Cyrus M. Kosar

The CAM-S: development and validation of a new scoring system for delirium severity in 2 cohorts

BACKGROUND Quantifying the severity of delirium is essential to advancing clinical care by improved understanding of delirium effect, prognosis, pathophysiology, and response to treatment. OBJECTIVE To develop and validate a new delirium severity measure (CAM-S) based on the Confusion Assessment Method. DESIGN Validation analysis in 2 independent cohorts. SETTING Three academic medical centers. PATIENTS The first cohort included 300 patients aged 70 years or older scheduled for major surgery. The second included 919 medical patients aged 70 years or older. MEASUREMENTS A 4-item short form and a 10-item long form were developed. Association of the maximum CAM-S score during hospitalization with hospital and posthospital outcomes related to delirium was evaluated. RESULTS Representative results included adjusted mean length of stay, which increased across levels of short-form severity from 6.5 days (95% CI, 6.2 to 6.9 days) to 12.7 days (CI, 11.2 to 14.3 days) (P for trend < 0.001) and across levels of long-form severity from 5.6 days (CI, 5.1 to 6.1 days) to 11.9 days (CI, 10.8 to 12.9 days) (P for trend < 0.001). Representative results for the composite outcome of adjusted relative risk of death or nursing home residence at 90 days increased progressively across levels of short-form severity from 1.0 (referent) to 2.5 (CI, 1.9 to 3.3) (P for trend < 0.001) and across levels of long-form severity from 1.0 (referent) to 2.5 (CI, 1.6 to 3.7) (P for trend < 0.001). LIMITATION Data on clinical outcomes were measured in an older data set limited to patients aged 70 years or older. CONCLUSION The CAM-S provides a new delirium severity measure with strong psychometric properties and strong associations with important clinical outcomes. PRIMARY FUNDING SOURCE National Institute on Aging.

Effect of Delirium and Other Major Complications on Outcomes After Elective Surgery in Older Adults.

IMPORTANCE Major postoperative complications and delirium contribute independently to adverse outcomes and high resource use in patients who undergo major surgery; however, their interrelationship is not well examined. OBJECTIVE To evaluate the association of major postoperative complications and delirium, alone and combined, with adverse outcomes after surgery. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study in 2 large academic medical centers of 566 patients who were 70 years or older without recognized dementia or a history of delirium and underwent elective major orthopedic, vascular, or abdominal surgical procedures with a minimum 3-day hospitalization between June 18, 2010, and August 8, 2013. Data analysis took place from December 13, 2013, through May 1, 2015. MAIN OUTCOMES AND MEASURES Major postoperative complications, defined as life-altering or life-threatening events (Accordion Severity grade 2 or higher), were identified by expert-panel adjudication. Delirium was measured daily with the Confusion Assessment Method and a validated medical record review method. The following 4 subgroups were analyzed: (1) no complications or delirium; (2) complications only; (3) delirium only; and (4) complications and delirium. Adverse outcomes included a length of stay (LOS) of more than 5 days, institutional discharge, and rehospitalization within 30 days of discharge. RESULTS In the 566 participants, the mean (SD) age was 76.7 (5.2) years, 236 (41.7%) were male, and 523 (92.4%) were white. Forty-seven patients (8.3%) developed major complications and 135 (23.9%) developed delirium. Compared with no complications or delirium as the reference group, major complications only contributed to prolonged LOS only (relative risk [RR], 2.8; 95% CI, 1.9-4.0); by contrast, delirium only significantly increased all adverse outcomes, including prolonged LOS (RR, 1.9; 95% CI, 1.4-2.7), institutional discharge (RR, 1.5; 95% CI, 1.3-1.7), and 30-day readmission (RR, 2.3; 95% CI, 1.4-3.7). The subgroup with complications and delirium had the highest rates of all adverse outcomes, including prolonged LOS (RR, 3.4; 95% CI, 2.3-4.8), institutional discharge (RR, 1.8; 95% CI, 1.4-2.5), and 30-day readmission (RR, 3.0; 95% CI, 1.3-6.8). Delirium exerted the highest attributable risk at the population level (5.8%; 95% CI, 4.7-6.8) compared with all other adverse events (prolonged LOS, institutional discharge, or readmission). CONCLUSIONS AND RELEVANCE Major postoperative complications and delirium are separately associated with adverse events and demonstrate a combined effect. Delirium occurs more frequently and has a greater effect at the population level than other major complications.

