Defining the Phenotype of Complicated Delirium Associated with Long-Term Cognitive Decline

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ABSTRACT Delirium has been considered a transient, reversible syndrome. However, long-term follow-up studies suggest delirium is not always transient and reversible, and is correlated with increased risk of bad outcomes, such as persistent and accelerated cognitive decline, Alzheimer's disease or dementia, death, and excess service utili- zation. We have demonstrated that about half of people who develop postoperative delirium return to preoper- ative baseline cognitive performance levels within about 8 weeks of surgery, but about a third of those who develop postoperative delirium show accelerated cognitive decline out to 36 months following surgery. Our working definition of complicated delirium, developed in our prior period of support, is delirium associated with a higher degree (or pace) of cognitive decline in long-term follow-up (i.e., ≥ 2-3 years). In this sub-group, the pace is similar to that observed among persons with mild cognitive impairment. Defining complicated delirium in terms of long-term cognitive decline is problematic since the outcome cannot be detected for years. Therefore, this Project will help identify predictors of complicated delirium to assist with early identification. Our aims are: (1) to identify predictors for early identification of complicated delirium using an expert panel, (2) identify predictors for early identification of complicated delirium using empiric data, and (3) to validate the predictive models in an independent sample (external validity) and against clinical outcomes (predictive validity). We will use information that is potentially available before, during and immediately following surgery. We will also evaluate models using biomarkers derived from cerebrospinal fluid, serum, neurophysiologic measures, and neuroimaging obtained before surgery. We will accomplish our aims with (a) the insights of experts in delirium in a modified Delphi process; (b) secondary data analysis of the rich data already collected in the SAGES I cohort, and (c) validation with new observational and clinical data collected within the context of the new SAGES II cohort study. We will develop multiple models including preoperative, perioperative, and postoperative predictor variable sets, and their combination. Our team includes experts in qualitative and quantitative methodology and field leaders in the study of delirium. The ultimate goal of this work is to improve delirium recognition and treatment by clinicians, and heighten the prognostic importance of delirium among clinicians, their patients, and policy makers.