Successful aging after elective surgery II: Study cohort description.

BACKGROUND: The Successful Aging after Elective Surgery (SAGES) II Study was designed to examine the relationship between delirium and Alzheimer's disease and related dementias (AD/ADRD), by capturing novel fluid biomarkers, neuroimaging markers, and neurophysiological measurements. The goal of this paper is to provide the first complete description of the enrolled cohort, which details the baseline characteristics and data completion. We also describe the study modifications necessitated by the COVID-19 pandemic, and lay the foundation for future work using this cohort. METHODS: SAGES II is a prospective observational cohort study of community-dwelling adults age 65 and older undergoing major non-cardiac surgery. Participants were assessed preoperatively, throughout hospitalization, and at 1, 2, 6, 12, and 18 months following discharge to assess cognitive and physical functioning. Since participants were enrolled throughout the COVID-19 pandemic, procedural modifications were designed to reduce missing data and allow for high data quality. RESULTS: About 420 participants were enrolled with a mean (standard deviation) age of 73.4 (5.6) years, including 14% minority participants. Eighty-eight percent of participants had either total knee or hip replacements; the most common surgery was total knee replacement with 210 participants (50%). Despite the challenges posed by the COVID-19 pandemic, which required the use of novel procedures such as video assessments, there were minimal missing interviews during hospitalization and up to 1-month follow-up; nearly 90% of enrolled participants completed interviews through 6-month follow-up. CONCLUSION: While there are many longitudinal studies of older adults, this study is unique in measuring health outcomes following surgery, along with risk factors for delirium through the application of novel biomarkers-including fluid (plasma and cerebrospinal fluid), imaging, and electrophysiological markers. This paper is the first to describe the characteristics of this unique cohort and the data collected, enabling future work using this novel and important resource.

Comparison of the frailty index and frailty phenotype and their associations with postoperative delirium incidence and severity.

BACKGROUND: Recent studies have reported an association between presurgical frailty and postoperative delirium. However, it remains unclear whether the frailty-delirium relationship differs by measurement tool (e.g., frailty index vs. frailty phenotype) and whether frailty is associated with delirium, independent of preoperative cognition. METHODS: We used the successful aging after elective surgery (SAGES) study, a prospective cohort of older adults age ≥70 undergoing major non-cardiac surgery (N = 505). Preoperative measurement of the modified mini-mental (3MS) test, frailty index and frailty phenotype were obtained. The confusion assessment method (CAM), supplemented by chart review, identified postoperative delirium. Delirium feature severity was measured by the sum of CAM-severity (CAM-S) scores. Generalized linear models were used to determine the relative risk of each frailty measure with delirium incidence and severity. Subsequent models adjusted for age, sex, surgery type, Charlson comorbidity index, and 3MS. RESULTS: On average, patients were 76.7 years old (standard deviation 5.22), 58.8% of women. For the frailty index, the incidence of delirium was 14% in robust, 17% in prefrail, and 31% in frail patients (p < 0.001). For the frailty phenotype, delirium incidence was 13% in robust, 21% in prefrail, and 27% in frail patients (p = 0.016). Frailty index, but not phenotype, was independently associated with delirium after adjustment for comorbidities (relative risk [RR] 2.13, 95% confidence interval [CI] 1.23-3.70; RR 1.61, 95% CI 0.77-3.37, respectively). Both frailty measures were associated with delirium feature severity. After adjustment for preoperative cognition, only the frailty index was associated with delirium incidence; neither index nor phenotype was associated with delirium feature severity. CONCLUSION: Both the frailty index and phenotype were associated with the development of postoperative delirium. The index showed stronger associations that remained significant after adjusting for baseline comorbidities and preoperative cognition. Measuring frailty prior to surgery can assist in identifying patients at risk for postoperative delirium.

Association of Loneliness With Change in Physical and Emotional Health of Older Adults During the COVID-19 Shutdown.

