Delirium is a common, serious, and often fatal disorder, affecting up to 60% of hospitalized seniors, and costing over $164 billion per year. The significance of delirium is heightened in Alzheimer’s disease and related dementias (ADRD), where it occurs with increased frequency (4-5 fold risk) and severity, compared to those without ADRD. Delirium severity is directly correlated with poor clinical outcomes, and its measurement is essential to stratify risk, target treatments, and monitor as an outcome for pathophysiologic studies and clinical trials. In our successful first cycle, we developed a new 17-item instrument for DELirium Severity, the DEL-S. With this proposal, we will extend this work with the novel concept that measurement of delirium severity should be distinct among persons with and without ADRD. Preexisting ADRD is well-known to lead to substantial over-estimation of delirium severity, and none of the >40 current delirium severity instruments were specifically developed or validated for use in persons with ADRD. Thus, our specific aims are: (1) to identify key items that assess the important domains of delirium severity among persons with ADRD, and to develop a new instrument, the DEL-S-AD (DELirium Severity in ADRD); (2) to conduct a multi-site prospective cohort study of 500 older adults (225 with CDR of 0, 50 with CDR of 0.5, and 225 with CDR 1-2) for validation of both the DEL-S and DEL-S-AD with a simultaneous reference standard rating; and (3) to compare the performance of the DEL-S and DEL-S-AD across different levels cognitive function, ranging from normal cognition to moderate ADRD. We will also harmonize DEL-S and DEL-S-AD scores, providing a framework to compare results on a unified metric. For these aims, we will focus on clarifying the construct of delirium severity in ADRD using our prior data and an expert panel. Second, we will validate distinct delirium severity instruments for those with and without ADRD in a multi-site cohort drawn from 3 unique yet complementary sites (BASIL II) with 500 older adults (225 with ADRD), who will be enrolled from medical and surgical populations, and long- term care. All participants will also have concurrent evaluation by skilled clinicians for a reference standard assessment, and all final diagnoses will be made by an experienced, interdisciplinary Adjudication Team. Performance of each instrument will be assessed for internal reliability, face and content validity, convergent validity (against legacy instruments), criterion validity (against reference standard) and predictive validity for relevant clinical outcomes. Finally, we will compare and harmonize the DEL-S and DEL-S-AD scores, to test whether the DEL-S will have superior performance in those with normal cognition or very mild degrees of cognitive impairment, and whether the DEL-S-AD will perform best in those with mild to moderate ADRD. This application will catalyze a paradigm shift in how delirium severity is measured in persons with and without ADRD. This work will yield the first validated instrument specifically for delirium severity in ADRD, and ultimately will help to advance our pathophysiologic understanding and testing of effective new treatments.

Project Narrative Delirium, an acute confusional state, is a common, serious, and potentially preventable condition in the older population, yet our ability to assess the severity of an episode of delirium is not well understood. Because the impact of a delirium episode may be even more important in Alzheimer’s disease and related dementias (ADRD), our goal is to develop new ways to measure delirium severity in persons both with and without ADRD. We cannot manage and treat a condition appropriately until we can measure its impact; thus, this application is a fundamental step to help develop and test new treatments for delirium in persons with and without ADRD, and ultimately, to improve healthcare and quality of life for older persons and their families.