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Sexual hormone oestradiol protects female brain in mid-life

Recent research suggests that increased visceral fat - that is body fat surrounding a number of important internal organs such as the liver, pancreas and intestines - carries the risk of cognitive impairment in later life. "Our goal was to investigate whether excess organ fat is associated with a reduction in the structural networks and storage capacity of our brain throughout its lifetime. We also wanted to find out whether this interaction can be influenced by oestradiol," said Rachel Zsido.

Oestradiol is a hormone consisting of cholesterol and is the strongest of the three naturally produced oestrogens. It is the most important hormone found in the female body and has many amazing functions - it contributes decisively to the maintenance of the female reproductive system. Men also produce oestradiol, but in much smaller amounts. In both sexes, oestradiol is also produced by fatty tissue, the brain and the walls of blood vessels. It also has a vasodilative and antioxidant effect. Oestradiol can help maintain myelin architecture - and thus the membrane that protects our nerves.

Although visceral fat and estradiol appear to play opposite roles in the healthy ageing process of the brain, it remains unclear how and at what point they interfere with brain structure. To solve this mystery, Zsido and her colleagues examined a large data set of healthy adults aged between 20 and 80, 501 men and 473 women, from the LIFE study. "We looked at the brain structure and body fat of the volunteers on images taken from the magnetic resonance tomograph, as well as their memory and oestradiol levels in the blood. Our results suggest that increased organ fat expands the negative influence of aging on brain networks in men and women. We have also found that men prepare this organ fat earlier, while women are particularly affected in mid-life," the scientist explains.

"The decrease in oestradiol in this middle phase of life accelerates the normal aging process. It seems, however, that oestradiol protects women's brains from structural damage to the gray matter during the middle of life", adds Julia Sacher, who along with her research group is investigating the effects of hormonal changes on mood, emotional well-being and cognition. "We took a closer look at a subgroup of women between the ages of 35 and 55 and found that a low level of oestradiol is associated with weaker memory performance in the middle of life. This is also the age range in which the transition to menopause occurs, which is initially characterised by abrupt oestradiol fluctuations and finally by a stop in the reproductive phase. We therefore believe that the pre-menopausal phase provides an important window of opportunity to prevent accelerated brain aging and the development of neurodegenerative diseases such as dementia or depression in women.

Hormones important in risk recognition for dementia or depression

A second joint study led by Julia Sacher and Steffi Riedel-Heller from the Institute for Social Medicine, Occupational Medicine and Public Health (ISAP) also showed a decisive interaction between unfavourable metabolic states and another important sex hormone, testosterone. The team found that elevated testosterone levels and changes in body weight have different effects on women's susceptibility to depression before and after menopause. "Together, the results from both studies emphasize the need to further consider sex differences and sex hormones when investigating the risk of neurodegenerative diseases," summarizes Julia Sacher. This is particularly important in mid-life, as this transitional phase offers women a special opportunity for prevention.

Abstract

Importance:

Changes in estradiol during aging are associated with increased dementia risk. It remains unclear how estradiol supports cognitive health and whether risk factors, such as midlife obesity, are exacerbated by estrogen loss.

Objectives:

To assess whether visceral adipose tissue (VAT) moderates the association between age and brain network structure and to investigate whether estradiol moderates the association between VAT and brain network structure.

Design, setting, and participants:

Cross-sectional study of data from 974 cognitively healthy adults in Germany who participated in the Health Study of the Leipzig Research Centre for Civilization Diseases, a previously described population-based cohort study. Two moderation analyses were performed, including VAT as the moderator variable between age and brain network structure and estradiol as the moderator variable between VAT and brain network structure. The study was conducted from August 1, 2011, to November 23, 2014. Analyses were conducted from August 2017 to September 2018.

Exposures:

Serum estradiol levels from fasting blood and visceral adipose tissue volume from T1-weighted magnetic resonance imaging (MRI).

Main outcomes and measures:

Brain network covariance (individual loading on structural network derived from T1-weighted MRI) and memory performance (composite score from the Consortium to Establish a Registry for Alzheimer Disease [CERAD] verbal episodic memory test on learning [score range, 0-30], recall [score range, 0-10], and recognition [score range, 0-20]).

Results:

Final analyses included data from 473 women (mean [SD] age, 50.10 [15.63] years) and 501 men (mean [SD] age, 51.24 [15.67] years). Visceral adipose tissue was associated with an exacerbation of the negative association of aging with network covariance for women (interaction term β = -0.02; 95% bias-corrected bootstrap CI, -0.03 to -0.01; P = .001) and men (interaction term β = -0.02; 95% bias-corrected bootstrap CI, -0.03 to -0.01; P < .001). Estradiol level was associated with a reduction in the negative association of VAT with network covariance in women (interaction term β = 0.63; 95% bias-corrected bootstrap CI, 0.14-1.12; P = .01), with no significant association in men. In the female midlife subgroup (age range, 35-55 years, when menopause transition occurs), low estradiol levels were associated with lower memory network covariance (Cohen d = 0.61; t80 = 2.76; P = .007) and worse memory performance (Cohen d = 0.63; t76 = 2.76; P = .007).

Conclusions and relevance:

This study reports a novel association between VAT, estradiol, and structural brain networks as a potential mechanism underlying cognitive decline in women. These findings appear to highlight the need for sex-specific strategies, including VAT and hormonal screening during midlife, to support healthy cognitive aging.

Reference

Zsido RG, Heinrich M, Slavich GM, Beyer F, Kharabian Masouleh S, Kratzsch J, Raschpichler M, Mueller K, Scharrer U, Löffler M, Schroeter ML, Stumvoll M, Villringer A, Witte AV, Sacher J.  Association of Estradiol and Visceral Fat With Structural Brain Networks and Memory Performance in Adults. JAMA Netw Open. 2019 Jun 5;2(6):e196126. doi: 10.1001/jamanetworkopen.2019.6126.

 

Content created 25 June 2019

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