The short-term and long-term relationship between delirium and cognitive trajectory in older surgical patients.

As the relationship between delirium and long‐term cognitive decline has not been well‐explored, we evaluated this association in a prospective study.

A Tale of Two Methods: Chart and Interview Methods for Identifying Delirium

To compare chart‐ and interview‐based methods for identification of delirium.

Effect of preoperative pain and depressive symptoms on the risk of postoperative delirium: a prospective cohort study

BACKGROUND Preoperative pain and depression predispose patients to delirium. Our goal was to determine whether pain and depressive symptoms interact to increase delirium risk. METHODS We enrolled 459 persons without dementia aged ≥70 years scheduled for elective orthopedic surgery. At baseline, participants reported their worst and average pain within seven days and current pain on a 0-10 scale. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale and chart. Delirium was assessed with the Confusion Assessment Method and chart. We examined the relationship between preoperative pain, depressive symptoms and delirium using multivariable analysis of pain and delirium stratified by presence of depressive symptoms. FINDINGS Delirium, occurring in 23% of the sample, was significantly higher in those with depressive symptoms at baseline than those without (relative risk, RR, 1·6, 95% confidence interval, CI, 1·2-2·3). Preoperative pain was associated with an increased adjusted risk for delirium across all pain measures (RR from 1·07-1·08 per point of pain). In stratified analyses, patients with depressive symptoms had a 21% increased risk for delirium for each one-point increase in worst pain score, demonstrating a significant interaction (P=0·049). Similarly, a significant 13% increased risk for delirium was demonstrated for a one-point increase in average pain score, but the interaction did not achieve statistical significance. INTERPRETATION Preoperative pain and depressive symptoms demonstrated increased risk for delirium independently and with substantial interaction, suggesting a cumulative impact. Thus, pain and depression are vulnerability factors for delirium that should be assessed before surgery. FUNDING U.S. National Institute on Aging.

Brain atrophy and white-matter hyperintensities are not significantly associated with incidence and severity of postoperative delirium in older persons without dementia

Postoperative delirium is a common complication in older people and is associated with increased mortality, morbidity, institutionalization, and caregiver burden. Although delirium is an acute confusional state characterized by global impairments in attention and cognition, it has been implicated in permanent cognitive impairment and dementia. The pathogenesis of delirium and the mechanisms leading to these disabling consequences remain unclear. The present study is the first to address the potential predisposing role of brain morphologic changes toward postoperative delirium in a large prospective cohort of patients undergoing elective surgery using state-of-the-art magnetic resonance imaging (MRI) techniques conducted before admission. We investigated the association of MRI-derived quantitative measures of white-matter damage, global brain, and hippocampal volume with the incidence and severity of delirium. Presurgical white-matter hyperintensities (WMHs), whole brain, and hippocampal volume were measured in 146 consecutively enrolled subjects, ≥70 years old, without dementia who were undergoing elective surgery. These 3 presurgical MRI indices were tested as predictors of incidence and severity of subsequent delirium. Out of 146 subjects, 32 (22%) developed delirium. We found no statistically significant differences in WMH, whole brain, or hippocampal volume between subjects with and without delirium. Both unadjusted and adjusted (age, gender, vascular comorbidity, and general cognitive performance) regression analyses demonstrated no statistically significant association between any of the MRI measures with respect to delirium incidence or severity. In persons without dementia, preexisting cerebral WMHs, general and hippocampal atrophy may not predispose to postoperative delirium or worsen its severity.

The Successful Aging After Elective Surgery Study: Cohort Description and Data Quality Procedures

To describe baseline characteristics and quality assurance procedures of the Successful Aging after Elective Surgery (SAGES) study, which was designed to examine novel risk factors and long‐term outcomes associated with delirium.

