Publications by authors named "Tamara G Fong"

68 Publications

Predictors of Caregiver Burden in Delirium: Patient and Caregiver Factors.

J Gerontol Nurs 2021 Sep 1;47(9):32-38. Epub 2021 Sep 1.

The current study examined the association of patient factors, patient/caregiver relationships, and living arrangements with caregiver burden due to delirium. The sample included a subset ( = 207) of hospitalized medical and surgical patients (aged >70 years) enrolled in the Better Assessment of Illness Study and their care-givers. The majority of caregivers were female (57%) and married (43%), and 47% reported living with the patient. Delirium occurred in 22% of the sample, and delirium severity, pre-existing cognitive impairment, and impairment of any activities of daily living (ADL) were associated with higher caregiver burden. However, only the ADL impairment of needing assistance with transfers was independently significantly associated with higher burden ( < 0.01). Child, child-in-law, and other relatives living with or apart from the patient reported significantly higher caregiver burden compared to spouse/partners ( < 0.01), indicating caregiver relationship and living arrangement are associated with burden. Future studies should examine additional factors contributing to delirium burden. [(9), 32-39.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3928/00989134-20210803-03DOI Listing
September 2021

Development and internal validation of a predictive model of cognitive decline 36 months following elective surgery.

Alzheimers Dement (Amst) 2021 21;13(1):e12201. Epub 2021 May 21.

Biogen Inc Cambridge Massachusetts USA.

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 ( ) 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dad2.12201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140204PMC
May 2021

Plasma and cerebrospinal fluid inflammation and the blood-brain barrier in older surgical patients: the Role of Inflammation after Surgery for Elders (RISE) study.

J Neuroinflammation 2021 Apr 30;18(1):103. Epub 2021 Apr 30.

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Background: Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation.

Methods: We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids.

Results: Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p < .01 for both) and IL-6 (PO1MO r = 0.48, p < .01) were observed, with higher correlations on PO1MO compared with baseline.

Conclusions: In this elective surgical sample of older adults, BBB integrity was similar between baseline and PO1MO, plasma-CSF correlations were observed for CRP and IL-6, plasma levels of all three markers (CRP, IL-6, and YKL-40) increased from PREOP to PO1MO, and CSF levels of only CRP increased between the two time points. Our identification of potential promising plasma markers of inflammation in the CNS may facilitate the early identification of patients at greatest risk for neuroinflammation and its associated adverse cognitive outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12974-021-02145-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088047PMC
April 2021

Association of CSF Alzheimer's disease biomarkers with postoperative delirium in older adults.

Alzheimers Dement (N Y) 2021 17;7(1):e12125. Epub 2021 Mar 17.

Aging Brain Center, Institute for Aging Research Hebrew SeniorLife Boston Massachusetts USA.

Introduction: The interaction between delirium and dementia is complex. We examined if Alzheimer's disease (AD) biomarkers in patients without clinical dementia are associated with increased risk of postoperative delirium, and whether AD biomarkers demonstrate a graded association with delirium severity.

Methods: Participants ( = 59) were free of clinical dementia, age 70 years, and scheduled for elective total knee or hip arthroplasties. Cerebrospinal fluid (CSF) was collected at the time of induction for spinal anesthesia. CSF AD biomarkers were measured by enzyme-linked immunosorbent assay (ELISA) (ADX/Euroimmun); cut points for amyloid, tau, and neurodegeneration (ATN) biomarker status were  = amyloid beta (Aβ) <175 pg/mL or Aβ ratio <0.07;  = p-tau >80 pg/mL; and  = t-tau >700 pg/mL. Confusion Assessment Method (CAM) and CAM-Severity (CAM-S) were rated daily post-operatively for delirium and delirium severity, respectively.

Results: Aβ, tau, and p-tau mean pg/mL (SD) were 361.5 (326.1), 618.3 (237.1), and 97.1 (66.1), respectively, for those with delirium, and 550.4 (291.6), 518.3 (213.5), and 54.6 (34.5), respectively, for those without delirium. Thirteen participants (22%) were ATN positive. Delirium severity by peak CAM-S [mean difference (95% confidence interval)] was 1.48 points higher (0.29-2.67),  = 0.02 among the ATN positive. Delirium in the ATN-positive group trended toward but did not reach statistical significance (23% vs. 7%, p = 0.10). Peak CAM-S [mean (SD)] in the delirium group was 7 (2.8) compared to no delirium group 2.5 (1.3), but when groups were further classified by ATN status, an incremental effect on delirium severity was observed, such that patients who were both ATN and delirium negative had the lowest mean (SD) peak CAM-S scores of 2.5 (1.3) points, whereas those who were ATN and delirium positive had CAM-S scores of 8.7 (2.3) points; other groups (either ATN or delirium positive) had intermediate CAM-S scores.

Discussion: The presence of AD biomarkers adds important information in predicting delirium severity. Future studies are needed to confirm this relationship and to better understand the role of AD biomarkers, even in pre-clinical phase, in delirium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/trc2.12125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968120PMC
March 2021

One-Year Medicare Costs Associated With Delirium in Older Patients Undergoing Major Elective Surgery.

JAMA Surg 2021 May;156(5):430-442

Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts.

Importance: Delirium is a common, serious, and potentially preventable problem for older adults, associated with adverse outcomes. Coupled with its preventable nature, these adverse sequelae make delirium a significant public health concern; understanding its economic costs is important for policy makers and health care leaders to prioritize care.

