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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, 2 months, and 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.

Electronic medical records (EMRs) offer the opportunity to streamline the search for patients with possible delirium. The purpose of the current study was to identify words and phrases commonly noted in charts of patients with delirium. The current study included 67 patients (nested within a cohort study of 300 patients) ages 70 and older undergoing major elective surgery with evidence of confusion in their medical charts. Eight keywords or phrases had positive predictive values of 60% to 100% for delirium. Keywords were charted more often in nursing notes than physician notes. A brief list of keywords may serve as a building block for a methodology to screen for possible delirium from charts, with particular attention to nursing notes, for research and real-time clinical decision making.

Background/Objectives Delirium is the most common complication of major elective surgery in older patients. The Successful Aging after Elective Surgery (SAGES) study was designed to examine novel risk factors and long-term outcomes associated with delirium. This report describes the cohort, quality assurance procedures, and results. Design Long-term prospective cohort study. Setting Three academic medical centers. Participants A total of 566 patients age 70 and older without recognized dementia scheduled for elective major surgery. Measurements Participants were assessed preoperatively, daily during hospitalization, and at variable monthly intervals for up to 36 months post-discharge. Delirium was assessed in hospital by trained study staff. Study outcomes included cognitive and physical function. Novel risk factors for delirium were assessed including genetic and plasma biomarkers, neuroimaging markers, and cognitive reserve markers. Interrater reliability (kappa and weighted kappa) was assessed for key variables in 119 of the patient interviews. Results Participants were an average of 77 years old and 58% were female. The majority of patients (81%) were undergoing orthopedic surgery and 24% developed delirium post-operatively. Over 95% of eligible patients were followed for 18 months. There was >99% capture of key study outcomes (cognitive and functional status) at every study interview and interrater reliability was high (weighted kappas for delirium = 0.92 and for overall cognitive and functional outcomes = 0.94 -1.0). Completion rates for plasma biomarkers (4 timepoints) were 95%-99% and for neuroimaging (one year follow-up) was 86%. Conclusion The SAGES study will contribute to the understanding of novel risk factors, pathophysiology and long-term outcomes of delirium. This manuscript describes the cohort and data quality procedures, and will serve as a reference source for future studies based on SAGES.

OBJECTIVES: To compare chart- and interview-based methods for identification of delirium. DESIGN: Prospective cohort study. SETTING: Two academic medical centers. PARTICIPANTS: Individuals aged 70 and older undergoing major elective surgery (N = 300) (majority orthopedic surgery). MEASUREMENTS: Participants were interviewed daily during hospitalization for delirium using the Confusion Assessment Method (CAM; interview-based method), and their medical charts were reviewed for delirium using a validated chart-review method (chart-based method). Rate of agreement of the two methods and characteristics of those identified using each approach were examined. Predictive validity for clinical outcomes (length of stay, postoperative complications, discharge disposition) was compared. In the absence of a criterion standard, predictive value could not be calculated. RESULTS: The cumulative incidence of delirium was 23% (n = 68) according to the interview-based method, 12% (n = 35) according to the chart-based method, and 27% (n = 82) according to the combined approach. Overall agreement was 80%; kappa was 0.30. The methods differed in detection of psychomotor features and time of onset. The chart-based method missed delirium in individuals that the CAM identified who were lacking features of psychomotor agitation or inappropriate behavior. The CAM-based method missed chart-identified cases occurring during the night shift. The combined method had high predictive validity for all clinical outcomes. CONCLUSIONS: Interview- and chart-based methods have specific strengths for identification of delirium. A combined approach captures the largest number and broadest range of delirium cases.

Background: Delirium (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. Methods: Older 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. Results: We 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. Conclusions: We 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.

