One-Year Aerobic Exercise Reduced Carotid Arterial Stiffness and Increased Cerebral Blood Flow in Amnestic Mild Cognitive Impairment

Abstract

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.

Understanding How Physical Exercise Improves Alzheimer’s Disease: Cholinergic and Monoaminergic Systems

“…Nowadays, physical activity and exercise have been widely acknowledged as effective strategies for improving AD pathology and AD-associated cognitive impairment ( Northey et al, 2018 ; Jia et al, 2019 ; de Farias et al, 2021 ). From a mechanistic perspective, macroscopically, regular exercise has been shown to alleviate some abnormalities of brain structure and function and to increase cerebral blood flow in subjects with mild cognitive impairment (MCI) and AD ( Broadhouse et al, 2020 ; Tomoto et al, 2021 ; Yu et al, 2021 ); microscopically, exercise training not only increases levels of exerkines (e.g., irisin, Lourenco et al, 2019 ; Islam et al, 2021 ) and metabolic factors (e.g., lactate, El Hayek et al, 2019 ) in the peripheral circulation, which act on the AD brain indirectly, but also exert direct neuroprotective effects by increasing levels of brain-derived neurotrophic factor (BDNF) ( Wang and Holsinger, 2018 ) and promoting adult hippocampal neurogenesis ( Choi et al, 2018 ), enhancing synaptic plasticity ( Mu et al, 2022 ), reducing neuroinflammation and oxidative stress ( Zhang et al, 2019 ), and ameliorating Aβ deposition and tau hyperphosphorylation ( Brown et al, 2019 ). Strikingly, the activity of central neurotransmitter systems seems to be strongly modulated by exercise.…”

Active Life for Brain Health: A Narrative Review of the Mechanism Underlying the Protective Effects of Physical Activity on the Brain

“…Observational studies have found that sedentary older adults had lower cerebral blood flow than active older adults ( Rogers et al, 1990 ; Thomas et al, 2013 ; Knight et al, 2021 ; Li et al, 2021 ). Recently, a small randomized controlled trial involving a 1-year aerobic exercise intervention reported increased cerebral blood flow in the exercise group ( Tomoto et al, 2021 ).…”

One-year aerobic exercise altered cerebral vasomotor reactivity in mild cognitive impairment

“…The vascular mechanisms for the observed increase in hypocapnic CVMR (vasoconstriction) and decrease in hypercapnic CVMR (vasodilation) with AET can only be speculated. Moderate-to-vigorous intensity AET may reduce the central and large cerebral artery stiffness, improve cerebral endothelial function (e.g., endothelium-dependent dilation), and decrease cerebral blood vessel wall smooth muscle tone (e.g., arterial stiffness) (38,44). For example, habitual exercise improved endothelium-dependent vasodilation measured from peripheral arteries, and decreased large elastic artery stiffness in healthy middle-aged and older adults including patients with MCI (38,44).…”

“…Moderate-to-vigorous intensity AET may reduce the central and large cerebral artery stiffness, improve cerebral endothelial function (e.g., endothelium-dependent dilation), and decrease cerebral blood vessel wall smooth muscle tone (e.g., arterial stiffness) (38,44). For example, habitual exercise improved endothelium-dependent vasodilation measured from peripheral arteries, and decreased large elastic artery stiffness in healthy middle-aged and older adults including patients with MCI (38,44). If AET reduces cerebral arterial stiffness, improves cerebral endothelial function, and reduces the cerebrovascular tone, cerebral vasoconstriction reserve during hypocapnia may increase whereas cerebral vasodilation reserve (i.e., the maximal vasodilation from baseline before CO 2 stimuli) during hypercapnia may decrease due to baseline vasodilation before CO 2 stimuli, consistent with the observations that AET improved endothelial function at rest (44).…”