Objective: To evaluate current 1-year health care costs attributable to postoperative delirium in older patients undergoing elective surgery.

Design, Setting, And Participants: This prospective cohort study included 497 patients from the Successful Aging after Elective Surgery (SAGES) study, an ongoing cohort study of older adults undergoing major elective surgery. Patients were enrolled from June 18, 2010, to August 8, 2013. Eligible patients were 70 years or older, English-speaking, able to communicate verbally, and scheduled to undergo major surgery at 1 of 2 Harvard-affiliated hospitals with an anticipated length of stay of at least 3 days. Eligible surgical procedures included total hip or knee replacement; lumbar, cervical, or sacral laminectomy; lower extremity arterial bypass surgery; open abdominal aortic aneurysm repair; and open or laparoscopic colectomy. Data were analyzed from October 15, 2019, to September 15, 2020.

Exposures: Major elective surgery and hospitalization.

Main Outcomes And Measures: Cumulative and period-specific costs (index hospitalization, 30-day, 90-day, and 1-year follow-up) were examined using Medicare claims and extensive clinical data. Total inflation-adjusted health care costs were determined using data from Medicare administrative claims files for the 2010 to 2014 period. Delirium was rated using the Confusion Assessment Method. We also examined whether increasing delirium severity was associated with higher cumulative and period-specific costs. Delirium severity was measured with the Confusion Assessment Method-Severity long form. Regression models were used to determine costs associated with delirium after adjusting for patient demographic and clinical characteristics.

Results: Of the 566 patients who were eligible for the study, a total of 497 patients (mean [SD] age, 76.8 [5.1] years; 281 women [57%]; 461 White participants [93%]) were enrolled after exclusion criteria were applied. During the index hospitalization, 122 patients (25%) developed postoperative delirium, whereas 375 (75%) did not. Patients with delirium had significantly higher unadjusted health care costs than patients without delirium (mean [SD] cost, $146 358 [$140 469] vs $94 609 [$80 648]). After adjusting for relevant confounders, the cumulative health care costs attributable to delirium were $44 291 (95% CI, $34 554-$56 673) per patient per year, with the majority of costs coming from the first 90 days: index hospitalization ($20 327), subsequent rehospitalizations ($27 797), and postacute rehabilitation stays ($2803). Health care costs increased directly and significantly with level of delirium severity (none-mild, $83 534; moderate, $99 756; severe, $140 008), suggesting an exposure-response relationship. The adjusted mean cumulative costs attributable to severe delirium were $56 474 (95% CI, $40 927-$77 440) per patient per year. Extrapolating nationally, the health care costs attributable to postoperative delirium were estimated at $32.9 billion (95% CI, $25.7 billion-$42.2 billion) per year.

Conclusions And Relevance: These findings suggest that the economic outcomes of delirium and severe delirium after elective surgery are substantial, rivaling costs associated with cardiovascular disease and diabetes. These results highlight the need for policy imperatives to address delirium as a large-scale public health issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamasurg.2020.7260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905699PMC
May 2021

Proteome-Wide Analysis using SOMAscan Identifies and Validates Chitinase-3-Like Protein 1 as a Risk and Disease Marker of Delirium Among Older Adults Undergoing Major Elective Surgery.

J Gerontol A Biol Sci Med Sci 2021 Feb 4. Epub 2021 Feb 4.

Beth Israel Deaconess Medical Center.

Background: Delirium (an acute change in cognition) is a common, morbid, and costly syndrome seen primarily in aging adults. Despite increasing knowledge of its epidemiology, delirium remains a clinical diagnosis with no established biomarkers to guide diagnosis or management. Advances in proteomics now provide opportunities to identify novel markers of risk and disease progression for postoperative delirium and its associated long-term consequences (e.g., long term cognitive decline and Alzheimer's disease [AD]).

Methods: In a nested matched case-control study (18 delirium/no-delirium pairs) within the Successful Aging after Elective Surgery study (N=556), we evaluated the association of 1,305 plasma proteins preoperatively [PREOP] and on postoperative day 2 [POD2]) with delirium using SOMAscan. Generalized linear models were applied to ELISA validation data of one protein across the full cohort. Multi-protein modeling included delirium biomarkers identified in prior work (C-reactive protein, interleukin-6 [IL6]).

Results: We identified chitinase-3-like-protein-1 (CHI3L1/YKL-40) as the sole delirium-associated protein in both a PREOP and a POD2 predictor model, a finding confirmed by ELISA. Multi-protein modeling found high PREOP CHI3L1/YKL-40 and POD2 IL6 increased the risk of delirium (relative risk [95% confidence interval] Quartile [Q]4 vs. Q1: 2.4[1.2-5.0] and 2.1[1.1-4.1], respectively).

Conclusions: Our identification of CHI3L1/YKL-40 in postoperative delirium parallels reports of CHI3L1/YKL-40 and its association with aging, mortality, and age-related conditions including AD onset and progression. This highlights the type 2 innate immune response, involving CHI3L1/YKL-40, as an underlying mechanism of postoperative delirium, a common, morbid, and costly syndrome that threatens the independence of older adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gerona/glaa326DOI Listing
February 2021

Targeted metabolomics analysis of postoperative delirium.

Sci Rep 2021 01 15;11(1):1521. Epub 2021 Jan 15.

Department of Electrical and Computer Engineering, University of Nebraska-Lincoln, Nebraska Hall E419, P.O. Box 880511, Lincoln, NE, 68588, USA.