OBJECTIVES: To examine factors influencing loneliness and the effect of loneliness on physical and emotional health, in the context of the COVID-19 pandemic. DESIGN: Prospective, observational cohort. SETTING: Community-dwelling participants. PARTICIPANTS: Older adults (n = 238) enrolled in a longitudinal study. MEASUREMENTS: Interviews were completed July-December 2020. Loneliness was measured with the UCLA 3-item loneliness scale. Data including age, marriage, education, cognitive functioning, functional impairment, vision or hearing impairment, depression, anxiety, medical comorbidity, social network size, technology use, and activity engagement were collected. Health outcomes included self-rated health, and physical and mental composites from the 12-item Short Form Survey. Physical function was measured by a PROMIS-scaled composite score. RESULTS: Thirty-nine (16.4%) participants reported loneliness. Vulnerability factors for loneliness included age (RR = 1.08, 95% CI 1.02-1.14); impairment with instrumental activities of daily living (RR = 2.08, 95% CI 1.14-3.80); vision impairment (RR = 2.09, 95% CI 1.10-3.97); depression (RR = 1.34, 95% CI 1.25-1.43); and anxiety (RR = 1.92, 95% CI 1.55-2.39). Significant resilience factors included high cognitive functioning (RR = 0.88, 95% CI 0.83-0.94); large social network size (RR = 0.92, 95% CI 0.88-0.96); technology use (RR = 0.81, 95% CI 0.73-0.90); and social and physical activity engagement (RR = 0.91, 95% CI 0.85-0.98). Interaction analyses showed that larger social network size moderated the effect of loneliness on physical function (protective interaction effect, RR = 0.64, 95% CI 0.15-1.13, p <.01), and activity engagement moderated the effect of loneliness on mental health (protective interaction effect, RR = 0.65, 95% CI 0.25-1.05, p <.001). CONCLUSIONS: Resilience factors may mitigate the adverse health outcomes associated with loneliness. Interventions to enhance resilience may help to diminish the detrimental effects of loneliness and hold great importance for vulnerable older adults.

Benefits and Barriers of Technology for Home Function and Mobility Assessment: Perspectives of Older Patients With Blood Cancers, Caregivers, and Clinicians.

PURPOSE: Advances in digital health technology can overcome barriers to measurement of function and mobility for older adults with blood cancers, but little is known about how older adults perceive such technology for use in their homes. METHODS: To characterize potential benefits and barriers associated with using technology for home functional assessment, we conducted three semistructured focus groups (FGs) in January 2022. Eligible patients came from the Older Adult Hematologic Malignancies Program at Dana-Farber Cancer Institute (DFCI), which includes adults 73 years and older enrolled during their initial consult with their oncologist. Eligible caregivers were 18 years and older and identified by enrolled patients as their primary caregiver. Eligible clinicians were practicing DFCI hematologic oncologists, nurse practitioners, or physician assistants with ≥2 years of clinical experience. A qualitative researcher led thematic analysis of FG transcripts to identify key themes. RESULTS: Twenty-three participants attended the three FGs: eight patients, seven caregivers, and eight oncology clinicians. All participants valued function and mobility assessments and felt that technology could overcome barriers to their measurement. We identified three themes related to potential benefits: making it easier for oncology teams to consider function and mobility; providing standardized, objective data; and facilitating longitudinal data. We also identified four themes related to barriers to home functional assessment: concerns related to privacy and confidentiality, burden of measuring additional patient data, challenges in operating new technology, and concerns related to data improving care. CONCLUSION: These data suggest that specific concerns raised by older patients, caregivers, and oncology clinicians must be addressed to improve acceptability and uptake of technology used to measure function and mobility in the home.

Patterns and Persistence of Perioperative Plasma and Cerebrospinal Fluid Neuroinflammatory Protein Biomarkers After Elective Orthopedic Surgery Using SOMAscan.

