Association of Loneliness With Change in Physical and Emotional Health of Older Adults During the COVID-19 Shutdown.

OBJECTIVES: To examine factors influencing loneliness and the effect of loneliness on physical and emotional health, in the context of the COVID-19 pandemic. DESIGN: Prospective, observational cohort. SETTING: Community-dwelling participants. PARTICIPANTS: Older adults (n = 238) enrolled in a longitudinal study. MEASUREMENTS: Interviews were completed July-December 2020. Loneliness was measured with the UCLA 3-item loneliness scale. Data including age, marriage, education, cognitive functioning, functional impairment, vision or hearing impairment, depression, anxiety, medical comorbidity, social network size, technology use, and activity engagement were collected. Health outcomes included self-rated health, and physical and mental composites from the 12-item Short Form Survey. Physical function was measured by a PROMIS-scaled composite score. RESULTS: Thirty-nine (16.4%) participants reported loneliness. Vulnerability factors for loneliness included age (RR = 1.08, 95% CI 1.02-1.14); impairment with instrumental activities of daily living (RR = 2.08, 95% CI 1.14-3.80); vision impairment (RR = 2.09, 95% CI 1.10-3.97); depression (RR = 1.34, 95% CI 1.25-1.43); and anxiety (RR = 1.92, 95% CI 1.55-2.39). Significant resilience factors included high cognitive functioning (RR = 0.88, 95% CI 0.83-0.94); large social network size (RR = 0.92, 95% CI 0.88-0.96); technology use (RR = 0.81, 95% CI 0.73-0.90); and social and physical activity engagement (RR = 0.91, 95% CI 0.85-0.98). Interaction analyses showed that larger social network size moderated the effect of loneliness on physical function (protective interaction effect, RR = 0.64, 95% CI 0.15-1.13, p <.01), and activity engagement moderated the effect of loneliness on mental health (protective interaction effect, RR = 0.65, 95% CI 0.25-1.05, p <.001). CONCLUSIONS: Resilience factors may mitigate the adverse health outcomes associated with loneliness. Interventions to enhance resilience may help to diminish the detrimental effects of loneliness and hold great importance for vulnerable older adults.

Patterns and Persistence of Perioperative Plasma and Cerebrospinal Fluid Neuroinflammatory Protein Biomarkers After Elective Orthopedic Surgery Using SOMAscan.

BACKGROUND: The neuroinflammatory response to surgery can be characterized by peripheral acute plasma protein changes in blood, but corresponding, persisting alterations in cerebrospinal fluid (CSF) proteins remain mostly unknown. Using the SOMAscan assay, we define acute and longer-term proteome changes associated with surgery in plasma and CSF. We hypothesized that biological pathways identified by these proteins would be in the categories of neuroinflammation and neuronal function and define neuroinflammatory proteome changes associated with surgery in older patients. METHODS: SOMAscan analyzed 1305 proteins in blood plasma (n = 14) and CSF (n = 15) samples from older patients enrolled in the Role of Inflammation after Surgery for Elders (RISE) study undergoing elective hip and knee replacement surgery with spinal anesthesia. Systems biology analysis identified biological pathways enriched among the surgery-associated differentially expressed proteins in plasma and CSF. RESULTS: Comparison of postoperative day 1 (POD1) to preoperative (PREOP) plasma protein levels identified 343 proteins with postsurgical changes ( P < .05; absolute value of the fold change [|FC|] > 1.2). Comparing postoperative 1-month (PO1MO) plasma and CSF with PREOP identified 67 proteins in plasma and 79 proteins in CSF with altered levels ( P < .05; |FC| > 1.2). In plasma, 21 proteins, primarily linked to immune response and inflammation, were similarly changed at POD1 and PO1MO. Comparison of plasma to CSF at PO1MO identified 8 shared proteins. Comparison of plasma at POD1 to CSF at PO1MO identified a larger number, 15 proteins in common, most of which are regulated by interleukin-6 (IL-6) or transforming growth factor beta-1 (TGFB1) and linked to the inflammatory response. Of the 79 CSF PO1MO-specific proteins, many are involved in neuronal function and neuroinflammation. CONCLUSIONS: SOMAscan can characterize both short- and long-term surgery-induced protein alterations in plasma and CSF. Acute plasma protein changes at POD1 parallel changes in PO1MO CSF and suggest 15 potential biomarkers for longer-term neuroinflammation that warrant further investigation.

One-year Medicare costs associated with delirium in older hospitalized patients with and without Alzheimer's disease dementia and related disorders.