Postoperative delirium is the most common complication among older adults undergoing major surgery. The pathophysiology of delirium is poorly understood, and no blood-based, predictive markers are available. We characterized the plasma metabolome of 52 delirium cases and 52 matched controls from the Successful Aging after Elective Surgery (SAGES) cohort (N = 560) of patients ≥ 70 years old without dementia undergoing scheduled major non-cardiac surgery. We applied targeted mass spectrometry with internal standards and pooled controls using a nested matched case-control study preoperatively (PREOP) and on postoperative day 2 (POD2) to identify potential delirium risk and disease markers. Univariate analyses identified 37 PREOP and 53 POD2 metabolites associated with delirium and multivariate analyses achieved significant separation between the two groups with an 11-metabolite prediction model at PREOP (AUC = 83.80%). Systems biology analysis using the metabolites with differential concentrations rendered "valine, leucine, and isoleucine biosynthesis" at PREOP and "citrate cycle" at POD2 as the most significantly enriched pathways (false discovery rate < 0.05). Perturbations in energy metabolism and amino acid synthesis pathways may be associated with postoperative delirium and suggest potential mechanisms for delirium pathogenesis. Our results could lead to the development of a metabolomic delirium predictor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-80412-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810737PMC
January 2021

Delirium in Older Patients With COVID-19 Presenting to the Emergency Department.

JAMA Netw Open 2020 11 2;3(11):e2029540. Epub 2020 Nov 2.

Aging Brain Center, Marcus Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, Massachusetts.

Importance: Delirium is common among older emergency department (ED) patients, is associated with high morbidity and mortality, and frequently goes unrecognized. Anecdotal evidence has described atypical presentations of coronavirus disease 2019 (COVID-19) in older adults; however, the frequency of and outcomes associated with delirium in older ED patients with COVID-19 infection have not been well described.

Objective: To determine how frequently older adults with COVID-19 present to the ED with delirium and their associated hospital outcomes.

Design, Setting, And Participants: This multicenter cohort study was conducted at 7 sites in the US. Participants included consecutive older adults with COVID-19 presenting to the ED on or after March 13, 2020.

Exposure: COVID-19 was diagnosed by positive nasal swab for severe acute respiratory syndrome coronavirus 2 (99% of cases) or classic radiological findings (1% of cases).

Main Outcomes And Measures: The primary outcome was delirium as identified from the medical record according to a validated record review approach.

Results: A total of 817 older patients with COVID-19 were included, of whom 386 (47%) were male, 493 (62%) were White, 215 (27%) were Black, and 54 (7%) were Hispanic or Latinx. The mean (SD) age of patients was 77.7 (8.2) years. Of included patients, 226 (28%) had delirium at presentation, and delirium was the sixth most common of all presenting symptoms and signs. Among the patients with delirium, 37 (16%) had delirium as a primary symptom and 84 (37%) had no typical COVID-19 symptoms or signs, such as fever or shortness of breath. Factors associated with delirium were age older than 75 years (adjusted relative risk [aRR], 1.51; 95% CI, 1.17-1.95), living in a nursing home or assisted living (aRR, 1.23; 95% CI, 0.98-1.55), prior use of psychoactive medication (aRR, 1.42; 95% CI, 1.11-1.81), vision impairment (aRR, 1.98; 95% CI, 1.54-2.54), hearing impairment (aRR, 1.10; 95% CI 0.78-1.55), stroke (aRR, 1.47; 95% CI, 1.15-1.88), and Parkinson disease (aRR, 1.88; 95% CI, 1.30-2.58). Delirium was associated with intensive care unit stay (aRR, 1.67; 95% CI, 1.30-2.15) and death (aRR, 1.24; 95% CI, 1.00-1.55).

Conclusions And Relevance: In this cohort study of 817 older adults with COVID-19 presenting to US emergency departments, delirium was common and often was seen without other typical symptoms or signs. In addition, delirium was associated with poor hospital outcomes and death. These findings suggest the clinical importance of including delirium on checklists of presenting signs and symptoms of COVID-19 that guide screening, testing, and evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2020.29540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677760PMC
November 2020

Detecting Delirium: A Systematic Review of Identification Instruments for Non-ICU Settings.

J Am Geriatr Soc 2021 02 2;69(2):547-555. Epub 2020 Nov 2.

Departments of Psychiatry and Human Behavior and Neurology, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA.

Background/objectives: Delirium manifests clinically in varying ways across settings. More than 40 instruments currently exist for characterizing the different manifestations of delirium. We evaluated all delirium identification instruments according to their psychometric properties and frequency of citation in published research.

Design: We conducted the systematic review by searching Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Excerpta Medica Database (Embase), PsycINFO, PubMed, and Web of Science from January 1, 1974, to January 31, 2020, with the keywords "delirium" and "instruments," along with their known synonyms. We selected only systematic reviews, meta-analyses, or narrative literature reviews including multiple delirium identification instruments.

Measurements: Two reviewers assessed the eligibility of articles and extracted data on all potential delirium identification instruments. Using the original publication on each instrument, the psychometric properties were examined using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) framework.

Results: Of 2,542 articles identified, 75 met eligibility criteria, yielding 30 different delirium identification instruments. A count of citations was determined using Scopus for the original publication for each instrument. Each instrument underwent methodological quality review of psychometric properties using COSMIN definitions. An expert panel categorized key domains for delirium identification based on criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM)-III through DSM-5. Four instruments were notable for having at least two of three of the following: citation count of 200 or more, strong validation methodology in their original publication, and fulfillment of DSM-5 criteria. These were, alphabetically, Confusion Assessment Method, Delirium Observation Screening Scale, Delirium Rating Scale-Revised-98, and Memorial Delirium Assessment Scale.

