Sonya Kaur

Central Adiposity and Cortical Thickness in Midlife.

Objectives Excessive visceral fat is associated with greater metabolic fluctuation and increased risk for dementia in older adults. The aim of the current study is to directly determine the impact of central adiposity on brain structure at midlife by examining the thickness of the cerebral cortex. Methods High-resolution magnetization-prepared rapid acquisition gradient-echo images were obtained from 103 participants aged 40 to 60 years (mean [standard deviation] = 49.63 [6.47] years) on a 3-T Siemens Skyra scanner. Visceral fat was measured using dual-energy x-ray absorptiometry. Results Individuals with higher visceral fat mass and volume had significantly thicker cortex in the right posterior cingulate gyrus (&bgr; = 0.29 [p = .019] and &bgr; = 0.31 [p = .011], respectively), controlling for age, systolic blood pressure, total cholesterol level, and blood glucose level. Conclusions Visceral fat was significantly associated with thicker cortex in the posterior cingulate gyrus. Although future studies are necessary, these results indicate that central adiposity is associated with significant metabolic changes that impinge upon the central nervous system in middle age.

Central adiposity and the functional magnetic resonance imaging response to cognitive challenge

Background:Excessive adipose tissue, particularly with a centralized distribution, propagates hormonal and metabolic disturbance. The detrimental effects of adiposity may extend beyond the periphery and target the central nervous system, increasing vulnerability to cognitive decline. The aim of the current study was to determine how central adiposity impacts the brain at midlife by examining the blood oxygen level-dependent (BOLD) response to a challenging cognitive task.Methods:Seventy-three adults, aged 40–60 years, completed a 2-back verbal working memory task during functional magnetic resonance imaging. Central adiposity was assessed with waist circumference. The association between waist circumference and task-related activation in a priori regions of interest was modeled using bootstrapping regression models corrected for multiple-comparisons.Results:Larger waist circumference was associated with diminished working-memory-related BOLD response in the right superior frontal gyrus (β=−0.008, P=0.001, 95% CI: −0.012 to −0.004) and left middle frontal gyrus (β=−0.009, P=0.002, 95% CI: −0.015 to −0.003), statistically adjusting for age, sex, systolic blood pressure and total cholesterol. Reduced task-related activation in the right superior frontal gyrus (r=−0.369, P=0.002) and left middle frontal gyrus (r=−0.266, P=0.025) were related to slower reaction time on the task, controlling for age and education.Conclusions:Larger waist circumference predicted alterations in the BOLD response that coupled with decrements in task performance. While future studies are necessary, the results suggest that similar to its role in the periphery, central adiposity may be a robust predictor of metabolic and hormonal alterations that impinge upon central nervous system functioning.

Abdominal obesity and white matter microstructure in midlife

The aging U.S. population and the recent rise in the prevalence of obesity are two phenomena of great importance to public health. In addition, research suggests that midlife body mass index (BMI) is a risk factor for dementia, a particularly costly disease, in later life. BMI could influence brain health by adversely impacting cerebral white matter. Recently, greater BMI has been associated with lower white matter fractional anisotropy (FA), an index of tissue microstructure, as measured by diffusion‐tensor imaging in midlife. The aim of this study was to investigate the role of abdominal obesity, the most metabolically active adipose tissue compartment, and white matter microstructure in midlife. Community dwelling participants (N = 168) between the ages of 40–62 underwent MRI scanning at 3T and a general health assessment. Inferences were made on whole brain white matter tracts using full‐tensor, high‐dimension normalization, and tract‐based spatial statistics. Higher waist circumference was associated with higher FA, indicating more directional diffusion in several white matter tracts controlling for age, sex, triglycerides, systolic blood pressure, fasting glucose, and HDL‐cholesterol. Post hoc analysis revealed that greater waist circumference was associated with lower axial diffusivity, indicating lower parallel diffusion; lower radial diffusivity, indicating lower perpendicular diffusion; and lower mean diffusivity, indicating restricted diffusion. This is the first study to report a positive relationship between obesity and FA, indicating a more complicated view of this relationship in the aging brain. Hum Brain Mapp 38:3337–3344, 2017.

