Publications

2019

Mei X, Chen Y, Zheng H, et al. The Reliability and Validity of the Chinese Version of Confusion Assessment Method Based Scoring System for Delirium Severity (CAM-S). Journal of Alzheimer’s disease : JAD. 2019;69(3):709-716. doi:10.3233/JAD-181288

Previous studies showed that the Confusion Assessment Method based delirium severity evaluation tool (CAM-S) had good reliability and validity. However, there is no Chinese version of the CAM-S. Therefore, we set out to perform a prospective investigation in older Chinese patients who had total joint replacement surgery under general anesthesia in Tenth People's Hospital in Shanghai, P.R. China. A total of 576 participants, aged 60 years or older, were screened, 179 participants were enrolled, and 125 of them were included for the final analysis. Pre-operative evaluations were conducted one day before the surgery. Postoperative evaluations were conducted twice daily from postoperative day 1 to day 3. The incidence of postoperative delirium was 24.8%. The Chinese version of CAM-S [including a Short Form (CAM-S Short Form) and a Long Form (CAM-S Long Form)] had an optimal reliability reflected by internal consistency (Cronbach's α= 0.748 and 0.839 for CAM-S Short Form and CAM-S Long Form respectively), split-halves reliability (Pearson correlation coefficient = 0.372 and 0.384 for CAM-S Short Form and CAM-S Long Form respectively), and inter-rater reliability (intra-class correlation coefficients = 0.629 and 0.945 for CAM-S Short Form and CAM-S Long Form respectively). Additionally, the Chinese version of CAM-S also showed a good discriminate validity. The domain scores of CAM-S were inversely correlated with corresponding domain scores of the MMSE. Finally, a receiver operating characteristic (ROC) analysis obtained an optimal cutoff point of 2.5 for CAM-S Short Form and 3.5 for CAM-S Long Form in recognizing delirium diagnosed by CAM. The areas under the ROC were 0.989 (95% CI 0.972 - 1.000, p < 0.001) and 0.964 (95% CI 0.946 - 0.982, p < 0.001), respectively. These data suggest that the Chinese version of CAM-S has good reliability and validity in evaluating postoperative delirium in geriatric Chinese patients and may be a useful tool to assess the severity of delirium.

Daiello LA, Racine AM, Gou RY, et al. Postoperative Delirium and Postoperative Cognitive Dysfunction: Overlap and Divergence. Anesthesiology. 2019;131(3):477-491. doi:10.1097/ALN.0000000000002729

BACKGROUND: Postoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up.

METHODS: This study used data from an observational study of cognitive outcomes after major noncardiac surgery, the Successful Aging after Elective Surgery study. Postoperative delirium was evaluated each hospital day with confusion assessment method-based interviews supplemented by chart reviews. Postoperative cognitive dysfunction was determined using methods adapted from the International Study of Postoperative Cognitive Dysfunction. Associations between delirium and postoperative cognitive dysfunction were examined at 1, 2, and 6 months.

RESULTS: One hundred thirty-four of 560 participants (24%) developed delirium during hospitalization. Slightly fewer than half (47%, 256 of 548) met the International Study of Postoperative Cognitive Dysfunction-defined threshold for postoperative cognitive dysfunction at 1 month, but this proportion decreased at 2 months (23%, 123 of 536) and 6 months (16%, 85 of 528). At each follow-up, the level of agreement between delirium and postoperative cognitive dysfunction was poor (kappa less than .08) and correlations were small (r less than .16). The relative risk of postoperative cognitive dysfunction was significantly elevated for patients with a history of postoperative delirium at 1 month (relative risk = 1.34; 95% CI, 1.07-1.67), but not 2 months (relative risk = 1.08; 95% CI, 0.72-1.64), or 6 months (relative risk = 1.21; 95% CI, 0.71-2.09).

CONCLUSIONS: Delirium significantly increased the risk of postoperative cognitive dysfunction in the first postoperative month; this relationship did not hold in longer-term follow-up. At each evaluation, postoperative cognitive dysfunction was more common among patients without delirium. Postoperative delirium and postoperative cognitive dysfunction may be distinct manifestations of perioperative neurocognitive deficits.

