Efficacy and mechanisms of combined aerobic exercise and cognitive training in mild cognitive impairment: study protocol of the ACT trial.
BACKGROUNDDeveloping non-pharmacological interventions with strong potential to prevent or delay the onset of Alzheimer's disease (AD) in high-risk populations is critical. Aerobic exercise and cognitive training are two promising interventions. Aerobic exercise increases aerobic fitness, which in turn improves brain structure and function, while cognitive training improves selective brain function intensively. Hence, combined aerobic exercise and cognitive training may have a synergistic effect on cognition by complementary strengthening of different neural functions. Few studies have tested the effects of such a combined intervention, and the findings have been discrepant, largely due to varying doses and formats of the interventions.
METHODS/DESIGNThe purpose of this single-blinded, 2 × 2 factorial phase II randomized controlled trial is to test the efficacy and synergistic effects of a 6-month combined cycling and speed of processing training intervention on cognition and relevant mechanisms (aerobic fitness, cortical thickness, and functional connectivity in the default mode network) in older adults with amnestic mild cognitive impairment. This trial will randomize 128 participants equally to four arms: cycling and speed of processing, cycling only, speed of processing only, or attention control for 6 months, and then follow them for another 12 months. Cognition and aerobic fitness will be assessed at baseline and at 3, 6, 12, and 18 months; cortical thickness and functional connectivity at baseline and at 6, 12, and 18 months; Alzheimer's disease (AD) conversion at 6, 12, and 18 months. The specific aims are to (1) determine the efficacy and synergistic effects of the combined intervention on cognition over 6 months, (2) examine the underlying mechanisms of the combined intervention, and (3) calculate the long-term effect sizes of the combined intervention on cognition and AD conversion. The analysis will use intention-to-treat and linear mixed-effects modeling.
DISCUSSIONThis trial will be among the first to test the synergistic effects on cognition and mechanisms (relevant to Alzheimer's-associated neurodegeneration) of a uniquely conceptualized and rigorously designed aerobic exercise and cognitive training intervention in older adults with mild cognitive impairment. It will advance Alzheimer's prevention research by providing precise effect-size estimates of the combined intervention.
TRIAL REGISTRATIONClinicalTrials.gov, NCT03313895 . Registered on 18 October 2017.
University of Minnesota School of Nursing, 5-160 WDH 1331, 308 Harvard St SE, Minneapolis, MN, 55455, USA. firstname.lastname@example.org.,
University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY, 14642, USA. email@example.com.,
University of Minnesota School of Nursing, 5-160 WDH 1331, 308 Harvard St SE, Minneapolis, MN, 55455, USA.,
University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY, 14642, USA.,
University of Minnesota School of Medicine, Minneapolis, MN, USA.,
University of Minnesota Division of Biostatistics, Minneapolis, MN, USA.,
University of St. Thomas, Minneapolis, MN, USA.,
University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY, 14642, USA.
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Clinical Trials, Phase II as Topic
Cognitive Behavioral Therapy
Magnetic Resonance Imaging
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
Pub Type(s)Clinical Trial Protocol