The ACT Trial: Effects of Combined Aerobic Exercise and Cognitive Training in MCI

Because almost all drug trials for Alzheimer's disease (AD) have failed, developing
non-pharmacological interventions with strong potential to prevent or delay the onset of AD
in high-risk populations (e.g., those with mild cognitive impairment [MCI]) is critically
important. Aerobic exercise and cognitive training are 2 promising interventions for
preventing AD. Aerobic exercise increases aerobic fitness, which in turn improves brain
structure and function, while cognitive training improves selective neural function
intensively. Hence, combined Aerobic exercise and Cognitive Training (ACT) may very well have
an additive or synergistic effect on cognition by complementary strengthening of different
neural functions. Few studies have tested ACT's effects, and those studies have reported
discrepant findings, largely due to varying ACT programs. The purpose of this single-blinded,
2×2 factorial Phase II randomized controlled trial (RCT) is to test the efficacy and
additive/synergistic effects of a 6-month combined cycling and speed of processing (SOP)
training intervention on cognition and relevant mechanisms (aerobic fitness, AD signature
cortical thickness, and functional connectivity in the default mode network [DMN]) in older
adults with amnestic MCI (aMCI).

Inclusion Criteria:

- A clinical diagnosis of MCI, Community-dwelling, Age 65 years and older,
English-speaking, Adequate visual acuity, Verified exercise safety by medical
provider, Stable on drugs affecting cognitive and psychological status, Verified MRI
safety, and Capacity to consent.

Exclusion Criteria:

- Geriatric Depression Scale < 5, Resting heart rate (HR) ≤50 due to arrhythmia or ≥100
beats/min, Neurological (e.g., dementia, head trauma), psychiatric (e.g., bipolar,
schizophrenia, or depression), or substance dependency (alcohol or chemical
dependency) in the past 5 years that are the main contributor to MCI,
Contraindications to exercise, e.g. unstable angina, recent surgery, New symptoms or
diseases that have not been evaluated by a health care provider, Current enrollment in
another intervention study related to cognitive improvement (reduce confounding
effects on outcomes), and Abnormal MRI findings.