Higher waist-to-hip ratio was linked to poorer cognitive performance in early postmenopause, though it did not alter hormone therapy effects.
A secondary analysis of data from the Kronos Early Estrogen Prevention Study Cognitive and Affective substudy (KEEPS-Cog) found that central adiposity, measured by waist-to-hip ratio, was associated with poorer cognitive performance in recently postmenopausal women.1,2
The findings were published in Menopause, the journal of The Menopause Society. The accompanying press release emphasized that visceral adipose tissue and declining estrogen levels during the perimenopause and postmenopause periods have been linked with adverse metabolic and inflammatory changes. The study results suggest that central adiposity may serve as an early indicator of risk for both metabolic dysfunction and domain-specific cognitive decline.
The study, titled “Association between central adiposity and cognitive domain function in recently postmenopausal women: an analysis from the KEEPS-Cog sub-study of the Kronos Early Estrogen Preventive Study,” evaluated more than 700 women aged 42 to 58 years who were within 36 months of natural menopause. Participants were randomly assigned to oral conjugated equine estrogen, transdermal estradiol, or placebo for 48 months. Cognitive testing occurred at baseline and at multiple follow-up points. Waist-to-hip ratio was measured at baseline and used as the primary estimate of central adiposity.
The press release noted that “Weight gain, especially at the waist, is common during the perimenopause and postmenopause period.” Visceral adipose tissue has been associated with metabolic syndrome, cardiovascular disease, diabetes, and Alzheimer's disease, and related dementias. Estrogen receptors in the brain are concentrated in regions involved in memory and executive function, supporting investigation into how central adiposity may influence cognitive outcomes.
Higher baseline waist-to-hip ratio was significantly associated with poorer performance across all cognitive domains at baseline, including verbal learning and memory, auditory attention and working memory, visual attention and executive function, and speeded language and mental flexibility. These findings indicate that even in a population without overt metabolic disease, central adiposity was linked to measurable cognitive differences early in the postmenopausal period.
Longitudinally, a higher baseline waist-to-hip ratio predicted decline in visual attention and executive function over the 4-year study. This association suggests that central adiposity may contribute to early changes in cognitive processes tied to executive functioning.
The study evaluated whether central adiposity moderated the cognitive effects of menopausal hormone therapy. No significant interaction was found between waist-to-hip ratio and treatment assignment. Women receiving oral conjugated equine estrogen or transdermal estradiol did not differ from placebo in cognitive outcomes when accounting for waist-to-hip ratio. These results align with earlier KEEPS-Cog analyses showing no cognitive benefit or harm associated with menopausal hormone therapy in recently postmenopausal women.
Additional analyses compared waist-to-hip ratio with waist circumference and insulin resistance measured by the homeostatic model assessment. Unlike waist-to-hip ratio, neither waist circumference nor insulin resistance showed longitudinal associations with domain-specific cognitive performance. Waist-to-hip ratio appeared more sensitive to cognitive differences in this population of generally healthy, early postmenopausal women.
The Menopause Society highlighted the importance of proactive risk assessment. As stated by Monica Christmas, MD, associate medical director of The Menopause Society, “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.”
The findings support ongoing research into how central adiposity, metabolic health, and cognitive function intersect during the menopausal transition. While hormone therapy did not modify the associations observed, early attention to metabolic risk factors may be important for understanding long-term cognitive health trajectories in women.
References