Background Delirium is common after cardiac surgery and may be associated with long-term changes in cognitive function. We examined postoperative delirium and the cognitive trajectory during the first year after cardiac surgery. Methods We enrolled 225 patients 60 years of age or older who were planning to undergo coronary-artery bypass grafting or valve replacement. Patients were assessed preoperatively, daily during hospitalization beginning on postoperative day 2, and at 1, 6, and 12 months after surgery. Cognitive function was assessed with the use of the Mini–Mental State Examination (MMSE; score range, 0 to 30, with lower scores indicating poorer performance). Delirium was diagnosed with the use of the Confusion Assessment Method. We examined performance on the MMSE in the first year after surgery, controlling for demographic characteristics, coexisting conditions, hospital, and surgery type. Results The 103 participants (46%) in whom delirium developed postoperatively had lower preoperative mean MMSE scores than those in whom delirium did not develop (25.8 vs. 26.9, P<0.001). In adjusted models, those with delirium had a larger drop in cognitive function (as measured by the MMSE score) 2 days after surgery than did those without delirium (7.7 points vs. 2.1, P<0.001) and had significantly lower postoperative cognitive function than those without delirium, both at 1 month (mean MMSE score, 24.1 vs. 27.4; P<0.001) and at 1 year (25.2 vs. 27.2, P<0.001) after surgery. With adjustment for baseline differences, the between-group difference in mean MMSE scores was significant 30 days after surgery (P<0.001) but not at 6 or 12 months (P=0.056 for both). A higher percentage of patients with delirium than those without delirium had not returned to their preoperative baseline level at 6 months (40% vs. 24%, P=0.01), but the difference was not significant at 12 months (31% vs. 20%, P=0.055). Conclusions Delirium is associated with a significant decline in cognitive ability during the first year after cardiac surgery, with a trajectory characterized by an initial decline and prolonged impairment.

OBJECTIVES: To use an expert consensus process to identify indicators of delirium features to help enhance bedside recognition of delirium. DESIGN: Modified Delphi consensus process to assign existing cognitive and delirium assessment items to delirium features in the Confusion Assessment Method (CAM) diagnostic algorithm. SETTING: Meetings of expert panel. PARTICIPANTS: Panel of seven interdisciplinary clinical experts. MEASUREMENTS: Panelists' assignments of each assessment item to indicate CAM features. RESULTS: From an initial pool of 119 assessment items, the panel assigned 66 items to at least one CAM feature, and many items were assigned to more than one feature. Experts achieved a high level of consensus, with a postmeeting kappa for agreement of 0.98. The study staff compiled the assignment results to create a comprehensive list of CAM feature indicators, consisting of 107 patient interview questions, cognitive tasks, and interviewer observations, with some items assigned to multiple features. A subpanel shortened this list to 28 indicators of important delirium features. CONCLUSION: A systematic, well-described qualitative methodology was used to create a list of indicators for delirium based on the features of the CAM diagnostic algorithm. This indicator list may be useful as a clinical tool for enhancing delirium recognition at the bedside and for aiding in the development of a brief delirium screening instrument.

Objectives: Delirium, a costly, life-threatening, and potentially preventable condition, is a common complication for older adults following major surgery. Although the basic epidemiology of delirium after surgery has been defined, the contribution of delirium to long term outcomes remains uncertain, and novel biomarkers from plasma and neuroimaging have yet to be examined. This program project was designed to contribute to our understanding of the complex multifactorial syndrome of delirium. Design: Long term prospective cohort study. Setting: Three academic medical centers (2 hospitals and 1 coordinating center). Participants: Patients without recognized dementia (targeted cohort = 550 patients) age 70 and older scheduled to undergo elective major surgery are assessed at baseline before surgery, daily during their hospital stay, and for 18 to 36 months after discharge. Measurements: The Successful Aging after Elective Surgery (SAGES) study is an innovative, interdisciplinary study that includes biomarkers, neuroimaging, cognitive reserve markers, and serial neuropsychological testing to examine the contribution of delirium to long term cognitive and functional decline. The primary goal is to examine the contribution of delirium to long term cognitive and functional decline. In addition, novel risk markers for delirium are being examined, including plasma biomarkers (eg, cytokines, proteomics), advanced neuroimaging markers (eg, volumetric, white matter hyperintensity, noncontrast blood flow, and diffusion tensor measures), and cognitive reserve markers (eg, education, occupation, lifetime activities). Conclusion: Results from this study will contribute to a fuller understanding of the etiology and prognosis of delirium. Ultimately, we hope this project will provide the groundwork for future development of prevention and treatment strategies for delirium, designed to minimize the long term negative impact of delirium in older adults.

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.