Conclusion: Four commonly used and well-validated instruments can be recommended for clinical and research use. An important area for future investigation is to harmonize these measures to compare and combine studies on delirium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgs.16879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902461PMC
February 2021

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.

J Gen Intern Med 2021 02 19;36(2):265-273. Epub 2020 Oct 19.

Department of Psychiatry & Human Behavior, and Neurology, Brown University Warren Alpert Medical School, Providence, RI, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11606-020-06238-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878663PMC
February 2021

Association of Plasma Neurofilament Light with Postoperative Delirium.

Ann Neurol 2020 11 15;88(5):984-994. Epub 2020 Sep 15.

Aging Brain Center, Hebrew SeniorLife, Boston, Massachusetts, USA.

Objective: To examine the association of the plasma neuroaxonal injury markers neurofilament light (NfL), total tau, glial fibrillary acid protein, and ubiquitin carboxyl-terminal hydrolase L1 with delirium, delirium severity, and cognitive performance.

Methods: Delirium case-no delirium control (n = 108) pairs were matched by age, sex, surgery type, cognition, and vascular comorbidities. Biomarkers were measured in plasma collected preoperatively (PREOP), and 2 days (POD2) and 30 days postoperatively (PO1MO) using Simoa technology (Quanterix, Lexington, MA). The Confusion Assessment Method (CAM) and CAM-S (Severity) were used to measure delirium and delirium severity, respectively. Cognitive function was measured with General Cognitive Performance (GCP) scores.

Results: Delirium cases had higher NfL on POD2 and PO1MO (median matched pair difference = 16.2pg/ml and 13.6pg/ml, respectively; p < 0.05). Patients with PREOP and POD2 NfL in the highest quartile (Q4) had increased risk for incident delirium (adjusted odds ratio [OR] = 3.7 [95% confidence interval (CI) = 1.1-12.6] and 4.6 [95% CI = 1.2-18.2], respectively) and experienced more severe delirium, with sum CAM-S scores 7.8 points (95% CI = 1.6-14.0) and 9.3 points higher (95% CI = 3.2-15.5). At PO1MO, delirium cases had continued high NfL (adjusted OR = 9.7, 95% CI = 2.3-41.4), and those with Q4 NfL values showed a -2.3 point decline in GCP score (-2.3 points, 95% CI = -4.7 to -0.9).

Interpretation: Patients with the highest PREOP or POD2 NfL levels were more likely to develop delirium. Elevated NfL at PO1MO was associated with delirium and greater cognitive decline. These findings suggest NfL may be useful as a predictive biomarker for delirium risk and long-term cognitive decline, and once confirmed would provide pathophysiological evidence for neuroaxonal injury following delirium. ANN NEUROL 2020;88:984-994.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581557PMC
November 2020

Neighborhood-Level Social Disadvantage and Risk of Delirium Following Major Surgery.

J Am Geriatr Soc 2020 12 31;68(12):2863-2871. Epub 2020 Aug 31.

Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research at the Hebrew SeniorLife, Boston, Massachusetts, USA.

Background/objectives: Delirium is a common postoperative complication associated with prolonged length of stay, hospital readmission, and premature mortality. We explored the association between neighborhood-level characteristics and delirium incidence and severity, and compared neighborhood- with individual-level indicators of socioeconomic status in predicting delirium incidence.

Design: A prospective observational cohort of patients enrolled between June 18, 2010, and August 8, 2013. Baseline interviews were conducted before surgery, and delirium/delirium severity was evaluated daily during hospitalization. Research staff evaluating delirium were blinded to baseline cognitive status.

Setting: Two academic medical centers in Boston, MA.

Participants: A total of 560 older adults, aged 70 years or older, undergoing major noncardiac surgery.

Intervention: The Area Deprivation Index (ADI) was used to characterize each neighborhood's socioeconomic disadvantage.

Measurements: Delirium was assessed using the Confusion Assessment Method (CAM) long form. Delirium severity was calculated using the highest value of CAM Severity score (CAM-S) occurring during daily hospital assessments (CAM-S Peak).

Results: Residing in the most disadvantaged neighborhoods (ADI > 44) was associated with a higher risk of incident delirium (12/26; 46%), compared with the least disadvantaged neighborhoods (122/534; 23%) (risk ratio (RR) (95% confidence interval (CI)) = 2.0 (1.3-3.1). The CAM-S Peak score was significantly associated with ADI (Spearman rank correlation, ρ = 0.11; P = .009). Mean CAM-S Peak scores generally rose from 3.7 to 5.3 across levels of increasing neighborhood disadvantage. The RR (95% CI) values associated with individual-level markers of socioeconomic status and cultural background were: 1.2 (0.9-1.7) for education of 12 years or less; 1.3 (0.8-2.1) for non-White race; and 1.7 (1.1-2.6) for annual household income of less than $20,000. None of these individual-level markers exceeded the ADI in terms of effect size or significance for prediction of delirium risk.

Conclusions: Neighborhood-level makers of social disadvantage are associated with delirium incidence and severity, and demonstrated an exposure-response relationship. Future studies should consider contextual-level metrics, such as the ADI, as risk markers of social disadvantage that can help to guide delirium treatment and prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgs.16782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744425PMC
December 2020

The Role of Inflammation after Surgery for Elders (RISE) study: Examination of [C]PBR28 binding and exploration of its link to post-operative delirium.

