Mechanistic Effects of Aerobic Exercise in Alzheimer's Disease: Imaging Findings From the Pilot FIT-AD Trial
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 ae...
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2021.703691/full |
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| author | Fang Yu Fang Yu Michelle A. Mathiason SeungYong Han Jeffrey L. Gunter David Jones Hugo Botha Clifford Jack |
| author_facet | Fang Yu Fang Yu Michelle A. Mathiason SeungYong Han Jeffrey L. Gunter David Jones Hugo Botha Clifford Jack |
| author_sort | Fang Yu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T09:07:31Z |
| format | Article |
| id | doaj.art-62f9d2eb4c9c4911b728003ce416f0d4 |
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| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-22T09:07:31Z |
| publishDate | 2021-10-01 |
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| spelling | doaj.art-62f9d2eb4c9c4911b728003ce416f0d42022-12-21T18:31:33ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-10-011310.3389/fnagi.2021.703691703691Mechanistic Effects of Aerobic Exercise in Alzheimer's Disease: Imaging Findings From the Pilot FIT-AD TrialFang Yu0Fang Yu1Michelle A. Mathiason2SeungYong Han3Jeffrey L. Gunter4David Jones5Hugo Botha6Clifford Jack7Arizona State University Edson College of Nursing and Health Innovation, Phoenix, AZ, United StatesUniversity of Minnesota School of Nursing, Minneapolis, MN, United StatesUniversity of Minnesota School of Nursing, Minneapolis, MN, United StatesArizona State University Edson College of Nursing and Health Innovation, Phoenix, AZ, United StatesMayo Clinic Department of Radiology, Rochester, MN, United StatesMayo Clinic Department of Radiology, Rochester, MN, United StatesMayo Clinic Department of Radiology, Rochester, MN, United StatesMayo Clinic Department of Radiology, Rochester, MN, United StatesDespite 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.https://www.frontiersin.org/articles/10.3389/fnagi.2021.703691/fullexerciseAlzheimer's diseasedementiaimagingMRIhippocampal volume |
| spellingShingle | Fang Yu Fang Yu Michelle A. Mathiason SeungYong Han Jeffrey L. Gunter David Jones Hugo Botha Clifford Jack Mechanistic Effects of Aerobic Exercise in Alzheimer's Disease: Imaging Findings From the Pilot FIT-AD Trial Frontiers in Aging Neuroscience exercise Alzheimer's disease dementia imaging MRI hippocampal volume |
| title | Mechanistic Effects of Aerobic Exercise in Alzheimer's Disease: Imaging Findings From the Pilot FIT-AD Trial |
| title_full | Mechanistic Effects of Aerobic Exercise in Alzheimer's Disease: Imaging Findings From the Pilot FIT-AD Trial |
| title_fullStr | Mechanistic Effects of Aerobic Exercise in Alzheimer's Disease: Imaging Findings From the Pilot FIT-AD Trial |
| title_full_unstemmed | Mechanistic Effects of Aerobic Exercise in Alzheimer's Disease: Imaging Findings From the Pilot FIT-AD Trial |
| title_short | Mechanistic Effects of Aerobic Exercise in Alzheimer's Disease: Imaging Findings From the Pilot FIT-AD Trial |
| title_sort | mechanistic effects of aerobic exercise in alzheimer s disease imaging findings from the pilot fit ad trial |
| topic | exercise Alzheimer's disease dementia imaging MRI hippocampal volume |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2021.703691/full |
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