BACKGROUND: The neuroinflammatory response to surgery can be characterized by peripheral acute plasma protein changes in blood, but corresponding, persisting alterations in cerebrospinal fluid (CSF) proteins remain mostly unknown. Using the SOMAscan assay, we define acute and longer-term proteome changes associated with surgery in plasma and CSF. We hypothesized that biological pathways identified by these proteins would be in the categories of neuroinflammation and neuronal function and define neuroinflammatory proteome changes associated with surgery in older patients. METHODS: SOMAscan analyzed 1305 proteins in blood plasma (n = 14) and CSF (n = 15) samples from older patients enrolled in the Role of Inflammation after Surgery for Elders (RISE) study undergoing elective hip and knee replacement surgery with spinal anesthesia. Systems biology analysis identified biological pathways enriched among the surgery-associated differentially expressed proteins in plasma and CSF. RESULTS: Comparison of postoperative day 1 (POD1) to preoperative (PREOP) plasma protein levels identified 343 proteins with postsurgical changes ( P < .05; absolute value of the fold change [|FC|] > 1.2). Comparing postoperative 1-month (PO1MO) plasma and CSF with PREOP identified 67 proteins in plasma and 79 proteins in CSF with altered levels ( P < .05; |FC| > 1.2). In plasma, 21 proteins, primarily linked to immune response and inflammation, were similarly changed at POD1 and PO1MO. Comparison of plasma to CSF at PO1MO identified 8 shared proteins. Comparison of plasma at POD1 to CSF at PO1MO identified a larger number, 15 proteins in common, most of which are regulated by interleukin-6 (IL-6) or transforming growth factor beta-1 (TGFB1) and linked to the inflammatory response. Of the 79 CSF PO1MO-specific proteins, many are involved in neuronal function and neuroinflammation. CONCLUSIONS: SOMAscan can characterize both short- and long-term surgery-induced protein alterations in plasma and CSF. Acute plasma protein changes at POD1 parallel changes in PO1MO CSF and suggest 15 potential biomarkers for longer-term neuroinflammation that warrant further investigation.

Successful aging after elective surgery II: Study design and methods.

BACKGROUND: The Successful Aging after Elective Surgery (SAGES) II study was designed to increase knowledge of the pathophysiology and linkages between delirium and dementia. We examine novel biomarkers potentially associated with delirium, including inflammation, Alzheimer's disease (AD) pathology and neurodegeneration, neuroimaging markers, and neurophysiologic markers. The goal of this paper is to describe the study design and methods for the SAGES II study. METHODS: The SAGES II study is a 5-year prospective observational study of 400-420 community dwelling persons, aged 65 years and older, assessed prior to scheduled surgery and followed daily throughout hospitalization to observe for development of delirium and other clinical outcomes. Delirium is measured with the Confusion Assessment Method (CAM), long form, after cognitive testing. Cognitive function is measured with a detailed neuropsychologic test battery, summarized as a weighted composite, the General Cognitive Performance (GCP) score. Other key measures include magnetic resonance imaging (MRI), transcranial magnetic stimulation (TMS)/electroencephalography (EEG), and Amyloid positron emission tomography (PET) imaging. We describe the eligibility criteria, enrollment flow, timing of assessments, and variables collected at baseline and during repeated assessments at 1, 2, 6, 12, and 18 months. RESULTS: This study describes the hospital and surgery-related variables, delirium, long-term cognitive decline, clinical outcomes, and novel biomarkers. In inter-rater reliability assessments, the CAM ratings (weighted kappa = 0.91, 95% confidence interval, CI = 0.74-1.0) in 50 paired assessments and GCP ratings (weighted kappa = 0.99, 95% CI 0.94-1.0) in 25 paired assessments. We describe procedures for data quality assurance and Covid-19 adaptations. CONCLUSIONS: This complex study presents an innovative effort to advance our understanding of the inter-relationship between delirium and dementia via novel biomarkers, collected in the context of major surgery in older adults. Strengths include the integration of MRI, TMS/EEG, PET modalities, and high-quality longitudinal data.

One-year Medicare costs associated with delirium in older hospitalized patients with and without Alzheimer's disease dementia and related disorders.

