BackgroundAmnestic mild cognitive impairment (aMCI) is often a precursor stage to Alzheimer's disease (AD). Aerobic exercise (AE) has received increasing attention in the prevention of AD. While there is some evidence that it improves neurocognitive function in older individuals, the effect of exercise in the long-term is not well understood.ObjectiveTo assess the effect of long-term exercise on cognition, fitness, vascular stiffness, and cerebrovascular reactivity (CVR).MethodsIn this prospective clinical trial, 27 aMCI participants were enrolled into two groups and underwent 12 months of intervention. One group (n = 11) underwent AE training (6M/5F, age = 66.2 years), and the control group (n = 16) performed stretch training (ST group, 9M/7F, age = 66.4 years). Both groups performed training three times per week with duration and intensity gradually increased over time. CVR was measured at pre- and post-training using blood-oxygenation-level-dependent MRI.ResultsIn the AE group, aerobic fitness improved (p = 0.034) and carotid artery stiffness decreased (p = 0.005), which was not observed in the ST group. In all participants, decreases in carotid artery stiffness were associated with increases in aerobic fitness (p = 0.043). The AE group displayed decreases in CVR in the anterior cingulate cortex and middle frontal gyrus (p < 0.05, FWE corrected); the ST group did not show significant changes in CVR. Several measures of cognition (i.e., inhibition and delayed recall), neuropsychiatric symptoms, and functional status ratings improved only in the AE group.ConclusionsThese results suggest that AE may alter cerebral hemodynamics in patients with aMCI which may improve cognitive, psychological, and functional status.