Douglas Tommet

Adverse Outcomes After Hospitalization and Delirium in Persons With Alzheimer Disease

BACKGROUND Hospitalization, frequently complicated by delirium, can be a life-changing event for patients with Alzheimer disease (AD). OBJECTIVE To determine risks for institutionalization, cognitive decline, or death associated with hospitalization and delirium in patients with AD. DESIGN Prospective cohort enrolled between 1991 and 2006 into the Massachusetts Alzheimers Disease Research Center (MADRC) patient registry. SETTING Community-based. PARTICIPANTS 771 persons aged 65 years or older with a clinical diagnosis of AD. MEASUREMENTS Hospitalization, delirium, death, and institutionalization were identified through administrative databases. Cognitive decline was defined as a decrease of 4 or more points on the Blessed Information-Memory-Concentration test score. Multivariate analysis was used to calculate adjusted relative risks (RRs). RESULTS Of 771 participants with AD, 367 (48%) were hospitalized and 194 (25%) developed delirium. Hospitalized patients who did not have delirium had an increased risk for death (adjusted RR, 4.7 [95% CI, 1.9 to 11.6]) and institutionalization (adjusted RR, 6.9 [CI, 4.0 to 11.7]). With delirium, risk for death (adjusted RR, 5.4 [CI, 2.3 to 12.5]) and institutionalization (adjusted RR, 9.3 [CI, 5.5 to 15.7]) increased further. With hospitalization and delirium, the adjusted RR for cognitive decline for patients with AD was 1.6 (CI, 1.2 to 2.3). Among hospitalized patients with AD, 21% of the incidences of cognitive decline, 15% of institutionalization, and 6% of deaths were associated with delirium. LIMITATIONS Cognitive outcome was missing in 291 patients. Sensitivity analysis was performed to test the effect of missing data, and a composite outcome was used to decrease the effect of missing data. CONCLUSION Approximately 1 in 8 hospitalized patients with AD who develop delirium will have at least 1 adverse outcome, including death, institutionalization, or cognitive decline, associated with delirium. Delirium prevention may represent an important strategy for reducing adverse outcomes in this population.

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.

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.

Cognitive decline in the elderly: an analysis of population heterogeneity

BACKGROUND studies of cognitive ageing at the group level suggest that age is associated with cognitive decline; however, there may be individual differences such that not all older adults will experience cognitive decline. OBJECTIVE to evaluate patterns of cognitive decline in a cohort of older adults initially free of dementia. DESIGN, SETTING AND SUBJECTS elderly Catholic clergy members participating in the Religious Orders Study were followed for up to 15 years. Cognitive performance was assessed annually. METHODS performance on a composite global measure of cognition was analysed using random effects models for baseline performance and change over time. A profile mixture component was used to identify subgroups with different cognitive trajectories over the study period. RESULTS from a sample of 1,049 participants (mean age 75 years), three subgroups were identified based on the distribution of baseline performance and change over time. The majority (65%) of participants belonged to a slow decline class that did not experience substantial cognitive decline over the observation period [-0.04 baseline total sample standard deviation (SD) units/year]. About 27% experienced moderate decline (-0.19 SD/year), and 8% belonged to a class experiencing rapid decline (-0.57 SD/year). A subsample analysis revealed that when substantial cognitive decline does occur, the magnitude and rate of decline is correlated with neuropathological processes. CONCLUSIONS in this sample, the most common pattern of cognitive decline is extremely slow, perceptible on a time scale measured by decades, not years. While in need of cross validation, these findings suggest that cognitive changes associated with ageing may be minimal and emphasise the importance of understanding the full range of age-related pathologies that may diminish brain function.

Development of a unidimensional composite measure of neuropsychological functioning in older cardiac surgery patients with good measurement precision

The objective of this analysis was to develop a measure of neuropsychological performance for cardiac surgery and to assess its psychometric properties. Older patients (n = 210) underwent a neuropsychological battery using nine assessments. The number of factors was identified with variable reduction methods. Factor analysis methods based on item response theory were used to evaluate the measure. Modified parallel analysis supported a single factor, and the battery formed an internally consistent set (coefficient alpha = .82). The developed measure provided a reliable, continuous measure (reliability > .90) across a broad range of performance (–1.5 SDs to +1.0 SDs) with minimal ceiling and floor effects.