Neuroimage Clin 2020 14;27:102346. Epub 2020 Jul 14.

Harvard Medical School, Boston, MA, United States; Frontotemporal Disorders Unit, Massachusetts General Hospital, Boston, MA, United States; Department of Neurology, Massachusetts General Hospital, Boston, MA, United States; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, United States.

Major surgery is associated with a systemic inflammatory cascade that is thought, in some cases, to contribute to transient and/or sustained cognitive decline, possibly through neuroinflammatory mechanisms. However, the relationship between surgery, peripheral and central nervous system inflammation, and post-operative cognitive outcomes remains unclear in humans, primarily owing to limitations of in vivo biomarkers of neuroinflammation which vary in sensitivity, specificity, validity, and reliability. In the present study, [C]PBR28 positron emission tomography, cerebrospinal fluid (CSF), and blood plasma biomarkers of inflammation were assessed pre-operatively and 1-month post-operatively in a cohort of patients (N = 36; 30 females; ≥70 years old) undergoing major orthopedic surgery under spinal anesthesia. Delirium incidence and severity were evaluated daily during hospitalization. Whole-brain voxel-wise and regions-of-interest analyses were performed to determine the magnitude and spatial extent of changes in [C]PBR28 uptake following surgery. Results demonstrated that, compared with pre-operative baseline, [C]PBR28 binding in the brain was globally downregulated at 1 month following major orthopedic surgery, possibly suggesting downregulation of the immune system of the brain. No significant relationship was identified between post-operative delirium and [C]PBR28 binding, possibly due to a small number (n = 6) of delirium cases in the sample. Additionally, no significant relationships were identified between [C]PBR28 binding and CSF/plasma biomarkers of inflammation. Collectively, these results contribute to the literature by demonstrating in a sizeable sample the effect of major surgery on neuroimmune activation and preliminary evidence identifying no apparent associations between [C]PBR28 binding and fluid inflammatory markers or post-operative delirium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2020.102346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390821PMC
June 2021

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

Dement Geriatr Cogn Disord 2020 17;49(1):77-90. Epub 2020 Jun 17.

Department of Psychiatry and Human Behavior, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000506700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484102PMC
January 2021

Does Alzheimer's Disease and Related Dementias Modify Delirium Severity and Hospital Outcomes?

J Am Geriatr Soc 2020 08 7;68(8):1722-1730. Epub 2020 Apr 7.

Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research, Boston, Massachusetts, USA.

Objectives: We examined the association between delirium severity and outcomes of delirium among persons with and without Alzheimer's disease and related dementias (ADRD).

Design: Prospective cohort study.

Setting: Academic tertiary medical center.

Participants: A total of 352 medical and surgical patients.

Measurements: Delirium incidence and severity were rated daily using the Confusion Assessment Method (CAM) and CAM-Severity (CAM-S) score during hospitalization. Severe delirium was defined as a CAM-S Short Form score in the highest tertile (3-7 points out of 7). ADRD status was determined by a clinical consensus process. Clinical outcomes included prolonged length of stay (>6 d), discharge to post-acute nursing facility, any decline in activities of daily living (ADLs) at 1 month from prehospital baseline, ongoing nursing facility stay, and mortality.

Results: Patients with ADRD (n = 85 [24%]) had a significantly higher relative risk (RR) for incident delirium (RR = 2.31; 95% confidence interval [CI] = 1.64-3.28) and higher peak CAM-S scores (mean difference = 1.24 points; CI = .83-1.65; P < .001). Among patients with ADRD, severe delirium significantly increased the RR for nursing facility stay (RR = 2.22; CI = 1.05-4.69; P = .04) and increased the RR for mortality (RR = 2.10; CI = .89-4.98; P = .09). Among patients without ADRD, severe delirium was associated with a significantly increased risk for all poor outcomes except mortality including prolonged length of stay in the hospital (RR = 1.47; CI = 1.18-1.82) and discharge to a post-acute nursing facility (RR = 2.17; CI = 1.58-2.98) plus decline in ADLs (RR = 1.30; CI = 1.05-1.60) and nursing facility stay at 1 month (RR = 1.93; CI = 1.31-2.83).

Conclusion: Severe delirium is associated with increased risk for poor clinical outcomes in patients with and without ADRD. In both groups, severe delirium increased risk of nursing home placement. In patients with ADRD, delirium was more severe and associated with a trend toward increased mortality at 1 month. Although the increased risk remains substantial by RR, the study had limited power to examine the rarer outcome of death. J Am Geriatr Soc 68:1722-1730, 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgs.16420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725352PMC
August 2020

Older Patients with Alzheimer's Disease-Related Cortical Atrophy Who Develop Post-Operative Delirium May Be at Increased Risk of Long-Term Cognitive Decline After Surgery.

J Alzheimers Dis 2020 ;75(1):187-199

Harvard Medical School, Boston, MA, USA.

Background: Older surgical patients with Alzheimer's disease (AD) dementia and delirium are at increased risk for accelerated long-term cognitive decline.

Objective: Investigate associations between a probabilistic marker of preclinical AD, delirium, and long-term cognitive decline.