INTRODUCTION: One-year health-care costs associated with delirium in older hospitalized patients with and without Alzheimer's disease and related dementias (ADRD) have not been examined previously. METHODS: Medicare costs were determined prospectively at discharge, and at 30, 90, and 365 days in a cohort (n = 311) of older adults after hospital admission. RESULTS: Seventy-six (24%) patients had ADRD and were more likely to develop delirium (51% vs. 24%, P < 0.001) and die within 1 year (38% vs. 21%, P = 0.002). In ADRD patients with versus without delirium, adjusted mean difference in costs associated with delirium were $34,828; most of the excess costs were incurred between 90 and 365 days (P = 0.03). In non-ADRD patients, delirium was associated with increased costs at all timepoints. Excess costs associated with delirium in ADRD patients increased progressively over 1 year, whereas in non-ADRD patients the increase was consistent across time periods. DISCUSSION: Our findings highlight the complexity of health-care costs for ADRD patients who develop delirium, a potentially preventable source of expenditures. HIGHLIGHTS: Novel examination of health-care costs of delirium in persons with and without Alzheimer's disease and related dementias (ADRD). Increased 1-year costs of $34,828 in ADRD patients with delirium (vs. without). Increased costs for delirium in ADRD occur later during the 365-day study period. For ADRD patients, cost differences between those with and without delirium increased over 1 year. For non-ADRD patients, the parallel cost differences were consistent over time.

Association of Polypharmacy and Potentially Inappropriate Medications With Frailty Among Older Adults With Blood Cancers.

BACKGROUND: Polypharmacy and potentially inappropriate medications (PIMs) are common among older adults with blood cancers, but their association with frailty and how to manage them optimally remain unclear. PATIENTS AND METHODS: From 2015 to 2019, patients aged ≥75 years presenting for initial oncology consult underwent screening geriatric assessment. Patients were determined to be robust, prefrail, or frail via deficit accumulation and phenotypic approaches. We quantified each patient's total number of medications and PIMs using the Anticholinergic Risk Scale (ARS) and a scale we generated using the NCCN Medications of Concern called the Geriatric Oncology Potentially Inappropriate Medications (GO-PIM) scale. We assessed cross-sectional associations of PIMs with frailty in multivariable regression models adjusting for age, gender, and comorbidity. RESULTS: Of 785 patients assessed, 603 (77%) were taking ≥5 medications and 421 (54%) were taking ≥8 medications; 201 (25%) were taking at least 1 PIM based on the ARS and 343 (44%) at least 1 PIM based on the GO-PIM scale. Among the 468 (60%) patients on active cancer treatment, taking ≥8 medications was associated with frailty (adjusted odds ratio [aOR], 2.82; 95% CI, 1.92-4.17). With each additional medication, the odds of being prefrail or frail increased 8% (aOR, 1.08; 95% CI, 1.04-1.12). With each 1-point increase on the ARS, the odds of being prefrail or frail increased 19% (aOR, 1.19; 95% CI, 1.03-1.39); with each additional PIM based on the GO-PIM scale, the odds increased 65% (aOR, 1.65; 95% CI, 1.34-2.04). CONCLUSIONS: Polypharmacy and PIMs are prevalent among older patients with blood cancers; taking ≥8 medications is strongly associated with frailty. These data suggest careful medication reconciliation for this population may be helpful, and deprescribing when possible is high-yield, especially for PIMs on the GO-PIM scale.

Identifying Delirium in Persons With Moderate or Severe Dementia: Review of Challenges and an Illustrative Approach.

Delirium and dementia are common causes of cognitive impairment among older adults, which often coexist. Delirium is associated with poor clinical outcomes, and is more frequent and more severe in patients with dementia. Identifying delirium in the presence of dementia, also described as delirium superimposed on dementia (DSD), is particularly challenging, as symptoms of delirium such as inattention, cognitive dysfunction, and altered level of consciousness, are also features of dementia. Because DSD is associated with poorer clinical outcomes than dementia alone, detecting delirium is important for reducing morbidity and mortality in this population. We review a number of delirium screening instruments that have shown promise for use in DSD, including the 4-DSD, combined Six Item Cognitive Impairment Test (6-CIT) and 4 'A's Test (4AT), Confusion Assessment Method (CAM), and the combined UB2 and 3D-CAM (UB-CAM). Each has advantages and disadvantages. We then describe the operationalization of a CAM-based approach in a current ECT in dementia project as an example of modifying an existing instrument for patients with moderate to severe dementia. Ultimately, any instrument modified will need to be validated against a standard clinical reference, in order to fully establish its sensitivity and specificity in the moderate to severe dementia population. Future work is greatly needed to advance the challenging area of accurate identification of delirium in moderate or severe dementia.