Cognitive and brain reserve are well studied in the context of age-associated cognitive impairment and dementia. However, there is a paucity of research that examines the role of cognitive or brain reserve in delirium. Indicators (or proxy measures) of cognitive or brain reserve (such as brain size, education, and activities) pose challenges in the context of the long prodromal phase of Alzheimer disease but are diminished in the context of delirium, which is of acute onset. This article provides a review of original articles on cognitive and brain reserve across many conditions affecting the central nervous system, with a focus on delirium. The authors review current definitions of reserve. The authors identify indicators for reserve used in earlier studies and discuss these indicators in the context of delirium. The authors highlight future research directions to move the field ahead. Reserve may be a potentially modifiable characteristic. Studying the role of reserve in delirium can advance prevention strategies for delirium and may advance knowledge of reserve and its role in aging and neuropsychiatric disease generally.

OBJECTIVES: To determine whether patients who developed delirium after cardiac surgery were at risk of functional decline. DESIGN: Prospective cohort study. SETTING: Two academic hospitals and a Veterans Affairs Medical Center. PARTICIPANTS: One hundred ninety patients aged 60 and older undergoing elective or urgent cardiac surgery. MEASUREMENTS: Delirium was assessed daily and was diagnosed according to the Confusion Assessment Method. Before surgery and 1 and 12 months postoperatively, patients were assessed for function using the instrumental activities of daily living (IADL) scale. Functional decline was defined as a decrease in ability to perform one IADL at follow-up. RESULTS: Delirium occurred in 43.1% (n=82) of the patients (mean age 73.7±6.7). Functional decline occurred in 36.3% (n=65/179) at 1 month and in 14.6% (n=26/178) at 12 months. Delirium was associated with greater risk of functional decline at 1 month (relative risk (RR)=1.9, 95% confidence interval (CI)=1.3–2.8) and tended toward greater risk at 12 months (RR=1.9, 95% CI=0.9–3.8). After adjustment for age, cognition, comorbidity, and baseline function, delirium remained significantly associated with functional decline at 1 month (adjusted RR=1.8, 95% CI=1.2–2.6) but not at 12 months (adjusted RR=1.5, 95% CI=0.6–3.3). CONCLUSION: Delirium was independently associated with functional decline at 1 month and had a trend toward association at 12 months. These findings provide justification for intervention trials to evaluate whether delirium prevention or treatment strategies might improve postoperative functional recovery.

Background Brief cognitive screening measures are valuable tools for both research and clinical applications. The most widely used instrument, the Mini-Mental State Examination (MMSE), is limited in that it must be administered face-to-face, cannot be used in participants with visual or motor impairments, and is protected by copyright. Screening instruments such as the Telephone Interview for Cognitive Status (TICS) were developed to provide a valid alternative, with comparable cut-point scores to rate global cognitive function. Methods The MMSE, TICS-30, and TICS-40 scores from 746 community-dwelling elders who participated in the Aging, Demographics, and Memory Study (ADAMS) were analyzed with equipercentile equating, a statistical process of determining comparable scores based on percentile equivalents for different forms of an examination. Results Scores from the MMSE and TICS-30 and TICS-40 corresponded well, and clinically relevant cut-point scores were determined. For example, an MMSE score of 23 is equivalent to 17 and 20 on the TICS-30 and TICS-40, respectively. Conclusions These findings indicate that TICS and MMSE scores can be linked directly. Clinically relevant and important MMSE cut points and the respective ADAMS TICS-30 and TICS-40 cut-point scores are included, to identify the degree of cognitive impairment among respondents with any type of cognitive disorder. These results will help in the widespread application of TICS in both research and clinical practice.

OBJECTIVES: To examine the association between persistent delirium and 1-year mortality in newly admitted post-acute care (PAC) facility patients with delirium who were followed regardless of residence. DESIGN: Observational cohort study. SETTING: Eight greater-Boston skilled nursing facilities specializing in PAC. PARTICIPANTS: Four hundred twelve PAC patients with delirium at admission after an acute hospitalization. MEASUREMENTS: Assessments were done at baseline and four follow-up times: 2, 4, 12, and 26 weeks. Delirium, defined using the Confusion Assessment Method, was assessed, as were factors used as covariates in analyses: age, sex, comorbidity, functional status, and dementia. The outcome was 1-year mortality determined according to the National Death Index and corroborated using medical record and proxy telephone interview. RESULTS: Nearly one-third of subjects remained delirious at 6 months. Cumulative 1-year mortality was 39%. Independent of age, sex, comorbidity, functional status, and dementia, subjects with persistent delirium were 2.9 (95% confidence interval=1.9–4.4) times as likely to die during the 1-year follow-up as subjects whose delirium resolved. This association remained strong and significant in groups with and without dementia. Additionally, when delirium resolved, the risk of death diminished thereafter. CONCLUSION: In patients who were delirious at the time of PAC admission, persistent delirium was a significant independent predictor of 1-year mortality.

