Sundowning syndrome (SDS) in patients with Alzheimer’s disease (AD) is characterized by the intensification of behavioral disorders at sunset. Despite SDS etiology being unclear, a strong relationship between high cortisol levels and SDS has been reported. Aerobic exercise (AE) and cognitive training (CT) can reduce cortisol levels. However, whether SDS would benefit from AE and CT is still unknown. Therefore, the aim of this study was to investigate whether AE and CT treatments are effective in reducing SDS via downregulation of cortisol levels. The possible additive effects of combined AE+CT were also assessed. Eighty AD patients were randomly assigned to AE ( n = 20), CT ( n = 20), AE+CT ( n = 20), and standard therapy (no treatment, NT; n = 20). Treatments were administered for 3 months, 5 days/week, 1 hour before sunset. Before and after treatments, salivary cortisol levels were sampled at 7, 11, 15, at sunset, and 20 (time of day). Blind assessment of behavioral disorders (neuropsychiatric inventory, NPI) and agitation (agitated behavior scale, ABS) were also performed. After interventions, cortisol levels were reduced in AE and AE+CT by ∼26%. In the same groups, NPI and ABS decreased by ∼50%. By contrast, cortisol and behavioral disorders were similar to baseline in CT and NT. Changes in NPI and ABS were significantly correlated with the reduction in cortisol levels. AE or AE+CT effects on SDS and cortisol levels and the lack of effect of CT alone indicate the effectiveness of an exercise-based treatment on SDS, suggesting a possible hypothalamic–pituitary–adrenal axis dysregulation underpinning SDS.

Key points: Vascular function and arterial stiffness are important markers of cardiovascular health and cardiovascular co‐morbidity. Transitional phases of hypoemia and hypermia, with consequent fluctuations in shear rate, occuring during repetitive passive stretching adminstration (passive stretching training) may constitute an effective stimulus to induce an amelioration in vascular function, arterial stiffness and vascular remodelling by improving central and local blood flow control mechanisms. Vascular function, arterial stiffness and vascular remodelling were evaluated before and after 12 weeks of passive stretching training and after 6 weeks from training cessation, in the femoral, popliteal (treated with stretching), and brachial arteries (untreated) of both sides. After passive stretching training, vascular function and arterial remodelling improved, and arterial stiffness decreased in all the arteries, suggesting modifications of both central and local blood flow control mechanisms. Passive stretching‐induced improvements related to central mechanisms seemed to have a short duration, as they returned to pre‐training baseline within 6 weeks from training cessation, whereas those more related to a local mechanism persisted in the follow‐up. Acute passive stretching (PS) effects on blood flow (), shear rate (), and vascular function in the feeding arteries of the stretched muscle have been extensively investigated; however, few data are available on vascular adjustments induced by long‐term PS training. We investigated the effects of PS training on vascular function and stiffness of the involved (femoral and popliteal) and uninvolved (brachial) arteries. Our hypothesis was that PS‐induced changes in and would improve central and local mechanisms of control. Thirty‐nine participants were randomly assigned to bilateral PS (n = 14), monolateral PS (n = 13) or no PS training (n = 12). Vascular function was measured before and after 12 weeks of knee extensor and plantar flexor muscles’ PS training by single passive limb movement and flow‐mediated dilatation (FMD). Central (carotid‐femoral artery PWV, PWV_CF) and peripheral (carotid‐radial artery PWV, PWV_CR) arterial stiffness was measured by pulse‐wave velocity (PWV), together with systolic (SBP) and diastolic (DBP) blood pressure. After PS training, increases of 30%, 25% and 8% (P < 0.05) in femoral Δ, popliteal and brachial artery FMD%, respectively, occurred in both PS training groups. A decrease in PWV_CF, PWV_CR, SBP and DBP (−25%, −17%, −4% and −8%, respectively; P < 0.05) was noted. No changes occurred in controls. Vascular function improved and arterial stiffness reduced in the arteries involved and uninvolved with PS training, suggesting modifications in both central and local control mechanisms. PS‐induced improvements had a short duration in some of vascular function parameters, as they returned to baseline within 6 weeks of PS training cessation.