INTRODUCTION: One-year health-care costs associated with delirium in older hospitalized patients with and without Alzheimer's disease and related dementias (ADRD) have not been examined previously. METHODS: Medicare costs were determined prospectively at discharge, and at 30, 90, and 365 days in a cohort (n = 311) of older adults after hospital admission. RESULTS: Seventy-six (24%) patients had ADRD and were more likely to develop delirium (51% vs. 24%, P < 0.001) and die within 1 year (38% vs. 21%, P = 0.002). In ADRD patients with versus without delirium, adjusted mean difference in costs associated with delirium were $34,828; most of the excess costs were incurred between 90 and 365 days (P = 0.03). In non-ADRD patients, delirium was associated with increased costs at all timepoints. Excess costs associated with delirium in ADRD patients increased progressively over 1 year, whereas in non-ADRD patients the increase was consistent across time periods. DISCUSSION: Our findings highlight the complexity of health-care costs for ADRD patients who develop delirium, a potentially preventable source of expenditures. HIGHLIGHTS: Novel examination of health-care costs of delirium in persons with and without Alzheimer's disease and related dementias (ADRD). Increased 1-year costs of $34,828 in ADRD patients with delirium (vs. without). Increased costs for delirium in ADRD occur later during the 365-day study period. For ADRD patients, cost differences between those with and without delirium increased over 1 year. For non-ADRD patients, the parallel cost differences were consistent over time.

Association of Polypharmacy and Potentially Inappropriate Medications With Frailty Among Older Adults With Blood Cancers.

BACKGROUND: Polypharmacy and potentially inappropriate medications (PIMs) are common among older adults with blood cancers, but their association with frailty and how to manage them optimally remain unclear. PATIENTS AND METHODS: From 2015 to 2019, patients aged ≥75 years presenting for initial oncology consult underwent screening geriatric assessment. Patients were determined to be robust, prefrail, or frail via deficit accumulation and phenotypic approaches. We quantified each patient's total number of medications and PIMs using the Anticholinergic Risk Scale (ARS) and a scale we generated using the NCCN Medications of Concern called the Geriatric Oncology Potentially Inappropriate Medications (GO-PIM) scale. We assessed cross-sectional associations of PIMs with frailty in multivariable regression models adjusting for age, gender, and comorbidity. RESULTS: Of 785 patients assessed, 603 (77%) were taking ≥5 medications and 421 (54%) were taking ≥8 medications; 201 (25%) were taking at least 1 PIM based on the ARS and 343 (44%) at least 1 PIM based on the GO-PIM scale. Among the 468 (60%) patients on active cancer treatment, taking ≥8 medications was associated with frailty (adjusted odds ratio [aOR], 2.82; 95% CI, 1.92-4.17). With each additional medication, the odds of being prefrail or frail increased 8% (aOR, 1.08; 95% CI, 1.04-1.12). With each 1-point increase on the ARS, the odds of being prefrail or frail increased 19% (aOR, 1.19; 95% CI, 1.03-1.39); with each additional PIM based on the GO-PIM scale, the odds increased 65% (aOR, 1.65; 95% CI, 1.34-2.04). CONCLUSIONS: Polypharmacy and PIMs are prevalent among older patients with blood cancers; taking ≥8 medications is strongly associated with frailty. These data suggest careful medication reconciliation for this population may be helpful, and deprescribing when possible is high-yield, especially for PIMs on the GO-PIM scale.

Identifying Delirium in Persons With Moderate or Severe Dementia: Review of Challenges and an Illustrative Approach.

Delirium and dementia are common causes of cognitive impairment among older adults, which often coexist. Delirium is associated with poor clinical outcomes, and is more frequent and more severe in patients with dementia. Identifying delirium in the presence of dementia, also described as delirium superimposed on dementia (DSD), is particularly challenging, as symptoms of delirium such as inattention, cognitive dysfunction, and altered level of consciousness, are also features of dementia. Because DSD is associated with poorer clinical outcomes than dementia alone, detecting delirium is important for reducing morbidity and mortality in this population. We review a number of delirium screening instruments that have shown promise for use in DSD, including the 4-DSD, combined Six Item Cognitive Impairment Test (6-CIT) and 4 'A's Test (4AT), Confusion Assessment Method (CAM), and the combined UB2 and 3D-CAM (UB-CAM). Each has advantages and disadvantages. We then describe the operationalization of a CAM-based approach in a current ECT in dementia project as an example of modifying an existing instrument for patients with moderate to severe dementia. Ultimately, any instrument modified will need to be validated against a standard clinical reference, in order to fully establish its sensitivity and specificity in the moderate to severe dementia population. Future work is greatly needed to advance the challenging area of accurate identification of delirium in moderate or severe dementia.

