Visceral adipose tissue is associated with increased risk for compromised brain network structure and cognitive impairment in men and women. Estradiol (E2) was found to have a potential protective effect in women through the maintenance of gray matter network integrity, according to study results published in JAMA Network Open.

The investigators of this study explained that excess visceral adipose tissue is associated with increased proinflammatory cytokines and reduced anti-inflammatory proteins. In addition, it is associated with dysregulation of the hypothalamic-pituitary-adrenal axis, and thus may influence cortisol response to stress. This association between visceral adipose tissue with systemic inflammation and hormonal dysregulation may compromise brain structure integrity. On the other hand, E2 has anti-inflammatory properties and can strengthen the hypothalamic-pituitary-adrenal axis; thus, E2 may provide protection from these changes.

The goal of this study was to investigate the influence of visceral adipose tissue in age-related changes in brain network structure and the potential protective effect of E2.

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The cross-section study enrolled 974 cognitively healthy adults aged 19 to 79 years (473 women, mean age: 50.10±15.63 years; 501 men, mean age: 51.24±15.67 years). Patients were part of a population-based cohort study, the Health Study of the Leipzig Research Centre for Civilization Diseases. Brain and abdominal magnetic resonance imaging (MRI) were used to assess brain volume and visceral tissue volume. Serum E2 was measured from fasting blood samples. The main outcomes were brain network covariance and memory performance.

There was an interaction of visceral adipose tissue and sex on memory network covariance (P =.02), with a stronger negative association between visceral adipose tissue and network covariance in men (adjusted R2=0.33; β=-0.57; P <.001) than in women (adjusted R2=0.29; β=-0.54; P <.001). The interaction of visceral adipose tissue and age was significant for women (β=-0.02; P =.001) and men (β=-0.02; P <.001), suggesting that visceral adipose tissue is a moderator of the association between age and memory network covariance for both.

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After adjustment for age, E2 levels were positively associated with memory network covariance in women (adjusted R2=0.07; P =.002). The interaction of visceral adipose tissue and E2 level was only significant for women (β=0.63; P =.01), suggesting that E2 is a moderator of the association between visceral adiposity and memory network covariance for women and may protect the female brain against the associated structural changes.

In a subgroup of women aged 35 to 55 years, researchers reported an association between low E2 levels with lower memory network covariance and worse memory performance (P =.007 for both).

The researchers acknowledged several limitations of the study, including those related to the cross-sectional design, missing data because of technical reasons, and limitations secondary to extraction of morphologic features from MRI to understand cellular mechanisms.

“These data underscore the need to consider adipose tissue and hormonal profiles during primary care visits in midlife to support healthy brain aging and maintain cognitive abilities in later life,” concluded the researchers.

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Zsido RG, Heinrich M, Slavich GM, et al. Association of estradiol and visceral fat with structural brain networks and memory performance in adults. JAMA Netw Open. 2019;2(6):e196126.