Calibration and validation of an innovative approach for estimating general cognitive performance

Objective: To evaluate a new approach for creating a composite measure of cognitive function, we calibrated a measure of general cognitive performance from existing neuropsychological batteries. Methods: We applied our approach in an epidemiological study and scaled the composite to a nationally representative sample of older adults. Criterion validity was evaluated against standard clinical diagnoses. Convergent validity was evaluated against the Mini-Mental State Examination (MMSE). Results: The general cognitive performance factor was scaled to have a mean of 50 and standard deviation of 10 in a nationally representative sample of older adults. A cutoff point of approximately 45, corresponding to an MMSE of 23/24, optimally discriminated participants with and without dementia (sensitivity = 0.94, specificity = 0.90, area under the curve = 0.97). The general cognitive performance factor was internally consistent (Cronbachs α = 0.91) and provided reliable measures of functional ability across a wide range of cognitive functioning. It demonstrated minimal floor and ceiling effects, which is an improvement over most individual cognitive tests. Conclusions: The cognitive composite is a highly reliable measure, with minimal floor and ceiling effects. We calibrated it using a nationally representative sample of adults over the age of 70 in the USA and established diagnostically relevant cutoff points. Our methods can be used to harmonize neuropsychological test results across diverse settings and studies.

Development and Validation of a Brief Cognitive Assessment Tool: The Sweet 16

BACKGROUND Cognitive impairment is often unrecognized among older adults. Meanwhile, current assessment instruments are underused, lack sensitivity, or may be restricted by copyright laws. To address these limitations, we created a new brief cognitive assessment tool: the Sweet 16. METHODS The Sweet 16 was developed in a cohort from a large post-acute hospitalization study (n=774) and compared with the Mini-Mental State Examination (MMSE). Equipercentile equating identified Sweet 16 cut points that correlated with widely used MMSE cut points. Sweet 16 performance characteristics were independently validated in a cohort from the Aging, Demographics, and Memory Study (n=709) using clinical consensus diagnosis, the modified Blessed Dementia Rating Scale, and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS The Sweet 16 correlated highly with the MMSE (Spearman r, 0.94; P<.001). Validated against the IQCODE, the area under the curve was 0.84 for the Sweet 16 and 0.81 for the MMSE (P=.06). A Sweet 16 score of less than 14 (approximating an MMSE score <24) demonstrated a sensitivity of 80% and a specificity of 70%, whereas an MMSE score of less than 24 showed a sensitivity of 64% and a specificity of 86% against the IQCODE. When compared with clinical diagnosis, a Sweet 16 score of less than 14 showed a sensitivity of 99% and a specificity of 72% in contrast to an MMSE score with a sensitivity of 87% and a specificity of 89%. For education of 12 years or more, the area under the curve was 0.90 for the Sweet 16 and 0.84 for the MMSE (P=.03). CONCLUSIONS The Sweet 16 is simple, quick to administer, and will be available open access. The performance of the Sweet 16 is equivalent or superior to that of the MMSE.

Selecting optimal screening items for delirium: An application of item response theory

