Using Bayesian item response theory for multicohort repeated measure design to estimate individual latent change scores.

Repeated measure data design has been used extensively in a wide range of fields, such as brain aging or developmental psychology, to answer important research questions exploring relationships between trajectory of change and external variables. In many cases, such data may be collected from multiple study cohorts and harmonized, with the intention of gaining higher statistical power and enhanced external validity. When psychological constructs are measured using survey scales, a fundamental psychometric challenge for data harmonization is to create commensurate measures for the constructs of interest across studies. Traditional analysis may fit a unidimensional item response theory model to data from one time point and one cohort to obtain item parameters and fix the same parameters in subsequent analyses. Such a simplified approach ignores item residual dependencies in the repeated measure design on one hand, and on the other hand, it does not exploit accumulated information from different cohorts. Instead, two alternative approaches should serve such data designs much better: an integrative approach using multiple-group two-tier model via concurrent calibration, and if such calibration fails to converge, a Bayesian sequential calibration approach that uses informative priors on common items to establish the scale. Both approaches use a Markov chain Monte Carlo algorithm that handles computational complexity well. Through a simulation study and an empirical study using Alzheimer's diseases neuroimage initiative cognitive battery data (i.e., language and executive functioning), we conclude that latent change scores obtained from these two alternative approaches are more precisely recovered. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Linking self-perceived cognitive functioning questionnaires using item response theory: The subjective cognitive decline initiative.

OBJECTIVE: Self-perceived cognitive functioning, considered highly relevant in the context of aging and dementia, is assessed in numerous ways-hindering the comparison of findings across studies and settings. Therefore, the present study aimed to link item-level self-report questionnaire data from international aging studies. METHOD: We harmonized secondary data from 24 studies and 40 different questionnaires with item response theory (IRT) techniques using a graded response model with a Bayesian estimator. We compared item information curves to identify items with high measurement precision at different levels of the self-perceived cognitive functioning latent trait. Data from 53,030 neuropsychologically intact older adults were included, from 13 English language and 11 non-English (or mixed) language studies. RESULTS: We successfully linked all questionnaires and demonstrated that a single-factor structure was reasonable for the latent trait. Items that made the greatest contribution to measurement precision (i.e., "top items") assessed general and specific memory problems and aspects of executive functioning, attention, language, calculation, and visuospatial skills. These top items originated from distinct questionnaires and varied in format, range, time frames, response options, and whether they captured ability and/or change. CONCLUSIONS: This was the first study to calibrate self-perceived cognitive functioning data of geographically diverse older adults. The resulting item scores are on the same metric, facilitating joint or pooled analyses across international studies. Results may lead to the development of new self-perceived cognitive functioning questionnaires guided by psychometric properties, content, and other important features of items in our item bank. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Six-Year Cognitive Trajectory in Older Adults Following Major Surgery and Delirium.

Importance: The study results suggest that delirium is the most common postoperative complication in older adults and is associated with poor outcomes, including long-term cognitive decline and incident dementia. Objective: To examine the patterns and pace of cognitive decline up to 72 months (6 years) in a cohort of older adults following delirium. Design, Setting, and Participants: This was a prospective, observational cohort study with long-term follow-up including 560 community-dwelling older adults (older than 70 years) in the ongoing Successful Aging after Elective Surgery study that began in 2010. The data were analyzed from 2021 to 2022. Exposure: Development of incident delirium following major elective surgery. Main Outcomes and Measures: Delirium was assessed daily during hospitalization using the Confusion Assessment Method, which was supplemented with medical record review. Cognitive performance using a comprehensive battery of neuropsychological tests was assessed preoperatively and across multiple points postoperatively to 72 months of follow-up. We evaluated longitudinal cognitive change using a composite measure of neuropsychological performance called the general cognitive performance (GCP), which is scaled so that 10 points on the GCP is equivalent to 1 population SD. Retest effects were adjusted using cognitive test results in a nonsurgical comparison group. Results: The 560 participants (326 women [58%]; mean [SD] age, 76.7 [5.2] years) provided a total of 2637 person-years of follow-up. One hundred thirty-four participants (24%) developed postoperative delirium. Cognitive change following surgery was complex: we found evidence for differences in acute, post-short-term, intermediate, and longer-term change from the time of surgery that were associated with the development of postoperative delirium. Long-term cognitive change, which was adjusted for practice and recovery effects, occurred at a pace of about -1.0 GCP units (95% CI, -1.1 to -0.9) per year (about 0.10 population SD units per year). Participants with delirium showed significantly faster long-term cognitive change with an additional -0.4 GCP units (95% CI, -0.1 to -0.7) or -1.4 units per year (about 0.14 population SD units per year). Conclusions and Relevance: This cohort study found that delirium was associated with a 40% acceleration in the slope of cognitive decline out to 72 months following elective surgery. Because this is an observational study, we cannot be sure whether delirium directly causes subsequent cognitive decline, or whether patients with preclinical brain disease are more likely to develop delirium. Future research is needed to understand the causal pathway between delirium and cognitive decline.

