Improving the Recovery and Outcome Every Day After the ICU

Primary Specific Aim: Determine the effect of the combined physical exercise and cognitive training on the cognitive function of ICU survivors aged 50 and older. Hypothesis: In comparison to older ICU survivors randomized to attention control or either intervention alone, those randomized to 12 weeks of combined physical exercise and cognitive training will have higher total index cognitive scores as assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at 3 and 6 months post randomization. Secondary Specific Aim 1: Determine the effect of the combined physical exercise and cognitive training on physical performance, anxiety and depressive symptoms, and quality of life of ICU survivors aged 50 and older. Hypotheses: In comparison to older ICU survivors randomized to attention control or either intervention alone, those randomized to 12 weeks of combined physical exercise and cognitive training will have higher physical performance as measured by short physical performance battery (SPPB) and two-minute step test, lower mood and anxiety symptoms as measured by Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scale, and higher quality of life as measured by the Medical Outcomes Study 36-item short form (SF-36) at 3 and 6-months post randomization. Exploratory Aim 2: To examine the mechanisms of action of combined training. Hypothesis: At the completion of treatment, the combined intervention group will show reduced serum levels of CRP, IL-1, IL-6, IL-8, TNF-α, S-100β, and GFAP and increased levels of BDNF, VEGF, and IGF-1 compared to the attention control, or either intervention alone groups.