Sleep and Circadian Rhythm Biomarkers of Postoperative Neurocognitive Recovery (SLEEP-POD2) - PROJECT SUMMARY Developing effective interventions for postoperative delirium (POD), one of the most common surgical complications in older adults urgently requires a better understanding of modifiable risk factors and underlying mechanisms. Sleep health has emerged as a key public health initiative for optimizing health outcomes in older patients. There is evidence that alterations in the ~24-hour sleep/wake cycle, regulated by our underlying circadian rhythms, worsen after surgical insult to coincide with POD. Sleep and circadian rhythm disturbances are not only more common in older patients and Alzheimer’s disease (AD) and Related Dementias (ADRD) but also track preclinical AD pathology (e.g., tauopathy) and cognitive decline, major delirium sequelae. Our recent work showed that poor sleep traits and 24-hour rest/activity rhythm disturbances were associated with POD risk and predicted ADRD progression. However, these findings have not been rigorously tested in a dedicated surgical cohort with longitudinal sleep/circadian rhythm tracking. Our central hypothesis is that perioperative sleep/circadian disruption promotes POD vulnerability and long-term cognitive decline via AD pathology burden. To address this, we propose SLEEP-POD2, a multisite longitudinal cohort involving 400 older non-cardiac surgery patients (>65 years) from Boston and Baltimore with their representative populations. Leveraging our established perioperative sleep/geriatric research infrastructure (including retention strategies and psychological expertise for delirium sequelae from our first pilot SLEEP-POD study), this proposal will comprehensively assess repeated sleep/circadian measures (ambulatory 7-day actigraphy, electronic sleep diary, & 3-day EEG headband), preclinical AD pathology (via plasma amyloid, tau, neurodegeneration, ATN), and cognition (NIH Toolbox Cognition Battery) at baseline, 1-, 3-month, and 1-year post-surgery. This will establish sleep/circadian health as a potential target for POD prevention and novel insights into neurocognitive recovery after surgery. Guided by strong preliminary data, we propose the following Specific Aims: 1) Determine the effect of preoperative sleep/circadian disruption on POD risk, cognitive decline, and morbidity outcomes, 2) Examine the longitudinal relationship between sleep/circadian disruption and AD pathology, and its relevance to cognitive decline, and Ancillary 3) Establish a biophysiological repository for novel insights into POD, cognitive decline, and AD/ADRDs. Significance: This proposal addresses a key gap in understanding sleep and circadian health in older persons undergoing major surgery. It builds on prior work to provide direct clinical evidence to guide perioperative sleep interventions in older patients that may benefit the most. Innovation: Few studies have leveraged this comprehensive, multidisciplinary approach tailored to older patients to understand sleep before and after surgery. Impact: Successful completion will accrue clinical data to establish potential sleep or life rhythm targets that optimize POD prevention and aid cognitive recovery in older surgical patients.
