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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.