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

Article type: Research Article

Authors: Tomoto, Tsubasa^{a; b} | Liu, Jie^c | Tseng, Benjamin Y.^d | Pasha, Evan P.^a | Cardim, Danilo^{a; b} | Tarumi, Takashi^{a; b; e} | Hynan, Linda S.^{f; g} | Munro Cullum, C.^{b; f} | Zhang, Rong^{a; b; h; *}

Affiliations: [a] Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, TX, USA | [b] Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA | [c] Department of Pharmacology, Physiology and Neuroscience, Rutgers University, Newark, NJ, USA | [d] Department of Health and Kinesiology, The University of Texas at Tyler, Tyler, TX, USA | [e] Human Informatics Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan | [f] Department of psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA | [g] Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA | [h] Internal Medicine University of Texas Southwestern Medical Center, Dallas, TX, USA

Correspondence: [*] Correspondence to: Rong Zhang, PhD, Office Address: 7232 Greenville Ave, Dallas, TX 75231, USA. Tel.: +1 214 345 4670; Fax: +1 214 345 4618; E-mail: RongZhang@TexasHealth.org.

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.

Keywords: Aerobic exercise, arterial stiffness, carotid artery, cerebral blood flow, cognitive function, mild cognitive impairment

DOI: 10.3233/JAD-201456

Journal: Journal of Alzheimer's Disease, vol. 80, no. 2, pp. 841-853, 2021