Gait speed, grip strength, and clinical outcomes in older patients with hematologic malignancies.

This study aimed to evaluate whether gait speed and grip strength predicted clinical outcomes among older adults with blood cancers. We prospectively recruited 448 patients aged 75 years and older presenting for initial consultation at the myelodysplastic syndrome/leukemia, myeloma, or lymphoma clinic of a large tertiary hospital, who agreed to assessment of gait and grip. A subset of 314 patients followed for ≥6 months at local institutions was evaluated for unplanned hospital or emergency department (ED) use. We used Cox proportional hazard models calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for survival, and logistic regression to calculate odds ratios (ORs) for hospital or ED use. Mean age was 79.7 (± 4.0 standard deviation) years. After adjustment for age, sex, Charlson comorbidity index, cognition, treatment intensity, and cancer aggressiveness/type, every 0.1-m/s decrease in gait speed was associated with higher mortality (HR, 1.20; 95% CI, 1.12-1.29), odds of unplanned hospitalizations (OR, 1.33; 95% CI, 1.16-1.51), and ED visits (OR, 1.34; 95% CI, 1.17-1.53). Associations held among patients with good Eastern Cooperative Oncology Group performance status (0 or 1). Every 5-kg decrease in grip strength was associated with worse survival (adjusted HR, 1.24; 95% CI, 1.07-1.43) but not hospital or ED use. A model with gait speed and all covariates had comparable predictive power to comprehensive validated frailty indexes (phenotype and cumulative deficit) and all covariates. In summary, gait speed is an easily obtained "vital sign" that accurately identifies frailty and predicts outcomes independent of performance status among older patients with blood cancers.

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

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

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

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

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

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.

Hospital Elder Life Program: Systematic Review and Meta-analysis of Effectiveness.

BACKGROUND: Delirium, defined as an acute disorder of attention and cognition with high morbidity and mortality, can be prevented by multicomponent nonpharmacological interventions. The Hospital Elder Life Program (HELP) is the original evidence-based approach targeted to delirium risk factors, which has been widely disseminated. OBJECTIVE: To summarize the current state of the evidence regarding HELP and to highlight its effectiveness and cost savings. METHODS: Systematic review of Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from 1999 to 2017, using a combination of controlled vocabulary and keyword terms. RESULTS: Of the 44 final articles included, 14 were included in the meta-analysis for effectiveness and 30 were included for examining cost savings, adherence and adaptations, role of volunteers, successes and barriers, and issues in sustainability. The results for delirium incidence, falls, length of stay, and institutionalization were pooled for meta-analyses. Overall, 14 studies demonstrated significant reductions in delirium incidence (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.37-0.59). The rate of falls was reduced by 42% among intervention patients in three comparative studies (OR 0.58, 95% CI 0.35-0.95). In nine studies on cost savings, the program saved $1600-$3800 (2018 U.S. dollars) per patient in hospital costs and over $16,000 (2018 U.S. dollars) per person-year in long-term care costs in the year following delirium. The systematic review revealed that programs were generally successful in adhering to or appropriately adapting HELP (n = 13 studies) and in finding the volunteer role to be valuable (n = 6 studies). Successes and barriers to implementation were examined in 6 studies, including ensuring effective clinician leadership, finding senior administrative champions, and shifting organizational culture. Sustainability factors were examined in 10 studies, including adapting to local circumstances, documenting positive impact and outcomes, and securing long-term funding. CONCLUSION: The Hospital Elder Life Program is effective in reducing incidence of delirium and rate of falls, with a trend toward decreasing length of stay and preventing institutionalization. With ongoing efforts in continuous program improvement, implementation, adaptations, and sustainability, HELP has emerged as a reference standard model for improving the quality and effectiveness of hospital care for older persons worldwide.

Trajectory of Functional Recovery After Postoperative Delirium in Elective Surgery.

