A Multi-Modal Combination Intervention to Promote Cognitive Function in Older Intensive Care Unit Survivors

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The purpose of this Mentored Patient-Oriented Research Career Development Award is to prepare the candidate, Dr. Maya Elias, for an independent program of geriatric critical care research. More than 60% of intensive care unit (ICU) patients are adults ages 60 and older. Following hospital discharge, about 25% of ICU survivors experience cognitive impairment comparable in severity to mild Alzheimer’s disease and related dementias. Moreover, ICU survivors often experience sleep disturbances and inactivity, and almost 80% of ICU patients experience disturbances in circadian rhythm, which may affect cognitive function. The scientific premises of the proposed study are: 1) a combined sleep promotion and cognitive training intervention will have synergistic effects to mitigate the risk of cognitive impairment and development of Alzheimer’s disease and related dementias in older ICU survivors; and 2) chronotherapeutic timing of interventions (i.e., adjusting timing of interventions according to circadian rhythm profiles) may improve intervention efficacy. The proposed research and training build upon prior NIH-funded postdoctoral research conducted by Dr. Elias (F32NR018585). Training Aim 1 will develop expertise in designing and refining behavioral sleep and cognitive interventions through training in clinical trial methodologies and statistical analyses. Training Aim 2 will expand knowledge of circadian science and chronotherapy to examine circadian rhythm as a mechanistic factor underlying delirium and cognitive decline related to Alzheimer’s disease and related dementias in older ICU survivors. This Career Development Award will also support Dr. Elias to lead a clinical trial, which will evaluate feasibility of existing behavioral sleep and cognitive interventions to inform the design of a larger randomized controlled trial. Using a 2 x 2 factorial design, 100 English- or Spanish-speaking older ICU survivors will be enrolled after discharge out of the ICU and randomized to one of 4 combinations of two interventions: SLEEP [nighttime use of earplugs and eye masks] and COG [daily computerized cognitive training sessions]. Specific Aim 1 will test the separate and combined effects of SLEEP and COG, versus AC [active control], in improving cognitive function for older ICU survivors. Specific Aim 2 will examine circadian rhythm parameters of continuous body temperature to determine the optimal window for timing of the COG intervention. Specific Aim 3 will examine if the effects of each intervention [SLEEP + COG, SLEEP, COG] on cognitive function are mediated by sleep and activity, and will examine if selected biological and clinical factors moderate the intervention effects. Exploratory Aim 4 will explore the effect of each intervention on cognitive function at 1 month and incident Alzheimer’s disease and related dementias at 6 months and 12 months after hospital discharge. Results will yield crucial preliminary data for future clinical trials and will guide Dr. Elias to establish a program of research testing interventions that will improve outcomes for older ICU survivors throughout recovery from critical illness.