The purpose of this analysis was to determine if postoperative delirium was associated with early postoperative cognitive dysfunction (at 7 days) and long-term postoperative cognitive dysfunction (at 3 months). The International Study of Postoperative Cognitive Dysfunction recruited 1218 subjects ≥ 60 years old undergoing elective, non-cardiac surgery. Postoperatively, subjects were evaluated for delirium using the criteria of the Diagnostic and Statistical Manual. Subjects underwent neuropsychological testing pre-operatively and postoperatively at 7 days (n = 1018) and 3 months (n = 946). Postoperative cognitive dysfunction was defined as a composite Z-score > 2 across tests or at least two individual test Z-scores > 2. Subjects with delirium were significantly less likely to participate in postoperative testing. Delirium was associated with an increased incidence of early postoperative cognitive dysfunction (adjusted risk ratio 1.6, 95% CI 1.1–2.1), but not long-term postoperative cognitive dysfunction (adjusted risk ratio 1.3, 95% CI 0.6–2.4). Delirium was associated with early postoperative cognitive dysfunction, but the relationship of delirium to long-term postoperative cognitive dysfunction remains unclear.

Background— Delirium is a common outcome after cardiac surgery. Delirium prediction rules identify patients at risk for delirium who may benefit from targeted prevention strategies, early identification, and treatment of underlying causes. The purpose of the present prospective study was to develop a prediction rule for delirium in a cardiac surgery cohort and to validate it in an independent cohort. Methods and Results— Prospectively, cardiac surgery patients ≥60 years of age were enrolled in a derivation sample (n=122) and then a validation sample (n=109). Beginning on the second postoperative day, patients underwent a standardized daily delirium assessment, and delirium was diagnosed according to the confusion assessment method. Delirium occurred in 63 (52%) of the derivation cohort patients. Multivariable analysis identified 4 variables independently associated with delirium: prior stroke or transient ischemic attack, Mini Mental State Examination score, abnormal serum albumin, and the Geriatric Depression Scale. Points were assigned to each variable: Mini Mental State Examination ≤23 received 2 points, and Mini Mental State Examination score of 24 to 27 received 1 point; Geriatric Depression Scale >4, prior stroke/transient ischemic attack, and abnormal albumin received 1 point each. In the derivation sample, the cumulative incidence of delirium for point levels of 0, 1, 2, and ≥3 was 19%, 47%, 63%, and 86%, respectively (C statistic, 0.74). The corresponding incidence of delirium in the validation sample was 18%, 43%, 60%, and 87%, respectively (C statistic, 0.75). Conclusions— Delirium occurs frequently after cardiac surgery. Using 4 preoperative characteristics, clinicians can determine cardiac surgery patients’ risk for delirium. Patients at higher delirium risk could be candidates for close postoperative monitoring and interventions to prevent delirium.

Background: Unplanned hospitalization often represents a costly and hazardous event for the older population. Objectives: To develop and validate a predictive model for unplanned medical hospitalization from administrative data. Research Design: Model development and validation. Subjects: A total of 3919 patients aged >=70 years who were followed for at least 1 year in primary care clinics of an academic medical center. Measures: Risk factor data and the primary outcome of unplanned medical hospitalization were obtained from administrative data. Results: Of 1932 patients in the development cohort, 299 (15%) were hospitalized during 1 year follow up. Five independent risk factors were identified in the preceding year: Deyo-Charlson comorbidity score >=2 [adjusted relative risk (RR) = 1.8; 95% confidence interval (CI): 1.4–2.2], any prior hospitalization (RR = 1.8; 95% CI: 1.5–2.3), 6 or more primary care visits (RR = 1.6; 95% CI: 1.3–2.0), age >=85 years (RR = 1.4; 95% CI: 1.1–1.7), and unmarried status (RR = 1.4; 95% CI: 1.1–1.7). A risk stratification system was created by adding 1 point for each factor present. Rates of hospitalization for the low- (0 factor), intermediate- (1–2 factors), and high-risk (>=3 factors) groups were 5%, 15%, and 34% (P < 0.0001). The corresponding rates in the validation cohort, where 328/1987 (17%) were hospitalized, were 6%, 16%, and 36% (P < 0.0001). Conclusions: A predictive model based on administrative data has been successfully validated for prediction of unplanned hospitalization. This model will identify patients at high risk for hospitalization who may be candidates for preventive interventions.