Steensma E, Zhou W, Ngo L, et al. Ultra-brief Screeners for Detecting Delirium Superimposed on Dementia. Journal of the American Medical Directors Association. 2019;20(11):1391-1396.e1. doi:10.1016/j.jamda.2019.05.011

OBJECTIVE: Delirium superimposed on dementia (DSD) is common, morbid, and costly, yet frequently undiagnosed. Our study aimed to develop a brief screening test to improve health care worker recognition of DSD.

DESIGN/SETTING/PARTICIPANTS: Older hospitalized adults with dementia were prospectively enrolled from medical and surgical inpatient units of 3 hospitals (2 in Pennsylvania, 1 in Tennessee).

MEASURES: The reference standard delirium assessment used Confusion Assessment Method (CAM) criteria and was based on a structured interview including the Mini-Mental State Examination, interviewer observations, and medical record review. To develop the screening test, 1-, 2-, and 3-item combinations from the reference standard assessment were analyzed to determine their sensitivity and specificity in diagnosing delirium presence in a dementia population compared to the reference standard. For multiple-item screeners, error on 1 or more items was considered a positive screen.

RESULTS: Overall, 391 older adults with dementia were enrolled (mean age: 83.9 years, 71.1% female), and 95 (24.4%) developed DSD during their hospitalization, based on the reference standard. The best single-item screen for DSD was "What day of the week is it?" with 84% sensitivity [95% confidence interval (CI): 0.75, 0.91] and 41% specificity (CI: 0.35, 0.47). The best 2-item screen was "list the days of the week backwards" and "What day of the week is it?" with 93% sensitivity (CI: 0.85, 0.97) and 30% specificity (CI: 0.25, 0.36). The best 3-item screen was "list the days of the week backwards," "What type of place is this? [hospital]" and "Does the patient appear sleepy?" with 94% sensitivity (CI: 0.87, 0.98) and 42% specificity (CI: 0.36, 0.48).

CONCLUSIONS/IMPLICATIONS: We identified a 3-item DSD screener with excellent sensitivity but limited specificity. This screener can be used to quickly rule out DSD in populations with a high prevalence of dementia and is a promising step toward developing efficient tools for DSD recognition among care providers.

Shi Z, Mei X, Li C, et al. Postoperative Delirium Is Associated with Long-term Decline in Activities of Daily Living. Anesthesiology. 2019;131(3):492-500. doi:10.1097/ALN.0000000000002849

BACKGROUND: Postoperative delirium is one of the most common complications in the elderly surgical population. However, its long-term outcomes remain largely to be determined. Therefore a prospective cohort study was conducted to determine the association between postoperative delirium and long-term decline in activities of daily living and postoperative mortality. The hypothesis in the present study was that postoperative delirium was associated with a greater decline in activities of daily living and higher mortality within 24 to 36 months after anesthesia and surgery.

METHODS: The participants (at least 65 yr old) having the surgeries of (1) proximal femoral nail, (2) hip replacement, or (3) open reduction and internal fixation under general anesthesia were enrolled. The Confusion Assessment Method algorithm was administered to diagnose delirium before and on the first, second, and fourth days after the surgery. Activities of daily living were evaluated by using the Chinese version of the activities of daily living scale (range, 14 to 56 points), and preoperative cognitive function was assessed by using the Chinese Mini-Mental State Examination (range, 0 to 30 points). The follow-up assessments, including activities of daily living and mortality, were conducted between 24 and 36 months after anesthesia and surgery.

RESULTS: Of 130 participants (80 ± 6 yr, 24% male), 34 (26%) developed postoperative delirium during the hospitalization. There were 32% of the participants who were lost to follow-up, resulting in 88 participants who were finally included in the data analysis. The participants with postoperative delirium had a greater decline in activities of daily living (16 ± 15 vs. 9 ± 15, P = 0.037) and higher 36-month mortality (8 of 28, 29% vs. 7 of 75, 9%; P = 0.009) as compared with the participants without postoperative delirium.

CONCLUSIONS: Postoperative delirium was associated with long-term detrimental outcomes, including greater decline in activities of daily living and a higher rate of postoperative mortality.