BackgroundDelirium (acute confusion), is a common, morbid, and costly complication of acute illness in older adults. Yet, researchers and clinicians lack short, efficient, and sensitive case identification tools for delirium. Though the Confusion Assessment Method (CAM) is the most widely used algorithm for delirium, the existing assessments that operationalize the CAM algorithm may be too long or complicated for routine clinical use. Item response theory (IRT) models help facilitate the development of short screening tools for use in clinical applications or research studies. This study utilizes IRT to identify a reduced set of optimally performing screening indicators for the four CAM features of delirium.MethodsOlder adults were screened for enrollment in a large scale delirium study conducted in Boston-area post-acute facilities (n = 4,598). Trained interviewers conducted a structured delirium assessment that culminated in rating the presence or absence of four features of delirium based on the CAM. A pool of 135 indicators from established cognitive testing and delirium assessment tools were assigned by an expert panel into two indicator sets per CAM feature representing (a) direct interview questions, including cognitive testing, and (b) interviewer observations. We used IRT models to identify the best items to screen for each feature of delirium.ResultsWe identified 10 dimensions and chose up to five indicators per dimension. Preference was given to items with peak psychometric information in the latent trait region relevant for screening for delirium. The final set of 48 indicators, derived from 39 items, maintains fidelity to clinical constructs of delirium and maximizes psychometric information relevant for screening.ConclusionsWe identified optimal indicators from a large item pool to screen for delirium. The selected indicators maintain fidelity to clinical constructs of delirium while maximizing psychometric information important for screening. This reduced item set facilitates development of short screening tools suitable for use in clinical applications or research studies. This study represents the first step in the establishment of an item bank for delirium screening with potential questions for clinical researchers to select from and tailor according to their research objectives.

Preoperative Cognitive Performance Dominates Risk for Delirium Among Older Adults.

Background: Cognitive impairment is a well-recognized risk factor for delirium. Our goal was to determine whether the level of cognitive performance across the nondemented cognitive ability spectrum is correlated with delirium risk and to gauge the importance of cognition relative to other known risk factors for delirium. Methods: The Successful Aging after Elective Surgery study enrolled 566 adults aged ≥70 years scheduled for major surgery. Patients were assessed preoperatively and daily during hospitalization for the occurrence of delirium using the Confusion Assessment Method. Cognitive function was assessed preoperatively with an 11-test neuropsychological battery combined into a composite score for general cognitive performance (GCP). We examined the risk for delirium attributable to GCP, as well as demographic factors, vocabulary ability, and informant-rated cognitive decline, and compared the strength of association with risk factors identified in a previously published delirium prediction rule for delirium. Results: Delirium occurred in 135 (24%) patients. Lower GCP score was strongly and linearly predictive of delirium risk (relative risk = 2.0 per each half standard deviation difference in GCP score, 95% confidence interval, 1.5-2.5). This effect was not attenuated by statistical adjustment for demographics, vocabulary ability, and informant-rated cognitive decline. The effect was stronger than, and largely independent from, both standard delirium risk factors and comorbidity. Conclusion: Risk of delirium is linearly and strongly related to presurgical cognitive performance level even at levels above the population median, which would be considered unimpaired.

Delirium Severity Post-Surgery and its Relationship with Long-Term Cognitive Decline in a Cohort of Patients without Dementia

BACKGROUND Delirium has been associated with more rapid cognitive decline. However, it is unknown whether increased delirium severity is associated with a higher rate of long-term cognitive decline. OBJECTIVE To evaluate delirium severity and the presence and rate of cognitive decline over 36 months following surgery. METHODS We examined patients from the Successful Aging after Elective Surgery Study, who were age ≥70 years undergoing major elective surgery (N = 560). Delirium severity was determined by the peak Confusion Assessment Method-Severity (CAM-S) score for each patients hospitalization and grouped based on the sample distribution: scores of 0-2, 3-7, and 8-19. A neuropsychological composite, General Cognitive Performance (GCP), and proxy-reported Informant Questionnaire for Cognitive Decline (IQCODE) were used to examine cognitive outcomes following surgery at 0, 1, and 2 months, and then every 6 months for up to 3 years. RESULTS No significant cognitive decline was observed for patients with peak CAM-S scores 0-2 (-0.17 GCP units/year, 95% confidence interval [CI] -0.35, 0.01). GCP scores decreased significantly in the group with peak CAM-S scores 3-7 (-0.30 GCP units/year, 95% CI -0.51, -0.09), and decreased almost three times faster in the highest delirium severity group (peak CAM-S scores 8-19; -0.82 GCP units/year, 95% CI -1.28, -0.37). A similar association was found for delirium severity and the proportion of patients who developed IQCODE impairment over time. CONCLUSION Patients with the highest delirium severity experienced the greatest rate of cognitive decline, which exceeds the rate previously observed for patients with dementia, on serial neuropsychological testing administered over 3 years, with a dose-response relationship between delirium severity and long-term cognitive decline.