This two-year study will evaluate the feasibility of an exercise training augmentation for cognitive training intervention to improve memory performance in Veterans with a diagnosis of amnestic Mild Cognitive Impairment (aMCI). This is a two-phased trial: 1) an exercise phase and 2) a cognitive training program. The exercise phase will be an aquatic based exercise program. A combination of exercise and cognitive training programs designed for persons without cognitive impairment have significantly improved memory more than other single intervention groups (exercise only, cognitive training only) and given the success of combination training programs with healthy older adults, it is important to adapt these programs for persons beginning to exhibit clinically significant memory problems, such as those with aMCI.

The primary research question of the proposed study is this: Is a combination water-based physical exercise + cognitive training program for older Veterans with amnestic Mild Cognitive Impairment (MCI) feasible? The primary aims of the proposed research are: 1) demonstrate adequate recruitment and retention rates; 2) refinement of inclusion/exclusion criteria; and 3) further refine the combination waterbased physical exercise + cognitive training (WATER+CT) intervention.

These aims will be tested in a two-phase clinical trial with a single group design: 1) exercise training phase and 2) a cognitive training phase. The exercise training phase consists of a water-based physical exercise program that emphasizes cardiovascular fitness and strength training through a combination of non-weight bearing exercises that include land-based stretching and water-based activities. This 2-year pilot project will include 50 Veterans diagnosed with amnestic MCI age 50-90. The exercise component consists of a six-month water-based exercise program followed by a four-week cognitive training program. For the first two months of the water-based exercise program, Veterans will come to thrice-weekly group sessions at Aquatic Therapy Center at the VA Palo Alto Health Care System. This will transition to a self-paced exercise program for the remaining four months. After completion of the exercise program, Veterans will begin classroom-based cognitive training at the VA Palo Alto Health Care System (VAPAHCS). The cognitive training is based on an efficacious cognitive program that is structured around two components, pre-training and mnemonic training, both of which have been used successfully in persons with aMCI. Assessments of adherence will be administered throughout treatment and measures of feasibility will be completed post-treatment.

Participants will complete a variety of neuropsychological measures taping into areas of cognition such as attention, executive functioning, and memory. To study possible predictors of treatment response, the investigators will also collect biological (cardiovascular functioning and brain derived neurotrophic factor [BDNF] plasma levels) and genetic data (APOE and BDNF genotypes) from these participants. The investigators hope to provide initial evidence of the feasibility of a waterbased exercise training augmentation for cognitive training thus laying the groundwork for full-scale clinical trials targeting the lessening of cognitive impairment in persons with amnestic MCI by non-pharmacological means.

Inclusion Criteria:

• Veterans aged 50 - 90
• diagnosis of aMCI
• available informant
• at least one musculoskeletal problem
• sufficient visual and auditory acuity to allow neuropsychological testing
• willingness to participate in exercise training +cognitive training program for eight months
• approval of primary provider to participate in an exercise trial

Exclusion Criteria:

• current untreated severe psychiatric disorder, such as:

  • Bipolar I
  • Schizophrenia
  • or Major Depressive Disorder, determined by the Mini International Neuropsychiatric Interview (MINI)

• diagnosis of dementia, Clinical Dementia Rating (CDR) > 0.5; modified Hachinski score 4; or delirium

• history of neurological disorder, e.g.:

  • multiple sclerosis
  • seizure disorder
  • stroke

• history of transient ischemic attacks, or systemic illness affecting central nervous system (CNS) function, e.g.:

  • liver failure
  • kidney failure
  • congestive heart failure
  • systemic cancer

• acute illness or unstable chronic illness e.g., history of severe liver disease

  • cirrhosis
  • esophageal
  • varices
  • ascites
  • portal hypertension
  • hepatic encephalopathy

• current severe cardiac disease, e.g.:

  • uncontrolled atrial fibrillation, defined as mean 24 hour heart rate >85 beats/min, or 24 hour maximal ventricular rate >150 beats/min
  • uncontrolled ventricular arrhythmias, defined as recurrent ventricular tachycardia > 3 beats in succession, or 24 hour packed cell volume (PVC) count > 20%; active
  • pericarditis or myocarditis
  • Class III/IV heart failure and / or ejection fraction < 20%
  • thrombophlebitis
  • pulmonary disease with a drop in O2 Sat with exercise to 90% without oxygen
  • embolism within past six months

• inability to participate in an exercise stress test or inability to exercise consistently because of orthopedic or musculoskeletal problems

• morbid obesity (BMI > 39)

• inability to read, verbalize understanding and voluntarily sign the Informed Consent

AEs, SAEs, and UAPs were collected from the time of study entry until the end of study participation, an average of 8 months

The definition of AEs and SEs does not differ from the provided definition. AEs and SAEs were collected at each study visit.

The final participant completed cognitive training in a remote environment due to COVID19 shelter-in-place orders.