OBJECTIVE: To describe functional recovery after elective surgery and to determine whether improvements differ among individuals who develop delirium. BACKGROUND: No large studies of older adults have investigated whether delirium influences the trajectory of functional recovery after elective surgery. The prospective observational study assessed this association among 566 individuals aged 70 years and older. METHODS: Patients undergoing major elective surgery were assessed daily while in hospital for presence and severity of delirium using the Confusion Assessment Method, and their functional recovery was followed for 18 months thereafter. The Activities of Daily Living and Instrumental Activities of Daily Living Scales and the Physical Component Summary of the Short Form-12 were obtained before surgery and at 1, 2, 6, 12, and 18 months. A composite index (standard deviation 10, minimally clinically significant difference 2) derived from these scales was then analyzed using mixed-effects regression. RESULTS: Mean age was 77 years; 58% of participants were women and 24% developed postoperative delirium. Participants with delirium demonstrated lesser functional recovery than their counterparts without delirium; at 1 month, the covariate-adjusted mean difference on the physical function composite was -1.5 (95% confidence interval -3.3, -0.2). From 2 to 18 months, the corresponding difference was -1.8 (95% confidence interval -3.2, -0.3), an effect comparable with the minimally clinically significant difference. CONCLUSIONS: Delirium was associated with persistent and clinically meaningful impairment of functional recovery, to 18 months. Use of multifactorial preventive interventions for patients at high risk for delirium and tailored transitional care planning may help to maximize the functional benefits of elective surgery.

Neural substrates of vulnerability to postsurgical delirium as revealed by presurgical diffusion MRI.

Despite the significant impact of postoperative delirium on surgical outcomes and the long-term prognosis of older patients, its neural basis has not yet been clarified. In this study we investigated the impact of premorbid brain microstructural integrity, as measured by diffusion tensor imaging before surgery, on postoperative delirium incidence and severity, as well as the relationship among presurgical cognitive performance, diffusion tensor imaging abnormalities and postoperative delirium. Presurgical diffusion tensor imaging scans of 136 older (≥70 years), dementia-free subjects from the prospective Successful Aging after Elective Surgery study were analysed blind to the clinical data and delirium status. Primary outcomes were postoperative delirium incidence and severity during the hospital stay, as assessed by the Confusion Assessment Method. We measured cognition before surgery using general cognitive performance, a composite score based on a battery of neuropsychological tests. We investigated the association between presurgical diffusion tensor imaging parameters of brain microstructural integrity (i.e. fractional anisotropy, axial, mean and radial diffusivity) with postoperative delirium incidence and severity. Analyses were adjusted for the following potential confounders: age, gender, vascular comorbidity status, and general cognitive performance. Postoperative delirium occurred in 29 of 136 subjects (21%) during hospitalization. Presurgical diffusion tensor imaging abnormalities of the cerebellum, cingulum, corpus callosum, internal capsule, thalamus, basal forebrain, occipital, parietal and temporal lobes, including the hippocampus, were associated with delirium incidence and severity, after controlling for age, gender and vascular comorbidities. After further controlling for general cognitive performance, diffusion tensor imaging abnormalities of the cerebellum, hippocampus, thalamus and basal forebrain still remained associated with delirium incidence and severity. This study raises the intriguing possibility that structural dysconnectivity involving interhemispheric and fronto-thalamo-cerebellar networks, as well as microstructural changes of structures involved in limbic and memory functions predispose to delirium under the stress of surgery. While the diffusion tensor imaging abnormalities observed in the corpus callosum, cingulum, and temporal lobe likely constitute the neural substrate for the association between premorbid cognition, as measured by general cognitive performance, and postoperative delirium, the microstructural changes observed in the cerebellum, hippocampus, thalamus and basal forebrain seem to constitute a separate phenomenon that predisposes to postsurgical delirium independent of presurgical cognitive status.

The SAGES telephone neuropsychological battery: correlation with in-person measures.

OBJECTIVE: Neuropsychological test batteries are administered in person to assess cognitive function in both clinical and research settings. However, in-person administration holds a number of logistical challenges that makes it difficult to use in large or remote populations or for multiple serial assessments over time. The purpose of this descriptive study was to determine whether a telephone-administered neuropsychological test battery correlated well with in-person testing. METHODS: Fifty English-speaking patients without dementia, over 70 years old, and part of a cohort of patients in a prospective cohort study examining cognitive outcomes following elective surgery were enrolled in this study. Five well-validated neuropsychological tests were administered by telephone to each participant by a trained interviewer within 2-4 weeks of the most recent in-person interview. Tests included the Hopkins Verbal Learning Test-Revised, Digit Span, Category Fluency, Phonemic Fluency, and Boston Naming Test. A General Cognitive Performance composite score was calculated from individual subtest scores as a Z-score. RESULTS: Mean age was 74.9 years (SD = 4.1), 66% female, and 4% non-White. Mean and interquartile distributions of telephone scores were similar to in-person scores. Correlation analysis of test scores revealed significant correlations between telephone and in-person results for each individual subtest, as well as for the overall composite score. A Bland-Altman plot revealed no bias or trends in scoring for either test administration type. CONCLUSIONS: In this descriptive study, the telephone version of a neuropsychological test battery correlated well with the in-person version and may provide a feasible supplement in clinical and research applications. Copyright © 2016 John Wiley & Sons, Ltd.