Methods: The Successful Aging after Elective Surgery cohort includes older adults (≥70 years) without dementia who underwent elective surgery. 140 patients underwent preoperative magnetic resonance imaging and had≥6 months cognitive follow-up. Cortical thickness was measured in 'AD-Signature' regions. Delirium was evaluated each postoperative day by the Confusion Assessment Method. Cognitive performance was assessed using a detailed neuropsychological battery at baseline; months 1, 2, and 6; and every 6 months thereafter until 36 months. Using either a General Cognitive Performance composite (GCP) or individual test scores as outcomes, we performed linear mixed effects models to examine main effects of AD-signature atrophy and the interaction of AD-signature atrophy and delirium on slopes of cognitive change from post-operative months 2-36.

Results: Reduced baseline AD-signature cortical thickness was associated with greater 36-month cognitive decline in GCP (standardized beta coefficient, β = -0.030, 95% confidence interval [-0.060, -0.001]). Patients who developed delirium who also had thinner AD signature cortex showed greater decline on a verbal learning test (β = -0.100 [-0.192, -0.007]).

Conclusion: Patients with the greatest baseline AD-related cortical atrophy who develop delirium after elective surgery appear to experience the greatest long-term cognitive decline. Thus, atrophy suggestive of preclinical AD and the development of delirium may be high-risk indicators for long-term cognitive decline following surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-190380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304614PMC
May 2021

Apolipoprotein E genotype and the association between C-reactive protein and postoperative delirium: Importance of gene-protein interactions.

Alzheimers Dement 2020 03 4;16(3):572-580. Epub 2020 Jan 4.

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Introduction: Apolipoprotein E (APOE) status may modify the risk of postoperative delirium conferred by inflammation.

Methods: We tested whether APOE modifies the established association between C-reactive protein (CRP) and delirium incidence, severity, and duration in 553 noncardiac surgical patients aged 70 and older. High postoperative plasma CRP (≥234.12 mg/L) was defined by the highest sample-based quartile. Delirium was determined using the Confusion Assessment Method and chart review, and severity was determined by the Confusion Assessment Method-Severity score.

Results: APOE ε4 carrier prevalence was 19%, and postoperative delirium occurred in 24%. The relationship between CRP and delirium incidence, severity, and duration differed by ε4 status. Among ε4 carriers, there was a strong relationship between high CRP (vs. low CRP) and delirium incidence (relative risk [95% confidence interval], 3.0 [1.4-6.7]); however, no significant association was observed among non-ε4 carriers (relative risk [95% CI], 1.2 [0.8-1.7]).

Discussion: Our findings raise the possibility that APOE ε4 carrier status may modify the relationship between postoperative day 2 CRP levels and postoperative delirium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jalz.2019.09.080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086383PMC
March 2020

The Role of Inflammation after Surgery for Elders (RISE) study: Study design, procedures, and cohort profile.

Alzheimers Dement (Amst) 2019 Dec 6;11:752-762. Epub 2019 Nov 6.

Aging Brain Center, Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.

Introduction: The Role of Inflammation after Surgery for Elders study correlates novel inflammatory markers measured in blood, cerebrospinal fluid (CSF) assays, and [C]-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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dadm.2019.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849121PMC
December 2019

The Caregiver Burden of Delirium in Older Adults With Alzheimer Disease and Related Disorders.

J Am Geriatr Soc 2019 12 12;67(12):2587-2592. Epub 2019 Oct 12.

Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, Massachusetts.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgs.16199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898752PMC
December 2019

Use of an expert panel to identify domains and indicators of delirium severity.

Qual Life Res 2019 Sep 17;28(9):2565-2578. Epub 2019 May 17.

Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.

Purpose: Our purpose was to create a content domain framework for delirium severity to inform item development for a new instrument to measure delirium severity.

Methods: We used an established, multi-stage instrument development process during which expert panelists discussed best approaches to measure delirium severity and identified related content domains. We conducted this work as part of the Better ASsessment of ILlness (BASIL) study, a prospective, observational study aimed at developing and testing measures of delirium severity. Our interdisciplinary expert panel consisted of twelve national delirium experts and four expert members of the core research group. Over a one-month period, experts participated in two rounds of review.

Results: Experts recommended that the construct of delirium severity should reflect both the phenomena and the impact of delirium to create an accurate, patient-centered instrument useful to interdisciplinary clinicians and family caregivers. Final content domains were Cognitive, Level of consciousness, Inattention, Psychiatric-Behavioral, Emotional dysregulation, Psychomotor features, and Functional. Themes debated by experts included reconciling clinical geriatrics and psychiatric content, mapping symptoms to one specific domain, and accurate capture of unclear clinical presentations.

Conclusions: We believe this work represents the first application of instrument development science to delirium. The identified content domains are inclusive of various, wide-ranging domains of delirium severity and are reflective of a consistent framework that relates delirium severity to potential clinical outcomes. Our content domain framework provides a foundation for development of delirium severity instruments that can help improve care and quality of life for patients with delirium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11136-019-02201-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858057PMC
September 2019

Identification of Plasma Proteome Signatures Associated With Surgery Using SOMAscan.

Ann Surg 2021 04;273(4):732-742

Harvard Medical School, Boston, MA.

Objectives: To characterize the proteomic signature of surgery in older adults and association with postoperative outcomes.

Summary Of Background Data: Circulating plasma proteins can reflect the physiological response to and clinical outcomes after surgery.

Methods: Blood plasma from older adults undergoing elective surgery was analyzed for 1305 proteins using SOMAscan. Surgery-associated proteins underwent Ingenuity Pathways Analysis. Selected surgery-associated proteins were independently validated using Luminex or enzyme-linked immunosorbent assay methods. Generalized linear models estimated correlations with postoperative outcomes.