Psychometric Properties of a Delirium Severity Score for Older Adults and Association With Hospital and Posthospital Outcomes.

Importance: The ability to rate delirium severity is key to providing optimal care for older adults, and such ratings would allow clinicians to target patients with severe delirium and monitor response to treatment, recovery time, and prognosis; assess nursing burden and staffing needs; and, ultimately, provide more appropriate patient-centered care. Current delirium severity measures have been limited in their content, gradations, and measurement characteristics. Objective: To examine the internal consistency, reliability, and validity for clinical outcomes of the DEL-S delirium severity score, a measure of delirium severity that was developed using advanced psychometric approaches, analogous to those of the Patient-Reported Outcomes Measurement Information System initiative. Design, Setting, and Participants: This prospective cohort study was conducted at a large academic medical center in Boston, Massachusetts. Adults aged 70 years or older who were admitted or transferred to medical or surgical services as either emergency or elective admissions were enrolled between October 20, 2015, and March 15, 2017, and were monitored for 1 year. Data analysis was performed from June 2020 to August 2021. Exposures: Delirium severity, measured by scores on the delirium severity score short-form (SF; 6 items, scored 0-13, with higher scores indicating more severe delirium) and long-form (LF; 17 items, scored 0-21), considered continuously and grouped into 5 categories. Main Outcomes and Measures: The primary outcomes were in-hospital outcomes, including length of stay and hospital costs, and posthospital (30, 90, and 365 days) outcomes, including death, health care costs, and rehospitalization. Results: The 352 participants had a median (IQR) age of 79.7 (74.6-85.5) years, 204 (58.0%) were women, and they were highly educated (median [IQR] duration of education, 14 [7-20] years). Patients in the highest delirium severity score SF group (scores 6-9) had a longer length of stay (13.3 vs 6.9 days; P for trend < .001), greater in-hospital costs ($57 700 vs $34 200), greater cumulative health care costs ($168 700 vs $106 500; P for trend = .01), and increased mortality at 1 year (50% vs 17%; P for trend = .02) compared with patients in the lowest delirium severity score SF group (score 0). Similar trends and significant findings were demonstrated for the delirium severity score LF. Conclusions and Relevance: These findings suggest that the delirium severity score provides an approach for measuring delirium severity that is associated with adverse clinical outcomes in a direct exposure-response association and that the delirium severity score may help advance patient-centered care for delirium.

Randomized controlled trial of geriatric consultation versus standard care in older adults with hematologic malignancies.

We conducted a randomized controlled trial in older adults with hematologic malignancies to determine the impact of geriatrician consultation embedded in our oncology clinic alongside standard care. From February 2015 to May 2018, transplant-ineligible patients aged ≥75 years who presented for initial consultation for lymphoma, leukemia, or multiple myeloma at Dana-Farber Cancer Institute (Boston, MA, USA) were eligible. Pre-frail and frail patients, classified based on phenotypic and deficit-accumulation approaches, were randomized to receive either standard oncologic care with or without consultation with a geriatrician. The primary outcome was 1-year overall survival. Secondary outcomes included unplanned care utilization within 6 months of follow-up and documented end-of-life (EOL) goals-of-care discussions. Clinicians were surveyed as to their impressions of geriatric consultation. One hundred sixty patients were randomized to either geriatric consultation plus standard care (n=60) or standard care alone (n=100). The median age of the patients was 80.4 years (standard deviation = 4.2). Of those randomized to geriatric consultation, 48 (80%) completed at least one visit with a geriatrician. Consultation did not improve survival at 1 year compared to standard care (difference: 2.9%, 95% confidence interval: -9.5% to 15.2%, P=0.65), and did not significantly reduce the incidence of emergency department visits, hospital admissions, or days in hospital. Consultation did improve the odds of having EOL goals-of-care discussions (odds ratio = 3.12, 95% confidence interval: 1.03 to 9.41) and was valued by surveyed hematologic-oncology clinicians, with 62.9%-88.2% of them rating consultation as useful in the management of several geriatric domains.

