by Sara Hover, RPh, FAARM, PCCA Director of Clinical Services

In both men and women, the presence of VAT has been associated with an increased risk of compromised brain network structure and cognitive impairment. However, a fascinating discovery emerges when exploring the role of estradiol, a key female sex hormone, in mitigating the negative consequences of VAT, particularly in women during midlife.¹

Visceral Adipose Tissue and Cognitive Impairment

Visceral adipose tissue, the fat stored around internal organs, has long been implicated in various health conditions. Recent studies have uncovered its association with compromised brain network structure and cognitive decline. Both men and women with higher levels of VAT exhibit an increased risk of cognitive impairment, highlighting the importance of understanding the interplay between body composition and brain health.²

Women in Midlife: Accelerated Cognitive Aging and VAT

Notably, women during midlife face a unique set of challenges associated with changes in hormonal balance while transitioning into menopause. The presence of VAT during this phase has been linked to accelerated cognitive aging, possibly due to association with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. This suggests that the impact of VAT on cognitive function is particularly pronounced during the transition to menopause and the years that follow. Excess stress — and losing hormones is a stressor — can lead to metabolic changes resulting in weight gain. It has been noted that there is a significant relationship between the overactivity of the HPA axis and abdominal fat and/or metabolic syndrome. Chronic stress could lead to the development of obesity.³ VAT amplifies the negatives associated with age including cognitive health. It has been hypothesized that estradiol reduces the negative effects of VAT in women.

Estradiol's Protective Role Gets an A: Anti-Inflammatory, Anti-Apoptotic and Antioxidant

Amidst the concerning findings related to VAT and cognitive aging in women, the role of estradiol emerges as a potential protective factor. Estradiol, a form of estrogen, is known for its multifaceted functions in the female body. Research suggests that estradiol levels may play a crucial role in mitigating the negative consequences of VAT on brain structure and function.

First, it has been found that estradiol has anti-inflammatory properties. When women go through menopause, either naturally or surgically, many experience systemic inflammation. Neuroinflammation has negative effects on cognition.⁴ Estradiol is vasodilatory and thus promotes blood flow to the brain, therefore enhancing circulation. The delivery of oxygen and nutrients to the brain supports overall brain health. Another important function of estradiol is how it functions as an anti-apoptotic agent. Apoptosis, or programmed cell death, is a natural process in the body, but estradiol helps to prevent excessive cell death in the brain, preserving its integrity. Lastly, estradiol has antioxidant properties that help reduce oxidative damage to the brain. Oxidative stress is a common factor in age-related cognitive decline. Estradiol combats this to protect the brain.

Preserving Myelin Architecture: A Key Aspect of Cognitive Health

Myelin, the protective sheath around nerve fibers, is crucial for efficient neural communication. Research suggests that estradiol may play a vital role in preserving myelin architecture. This preservation is essential for maintaining the integrity of neural pathways and ensuring optimal cognitive function. Low-estrogen states, such as menopause, have long been recognized as a time where more women experience exacerbations of myelin-related diseases such as multiple sclerosis (MS).⁵ Therefore, estradiol’s role in protecting the myelin sheath has been the center of research in MS, but this research also has application for brain health and cognition.¹

Complex Interplay

The intersection of visceral adipose tissue, estradiol levels and cognitive health in women during midlife reveals a complex interplay with profound implications. VAT's association with compromised brain network structure and accelerated cognitive aging underscores the need for a holistic approach to health during this critical phase. The protective effects of estradiol, including vasodilation, anti-apoptosis and antioxidation, offer a ray of hope in understanding and potentially mitigating the cognitive consequences of VAT. As research continues to unfold, recognizing the importance of hormonal balance and lifestyle factors becomes paramount in promoting cognitive well-being, particularly for women navigating the intricate journey of midlife.

References

1. Zsido, R. G., Heinrich, M., Slavich, G. M., et al. (2019). Association of Estradiol and Visceral Fat With Structural Brain Networks and Memory Performance in Adults. JAMA network open, 2(6), e196126. Accessed January 2024 at https://doi.org/10.1001/jamanetworkopen.2019.6126
2. Anand S.S., Friedrich M.G., Lee D.S., et al. (2022) Evaluation of Adiposity and Cognitive Function in Adults. JAMA Netw Open. 5(2):e2146324. Accessed January 2024 at https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788555
3. Vicennati, V., Pasqui, F., Cavazza, C., Pagotto, U., & Pasquali, R. (2009). Stress-related development of obesity and cortisol in women. Obesity (Silver Spring, Md.), 17(9), 1678–1683. Accessed January 2024 at https://doi.org/10.1038/oby.2009.76
4. Villa, A., Vegeto, E., Poletti, A., & Maggi, A. (2016). Estrogens, Neuroinflammation, and Neurodegeneration. Endocrine reviews, 37(4), 372–402. Accessed January 2024 at https://doi.org/10.1210/er.2016-1007
5. Christianson, M. S., Mensah, V. A., & Shen, W. (2015). Multiple sclerosis at menopause: Potential neuroprotective effects of estrogen. Maturitas, 80(2), 133–139. Accessed January 2024 https://doi.org/10.1016/j.maturitas.2014.11.013