Person:

Marcantonio, Edward

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.

Objective: The neuropathogenesis of postoperative delirium remains unknown. Low cerebrospinal fluid (CSF) β-amyloid protein (Aβ) and high CSF Tau levels are associated with Alzheimer's disease. We, therefore, assessed whether lower preoperative CSF Aβ/Tau ratio was associated with higher incidence and greater severity of postoperative delirium. Methods: One hundred and fifty-three participants (71 ± 5 years, 53% men) who had total hip/knee replacement under spinal anesthesia were enrolled. CSF was obtained during initiation of spinal anesthesia. The incidence and severity of postoperative delirium were determined by Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS) on postoperative day 1 and 2. Aβ40, Aβ42, and Tau levels in the CSF were measured by enzyme-linked immunosorbent assay. The relationships among these variables were determined, adjusting for age and gender. Results: Participants in the lowest quartile of preoperative CSF Aβ40/Tau and Aβ42/Tau ratio had higher incidence (32% vs. 17%, P = 0.0482) and greater symptom severity of postoperative delirium (Aβ40/Tau ratio: 4 vs. 3, P = 0.034; Aβ42/Tau ratio: 4 vs. 3, P = 0.062, the median of the highest MDAS score) as compared to the combination of the rest of the quartiles. The preoperative CSF Aβ40/Tau or Aβ42/Tau ratio was inversely associated with MDAS score (Aβ40/Tau ratio: −0.12 ± 0.05, P = 0.014, adj. −0.12 ± 0.05, P = 0.018; Aβ42/Tau ratio: −0.65 ± 0.26, P = 0.013, adj. −0.62 ± 0.27, P = 0.022). Interpretation Lower CSF Aβ/Tau ratio could be associated with postoperative delirium, pending confirmation of our preliminary results in further studies. These findings suggest potential roles of Aβ and/or Tau in postoperative delirium neuropathogenesis.

Background: Difficulties with performance of functional activities may result from cognitive and/or physical impairments. To date, there has not been a clear delineation of the physical and cognitive demands of activities of daily living. Objectives: To quantify the relative physical and cognitive demands required to complete typical functional activities in older adults. Design: Expert panel survey. Setting: Web-based platform. Participants: Eleven experts from eight academic medical centers and 300 community dwelling elderly adults age 70 and older scheduled for elective non-cardiac surgery from two academic medical centers. Methods: Sum scores of expert ratings were calculated and then validated against objective data collected from a prospective longitudinal study. Main Outcome Measurements Correlation between expert ratings and objective neuropsychological tests (memory, language, complex attention) and physical measures (gait speed and grip strength) for performance-based tasks. Results: Managing money, self-administering medications, using the telephone, and preparing meals were rated as requiring significantly more cognitive demand, while walking and transferring, moderately strenuous activities, and climbing stairs were assessed as more physically demanding. Largely cognitive activities correlated with objective neuropsychological performance (r=0.13–0.23, p<.05) and largely physical activities correlated with physical performance (r=0.15–0.46, p<.05). Conclusions: Quantifying the degree of cognitive and/or physical demand for completing a specific task adds an additional dimension to standard measures of functional assessment. This additional information may significantly influence decisions about rehabilitation, post-acute care needs, treatment plans, and caregiver education.

Postoperative delirium is associated with increased morbidity, mortality and cost. However, its neuropathogenesis remains largely unknown, partially owing to lack of animal model(s). We therefore set out to employ a battery of behavior tests, including natural and learned behavior, in mice to determine the effects of laparotomy under isoflurane anesthesia (Anesthesia/Surgery) on these behaviors. The mice were tested at 24 hours before and at 6, 9 and 24 hours after the Anesthesia/Surgery. Composite Z scores were calculated. Cyclosporine A, an inhibitor of mitochondria permeability transient pore, was used to determine potential mitochondria-associated mechanisms of these behavioral changes. Anesthesia/Surgery selectively impaired behaviors, including latency to eat food in buried food test, freezing time and time spent in the center in open field test, and entries and duration in the novel arm of Y maze test, with acute onset and various timecourse. The composite Z scores quantitatively demonstrated the Anesthesia/Surgery-induced behavior impairment in mice. Cyclosporine A selectively ameliorated the Anesthesia/Surgery-induced reduction in ATP levels, the increases in latency to eat food, and the decreases in entries in the novel arm. These findings suggest that we could use a battery of behavior tests to establish a mouse model to study postoperative delirium.

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.

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.

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.

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.

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: 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.