Delirium in Older Persons: Advances in Diagnosis and Treatment.

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.

Head circumference as a useful surrogate for intracranial volume in older adults.

BACKGROUND: Intracranial volume (ICV) has been proposed as a measure of maximum lifetime brain size. Accurate ICV measures require neuroimaging which is not always feasible for epidemiologic investigations. We examined head circumference as a useful surrogate for ICV in older adults. METHODS: 99 older adults underwent Magnetic Resonance Imaging (MRI). ICV was measured by Statistical Parametric Mapping 8 (SPM8) software or Functional MRI of the Brain Software Library (FSL) extraction with manual editing, typically considered the gold standard. Head circumferences were determined using standardized tape measurement. We examined estimated correlation coefficients between head circumference and the two MRI-based ICV measurements. RESULTS: Head circumference and ICV by SPM8 were moderately correlated (overall r = 0.73, men r = 0.67, women r = 0.63). Head circumference and ICV by FSL were also moderately correlated (overall r = 0.69, men r = 0.63, women r = 0.49). CONCLUSIONS: Head circumference measurement was strongly correlated with MRI-derived ICV. Our study presents a simple method to approximate ICV among older patients, which may prove useful as a surrogate for cognitive reserve in large scale epidemiologic studies of cognitive outcomes. This study also suggests the stability of head circumference correlation with ICV throughout the lifespan.

Successful aging after elective surgery II: Study cohort description.

BACKGROUND: The Successful Aging after Elective Surgery (SAGES) II Study was designed to examine the relationship between delirium and Alzheimer's disease and related dementias (AD/ADRD), by capturing novel fluid biomarkers, neuroimaging markers, and neurophysiological measurements. The goal of this paper is to provide the first complete description of the enrolled cohort, which details the baseline characteristics and data completion. We also describe the study modifications necessitated by the COVID-19 pandemic, and lay the foundation for future work using this cohort. METHODS: SAGES II is a prospective observational cohort study of community-dwelling adults age 65 and older undergoing major non-cardiac surgery. Participants were assessed preoperatively, throughout hospitalization, and at 1, 2, 6, 12, and 18 months following discharge to assess cognitive and physical functioning. Since participants were enrolled throughout the COVID-19 pandemic, procedural modifications were designed to reduce missing data and allow for high data quality. RESULTS: About 420 participants were enrolled with a mean (standard deviation) age of 73.4 (5.6) years, including 14% minority participants. Eighty-eight percent of participants had either total knee or hip replacements; the most common surgery was total knee replacement with 210 participants (50%). Despite the challenges posed by the COVID-19 pandemic, which required the use of novel procedures such as video assessments, there were minimal missing interviews during hospitalization and up to 1-month follow-up; nearly 90% of enrolled participants completed interviews through 6-month follow-up. CONCLUSION: While there are many longitudinal studies of older adults, this study is unique in measuring health outcomes following surgery, along with risk factors for delirium through the application of novel biomarkers-including fluid (plasma and cerebrospinal fluid), imaging, and electrophysiological markers. This paper is the first to describe the characteristics of this unique cohort and the data collected, enabling future work using this novel and important resource.

Successful aging after elective surgery II: Study design and methods.

