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 (ß=-0.489; p=.003) and lower levels of circulating BDNF (ß=-0.345; p=.006). Linear regression and bootstrapping methods indicated that BDNF fully mediated the relationship between WHR and performance on the COWA (ß=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.

Cerebral/Peripheral Vascular Reactivity and Neurocognition in Middle-Age Athletes.

INTRODUCTION: Midlife vascular disease risk is associated with higher incidence of cognitive impairment in late life. Regular aerobic exercise improves vascular function, which in turn may translate into better cognitive function. The purpose of this study was to determine the associations among cardiorespiratory fitness, cerebral and peripheral vascular reactivity, and cognitive function in sedentary and endurance-trained middle-age adults. METHODS: Thirty-two endurance-trained and 27 healthy sedentary participants ages 43-65 yr underwent measurements of maximal oxygen uptake (VO2max), neurocognitive assessment, cerebrovascular reactivity to CO2 (CVR), and brachial artery flow-mediated dilation (FMD). RESULTS: There were no group differences in age, sex, education level, fasting blood glucose, and blood pressure. Compared with sedentary subjects, endurance-trained athletes demonstrated better cognitive performance on memory (z-score: -0.36 ± 1.11 vs 0.30 ± 0.76, P < 0.01), attention-executive function (z-score: -0.21 ± 0.53 vs 0.18 ± 0.72, P = 0.02), and total cognitive composite scores (z-score: -0.27 ± 0.63 vs 0.23 ± 0.57, P < 0.01). Furthermore, brachial FMD (4.70% ± 2.50% vs 7.13% ± 3.09%, P < 0.01) and CVR (4.19% ± 0.71%·mm Hg⁻¹ vs 4.69% ± 1.06%·mm Hg⁻¹, P = 0.052) were greater in endurance-trained individuals than in the sedentary subjects. Total cognitive composite scores showed a significant positive association with brachial FMD (r = 0.36, P < 0.01) and CVR (r = 0.30, P = 0.03). Finally, when brachial FMD and CVR were entered as covariates, fitness-related group differences in total cognitive composite score were significantly attenuated (all P > 0.05). CONCLUSION: Endurance-trained middle-age adults demonstrated better cognitive performance, which may, at least in part, be mediated by their enhanced vascular function, including cerebral and endothelial-dependent vascular reactivity.

Greater BOLD response to working memory in endurance-trained adults revealed by breath-hold calibration.

BACKGROUND: Cardiorespiratory fitness is associated with increased frontal and parietal activation during executive function tasks. While these findings suggest fitness-related enhancement of neuronal response, the utility of functional magnetic resonance imaging (fMRI) may be limited by potential fitness-related differences in global vascular reactivity. The aim of this study was to determine if highly fit adults display differential activation during working memory after calibration for vascular reactivity relative to their sedentary counterparts. METHODS: Thirty-two endurance-trained and 24 sedentary adults, aged 40-65 years, completed a 2-Back verbal working memory task and a breath-hold challenge during fMRI. Group differences in blood oxygen level-dependent (BOLD) response during working memory were examined across the whole brain and in a priori regions of interest (ROI) before and after breath-hold calibration using non-parametric permutation testing. Multiple regression was used to explore the association between cardiorespiratory fitness (VO2 max), age, and calibrated 2-Back-related activation within the one a priori ROI with significant group effects. RESULTS: In comparison to the endurance-trained group, the sedentary group exhibited greater BOLD signal changes in response to the breath-hold task. After, but not before calibration, the endurance-trained group displayed significantly higher 2-Back-related activation in the right middle frontal gyrus (P = 0.049). Older age predicted lower 2-Back-related activation (ß = -0.308, P = 0.031), whereas fitness predicted higher activation (ß = 0.372, P = 0.021) in this region. CONCLUSIONS: Breath-hold calibration increased detection of working memory-related BOLD response differences between sedentary and endurance-trained adults. Moreover, cardiorespiratory fitness appeared to mitigate age-related changes in BOLD during working memory in this region.

