women were part of a randomized trial and were assigned to one of three groups for four years: one group received estrogen in the form of an oral pill, another received estrogen through a skin patch, and a third group received a placebo.

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The scientists measured central adiposity using the waist-to-hip ratio, a simple calculation made by dividing the circumference of the waist by that of the hips. A higher ratio indicates a greater concentration of fat in the abdominal area. The participants’ cognitive abilities were assessed at the beginning of the study and then again at 18, 36, and 48 months.

These assessments involved a comprehensive set of tests designed to measure four distinct areas of mental function: verbal learning and memory; auditory attention and working memory; speeded language and mental flexibility; and visual attention and executive function.

At the beginning of the study, the analysis showed a clear pattern. Women with a higher waist-to-hip ratio tended to have lower scores across all four of the cognitive domains measured. This finding established a direct association between greater central adiposity and poorer cognitive performance at a single point in time for this group of recently postmenopausal women.

When the researchers examined how these cognitive scores changed over the four years of the study, they found that a higher initial waist-to-hip ratio was linked to a decline in one specific cognitive area: visual attention and executive function. This suggests that central adiposity may have a sustained negative effect on the brain systems that support skills like focusing on visual information and organizing complex tasks. The other cognitive domains did not show a similar decline linked to waist-to-hip ratio over the study’s duration.

The study also explored whether taking hormone therapy might influence this connection between body composition and brain function. The results indicated that it did not. The relationship between a higher waist-to-hip ratio and cognitive performance was consistent whether the women were taking oral estrogen, transdermal estrogen, or a placebo. Hormone therapy did not appear to protect against or worsen the cognitive associations linked to central adiposity in this population.

The authors note some limitations to their work. The study participants were predominantly non-Hispanic White, well-educated, and in good cardiovascular health, which means the results may not be generalizable to all women. Additionally, the waist-to-hip ratio is an accessible but indirect measure of abdominal fat. The four-year timeframe of the study may also be too short to observe longer-term cognitive changes or potential effects of hormone therapy.

Future research could explore these relationships in more diverse populations and over longer periods. The researchers suggest that continued follow-up of these participants, as is planned in a continuation study, may help clarify the long-term connections between metabolic health and cognition after menopause. These findings add to a growing body of evidence suggesting that metabolic factors, even in otherwise healthy individuals, may play a meaningful role in brain health as women age.

“Addressing modifiable risk factors early and often is critical to maintaining optimal health and independence as women age. The metabolic and cognitive changes that commonly occur during and after the menopause transition often catch women off-guard and are more difficult to address after the diagnosis has been made. Instituting preventive lifestyle strategies before the menopause transition will result in longitudinal health gains and reduced morbidity and mortality,” said Monica Christmas, associate medical director for The Menopause Society.

The study, “Association between central adiposity and cognitive domain function in recently postmenopausal women: an analysis from the KEEPS-Cog substudy of the Kronos Early Estrogen Preventive Study,” was authored by Taryn T. James, N. Maritza Dowling, Carola Ferrer Simó, Hector Salazar, Carol A. Van Hulle, Gilda Ennis, Adrienne L. Johnson, Mary F. Wyman, Lauren W. Y. McLester-Davis, Diane C. Gooding, Barbara Fischer, Shenikqua Bouges, Emre Umucu, Firat Kara, Juliana M. Kling, JoAnn E. Manson, Eliot A. Brinton, Marcelle I. Cedars, Rogerio A. Lobo, Genevieve Neal-Perry, Nanette F. Santoro, Frederick Naftolin, Sherman M. Harman, Lubna Pal, Virginia M. Miller, Kejal Kantarci, and Carey E. Gleason.