Results: Plasma from a subcohort (n = 36) of the Successful Aging after Elective Surgery (SAGES) study was used for SOMAscan. Systems biology analysis of 110 proteins with Benjamini-Hochberg (BH) corrected P value ≤0.01 and an absolute foldchange (|FC|) ≥1.5 between postoperative day 2 (POD2) and preoperative (PREOP) identified functional pathways with major effects on pro-inflammatory proteins. Chitinase-3-like protein 1 (CHI3L1), C-reactive protein (CRP), and interleukin-6 (IL-6) were independently validated in separate validation cohorts from SAGES (n = 150 for CRP, IL-6; n = 126 for CHI3L1). Foldchange CHI3L1 and IL-6 were associated with increased postoperative complications [relative risk (RR) 1.50, 95% confidence interval (95% CI) 1.21-1.85 and RR 1.63, 95% CI 1.18-2.26, respectively], length of stay (RR 1.35, 95% CI 0.77-1.92 and RR 0.98, 95% CI 0.52-1.45), and risk of discharge to postacute facility (RR 1.15, 95% CI 1.04-1.26 and RR 1.11, 95% CI 1.04-1.18); POD2 and PREOP CRP difference was associated with discharge to postacute facility (RR 1.14, 95% CI 1.04-1.25).

Conclusion: SOMAscan can identify novel and clinically relevant surgery-induced protein changes. Ultimately, proteomics may provide insights about pathways by which surgical stress contributes to postoperative outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832727PMC
April 2021

Delirium and Alzheimer disease: A proposed model for shared pathophysiology.

Int J Geriatr Psychiatry 2019 06 15;34(6):781-789. Epub 2019 Mar 15.

Aging Brain Center, Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gps.5088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830540PMC
June 2019

Assessment of Instruments for Measurement of Delirium Severity: A Systematic Review.

JAMA Intern Med 2019 02;179(2):231-239

Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts.

Importance: Measurement of delirium severity has been recognized as highly important for tracking prognosis, monitoring response to treatment, and estimating burden of care for patients both during and after hospitalization. Rather than simply rating delirium as present or absent, the ability to quantify its severity would enable development and monitoring of more effective treatment approaches for the condition.

Objectives: To present a comprehensive review of delirium severity instruments, conduct a methodologic quality rating of the original validation study of the most commonly used instruments, and select a group of top-rated instruments.

Evidence Review: This systematic review was conducted using literature from Embase, PsycINFO, PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature, from January 1, 1974, through March 31, 2017, with the key words delirium, severity, tests, measures, and intensity. Inclusion criteria were original articles assessing delirium severity and using a delirium-specific severity instrument. Final listings of articles were supplemented with hand searches of reference listings to ensure completeness. At least 2 reviewers independently completed each step of the review process: article selection, data extraction, and methodologic quality assessment of relevant articles using a validated rating scale. All discrepancies between raters were resolved by consensus.

Findings: Of 9409 articles identified, 228 underwent full text review, and we identified 42 different instruments of delirium severity. Eleven of the 42 tools were multidomain, delirium-specific instruments providing a quantitative rating of delirium severity; these instruments underwent a methodologic quality review. Applying prespecified criteria related to frequency of use, methodologic quality, construct or predictive validity, and broad domain coverage, an expert panel used an iterative modified Delphi process to select 6 final high-quality instruments meeting these criteria: the Confusion Assessment Method-Severity Score, Confusional State Examination, Delirium-O-Meter, Delirium Observation Scale, Delirium Rating Scale, and Memorial Delirium Assessment Scale.

Conclusions And Relevance: The 6 instruments identified may enable accurate measurement of delirium severity to improve clinical care for patients with this condition. This work may stimulate increased usage and head-to-head comparison of these instruments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamainternmed.2018.6975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382582PMC
February 2019

The Telephone Interview for Cognitive Status.

Cogn Behav Neurol 2018 09;31(3):156-157

Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNN.0000000000000165DOI Listing
September 2018

The Better Assessment of Illness Study for Delirium Severity: Study Design, Procedures, and Cohort Description.

Gerontology 2019 20;65(1):20-29. Epub 2018 Jul 20.

Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts, USA.

Background/objectives: To describe the design, procedures, and cohort for the Better ASsessment of ILlness -(BASIL) study, which is conducted to develop and test new delirium severity measures, compare them with existing measures, and examine related clinical outcomes.

Methods: Prospective cohort study with 1 year follow-up of study participants at a large teaching hospital in Boston, Massachusetts. After brief cognitive testing and the Delirium Symptom Interview, delirium and delirium severity were rated daily in the hospital using the Confusion Assessment Method (CAM) and CAM-Severity score, the Delirium Rating Scale-Revised-98 (DRS-R-98), and the Memorial Delirium Assessment Scale (MDAS). Other key study variables included comorbidity, physical function (basic and instrumental activities of daily living [ADL]), ratings of subjective health and well-being, and clinical outcomes (length of stay, 30 day rehospitalization, nursing home admission, healthcare utilization). Follow-up interviews occurred at 1- and 12-month with patients and families. In 42 patient interviews, inter-rater reliability for key variables was assessed.

