Cerebral White Matter Integrity in Amnestic Mild Cognitive Impairment: A 1-Year Randomized Controlled Trial of Aerobic Exercise Training

Article type: Research Article

Authors: Tarumi, Takashi^{a; b; c} | Thomas, Binu P.^d | Tseng, Benjamin Y.^e | Wang, Ciwen^a | Womack, Kyle B.^{b; f} | Hynan, Linda^{f; g} | Lu, Hanzhang^{d; h} | Cullum, C. Munro^{b; f} | Zhang, Rong^{a; b; i}

Affiliations: [a] Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, TX, USA | [b] Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA | [c] Human Informatics Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan | [d] Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA | [e] Department of Health and Kinesiology, The University of Texas at Tyler, Tyler, TX, USA | [f] Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA | [g] Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA | [h] Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA | [i] Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

Correspondence: [*] Correspondence to: Rong Zhang, PhD, 7232 Greenville Ave, Dallas, TX 75231, USA. Tel.: +1 214 345 8843; Fax: +1 214 345 4618; E-mail: [email protected].

Abstract: Cerebral white matter (WM) represents the structural substrate of neuronal communications which is damaged by Alzheimer’s disease (AD). Aerobic exercise training (AET) may improve WM integrity in cognitively normal older adults, but its efficacy remains unknown in patients with amnestic mild cognitive impairment (MCI), a prodromal phase of AD dementia. Therefore, we conducted a proof-of-concept study that randomized 70 amnestic MCI patients to a 1-year program of AET or a non-aerobic stretching and toning (SAT), active control group. Thirty-six patients completed both baseline and follow-up MRI scans, and cerebral WM integrity was measured by WM lesion volume and diffusion characteristics using fluid-attenuated-inversion-recovery and diffusion tensor imaging respectively. Peak oxygen uptake (VO2peak) and neuropsychological function were also measured. At baseline and 1-year follow-up, WM lesion volume and diffusion characteristics were similar between the AET and SAT groups, although VO2peak significantly improved after AET. The AET group showed slight improvement in neuropsychological performance. When analyzing individual data, tract-based spatial statistics demonstrated that VO2peak improvements are associated with attenuated elevations in mean and axial diffusivities, particularly the anterior WM fiber tracts (e.g., genu of corpus callosum). In patients with amnestic MCI, we found that although AET intervention did not improve WM integrity at group level analysis, individual cardiorespiratory fitness gains were associated with improved WM tract integrity of the prefrontal cortex.

Keywords: Aerobic exercise, cardiorespiratory fitness, diffusion tensor imaging, mild cognitive impairment, white matter integrity

DOI: 10.3233/JAD-190875

Journal: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 489-501, 2020