Carpenter CR, McFarland F, Avidan M, et al. Impact of Cognitive Impairment Across Specialties: Summary of a Report From the U13 Conference Series. Journal of the American Geriatrics Society. 2019;67(10):2011-2017. doi:10.1111/jgs.16093

Although declines in cognitive capacity are assumed to be a characteristic of aging, increasing evidence shows that it is age-related disease, rather than age itself, that causes cognitive impairment. Even so, older age is a primary risk factor for cognitive decline, and with individuals living longer as a result of medical advances, cognitive impairment and dementia are increasing in prevalence. On March 26 to 27, 2018, the American Geriatrics Society convened a conference in Bethesda, MD, to explore cognitive impairment across the subspecialties. Bringing together representatives from several subspecialties, this was the third of three conferences, supported by a U13 grant from the National Institute on Aging, to aid recipients of Grants for Early Medical/Surgical Specialists' Transition to Aging Research (GEMSSTAR) in integrating geriatrics into their subspecialties. Scientific sessions focused on the impact of cognitive impairment, sensory contributors, comorbidities, links between delirium and dementia, and issues of informed consent in cognitively impaired populations. Discussions highlighted the complexity not only of cognitive health itself, but also of the bidirectional relationship between cognitive health and the health of other organ systems. Thus, conference participants noted the importance of multidisciplinary team science in future aging research. This article summarizes the full conference report, "The Impact of Cognitive Impairment Across Specialties," and notes areas where GEMSSTAR scholars can contribute to progress as they embark on their careers in aging research. J Am Geriatr Soc 67:2011-2017, 2019.

Fong TG, Racine AM, Fick DM, et al. The Caregiver Burden of Delirium in Older Adults With Alzheimer Disease and Related Disorders. Journal of the American Geriatrics Society. 2019;67(12):2587-2592. doi:10.1111/jgs.16199

OBJECTIVES: To measure the burden of delirium in older adults with or without Alzheimer disease or related disorders (ADRDs).

DESIGN: Prospective, observational cohort.

SETTING: Inpatient hospital and study participants' homes.

PARTICIPANTS: A subset (n = 267) of older medical and surgical patients and their caregivers enrolled in the Better Assessment of Illness study.

MEASUREMENTS: Delirium burden was measured using the DEL-B instrument (range = 0-40, with higher scores indicating greater burden) in caregivers (DEL-B-C) and patients 1 month after hospitalization. Severity of cognitive impairment (Montreal Cognitive Assessment [MoCA]), delirium presence (Confusion Assessment Method [CAM]), and delirium severity (CAM-Severity [CAM-S]) were measured during hospitalization and at 1-month follow-up. ADRD diagnosis was determined by a clinical consensus process.

RESULTS: For patients with (n = 56) and without (n = 211) ADRD, both DEL-B instruments had good internal consistency. DEL-B-C scores had a median (interquartile range) among caregivers of patients with and without ADRD of 9 (5-15) and 5 (1-11), respectively (P < .05). If the patient developed delirium, caregivers experienced greater burden (β[delirium × ADRD] = -.29; P = .42), regardless of ADRD status. Further, caregiver burden was modestly correlated with patient MoCA scores (Spearman correlation coefficient, ρ = -0.18; P = .01). Patients with ADRD who developed delirium self-reported less burden than those without ADRD (β[delirium × ADRD] = -.67; P = .044). As with caregivers, delirium burden was modestly correlated with patient MoCA score (ρ = -0.18; P = .005) and correlated with the CAM-S in patients without ADRD (ρ = 0.38; P < .001) but not for patients with ADRD (ρ = -0.07; P = .61).

CONCLUSIONS: Delirium resulted in the same degree of increased caregiver burden regardless of whether a patient had ADRD, signifying delirium is equally stressful to caregivers, even among those with experience caring for someone with a chronic cognitive disorder. Delirium burden is only modestly associated with degree of cognitive impairment, suggesting that other aspects of delirium contribute to burden. J Am Geriatr Soc 67:2587-2592, 2019.

Hshieh TT, Vasunilashorn SM, D’Aquila ML, et al. The Role of Inflammation after Surgery for Elders (RISE) study: Study design, procedures, and cohort profile. Alzheimer’s & dementia (Amsterdam, Netherlands). 2019;11:752-762. doi:10.1016/j.dadm.2019.09.004

INTRODUCTION: The Role of Inflammation after Surgery for Elders study correlates novel inflammatory markers measured in blood, cerebrospinal fluid (CSF) assays, and [11C]-PBR28 positron-emission tomography imaging.

