Exercise in Adults With Mild Memory Problems

Inclusion Criteria

• Age between 65 and 89 years old, inclusive
• MMSE: ≥24 for participants with 13 or more years of education; ≥22 for participants with 12 or fewer years of education
• Global CDR score of 0.5 with a memory score of at least 0.5
• Profile of test scores and clinical ratings is consistent with amnestic mild cognitive impairment
• Speaks English fluently
• Visual and auditory acuity adequate for cognitive testing
• Completed at least 6 years of formal education or work history sufficient to exclude mental retardation
• Has an informant who knows the participant well, has regular contact, and is available to accompany the participant to clinic visits or complete study partner assessments remotely.
• Sedentary or underactive, determined by responses to the staff-administered EXERT Telephone Assessment of Physical Activity (TAPA) survey
• Willing to be randomized to either intervention group and to complete the assigned activities as specified for 18 months
• Willing and able to reliably travel to the identified YMCA, 4 times per week for 18 months
• Ability to safely participate in either intervention and complete the 400 m Walk Test within 15 min without sitting or use of any assistance
• Plans to reside in the area for at least 18 months
• For planned travel, total time away must be no more than 2 months over the course of the study, and no more than 1 month at any one time; participants must be willing to continue the assigned exercise program if travelling out of the area for more than 1 week
• In overall good general health with no disease or planned surgery that could interfere with study participation
• Modified Hachinski ≤4
• Stable use of cholinesterase inhibitors, memantine, vitamin E, estrogens, aspirin (81 300 mg daily), beta-blockers, or cholesterol-lowering agents for 12 weeks prior to screening (important for biomarker analyses)
• Stable use of antidepressants lacking significant anticholinergic side effects for 4 weeks prior to screening as long as the participant does not meet DSM V criteria for major depression currently or in the last 12 months; GDS scores are to be used to inform clinical decisions but there is no specified cut-off score for inclusion
• When applicable, willing to complete 4-week washout of psychoactive medications, including disallowed antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, and willing to avoid these medications for the duration of the trial
• Able to complete all baseline assessments

Exclusion Criteria

• Any significant neurologic disease, other than MCI, including any form of dementia, Parkinsons disease, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma with persistent neurologic sequelae or known structural brain abnormalities
• Sensory or musculoskeletal impairment sufficient to preclude successful and safe completion of the intervention or assessment protocols; must be able to walk safely and unassisted on a treadmill
• Contraindications for MRI studies, including claustrophobia, metal (ferromagnetic) implants, or cardiac pacemaker
• Brain MRI at screening shows evidence of infection, infarction, or other clinically significant focal lesions, including multiple lacunes in prefrontal or critical memory regions; inconclusive findings may be subject to review by the ADCS Imaging Core
• History of major depression or bipolar disorder (DSM V criteria), psychotic features, agitation or behavioral problems within the last 12 months
• History of schizophrenia, as per DSM V criteria
• History of alcohol or substance abuse or dependence within the past 2 years, as per DSM V criteria
• Currently consumes more than 3 alcoholic drinks per day
• Clinically significant or unstable medical condition, including uncontrolled hypertension or significant cardiac, pulmonar