Cognitive and brain reserve and the risk of postoperative delirium in older patients: analysis of data from a prospective observational study

BACKGROUND Cognitive and brain reserve theories suggest that aspects of neural architecture or cognitive processes modify the effect of neuropathological processes on cognitive outcomes. Although frequently studied in the context of dementia, reserve in delirium is understudied. METHODS Using data from a prospective observational study, we examined the association of three markers of brain reserve (head circumference, MRI-derived brain volume, and leisure time physical activity), five markers of cognitive reserve (education, vocabulary, cognitive activities, cognitive demand of lifetime occupation, and interpersonal demand of lifetime occupation), and the risk of postoperative delirium in 566 older adults (age ≥70 years) free of dementia undergoing scheduled surgery. FINDINGS 135 (24%) of 566 patients developed delirium during the postoperative hospital stay. Of the reserve markers examined, only the Wechsler Test of Adult Reading was associated with the risk of delirium. A 0·5 SD better performance on the Wechsler Test of Adult Reading was associated with a 38% reduction in delirium risk (adjusted risk ratio of 0·62, 95% CI 0·45-0·85; p=0·01). INTERPRETATION Most markers of reserve failed to predict delirium risk. The exception to this is the Wechsler Test of Adult Reading. Our findings suggest that the reserve markers that are important for delirium might be different from those thought to be important for dementia. FUNDING National Institute on Aging, National Heart Lung and Blood Institute.

Does Apolipoprotein E Genotype Increase Risk of Postoperative Delirium

OBJECTIVE To determine whether apolipoprotein E (ApoE) is associated with postoperative delirium incidence, severity, and duration in older patients free of dementia at baseline. METHODS The authors examined 557 nondemented patients aged 70 years or older undergoing major noncardiac surgery enrolled in the Successful Aging after Elective Surgery Study. Three ApoE measures were considered: ε2, ε4 carriers versus noncarriers, and a three-category ApoE measure. Delirium was determined using the Confusion Assessment Method (CAM) and chart review. We used generalized linear models to estimate the association between ApoE and delirium incidence, severity (peak CAM Severity [CAM-S] score), and days. RESULTS ApoE ε2 and ε4 was present in 15% and 19%, respectively, and postoperative delirium occurred in 24%. Among patients with delirium, the mean peak CAM-S score was 8.0 (standard deviation: 4), with most patients experiencing 1 or 2 delirium days (51% or 28%, respectively). After adjusting for age, sex, surgical procedure, and preoperative cognitive function, ApoE ε4 and ε2 carrier status were not associated with postoperative delirium: RR for ε4=1.0, 95% CI: 0.7-1.5 and RR for ε2=0.9, 95% CI: 0.6-1.4. No association between ApoE and delirium severity or number of delirium days was observed. CONCLUSION In older surgery patients free of dementia, our findings do not support the hypothesis that the ApoE genotype does not confer either risk or protection in postoperative delirium incidence, severity, or duration. Thus, an important genetic risk factor for Alzheimer disease does not affect risk of delirium.

Individualized Music Program is Associated with Improved Outcomes for U.S. Nursing Home Residents with Dementia

OBJECTIVES The objective of this study was to compare resident outcomes before and after implementation of an individualized music program, MUSIC & MEMORY (M&M), designed to address the behavioral and psychological symptoms associated with dementia (BPSD). SETTING 98 nursing homes trained in the M&M program during 2013 and 98 matched-pair comparisons. PARTICIPANTS Long-stay residents with Alzheimers disease and related dementias (ADRD) residing in M&M participating facilities (N = 12,905) and comparison facilities (N = 12,811) during 2012-2013. INTERVENTION M&M is a facility-level quality improvement program that provides residents with music specific to their personal histories and preferences. MEASUREMENTS Discontinuation of anxiolytic and antipsychotic medications, and reductions in behavioral problems and depressed mood in 2012 (pre-intervention) and 2013 (intervention), calculated using Minimum Data Set (MDS) assessments. RESULTS The proportion of residents who discontinued antipsychotic medication use over a 6-month period increased from 17.6% to 20.1% among M&M facilities, while remaining stable among comparison facilities (15.9% to 15.2%). The same trend was observed for anxiolytic medications: Discontinuation of anxiolytics increased in M&M facilities (23.5% to 24.4%), while decreasing among comparison facilities (24.8% to 20.0%). M&M facilities also demonstrated increased rates of reduction in behavioral problems (50.9% to 56.5%) versus comparison facilities (55.8% to 55.9%). No differences were observed for depressed mood. CONCLUSIONS These results offer the first evidence that the M&M individualized music program is associated with reductions in antipsychotic medication use, anxiolytic medication use, and BPSD symptoms among long-stay nursing home residents with ADRD.