Cognitive Effects of Aerobic Exercise in Alzheimer’s Disease: A Pilot Randomized Controlled Trial

Yu, Fang; Vock, David M.; Zhang, Lin; Salisbury, Dereck; Nelson, Nathaniel W.; Chow, Lisa S.; Smith, Glenn E.; Barclay, Terry R.; Dysken, Maurice W.; Wyman, Jean F.

doi:10.3233/jad-201100

Cited by 80 publications

(73 citation statements)

References 43 publications

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“…Previously, we have reported that our intervention participants had a smaller increase in global cognition as measured by the ADAS-Cog at 6 months (1.0 ± 4.6) than its natural course (3.2 ± 6.3-point increase; p = 0.001) (Yu et al, 2021). In this study, we found a significant negative correlation between the 6-month declines in hippocampal volume and the 6-month increases in ADAS-Cog, meaning that hippocampal atrophy was significantly associated with cognitive decline during the intervention period.…”

Section: Discussionmentioning

confidence: 57%

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

Mathiason

Han

et al. 2021

Front. Aging Neurosci.

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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.

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Section: Discussionmentioning

confidence: 57%

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

Mathiason

Han

et al. 2021

Front. Aging Neurosci.

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“…Table 1 lists the 26 participants’ baseline characteristics with a mean age (SD) of 77.6 (7.0) years, 65.4%men, a mean (SD) education of 15.4 (3.0) years, and an ADAS-Cog (SD) of 18.1 (7.8). The baseline characteristics of these 26 participants were consistent with the full cohort of the FIT-AD Trial, except that the percent of men were higher (65.4%versus 55%in the 96 participants) [ 16 ].…”

Section: Resultsmentioning

confidence: 86%

Plasma Neurofilament Light and Future Declines in Cognition and Function in Alzheimer’s Disease in the FIT-AD Trial

Zhang

Nelson

et al. 2021

ADR

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Background: Utilities of blood-based biomarkers in Alzheimer’s disease (AD) clinical trials remain unknown. Objective: To evaluate the ability of plasma neurofilament light chain (NfL) to predict future declines in cognition and activities of daily living (ADL) outcomes in 26 older adults with mild-to-moderate AD dementia from the FIT-AD Trial. Methods: Plasma NfL was measured at baseline and 3 and 6 months. Cognition and ADL were assessed using the AD Assessment Scale-Cognition (ADAS-Cog) and AD Uniform Dataset Instruments and Disability Assessment for Dementia (DAD), respectively, at baseline, 3, 6, 9, and 12 months. Linear mixed effects models were used to examine the associations between baseline or change in plasma NfL and changes in outcomes. Results: Higher baseline plasma NfL was associated with greater rate of decline in ADAS-Cog from baseline to 6 months (standardized estimate of 0.00462, p = 0.02853) and in ADL from baseline to 12 months (standardized estimate of –0.00284, p = 0.03338). Greater increase in plasma NfL in short term from baseline to 3 months was associated with greater rate of decline in memory and ADL from 3 to 6 months (standardized estimate of –0.04638 [0.003], p = 0.01635; standardized estimate of –0.03818, p = 0.0435) and greater rate of decline in ADL from 3 to 12 month (standardized estimate of –0.01492, p = 0.01082). Conclusion: This study demonstrated that plasma NfL might have the potential to predict cognitive and function decline up to 12 months. However, future studies with bigger sample sizes need to confirm the findings.

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“…Another study of the effects of exercise showed improved memory performance and reduced hippocampal atrophy, along with improved cardiorespiratory fitness, in AD patients [ 295 ]. Moderate-intensity cycling may reduce the decline in global cognition in older adults with mild-to-moderate AD dementia [ 296 ]. A meta-analysis study using a random-effects model compared different quantities of physical activity and exercise interventions for AD in detail and concluded that physical activity and exercise can improve cognition in older adults with AD [ 297 ].…”

Section: Lifestyle Modificationsmentioning

confidence: 99%

Disentangling Mitochondria in Alzheimer’s Disease

Johri

2021

IJMS

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Alzheimer’s disease (AD) is a major cause of dementia in older adults and is fast becoming a major societal and economic burden due to an increase in life expectancy. Age seems to be the major factor driving AD, and currently, only symptomatic treatments are available. AD has a complex etiology, although mitochondrial dysfunction, oxidative stress, inflammation, and metabolic abnormalities have been widely and deeply investigated as plausible mechanisms for its neuropathology. Aβ plaques and hyperphosphorylated tau aggregates, along with cognitive deficits and behavioral problems, are the hallmarks of the disease. Restoration of mitochondrial bioenergetics, prevention of oxidative stress, and diet and exercise seem to be effective in reducing Aβ and in ameliorating learning and memory problems. Many mitochondria-targeted antioxidants have been tested in AD and are currently in development. However, larger streamlined clinical studies are needed to provide hard evidence of benefits in AD. This review discusses the causative factors, as well as potential therapeutics employed in the treatment of AD.

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Cognitive Effects of Aerobic Exercise in Alzheimer’s Disease: A Pilot Randomized Controlled Trial

Cited by 80 publications

References 43 publications

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

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

Plasma Neurofilament Light and Future Declines in Cognition and Function in Alzheimer’s Disease in the FIT-AD Trial

Disentangling Mitochondria in Alzheimer’s Disease

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