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.

Sex differences in the genetic architecture of cognitive resilience to Alzheimer's disease.

Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer's disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer's disease neuropathology may uncover novel therapeutic targets to treat Alzheimer's disease. It is well established that there are sex differences in response to Alzheimer's disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience. We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts of cognitive ageing, in vivo amyloid PET across two cohorts, and autopsy measures of amyloid neuritic plaque burden across two cohorts. These data were leveraged to build robust, continuous resilience phenotypes. With these phenotypes, we performed sex-stratified [n (males) = 2093, n (females) = 2931] and sex-interaction [n (both sexes) = 5024] genome-wide association studies (GWAS), gene and pathway-based tests, and genetic correlation analyses to clarify the variants, genes and molecular pathways that relate to resilience in a sex-specific manner. Estimated among cognitively normal individuals of both sexes, resilience was 20-25% heritable, and when estimated in either sex among cognitively normal individuals, resilience was 15-44% heritable. In our GWAS, we identified a female-specific locus on chromosome 10 [rs827389, ß (females) = 0.08, P (females) = 5.76 × 10-09, ß (males) = -0.01, P(males) = 0.70, ß (interaction) = 0.09, P (interaction) = 1.01 × 10-04] in which the minor allele was associated with higher resilience scores among females. This locus is located within chromatin loops that interact with promoters of genes involved in RNA processing, including GATA3. Finally, our genetic correlation analyses revealed shared genetic architecture between resilience phenotypes and other complex traits, including a female-specific association with frontotemporal dementia and male-specific associations with heart rate variability traits. We also observed opposing associations between sexes for multiple sclerosis, such that more resilient females had a lower genetic susceptibility to multiple sclerosis, and more resilient males had a higher genetic susceptibility to multiple sclerosis. Overall, we identified sex differences in the genetic architecture of resilience, identified a female-specific resilience locus and highlighted numerous sex-specific molecular pathways that may underly resilience to Alzheimer's disease pathology. This study illustrates the need to conduct sex-aware genomic analyses to identify novel targets that are unidentified in sex-agnostic models. Our findings support the theory that the most successful treatment for an individual with Alzheimer's disease may be personalized based on their biological sex and genetic context.

Delirium Item Bank: Utilization to Evaluate and Create Delirium Instruments.

INTRODUCTION: The large number of heterogeneous instruments in active use for identification of delirium prevents direct comparison of studies and the ability to combine results. In a recent systematic review we performed, we recommended four commonly used and well-validated instruments and subsequently harmonized them using advanced psychometric methods to develop an item bank, the Delirium Item Bank (DEL-IB). The goal of the present study was to find optimal cut-points on four existing instruments and to demonstrate use of the DEL-IB to create new instruments. METHODS: We used a secondary analysis and simulation study based on data from three previous studies of hospitalized older adults (age 65+ years) in the USA, Ireland, and Belgium. The combined dataset included 600 participants, contributing 1,623 delirium assessments, and an overall incidence of delirium of about 22%. The measurements included the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnostic criteria for delirium, Confusion Assessment Method (long form and short form), Delirium Observation Screening Scale, Delirium Rating Scale-Revised-98 (total and severity scores), and Memorial Delirium Assessment Scale (MDAS). RESULTS: We identified different cut-points for each existing instrument to optimize sensitivity or specificity, and compared instrument performance at each cut-point to the author-defined cut-point. For instance, the cut-point on the MDAS that maximizes both sensitivity and specificity was at a sum score of 6 yielding 89% sensitivity and 79% specificity. We then created four new example instruments (two short forms and two long forms) and evaluated their performance characteristics. In the first example short form instrument, the cut-point that maximizes sensitivity and specificity was at a sum score of 3 yielding 90% sensitivity, 81% specificity, 30% positive predictive value, and 99% negative predictive value. DISCUSSION/CONCLUSION: We used the DEL-IB to better understand the psychometric performance of widely used delirium identification instruments and scorings, and also demonstrated its use to create new instruments. Ultimately, we hope that the DEL-IB might be used to create optimized delirium identification instruments and to spur the development of a unified approach to identify delirium.

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.

Machine Learning to Develop and Internally Validate a Predictive Model for Post-operative Delirium in a Prospective, Observational Clinical Cohort Study of Older Surgical Patients.

