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 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 mins, three times a week for 6 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, 6 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 6 months in hippocampal volume (2.64% in cycling vs. 2.89% in stretching) and 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 did not differ between groups. WMH volume increased significantly with the cycling group increasing less (10.9%) than stretching (24.5%) over 6 months (f = 4.47, p = 0.04) and over 12 months (12.1 vs. 27.6%, f = 5.88, p = 0.02). NFQ did not 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.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01954550.
Highlights
Dementia affects 47 million people worldwide and is projected to afflict 150 million by 2050 (International, 2016)
Community-dwelling older adults, who had a clinical diagnosis of Alzheimer’s disease (AD) dementia, were 66 years old and older, and spoke English were potentially eligible if they scored 15–26 on the Mini-Mental State Examination (MMSE) and 0.5–2 on Clinical Dementia Rating (CDR), had medical clearance for exercise and MRI, and were stable on AD drugs >1 month if prescribed
The protocol for the anatomic sequences and the study data extracted from each sequence were as follows: magnetization prepared rapid gradient echo imaging (MPRAGE) for measuring regions of interest (ROI)-wise brain volumes and cortical thickness, axial T2 star for assessing cerebral micro hemorrhages, T2 fluid-attenuated inversion recovery (FLAIR) for assessing cerebrovascular disease, axial diffusion-weighted imaging (DWI) for assessing acute hemorrhage, and axial multiband fMRI for assessing regional brain perfusion
Summary
Dementia affects 47 million people worldwide and is projected to afflict 150 million by 2050 (International, 2016). Emerging findings suggest that aerobic exercise may improve cortical thickness (Bae et al, 2020), functional connectivity (Boa Sorte Silva et al, 2020), and white matter hyperintensity (WMH) (Graff-Radford et al, 2019) Together, these findings suggest the need to examine whether and how aerobic exercise may modify limbic neurodegeneration in humans. These findings suggest the need to examine whether and how aerobic exercise may modify limbic neurodegeneration in humans The objective of this pilot RCT, the FIT-AD Trial, was to examine the effects of 6-month aerobic exercise on hippocampal volume, temporal meta-regions of interest (ROI) cortical thickness, WMH volume, and network failure quotient (NFQ) in community-dwelling older adults with mild-to-moderate AD dementia. We examined the correlations of the longitudinal changes of these MRI biomarkers and cognition over 6 and 12 months
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