AUTHOR=Yu Fang , Mathiason Michelle A. , Han SeungYong , Gunter Jeffrey L. , Jones David , Botha Hugo , Jack Clifford 

TITLE=Mechanistic Effects of Aerobic Exercise in Alzheimer's Disease: Imaging Findings From the Pilot FIT-AD Trial

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 13 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.703691

DOI=10.3389/fnagi.2021.703691

ISSN=1663-4365

ABSTRACT=Despite strong evidence from animal models of Alzheimer’s disease (AD) supporting aerobic exercise as a disease-modifying treatment for AD, human mechanistic studies are limited with mixed findings. The objective of this pilot randomized controlled trial was to examine the effects of 6-month aerobic exercise on hippocampal volume, temporal meta-regions of interest (ROI) cortical thickness, white matter hyperintensity (WMH) volume, and network failure quotient (NFQ), measured with magnetic resonance imaging (MRI), in community-dwelling older adults with AD dementia. Additionally, the relationships between 6- and 12-month changes in MRI biomarkers and the AD Assessment Scale-Cognition (ADAS-Cog) were examined. Sixty participants were randomized, but one was excluded because baseline MRI failed quality control: 38 randomized to cycling and 21 to stretching. The intervention was moderate intensity cycling for 20-50 minutes, 3 times a week for six months. Control was low intensity stretching. The study outcomes include hippocampal volume, temporal meta-ROI cortical thickness, WMH volume, and NFQ. Outcomes were measured at baseline, six months, and 12 months. The sample averaged 77.3±6.3 years old with 15.6±2.9 years of education and 53% men. Both groups experienced significant declines over six months in hippocampal volume (2.64% in cycling vs. 2.89% in stretching), temporal meta-ROI cortical thickness (0.94% vs. 1.54%) and over 12 months in hippocampal volume (4.47% vs. 3.84%) and temporal meta-ROI cortical thickness (2.27% vs. 1.79%). These declines didn’t differ between groups. WMH volume increased significantly with the cycling group increasing less (10.9%) than stretching (24.5%) over six months (f=4.47, p=.04) and over 12 months (12.1% vs. 27.6%, f=5.88, p=.02). NFQ didn’t change significantly over time. Pairwise correlational analyses showed a significant negative correlation between 6-month changes in hippocampal volume and ADAS-Cog (r=-0.34, p<0.05). To conclude, aerobic exercise may reduce the decline in hippocampal volume and temporal meta-ROI cortical thickness during the intervention period, but the effect sizes are likely to be very small and dose-dependent and reverse once the intervention stops. Aerobic exercise is effective on slowing down WMH progression but has no effect on NFQ. Hippocampal atrophy was associated with cognitive decline during the intervention period. This trial was registered at Clinicaltrials.gov NCT01954550.