This multi-site clinical trial occurs at the University of Minnesota and University of Rochester. It tests the efficacy and additive/synergistic effects of an ACT intervention on cognition and relevant mechanisms (aerobic fitness, Alzheimer's disease [AD] signature cortical thickness, and default mode network [DMN]) in older adults with amnestic MCI (aMCI).

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
• 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)
• Abnormal MRI findings