Exercise in Adults With Mild Memory Problems

Inclusion Criteria 1. Age between 65 and 89 years old, inclusive 2. MMSE: ≥24 for participants with 13 or more years of education; ≥22 for participants with 12 or fewer years of education 3. Global CDR score of 0.5 with a memory score of at least 0.5 4. Profile of test scores and clinical ratings is consistent with amnestic mild cognitive impairment 5. Speaks English fluently 6. Visual and auditory acuity adequate for cognitive testing 7. Completed at least 6 years of formal education or work history sufficient to exclude mental retardation 8. 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. 9. Sedentary or underactive, determined by responses to the staff-administered EXERT Telephone Assessment of Physical Activity (TAPA) survey 10. Willing to be randomized to either intervention group and to complete the assigned activities as specified for 18 months 11. Willing and able to reliably travel to the identified YMCA, 4 times per week for 18 months 12. Ability to safely participate in either intervention and complete the 400 m Walk Test within 15 min without sitting or use of any assistance 13. Plans to reside in the area for at least 18 months 14. 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 15. In overall good general health with no disease or planned surgery that could interfere with study participation 16. Modified Hachinski ≤4 17. 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) 18. 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 19. 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 20. Able to complete all baseline assessments Exclusion Criteria 1. 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 2. 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 3. Contraindications for MRI studies, including claustrophobia, metal (ferromagnetic) implants, or cardiac pacemaker 4. 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 5. History of major depression or bipolar disorder (DSM V criteria), psychotic features, agitation or behavioral problems within the last 12 months 6. History of schizophrenia, as per DSM V criteria 7. History of alcohol or substance abuse or dependence within the past 2 years, as per DSM V criteria 8. Currently consumes more than 3 alcoholic drinks per day 9. Clinically significant or unstable medical condition, including uncontrolled hypertension or significant cardiac, pulmonary, hematologic, renal, hepatic, gastrointestinal, endocrine, metabolic or other systemic disease in the opinion of clinic medical personnel that may put the participant at increased risk, influence the results or compromise the participants ability to participate in the study (treated atrial fibrillation for more than 1 year or occasional premature ventricular contractions on ECG are not exclusions) 10. History in the last 6 months of myocardial infarction, coronary artery angioplasty, bypass grafting, or STENT placement 11. History in the last 3 months of transient ischemic attack or small vessel stroke (if more than 3 months, small vessel stroke with no residual effects are permitted) 12. Expected joint replacement surgery within the next 18 months 13. History within the last 5 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen posttreatment 14. Hemoglobin A1c \>7.0 15. Clinically significant abnormalities in screening laboratory blood tests: low B12 is exclusionary, unless follow-up labs (homocysteine \[HCY\] and methylmalonic acid \[MMA\]) indicate that it is not physiologically significant 16. Current or past use of insulin to treat type 2 diabetes (other diabetes medications are acceptable if hemoglobin A1c ≤7) 17. Current use (within 60 days of screening) of psychoactive medications including tricyclic antidepressants, antipsychotics, mood-stabilizing psychotropic agents (e.g. lithium salts), psychostimulants, opiate analgesics, antiparkinsonian medications, anticonvulsant medications (except gabapentin and pregabalin for non-seizure indications), systemic corticosteroids, or medications with significant central anticholinergic activity. Limited use of antipsychotics (quetiapine ≤ 50mg/day or risperidone ≤ 0.5mg/day), and non-chronic use of opiate analgesics on an as needed basis is permitted; such medications must be avoided for 8 hours before clinic assessments 18. Chronic use of anxiolytics or sedative hypnotics except as follows: use of benzodiazepines for treatment on an as-needed basis for insomnia or daily dosing of anxiolytics is permitted; medications must be avoided for 8 hours before clinic assessments 19. Previous or current treatment involving active immunization against amyloid 20. Previous treatment with approved or investigational agents with anti-amyloid properties or passive immunization against amyloid are prohibited 12 months prior to screening and for the duration of the trial; treatment with other investigational agents are prohibited 3 months prior to screening and for the duration of the trial 21. For LP, current use of anticoagulants such as Coumadin, Plavix, or high dose Vitamin E 22. For LP, current blood clotting or bleeding disorder, or significantly abnormal prothrombin time (PT) or partial thromboplastin time (PTT) at screening 23. For LP, presence of physical distortions due to spinal surgery, severe degenerative joint disease or deformity, or obesity that could interfere with CSF collection (as per investigator judgment) 24. Participants whom the PI deems otherwise ineligible