Serum brain-derived neurotrophic factor mediates the relationship between abdominal adiposity and executive function in middle age

OBJECTIVES Excessive adipose tissue, especially in the abdominal area, is associated with increased risk of dementia in older adults. However, the mechanisms underlying this relationship are poorly understood. As increased adiposity is also associated with lower circulating levels of brain-derived neurotrophic factor (BDNF), a key molecule modulating brain plasticity and neuronal regeneration, we hypothesized that the changes in cognition that occur as a result of excessive abdominal adiposity would be driven by lower levels of circulating BDNF. METHODS Fasting blood samples were obtained from 60 participants aged 40-60 years (mean±SD=52.3±5.6) and BDNF levels were assessed with an enzyme linked immunosorbent assay. Abdominal adiposity was measured using a ratio of waist circumference to hip circumference (WHR). Participants also completed a neuropsychological assessment battery to assess executive function. Statistical mediation was assessed using traditional causal steps and nonparametric bootstrapping. RESULTS Higher WHR was significantly associated with poorer performance on the Controlled Oral Word Association (COWA) letter fluency test (β=-0.489; p=.003) and lower levels of circulating BDNF (β=-0.345; p=.006). Linear regression and bootstrapping methods indicated that BDNF fully mediated the relationship between WHR and performance on the COWA (β=0.60; 95% confidence interval [-3.79, -0.26]). CONCLUSIONS The relationship between higher WHR and verbal fluency was fully statistically mediated by circulating BDNF levels. The BDNF pathway is thus a useful probable mechanism through which executive function decline occurs in individuals with high abdominal adiposity. BDNF enhancing interventions (physical exercise and dietary restriction) could thus be used to improve executive function in these individuals.

Vascular Function, Cerebral Cortical Thickness, and Cognitive Performance in Middle-Aged Hispanic and Non-Hispanic Caucasian Adults

Hispanics are at increased risk for acquiring cardiovascular risk factors that contribute to cognitive dysfunction. To compare indices of vascular health with measures of cerebral gray matter integrity, 60 middle‐aged Hispanic and non‐Hispanic Caucasian participants were matched across age, sex, years of education, and mental status. Arterial stiffness was characterized by β‐stiffness index and carotid‐femoral pulse wave velocity, and magnetic resonance imaging estimated cortical thickness in a priori regions of interest known to be susceptible to vascular risk factors. Measures of arterial stiffness were significantly higher in Hispanics than in non‐Hispanic Caucasians. Hispanics exhibited thinner left inferior frontal gyrus (LIFG) cortical thickness (P=.04) with concurrently lower language (P=.02), memory (P=.03), and attention‐executive functioning (P=.02). These results suggest that compromised vascular health may occur simultaneously with cortical thinning of the LIFG as an early neuropathological alteration in Hispanics.

Phenotypic heterogeneity of obesity‐related brain vulnerability: one‐size interventions will not fit all

Intact memory and problem solving are key to functional independence and quality of life in older age. Considering the unprecedented demographic shift toward a greater number of older adults than children in the United States in the next few decades, it is critically important for older adults to maintain work productivity and functional independence for as long as possible. Implementing early interventions focused on modifiable risk factors for cognitive decline at midlife is a strategy with the highest chance of success at present, bearing in mind the current lack of dementia cures. We present a selective, narrative review of evidence linking nutrition, body composition, vascular health, and brain function in midlife to highlight the phenotypic heterogeneity of obesity‐related brain vulnerability and to endorse the development of individually tailored lifestyle modification plans for primary prevention of cognitive decline.

Depressive Symptoms Exacerbate the Effects of HSV-1 Infection on Cognitive Function in Middle Age

Objective: The purpose of this article is to examine how psychosocial distress and HSV-1 might interact to foster early cognitive vulnerability in otherwise healthy middle-aged adults. Several environmental risk factors, including mental stress and chronic viral infections, can increase cognitive vulnerability and lead to cognitive decline. Considering the anticipated dramatic increase in the number of older adults with dementia in the next 40 years and the current lack of dementia cures, it is imperative that we explore any modifiable risk factors for brain vulnerability that may facilitate the development of interventions to prevent or delay the onset of severe cognitive impairment. Methods: A total of 113 participants, 63 female and 50 male, were recruited for this study. 15 cc of blood was obtained by venipuncture from consenting volunteers and screened with the ELISA tests to assess seropositivity for HSV-1 IgG antibodies. Cognitive vulnerability was operationalized as lower cognitive function across any of the following 3 domains: global, memory, executive function. The Beck Depression Inventory (BDI-II) was used to assess depressive symptoms. Results: After controlling for age, gender, and education, there was a significant main effect for HSV-1, F(1,106)=7.908, p=0.01, but not for depressive symptoms, on global cognition. However, this main effect was qualified by a statistically significant interaction between the factors, F(1,106)=5.046, p=0.03. No significant main effects or interactions were found for memory or executive function. Conclusion: The results of this study show that even subclinical depressive symptoms can exacerbate the negative effect of HSV-1 infection on global cognitive function. We found that seropositive individuals reporting at least some depressive symptoms exhibited worse performance on a test of intelligence than seropositive individuals without depressive symptoms.