Deficits in cholinergic function have been postulated to cause delirium and cognitive decline. This review examines current understanding of the cholinergic deficiency hypothesis in delirium by synthesizing evidence on potential pathophysiological pathways. Acetylcholine synthesis involves various precursors, enzymes, and receptors, and dysfunction in these components can lead to delirium. Insults to the brain, like ischemia and immunological stressors, can precipitously alter acetylcholine levels. Imbalances between cholinergic and other neurotransmitter pathways may result in delirium. Furthermore, genetic, enzymatic, and immunological overlaps exist between delirium and dementia related to the cholinergic pathway. Important areas for future research include identifying biomarkers, determining genetic contributions, and evaluating response to cholinergic drugs in delirium. Understanding how the cholinergic pathway relates to delirium may yield innovative approaches in the diagnosis, prevention, and treatment of this common, costly, and morbid condition.

OBJECTIVES: To identify barriers and motivators to participation in long-term clinical research by high-risk elderly people and to develop procedures to maximize recruitment and retention. DESIGN: Quantitative and qualitative survey. SETTING: Academic primary care medicine and pre-anesthesia testing clinics. PARTICIPANTS: Fifty patients aged 70 and older, including 25 medical patients at high risk of hospitalization and 25 patients with planned major surgery. MEASUREMENTS: Fifteen- to 20-minute interviews involved open- and closed-ended questions guided by an in-depth script. Two planned study protocols were presented to each participant. Both involved serial neuropsychological assessments, blood testing, and magnetic resonance brain imaging (MRI); one added lumbar puncture (LP). Participants were asked whether they would be willing to participate in these protocols, rated barriers and incentives to participation, and were probed with open-ended questions. RESULTS: Of 50 participants (average age 78, 44% male, 40% nonwhite), 32 (64%) expressed willingness to participate in the LP-containing protocol, with LP cited as the strongest disincentive. Thirty-eight (76%) expressed willingness to participate in the protocol without LP, with phlebotomy and long interviews cited as the strongest disincentives. Altruism was a strong motivator for participation, whereas transportation was a major barrier. Study visits at home, flexible appointment times, assessments shorter than 75 minutes, and providing transportation and free parking were strategies developed to maximize study participation. CONCLUSION: Vulnerable elderly people expressed a high rate of willingness to participate in an 18-month prospective study. Participants identified incentives and barriers that enabled investigators to develop procedures to maximize recruitment and retention.

Background: Although guidelines recommend that clinicians consider life expectancy before screening older women for breast cancer, many older women with limited life expectancies are screened. We aimed to identify factors important to mammography screening decisions among women aged 80 and older compared to women aged 65–79. Methods: Telephone surveys of 107 women aged 80+ and 93 women aged 65–79 randomly selected from one academic primary care practice who were able to communicate in English (60% response rate). The survey addressed the following factors in regards to older women's mammography screening decisions: perceived importance of a history of breast disease, family history of breast cancer, doctor's recommendations, habit, reassurance, previous experience, mailed reminder cards, family/friend's recommendations or experience with breast cancer, age, health, and media. The survey also assessed older women's preferred role in decision making around mammography screening. Results: Of the 200 women, 65.5% were non-Hispanic white and 82.8% were in good to excellent health. Most (81.3%) had undergone mammography in the past 2 years. Regardless of age, older women ranked doctor's recommendations as the most important factor influencing their decision to get screened. Habit and reassurance were the next two highly ranked factors influencing older women to get screened. Among women who did not get screened, women aged 80 and older ranked age and doctor's counseling as the most influential factors and women aged 65–79 ranked a previous negative experience with mammography as the most important factor. There were no significant differences in preferred role in decision-making around mammography screening by age, however, most women in both age groups preferred to make the final decision on their own (46.6% of women aged 80+ and 50.5% of women aged 65–79). Conclusion: While a doctor's recommendation is the most important factor influencing elderly women's mammography screening decisions, habit and reassurance also strongly influence decision-making. Interventions aimed at improving clinician counseling about mammography, which include discussions around habit and reassurance, may result in better decision-making.