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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. (JINS, 2016, 22, 1–8)

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

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.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).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, P0.01), 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, P0.01). Furthermore, brachial FMD (4.70% ± 2.50% vs 7.13% ± 3.09%, P0.01) 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, P0.01) 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 P0.05).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.

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.