Effects of Aerobic Exercise on Brain Age and Health in Older Adults: A Single-Arm Clinical Trial

Backgrounds Exercise is an attractive, widely accessible intervention to promote cardiovascular health; however, evidence that exercise improves brain health is sparse. Here, we hypothesized that aerobic exercise would improve brain health of sedentary older adults, as reflected by cognition health, sleep macro- and micro-architecture, and brain age index (BAI), a biomarker of brain health derived from the overnight sleep electroencephalogram (EEG). Methods Sedentary older adults were recruited to complete a 12-week aerobic exercise. Home wearable devices were used to monitor heart rate and overnight sleep EEG over the period. NIH Toolbox Cognition Battery, in-lab overnight polysomnography, cardiopulmonary exercise testing and multiplex cytokine assay were employed to determine pre- and post-exercise brain health, exercise capacity and plasma proteins. Results 26 participants completed the initial assessment and exercise program, and 24 completed all procedures. Participants significantly increased maximal oxygen consumption (VO2max) and decreased resting and sleeping heart rate after the exercise regimen. Cognition performances were significantly improved following the exercise program while no significant differences were seen in BAI and sleep macro- and micro-architecture. Plasma IL-4 was elevated while IL-8 was reduced after the exercise regimen. Home sleep data revealed a 3.59% increase in the percentage of N3 sleep over a 12-week. Conclusions We conclude that cognitive function and N3 sleep were improved by a 12-week moderate-intensity exercise program in sedentary older adults, associated with improvements in VO2max and plasma cytokine profiles. Our data show the value of integrating multi-modal assessments to study the effect of brain health targeted approaches. Funding Dr. Westover received support during this work from the McCance Center for Brain Health, the Glenn Foundation for Medical Research and the American Federation for Aging Research through a Breakthroughs in Gerontology Grant; through the American Academy of Sleep Medicine through an AASM Foundation Strategic Research Award; by the Football Players Health Study (FPHS) at Harvard University; from the Department of Defense through a subcontract from Moberg ICU Solutions, Inc, and by grants from the NIH (R01NS102190, R01NS102574, R01NS107291, RF1AG064312, R01AG062989, R01AG073410), and NSF (2014431). Dr. Wrann was supported by a SPARC Award from the McCance Center for Brain Health. Dr. Tanzi and Dr. Zhang were supported by the Cure Alzheimer’s Fund. Clinical trial number National Clinical Trial: [NCT04210882][1] One Sentence Summary We observed that exercise improved slow wave sleep, increased circulating neuroprotective cytokines and improved cognition health in older adults. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT04210882 ### Funding Statement Dr. Westover received support during this work from the McCance Center for Brain Health, the Glenn Foundation for Medical Research and the American Federation for Aging Research through a Breakthroughs in Gerontology Grant; through the American Academy of Sleep Medicine through an AASM Foundation Strategic Research Award; by the Football Players Health Study (FPHS) at Harvard University; from the Department of Defense through a subcontract from Moberg ICU Solutions, Inc, and by grants from the NIH (R01NS102190, R01NS102574, R01NS107291, RF1AG064312, R01AG062989, R01AG073410), and NSF (2014431). Dr. Wrann was supported by a SPARC Award from the McCance Center for Brain Health. Dr. Tanzi and Dr. Zhang were supported by the Cure Alzheimer's Fund. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: MGH IRB: 2019P000673 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Not Applicable The data in the manuscript will be available as requested [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04210882&atom=%2Fmedrxiv%2Fearly%2F2022%2F06%2F14%2F2022.06.13.22276337.atom