Results: Of 768 eligible patients approached, 469 were screened and 352 enrolled, yielding an overall study response rate of 67% for potentially eligible participants. The mean participant was 80.3 years old (SD 6.8) and 203 (58%) were female. The majority of patients were medically complex with Charlson Comorbidity Scores ≥2 (192 patients, 55%), and 102 (29%) met criteria for dementia. Inter-rater reliability assessments (n = 42 pairs) were high for overall ratings of presence or absence of delirium by CAM (κ = 1.0), delirium severity by DRS-R-98 and MDAS (weighted kappa, κ = 1.0 for each) and for ADL impairment (κ = 1.0). For eligible participants at each time point, 278 out of 308 (90%) completed the 1-month follow-up and 132 out of 256 (53%) have completed the 12-month follow-up to date, which is still in progress. Among those who completed interviews, there was only 1-3% missing data on most major outcomes (delirium, basic ADL, and readmission).

Conclusion: The BASIL study presents an innovative effort to advance the conceptualization and measurement of delirium severity. Unique strengths include the diverse cohort with complete high quality data and longitudinal follow-up, along with detailed collection of multiple delirium measures daily during hospitalization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000490386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335161PMC
May 2019

Correction for retest effects across repeated measures of cognitive functioning: a longitudinal cohort study of postoperative delirium.

BMC Med Res Methodol 2018 07 3;18(1):69. Epub 2018 Jul 3.

Department of Psychiatry and Human Behavior and Neurology, Brown University Warren Alpert Medical School, Providence, RI, USA.

Background: Few studies have compared methods to correct for retest effects or practice effects in settings where an acute event could influence test performance, such as major surgery. Our goal in this study was to evaluate the use of different methods to correct for the effects of practice or retest on repeated test administration in the context of an observational study of older adults undergoing elective surgery.

Methods: In a cohort of older surgical patients (N = 560) and a non-surgical comparison group (N = 118), we compared changes on repeated cognitive testing using a summary measure of general cognitive performance (GCP) between patients who developed post-operative delirium and those who did not. Surgical patients were evaluated pre-operatively and at 1, 2, 6, 12, and 18 months following surgery. Inferences from linear mixed effects models using four approaches were compared: 1) no retest correction, 2) mean-difference correction, 3) predicted-difference correction, and 4) model-based correction.

Results: Using Approaches 1 or 4, which use uncorrected data, both surgical groups appeared to improve or remain stable after surgery. In contrast, Approaches 2 and 3, which dissociate retest and surgery effects by using retest-adjusted GCP scores, revealed an acute decline in performance in both surgical groups followed by a recovery to baseline. Relative differences between delirium groups were generally consistent across all approaches: the delirium group showed greater short- and longer-term decline compared to the group without delirium, although differences were attenuated after 2 months. Standard errors and model fit were also highly consistent across approaches.

Conclusion: All four approaches would lead to nearly identical inferences regarding relative mean differences between groups experiencing a key post-operative outcome (delirium) but produced qualitatively different impressions of absolute performance differences following surgery. Each of the four retest correction approaches analyzed in this study has strengths and weakness that should be evaluated in the context of future studies. Retest correction is critical for interpretation of absolute cognitive performance measured over time and, consequently, for advancing our understanding of the effects of exposures such as surgery, hospitalization, acute illness, and delirium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12874-018-0530-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029140PMC
July 2018

Clinical outcomes in older surgical patients with mild cognitive impairment.

Alzheimers Dement 2018 05 27;14(5):590-600. Epub 2017 Nov 27.

Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jalz.2017.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938115PMC
May 2018

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

J Alzheimers Dis 2018 ;61(1):347-358

Harvard Medical School, Boston, MA, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-170288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714669PMC
July 2018

Delirium in Older Persons: Advances in Diagnosis and Treatment.

JAMA 2017 09;318(12):1161-1174

Aging Brain Center, Hebrew SeniorLife, Boston, Massachusetts.

Importance: Delirium is defined as an acute disorder of attention and cognition. It is a common, serious, and often fatal condition among older patients. Although often underrecognized, delirium has serious adverse effects on the individual's function and quality of life, as well as broad societal effects with substantial health care costs.

Objective: To summarize the current state of the art in diagnosis and treatment of delirium and to highlight critical areas for future research to advance the field.

Evidence Review: Search of Ovid MEDLINE, Embase, and the Cochrane Library for the past 6 years, from January 1, 2011, until March 16, 2017, using a combination of controlled vocabulary and keyword terms. Since delirium is more prevalent in older adults, the focus was on studies in elderly populations; studies based solely in the intensive care unit (ICU) and non-English-language articles were excluded.

Findings: Of 127 articles included, 25 were clinical trials, 42 cohort studies, 5 systematic reviews and meta-analyses, and 55 were other categories. A total of 11 616 patients were represented in the treatment studies. Advances in diagnosis have included the development of brief screening tools with high sensitivity and specificity, such as the 3-Minute Diagnostic Assessment; 4 A's Test; and proxy-based measures such as the Family Confusion Assessment Method. Measures of severity, such as the Confusion Assessment Method-Severity Score, can aid in monitoring response to treatment, risk stratification, and assessing prognosis. Nonpharmacologic approaches focused on risk factors such as immobility, functional decline, visual or hearing impairment, dehydration, and sleep deprivation are effective for delirium prevention and also are recommended for delirium treatment. Current recommendations for pharmacologic treatment of delirium, based on recent reviews of the evidence, recommend reserving use of antipsychotics and other sedating medications for treatment of severe agitation that poses risk to patient or staff safety or threatens interruption of essential medical therapies.

Conclusions And Relevance: Advances in diagnosis can improve recognition and risk stratification of delirium. Prevention of delirium using nonpharmacologic approaches is documented to be effective, while pharmacologic prevention and treatment of delirium remains controversial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2017.12067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717753PMC
September 2017
-->