Working Memory and Physical Exercise Training in Patients With Mild Cognitive Impairment

Adaptive Working Memory and Physical Exercise Training to Improve Brain and Mitochondrial Function in MCI

The prevalence of dementia will double in the next three decades in the U.S.; effective treatment or prevention for dementia is urgently needed. The current exploratory project aims to evaluate and understand how the brain and cognition may improve after a 12-week intervention that combines brain training and aerobic exercise training to improve brain function, both in those with mild cognitive impairment (some with possible prodromal Alzheimer's disease) and with healthy aging. Findings from this pilot project will guide and refine the development of a future larger clinical trial that aligns with the goals of the National Alzheimer's Plan of Action (NAPA), especially regarding "Prevent and Effectively Treat Alzheimer's Disease (AD) by 2025.

Inclusion Criteria:

• Adult men and women of all races and ethnicities who are 50-80 years of age will be eligible.
• Only sedentary adults will be eligible (engaging in structured activity for exercise <3x/week) for Progressive aerobic exercise or Combined training
• Ability to use, and accessibility to, an iPad or computer is required for the Adaptive cognitive training and Combined training.
• Fluent in English.
• The diagnosis of MCI will first be confirmed at the screening evaluation using the clinical dementia rating (CDR) scale and the Montreal Cognitive Assessment (MoCA). We will also evaluate their ADL using instrumental activities of daily living (IADL) to ensure they have preserved independence in functional abilities despite the cognitive deficits. The primary caregivers will be interviewed (either in person or by phone) for the participants' IADL to corroborate the independent functional status.

Exclusion Criteria:

• Does not have access to a computer or internet to perform the Cogmed® training AND is unwilling to come to the lab for the training.
• Unable to undergo an MRI investigation based on claustrophobia or metal foreign bodies.
• Symptomatic heart disease, Coronary artery disease, congestive heart failure, uncontrolled hypertension, uncontrolled diabetes (HbA1c>10%), significant cardiovascular disorders (on EKG and graded exercise test) that would prevent the participant from the exercise training; neurologic, musculoskeletal, or other condition that limits the subject's ability to complete study physical assessments.
• Estimated verbal Intelligence Quotient (IQ) below 70 (based on the Wechsler Test of Adult Reading) which would invalidate the informed consent process for the study.
• Self-reported moderate to severe substance use disorder(s) (e.g., self-reported intake >3 oz liquor, or three 4 oz glasses of wine, or three 12 oz cans of beer per day or illicit drug use).
• Severe chronic or acute medical or other (non-MCI) neuropsychiatric conditions that might confound the cognitive or brain imaging measures (e.g., liver function tests >2.5 normal range or evidence for renal failure).
• Body mass index >40 kg/m2.