BACKGROUND: Our objective was to assess the performance of machine learning methods to predict post-operative delirium using a prospective clinical cohort. METHODS: We analyzed data from an observational cohort study of 560 older adults (≥ 70 years) without dementia undergoing major elective non-cardiac surgery. Post-operative delirium was determined by the Confusion Assessment Method supplemented by a medical chart review (N = 134, 24%). Five machine learning algorithms and a standard stepwise logistic regression model were developed in a training sample (80% of participants) and evaluated in the remaining hold-out testing sample. We evaluated three overlapping feature sets, restricted to variables that are readily available or minimally burdensome to collect in clinical settings, including interview and medical record data. A large feature set included 71 potential predictors. A smaller set of 18 features was selected by an expert panel using a consensus process, and this smaller feature set was considered with and without a measure of pre-operative mental status. RESULTS: The area under the receiver operating characteristic curve (AUC) was higher in the large feature set conditions (range of AUC, 0.62-0.71 across algorithms) versus the selected feature set conditions (AUC range, 0.53-0.57). The restricted feature set with mental status had intermediate AUC values (range, 0.53-0.68). In the full feature set condition, algorithms such as gradient boosting, cross-validated logistic regression, and neural network (AUC = 0.71, 95% CI 0.58-0.83) were comparable with a model developed using traditional stepwise logistic regression (AUC = 0.69, 95% CI 0.57-0.82). Calibration for all models and feature sets was poor. CONCLUSIONS: We developed machine learning prediction models for post-operative delirium that performed better than chance and are comparable with traditional stepwise logistic regression. Delirium proved to be a phenotype that was difficult to predict with appreciable accuracy.

Development and validation of language and visuospatial composite scores in ADNI.

INTRODUCTION: Composite scores may be useful to summarize overall language or visuospatial functioning in studies of older adults. METHODS: We used item response theory to derive composite measures for language (ADNI-Lan) and visuospatial functioning (ADNI-VS) from the cognitive battery administered in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We evaluated the scores among groups of people with normal cognition, mild cognitive impairment (MCI), and Alzheimer's disease (AD) in terms of responsiveness to change, association with imaging findings, and ability to differentiate between MCI participants who progressed to AD dementia and those who did not progress. RESULTS: ADNI-Lan and ADNI-VS were able to detect change over time and predict conversion from MCI to AD. They were associated with most of the pre-specified magnetic resonance imaging measures. ADNI-Lan had strong associations with a cerebrospinal fluid biomarker pattern. DISCUSSION: ADNI-Lan and ADNI-VS may be useful composites for language and visuospatial functioning in ADNI.

Lower practice effects as a marker of cognitive performance and dementia risk: A literature review.

BACKGROUND: Practice effects (PEs) are improvements in performance after repeated exposure to test materials, and typically viewed as a source of bias in repeated cognitive assessments. We aimed to determine whether characterizing PEs could also provide a useful marker of early cognitive decline. METHODS: We conducted a systematic review of the literature, searching PsycInfo (Ebsco) and PubMed databases for articles studying PEs in aging and dementia populations. Articles published between 1920 and 2019 were included. RESULT: We identified 259 articles, of which 27 studied PEs as markers of cognitive performance. These studies consistently showed that smaller, less-robust PEs were associated with current diagnostic status and/or future cognitive decline. In addition, lower PEs were associated with Alzheimer's disease risk factors and neurodegeneration biomarkers. CONCLUSION: PEs provide a potentially useful marker of cognitive decline, and could prove valuable as part of a cost-effective strategy to select individuals who are at-risk for dementia for future interventions.

New Delirium Severity Indicators: Generation and Internal Validation in the Better Assessment of Illness (BASIL) Study.

BACKGROUND: Delirium is a common and preventable geriatric syndrome. Moving beyond the binary classification of delirium present/absent, delirium severity represents a potentially important outcome for evaluating preventive and treatment interventions and tracking the course of patients. Although several delirium severity assessment tools currently exist, most have been developed in the absence of advanced measurement methodology and have not been evaluated with rigorous validation studies. OBJECTIVE: We aimed to report our development of new delirium severity items and the results of item reduction and selection activities guided by psychometric analysis of data derived from a field study. METHODS: Building on our literature review of delirium instruments and expert panel process to identify domains of delirium severity, we adapted items from existing delirium severity instruments and generated new items. We then fielded these items among a sample of 352 older hospitalized patients. RESULTS: We used an expert panel process and psychometric data analysis techniques to narrow a set of 303 potential items to 17 items for use in a new delirium severity instrument. The 17-item set demonstrated good internal validity and favorable psychometric characteristics relative to comparator instruments, including the Confusion Assessment Method - Severity (CAM-S) score, the Delirium Rating Scale Revised 98, and the Memorial Delirium Assessment Scale. CONCLUSION: We more fully conceptualized delirium severity and identified characteristics of an ideal delirium severity instrument. These characteristics include an instrument that is relatively quick to administer, is easy to use by raters with minimal training, and provides a severity rating with good content validity, high internal consistency reliability, and broad domain coverage across delirium symptoms. We anticipate these characteristics to be represented in the subsequent development of our final delirium severity instrument.

