Background: Central arterial stiffness and brain hypoperfusion are emerging risk factors of Alzheimer’s disease (AD). Aerobic exercise training (AET) may improve central arterial stiffness and brain perfusion. Objective: To investigate the effects of AET on central arterial stiffness and cerebral blood flow (CBF) in patients with amnestic mild cognitive impairment (MCI), a prodromal stage of AD. Methods: This is a proof-of-concept, randomized controlled trial that assigned 70 amnestic MCI patients into a 12-month program of moderate-to-vigorous AET or stretching-and-toning (SAT) intervention. Carotid β-stiffness index and CBF were measured by color-coded duplex ultrasonography and applanation tonometry. Total CBF was measured as the sum of CBF from both the internal carotid and vertebral arteries, and divided by total brain tissue mass assessed with MRI to obtain normalized CBF (nCBF). Episodic memory and executive function were assessed using standard neuropsychological tests (CVLT-II and D-KEFS). Changes in cardiorespiratory fitness were measured by peak oxygen uptake (VO2peak). Results: Total 48 patients (29 in SAT and 19 in AET) were completed one-year training. AET improved VO2peak, decreased carotid β-stiffness index and CBF pulsatility, and increased nCBF. Changes in VO2peak were associated positively with changes in nCBF (r = 0.388, p = 0.034) and negatively with carotid β-stiffness index (r = –0.418, p = 0.007) and CBF pulsatility (r = –0.400, p = 0.014). Decreases in carotid β-stiffness were associated with increases in cerebral perfusion (r = –0.494, p = 0.003). AET effects on cognitive performance were minimal compared with SAT. Conclusion: AET reduced central arterial stiffness and increased CBF which may precede its effects on neurocognitive function in patients with MCI.

Walking exercise with limb blood flow restriction (BFR) has been shown to increase muscular mass and strength even if it is performed at low exercise intensities. Despite mounting evidence for its efficacy and the increasing popularity, the safety of BFR exercise in relation to cardiac loads has not been established. The aim of this study was to determine the response of central hemodynamics during the BFR exercise to assess its impact on cardiac load. Fifteen apparently healthy sedentary or recreationally active adults (10 men and 5 women, 27 ± 1 yr) underwent five bouts of 2-min constant treadmill walking at 2 mph with 1-min rest intervals either with or without BFR on both proximal thighs. Beat-by-beat blood pressure and hemodynamics (via Modelflow method) were measured, and central arterial hemodynamics were evaluated with pulse wave analyses via general transfer function. Incident wave amplitude (IWA) and reflected wave amplitude (RWA) were obtained by the wave separation analysis. Peripheral systolic blood pressure (SBP) increased more substantially during walking with BFR (43 ± 5% vs. baseline) than without BFR (11 ± 4% vs. baseline). Aortic SBP did not change significantly during walking without BFR, but there was a substantial elevation in aortic SBP (43 ± 5% vs. baseline) during walking with BFR. Significant effect of BFR was seen in IWA but not in RWA. These findings suggest that even during slow-speed walking, leg BFR induces substantial hypertensive responses in the aorta. However, this response could not be explained by the augmented wave reflection.