From research to bedside: Incorporation of a CGA-based frailty index among multiple comanagement services.

The comprehensive geriatric assessment (CGA) is the core tool used by geriatricians across diverse clinical settings to identify vulnerabilities and estimate physiologic reserve in older adults. In this paper, we demonstrate the iterative process at our institution to identify and develop a feasible, acceptable, and sustainable bedside CGA-based frailty index tool (FI-CGA) that not only quantifies and grades frailty but also provides a uniform way to efficiently communicate complex geriatric concepts such as reserve and vulnerability with other teams. We describe our incorporation of the FI-CGA into the electronic health record (EHR) and dissemination among clinical services. We demonstrate that an increasing number of patients have documented FI-CGA in their initial assessment from 2018 to 2020, while additional comanagement services were established (Figure 2). The acceptability and sustainability of the FI-CGA, and its routine use by geriatricians in our division, were demonstrated by a survey where the majority of clinicians report using the FI-CGA when assessing a new patient and that the FI-CGA informs their clinical management. Finally, we demonstrate how we refined and updated the FI-CGA, we provide examples of applications of the FI-CGA across the institution and describe areas of ongoing process improvement and challenges for the use of this tailored yet standardized tool across diverse inpatient and outpatient services. The process outlined can be used by other geriatric departments to introduce and incorporate an FI-CGA.

Domains of delirium severity in Alzheimer's disease and related dementias.

BACKGROUND: The ability to rate delirium severity is key to providing optimal care for persons with Alzheimer's Disease and Related Dementias (ADRD). Such ratings would allow clinicians to assess response to treatment, recovery time and prognosis, nursing burden and staffing needs, and to provide nuanced, appropriate patient-centered care. Given the lack of existing tools, we defined content domains for a new delirium severity instrument for use in individuals with mild to moderate ADRD, the DEL-S-AD. METHODS: We built upon our previous study in which we created a content domain framework to inform development of a general delirium severity instrument, the DEL-S. We engaged a new expert panel to discuss issues of measurement in delirium and dementia and to determine which content domains from the prior framework were useful in characterizing delirium severity in ADRD. We also asked panelists to identify new domains. Our panel included eight interdisciplinary members with expertise in delirium and dementia. Panelists participated in two rounds of review followed by two surveys over 2 months. RESULTS: Panelists endorsed the same content domains as for general delirium severity, including Cognitive, Level of Consciousness, Inattention, Psychiatric-Behavioral, Emotional Dysregulation, Psychomotor Features, and Functional; however, they excluded six of the original subdomains which they considered unhelpful in the context of ADRD: cognitive impairment; anxiety; fear/sense of unease; depression; gait/walking; and incontinence. Debated measurement challenges included assessment at one point in time versus over time, accounting for differences in clinical settings, and accurate assessment of symptoms related to delirium versus dementia. CONCLUSIONS: By capturing a range of characteristics of delirium severity potentially present in patients with ADRD, a population that may already have attention, functional, and emotional changes at baseline, the DEL-S-AD provides a novel rating tool that will be useful for clinical and research purposes to improve patient care.

Development and internal validation of a predictive model of cognitive decline 36 months following elective surgery.