Clinical outcomes in older surgical patients with mild cognitive impairment.

INTRODUCTION: Older adults, including those with mild cognitive impairment (MCI), are increasingly undergoing surgery. METHODS: Relative risks (RRs) of MCI alone or with delirium on adverse outcomes were estimated in an ongoing prospective, observational cohort study of 560 nondemented adults aged ≥70 years. RESULTS: MCI (n = 61, 11%) was associated with increased RR of delirium (RR = 1.9, P < .001) and delirium severity (RR = 4.6, P < .001). Delirium alone (n = 107), but not MCI alone (n = 34), was associated with multiple adverse outcomes including more major postoperative complication(s) (RR = 2.5, P = .002) and longer length of stay (RR = 2.2, P < .001). Patients with concurrent MCI and delirium (n = 27) were more often discharged to a postacute facility (RR = 1.4, P < .001) and had synergistically increased risk for new impairments in cognitive functioning (RR = 3.6, P < .001). DISCUSSION: MCI is associated with increased risk of delirium incidence and severity. Patients with delirium and MCI have synergistically elevated risk of developing new difficulties in cognitively demanding tasks.

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 patient's 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.

Examining the Role of Race, Ethnicity, and Gender on Social and Behavioral Ratings Within the Autism Diagnostic Observation Schedule.

The Autism Diagnostic Observation Schedule (ADOS) is widely used to assess symptoms of autism spectrum disorder (ASD). Given well-documented differences in social behaviors across cultures, this study examined whether item-level biases exist in ADOS scores across sociodemographic groups (race, ethnicity, and gender). We examined a subset of ten ADOS items among participants (N = 2458). Holding level of overall ADOS behavioral symptoms constant, we found significant item level bias (measurement noninvariance) for race and ethnicity on three ADOS items. Item-level bias was not apparent across gender. Although the magnitude of bias was small, our findings highlight the need to reevaluate norms and operational definitions used in assessments to increase ASD diagnostic accuracy among culturally-diverse groups.

Association Between Hospital Readmission and Acute and Sustained Delays in Functional Recovery During 18 Months After Elective Surgery: The Successful Aging after Elective Surgery Study.

OBJECTIVES: To examine the effect of hospital readmission on functional recovery after elective surgery in older adults. DESIGN: Prospective cohort of individuals aged 70 and older undergoing elective surgery, enrolled from June 2010 to August 2013. SETTING: Two academic medical centers. PARTICIPANTS: Community-dwelling older adults (N = 566; mean age ± standard deviation 77 ± 5) undergoing major elective surgery and expected to be admitted for at least 3 days. MEASUREMENTS: Readmission was assessed in multiple interviews with participants and family members over 18 months and validated against medical record review. Physical function was assessed according to ability to perform instrumental activities of daily living (IADLs) and activities of daily living (ADL), Medical Outcomes Study 12-item Short-Form Survey Physical Component Summary score, and a standardized functional composite. RESULTS: Two hundred fifty-five (45%) participants experienced 503 readmissions. Readmissions were associated with delays in functional recovery in all measures of physical function. Having two or more readmissions over 18 months was associated with persistent and significantly greater risk of IADL dependence (relative risk (RR) = 1.8, 95% confidence interval (CI) = 1.5-2.3) and ADL dependence (RR = 3.3, 95% CI = 1.7-6.4). Degree of functional impairment increased progressively with number of readmissions. Readmissions within 2 months resulted in delayed functional recovery to baseline by 18 months, and readmissions between 12 and 18 months after surgery resulted in loss of functional recovery previously achieved. CONCLUSION: Readmission after elective surgery may contribute to delays in functional recovery and persistent functional deficits in older adults.

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.

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

INTRODUCTION: As the relationship between delirium and long-term cognitive decline has not been well-explored, we evaluated this association in a prospective study. METHODS: SAGES is an ongoing study involving 560 adults age 70 years or more without dementia scheduled for major surgery. Delirium was assessed daily in the postoperative period using the Confusion Assessment Method. General Cognitive Performance (GCP) and the Informant Questionnaire for Cognitive Decline in the Elderly were assessed preoperatively then repeatedly out to 36 months. RESULTS: On average, patients with postoperative delirium had significantly lower preoperative cognitive performance, greater immediate (1 month) impairment, equivalent recovery at 2 months, and significantly greater long-term cognitive decline relative to the nondelirium group. Proxy reports corroborated the clinical significance of the long-term cognitive decline in delirious patients. DISCUSSION: Cognitive decline after surgery is biphasic and accelerated among persons with delirium. The pace of long-term decline is similar to that seen with mild cognitive impairment.

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.

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 (Cronbach's 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.