Influence of endogenous estrogen on a network model of female brain integrity.

Recent reports document sex differences in midlife brain integrity and metabolic health, such that more relationships are detectable between metabolic syndrome (MetS) components and markers of brain health in females than in males. Midlife is characterized by a rapid decrease in endogenous estrogen levels for women which is thought to increase risk for cardiometabolic disease and neurocognitive decline. Our study used network models, designed to explore the interconnectedness and organization of relationships among many variables at once, to compare the influence of endogenous estrogen and chronological age on a network of brain and metabolic health in order to investigate the utility of estrogen as a biomarker for brain vulnerability. Data were analyzed from 82 females (ages 40-62). Networks consisted of known biomarkers of risk for late-life cognitive decline: the five components of MetS; Brain-predicted age difference calculated on gray and white matter volume; white matter hyperintensities; Default Mode Network functional connectivity; cerebral concentrations of N-acetyl aspartate, glutamate and myo-inositol; and serum concentrations of estradiol. A second network replaced estradiol with chronological age. Expected influence (EI) of estradiol on the network was -1.190, relative to chronological age at -0.524, indicating that estradiol had a stronger expected influence over the network than age. A negative expected influence indicates that higher levels of estradiol would be expected to decrease the number of relationships in the model, which is thought to indicate lower risk. Overall, levels of estradiol appear more influential than chronological age at midlife for relationships between brain integrity and metabolic health.

Network Modeling Sex Differences in Brain Integrity and Metabolic Health.

Hypothesis-driven studies have demonstrated that sex moderates many of the relationships between brain health and cardiometabolic disease, which impacts risk for later-life cognitive decline. In the present study, we sought to further our understanding of the associations between multiple markers of brain integrity and cardiovascular risk in a midlife sample of 266 individuals by using network analysis, a technique specifically designed to examine complex associations among multiple systems at once. Separate network models were constructed for male and female participants to investigate sex differences in the biomarkers of interest, selected based on evidence linking them with risk for late-life cognitive decline: all components of metabolic syndrome (obesity, hypertension, dyslipidemia, and hyperglycemia); neuroimaging-derived brain-predicted age minus chronological age; ratio of white matter hyperintensities to whole brain volume; seed-based resting state functional connectivity in the Default Mode Network, and ratios of N-acetyl aspartate, glutamate and myo-inositol to creatine, measured through proton magnetic resonance spectroscopy. Males had a sparse network (87.2% edges = 0) relative to females (69.2% edges = 0), indicating fewer relationships between measures of cardiometabolic risk and brain integrity. The edges in the female network provide meaningful information about potential mechanisms between brain integrity and cardiometabolic health. Additionally, Apolipoprotein ϵ4 (ApoE ϵ4) status and waist circumference emerged as central nodes in the female model. Our study demonstrates that network analysis is a promising technique for examining relationships between risk factors for cognitive decline in a midlife population and that investigating sex differences may help optimize risk prediction and tailor individualized treatments in the future.

Cognition, Brain Structure, and Brain Function in Individuals with Obesity and Related Disorders.

PURPOSE OF REVIEW: Obesity is one of the most serious public health concerns. Excess adipose tissue, particularly with a centralized distribution, is associated with cognitive decline. Indeed, obesity has been associated with a number of adverse changes in brain function and structure that can be detected by neuroimaging techniques. These obesity-associated changes in the brain are associated with cognitive dysfunction. RECENT FINDINGS: While the pathways by which excess adipose tissue affects brain function are not fully understood, available evidence points towards insulin resistance, inflammation, and vascular dysfunction, as possible mechanisms responsible for the observed relations between obesity and cognitive impairment. It appears that weight loss is related to better brain and cognitive outcomes and that cognitive impairment due to obesity may be reversible.

Effects of full-fat dairy products on subclinical vascular function in adults with elevated blood pressure: a randomized clinical trial.

BACKGROUND: High consumption of low- and non-fat dairy products improves vascular dysfunction associated with elevated arterial blood pressure (BP). Currently, it is unknown if conventional full-fat dairy products improve vascular functions. OBJECTIVES: To determine if adding whole milk and full-fat dairy products to the normal routine diet improves vascular function in adults with elevated BP. DESIGN: Sixty adults (age ± SEM; 58 ± 2 years) with elevated BP (systolic/diastolic; 120-159/ < 99 mmHg) were randomized into a controlled crossover intervention trial consisting of two 4-week dietary periods. The high dairy condition consisted of adding four daily servings of whole milk or full-fat dairy products to the normal diet and eliminated all dairy intake during the control (no dairy) condition. A 2-week washout period separated the dietary conditions. RESULTS: Carotid-femoral pulse wave velocity (cfPWV) did not differ significantly between high dairy (11.3 ± 0.3 versus 10.9 ± 0.3 m/sec) and no dairy conditions (11.2 ± 0.3 versus 11.0 ± 0.3 m/sec). The results were consistent when ultrasound-derived vascular distension measures (arterial compliance, beta-stiffness index, and elastic modulus) were evaluated. Cardiovagal baroreceptor sensitivity (via Valsalva maneuver) demonstrated no significant difference for either dietary condition. Brachial arterial flow-mediated dilation (FMD) did not differ significantly during the high dairy (5.7 ± 0.5 versus 5.4 ± 0.6%) and no dairy conditions (6.5 ± 0.5 versus 5.6 ± 0.6%). CONCLUSIONS: The solitary addition of whole milk and full-fat dairy products has no effect on subclinical vascular function in adults with elevated BP.

Heart-Thigh Cuff Pulse Wave Velocity: A Novel Nontechnical Measure of Arterial Stiffness.

BACKGROUND: Recently, a novel index of arterial stiffness was developed to eliminate the placements of transducers on the carotid and femoral arteries and to make the measurement substantially easier. We evaluated the agreement of this new methodology with the well-established carotid-femoral pulse wave velocity (cfPWV). METHODS: A total of 50 adults (28 men and 22 women) varying widely in age and blood pressure were studied. Heart-thigh pulse wave velocity (htPWV) and cfPWV were measured and compared. RESULTS: Mean values of cfPWV and htPWV were 713 ± 145 and 699 ± 150 cm/s and were not significantly different (P = 0.43). Both cfPWV and htPWV were significantly associated with age (r = 0.80 and 0.58), body mass index (r = 0.44 and 0.31), and systolic blood pressure (r = 0.42 and 0.41). The 2 pulse wave velocity measures demonstrated a strong linear association with a Pearson correlation coefficient of 0.64 (P < 0.001). This agreement was consistent with the results of the Bland-Altman plot. CONCLUSION: The automatic htPWV method, which permits the data acquisition with minimum technical skill, time, and intrusion in an operator-independent fashion, has good potential as a screening device for assessing arterial stiffness in a clinical setting.