INTRODUCTION: Our goal was to determine if features of surgical patients, easily obtained from the medical chart or brief interview, could be used to predict those likely to experience more rapid cognitive decline following surgery. METHODS: We analyzed data from an observational study of 560 older adults (≥70 years) without dementia undergoing major elective non-cardiac surgery. Cognitive decline was measured using change in a global composite over 2 to 36 months following surgery. Predictive features were identified as variables readily obtained from chart review or a brief patient assessment. We developed predictive models for cognitive decline (slope) and predicting dichotomized cognitive decline at a clinically determined cut. RESULTS: In a hold-out testing set, the regularized regression predictive model achieved a root mean squared error (RMSE) of 0.146 and a model r-square (R2 ) of .31. Prediction of "rapid" decliners as a group achieved an area under the curve (AUC) of .75. CONCLUSION: Some of our models could predict persons with increased risk for accelerated cognitive decline with greater accuracy than relying upon chance, and this result might be useful for stratification of surgical patients for inclusion in future clinical trials.

ED-DEL: Development of a change package and toolkit for delirium in the emergency department.

Delirium is a common and deadly problem in the emergency department affecting up to 30% of older adult patients. The 2013 Geriatric Emergency Department guidelines were developed to address the unique needs of the growing older population and identified delirium as a high priority area. The emergency department (ED) environment presents unique challenges for the identification and management of delirium, including patient crowding, time pressures, competing priorities, variable patient acuity, and limitations in available patient information. Accordingly, protocols developed for inpatient units may not be appropriate for use in the ED setting. We created a Delirium Change Package and Toolkit in the Emergency Department (ED-DEL) to provide protocols and guidance for implementing a delirium program in the ED setting. This article describes the multistep process by which the ED-DEL program was created and the key components of the program. Our ultimate goal is to create a resource that can be disseminated widely and used to improve delirium identification, prevention, and management in older adults in the ED.

Association of CSF Alzheimer's disease biomarkers with postoperative delirium in older adults.

INTRODUCTION: The interaction between delirium and dementia is complex. We examined if Alzheimer's disease (AD) biomarkers in patients without clinical dementia are associated with increased risk of postoperative delirium, and whether AD biomarkers demonstrate a graded association with delirium severity. METHODS: Participants (n = 59) were free of clinical dementia, age ≥ 70 years, and scheduled for elective total knee or hip arthroplasties. Cerebrospinal fluid (CSF) was collected at the time of induction for spinal anesthesia. CSF AD biomarkers were measured by enzyme-linked immunosorbent assay (ELISA) (ADX/Euroimmun); cut points for amyloid, tau, and neurodegeneration (ATN) biomarker status were A = amyloid beta (Aß)42 <175 pg/mL or Aß42/40 ratio <0.07; T = p-tau >80 pg/mL; and N = t-tau >700 pg/mL. Confusion Assessment Method (CAM) and CAM-Severity (CAM-S) were rated daily post-operatively for delirium and delirium severity, respectively. RESULTS: Aß42, tau, and p-tau mean pg/mL (SD) were 361.5 (326.1), 618.3 (237.1), and 97.1 (66.1), respectively, for those with delirium, and 550.4 (291.6), 518.3 (213.5), and 54.6 (34.5), respectively, for those without delirium. Thirteen participants (22%) were ATN positive. Delirium severity by peak CAM-S [mean difference (95% confidence interval)] was 1.48 points higher (0.29-2.67), P = 0.02 among the ATN positive. Delirium in the ATN-positive group trended toward but did not reach statistical significance (23% vs. 7%, p = 0.10). Peak CAM-S [mean (SD)] in the delirium group was 7 (2.8) compared to no delirium group 2.5 (1.3), but when groups were further classified by ATN status, an incremental effect on delirium severity was observed, such that patients who were both ATN and delirium negative had the lowest mean (SD) peak CAM-S scores of 2.5 (1.3) points, whereas those who were ATN and delirium positive had CAM-S scores of 8.7 (2.3) points; other groups (either ATN or delirium positive) had intermediate CAM-S scores. DISCUSSION: The presence of AD biomarkers adds important information in predicting delirium severity. Future studies are needed to confirm this relationship and to better understand the role of AD biomarkers, even in pre-clinical phase, in delirium.