METHODS: This study involved a prospective cohort design with patients who underwent elective hip and knee arthroplasty under spinal anesthesia. Sixty-five adults participated with their family members. Inflammatory biomarker assays were measured preoperatively on day 1 and postoperatively at one month.

RESULTS: On average, participants were 75 years old, and 72% were female. 54% underwent total knee arthroplasty, and 46% underwent total hip arthroplasty. The mean Modified Mini-Mental State (3MS) Examination score was 89.3; four patients (6%) scored ≤77 points. Plasma assays were completed in 63 (97%) participants, cerebrospinal fluid assays in 61 (94%), and PET imaging in 44 (68%).

DISCUSSION: This complex study presents an innovative effort to correlate peripheral and central inflammatory biomarkers before and after major surgery in older adults. Strengths include collecting concurrent blood, cerebrospinal fluid, and positron-emission tomography with detailed clinical characterization of delirium, cognition, and functional status.

2018

Oldham MA, Flanagan NM, Khan A, Boukrina O, Marcantonio ER. Responding to Ten Common Delirium Misconceptions With Best Evidence: An Educational Review for Clinicians. The Journal of neuropsychiatry and clinical neurosciences. 2018;30(1):51-57. doi:10.1176/appi.neuropsych.17030065

Delirium (acute confusion) is a serious, common health condition, and it predicts poor outcomes, including greater rates of mortality, institutionalization, prolonged hospitalization, and cognitive impairment. Expedient diagnosis and management are critical to address modifiable delirium causes and improve both quality of care and outcomes. Moreover, more than a third of delirium is preventable. Despite the clear significance of delirium and our increasingly sophisticated understanding of the condition, the gap between evidence and practice persists. The authors provide an educational review of 10 prevalent misconceptions of delirium pertaining to recognition, etiology, natural history, and best management. The authors respond to each with best evidence. Several themes emerge, chief among which is that casual observation is seldom sufficient to detect delirium. Use of open-ended questions, regular neurocognitive testing, and validated delirium screening instruments will aid in accurately identifying cases of delirium. Delirium is typically multifactorial, with several physiological and/or pharmacological contributors. Because of its multidetermined nature and its relationship with cognitive vulnerability, delirium can persist for days to months after acute causes have resolved. Furthermore, patients often have long-term cognitive impairment after delirium rather than returning to their predelirium cognitive baseline. Finally, nonpharmacological management of delirium is first-line, both for prevention and treatment. Psychotropic drugs such as neuroleptics are not recommended for routine use in delirium. They are best reserved for treating dangerous or distressing symptoms, including severe agitation, psychosis, or emotional lability. Challenging these 10 misconceptions stands to improve patient care, quality of life, and clinical outcomes substantially.

Miao H, Dong Y, Zhang Y, et al. Anesthetic Isoflurane or Desflurane Plus Surgery Differently Affects Cognitive Function in Alzheimer's Disease Transgenic Mice. Molecular neurobiology. 2018;55(7):5623-5638. doi:10.1007/s12035-017-0787-9

Anesthesia/surgery could be associated with cognitive impairment and Alzheimer's disease neuropathogenesis. However, whether surgery under different anesthetics has different effects on cognitive function remains largely unknown. We therefore set out to compare effects of anesthetic isoflurane or desflurane plus surgery on cognitive function and hippocampus levels of synaptic marker (postsynaptic density-95 and synaptophysin) and ATP. Five-month-old AD Transgenic (Tg) (FAD5X) and wild-type male mice received isoflurane or desflurane plus abdominal surgery. We assessed cognitive function in Barnes maze and measured hippocampus levels of postsynaptic density-95, synaptophysin, and ATP in the mice. We determined whether vitamin K2 could mitigate these anesthesia/surgery-induced changes. Isoflurane, but not desflurane, plus surgery increased escape latency and escape distance in Barnes maze probe test and reduced postsynaptic density-95, synaptophysin, and ATP levels as compared to control condition in AD Tg mice. Vitamin K2 attenuated the anesthesia/surgery-induced changes in the AD Tg mice. These findings suggest that isoflurane, but not desflurane, plus surgery might induce cognitive impairment via causing brain energy deficits. Pending confirmative studies in both animals and humans suggest desflurane could be a better choice for AD patients when surgery is needed. Moreover, vitamin K2 could treat cognitive deficiency associated with anesthesia and surgery.