Central artery stiffness, neuropsychological function, and cerebral perfusion in sedentary and endurance-trained middle-aged adults.

BACKGROUND: Midlife vascular disease risk is a strong risk factor for late-life dementia. Central arterial stiffness, a hallmark of vascular aging, is associated with accelerated brain aging and cognitive decline. Habitual aerobic exercise is an effective lifestyle strategy to reduce central arterial stiffness and is related to lower risk of cognitive impairment. OBJECTIVE: To determine the associations among cardiopulmonary fitness, neuropsychological function, central arterial stiffness, and cerebral perfusion in the sedentary and endurance-trained middle-aged adults. METHODS: Twenty-six sedentary and 32 endurance-trained middle-aged adults were measured for maximal oxygen consumption, central arterial stiffness determined by aortic pulse wave velocity and carotid ultrasound, neuropsychological function, and regional cerebral blood flow assessed by MRI. RESULTS: There were no group differences in age, sex, ethnicity, education, blood pressure, and carotid intima-media wall thickness (all P>0.05). Neuropsychological performance and occipitoparietal perfusion were greater, and central arterial stiffness was lower in endurance-trained individuals than in sedentary individuals (all P<0.05). Greater cardiopulmonary fitness was related to better cognitive composite scores, including memory and attention-executive function (r=0.28-0.40, P<0.05). Lower carotid arterial stiffness was associated with better neuropsychological outcome independent of age, sex, and education (r=-0.32 to -0.35, P<0.05), and correlated with greater occipitoparietal blood flow (r= -0.37 to -0.51, P<0.05). CONCLUSION: Lower carotid artery stiffness in endurance-trained adults is associated with better neuropsychological outcome and greater occipitoparietal perfusion.

Aerobic fitness and the brain: increased N-acetyl-aspartate and choline concentrations in endurance-trained middle-aged adults.

Engagement in regular aerobic exercise is associated with cognitive benefits, but information on the mechanisms governing these changes in humans is limited. The goal of the current study was to compare neurometabolite concentrations relating to cellular metabolism, structure, and viability in endurance-trained and sedentary middle-aged adults. Twenty-eight endurance-trained and 27 sedentary adults, aged 40-65 years, underwent general health assessment, cardiorespiratory fitness measurement, neuropsychological testing, and proton magnetic resonance spectroscopy ((1)H MRS). (1)H MRS was used to examine N-acetyl-aspartate (NAA), creatine (Cr), myo-inositol (mI), choline (Cho), and glutamate (Glu) concentrations in frontal and occipitoparietal grey matter. Group differences in concentrations of NAA, Cho, mI, and Glu, calculated as ratios over Cr, were explored using ANOVA. There were no significant differences in global cognitive function, memory, and executive function performance between the groups. In comparison to sedentary adults, the endurance-trained group displayed significantly higher NAA/Cr in the frontal grey matter (F(1, 53) = 5.367, p = 0.024) and higher Cho/Cr in the occipitoparietal grey matter (F(1, 53) = 5.138, p = 0.028). Within our middle-aged sample, endurance-trained adults demonstrated higher levels of NAA/Cr in the frontal grey matter and higher Cho/Cr in the occipitoparietal grey matter. Higher levels of NAA may indicate greater neuronal integrity and higher cerebral metabolic efficiency in association with cardiorespiratory fitness, whereas increased Cho may represent increased phospholipid levels secondary to neural plasticity.

Hypertension in a young golfer.

A collegiate freshman golfer was hypertensive at her preparticipation physical exam (PPE). Further investigation revealed coarctation of the aorta with secondary hypertension that had been asymptomatic. The PPE is a good forum for hypertensive screening because it may be one of the few times an apparently healthy adolescent is seen by any physician. This case emphasizes the need to screen for silent hypertension and discern its cause in adolescents.