BACKGROUND: The Successful Aging after Elective Surgery (SAGES) II study was designed to increase knowledge of the pathophysiology and linkages between delirium and dementia. We examine novel biomarkers potentially associated with delirium, including inflammation, Alzheimer's disease (AD) pathology and neurodegeneration, neuroimaging markers, and neurophysiologic markers. The goal of this paper is to describe the study design and methods for the SAGES II study. METHODS: The SAGES II study is a 5-year prospective observational study of 400-420 community dwelling persons, aged 65 years and older, assessed prior to scheduled surgery and followed daily throughout hospitalization to observe for development of delirium and other clinical outcomes. Delirium is measured with the Confusion Assessment Method (CAM), long form, after cognitive testing. Cognitive function is measured with a detailed neuropsychologic test battery, summarized as a weighted composite, the General Cognitive Performance (GCP) score. Other key measures include magnetic resonance imaging (MRI), transcranial magnetic stimulation (TMS)/electroencephalography (EEG), and Amyloid positron emission tomography (PET) imaging. We describe the eligibility criteria, enrollment flow, timing of assessments, and variables collected at baseline and during repeated assessments at 1, 2, 6, 12, and 18 months. RESULTS: This study describes the hospital and surgery-related variables, delirium, long-term cognitive decline, clinical outcomes, and novel biomarkers. In inter-rater reliability assessments, the CAM ratings (weighted kappa = 0.91, 95% confidence interval, CI = 0.74-1.0) in 50 paired assessments and GCP ratings (weighted kappa = 0.99, 95% CI 0.94-1.0) in 25 paired assessments. We describe procedures for data quality assurance and Covid-19 adaptations. CONCLUSIONS: This complex study presents an innovative effort to advance our understanding of the inter-relationship between delirium and dementia via novel biomarkers, collected in the context of major surgery in older adults. Strengths include the integration of MRI, TMS/EEG, PET modalities, and high-quality longitudinal data.

Psychometric Properties of a Delirium Severity Score for Older Adults and Association With Hospital and Posthospital Outcomes.

Importance: The ability to rate delirium severity is key to providing optimal care for older adults, and such ratings would allow clinicians to target patients with severe delirium and monitor response to treatment, recovery time, and prognosis; assess nursing burden and staffing needs; and, ultimately, provide more appropriate patient-centered care. Current delirium severity measures have been limited in their content, gradations, and measurement characteristics. Objective: To examine the internal consistency, reliability, and validity for clinical outcomes of the DEL-S delirium severity score, a measure of delirium severity that was developed using advanced psychometric approaches, analogous to those of the Patient-Reported Outcomes Measurement Information System initiative. Design, Setting, and Participants: This prospective cohort study was conducted at a large academic medical center in Boston, Massachusetts. Adults aged 70 years or older who were admitted or transferred to medical or surgical services as either emergency or elective admissions were enrolled between October 20, 2015, and March 15, 2017, and were monitored for 1 year. Data analysis was performed from June 2020 to August 2021. Exposures: Delirium severity, measured by scores on the delirium severity score short-form (SF; 6 items, scored 0-13, with higher scores indicating more severe delirium) and long-form (LF; 17 items, scored 0-21), considered continuously and grouped into 5 categories. Main Outcomes and Measures: The primary outcomes were in-hospital outcomes, including length of stay and hospital costs, and posthospital (30, 90, and 365 days) outcomes, including death, health care costs, and rehospitalization. Results: The 352 participants had a median (IQR) age of 79.7 (74.6-85.5) years, 204 (58.0%) were women, and they were highly educated (median [IQR] duration of education, 14 [7-20] years). Patients in the highest delirium severity score SF group (scores 6-9) had a longer length of stay (13.3 vs 6.9 days; P for trend < .001), greater in-hospital costs ($57 700 vs $34 200), greater cumulative health care costs ($168 700 vs $106 500; P for trend = .01), and increased mortality at 1 year (50% vs 17%; P for trend = .02) compared with patients in the lowest delirium severity score SF group (score 0). Similar trends and significant findings were demonstrated for the delirium severity score LF. Conclusions and Relevance: These findings suggest that the delirium severity score provides an approach for measuring delirium severity that is associated with adverse clinical outcomes in a direct exposure-response association and that the delirium severity score may help advance patient-centered care for delirium.

From research to bedside: Incorporation of a CGA-based frailty index among multiple comanagement services.

The comprehensive geriatric assessment (CGA) is the core tool used by geriatricians across diverse clinical settings to identify vulnerabilities and estimate physiologic reserve in older adults. In this paper, we demonstrate the iterative process at our institution to identify and develop a feasible, acceptable, and sustainable bedside CGA-based frailty index tool (FI-CGA) that not only quantifies and grades frailty but also provides a uniform way to efficiently communicate complex geriatric concepts such as reserve and vulnerability with other teams. We describe our incorporation of the FI-CGA into the electronic health record (EHR) and dissemination among clinical services. We demonstrate that an increasing number of patients have documented FI-CGA in their initial assessment from 2018 to 2020, while additional comanagement services were established (Figure 2). The acceptability and sustainability of the FI-CGA, and its routine use by geriatricians in our division, were demonstrated by a survey where the majority of clinicians report using the FI-CGA when assessing a new patient and that the FI-CGA informs their clinical management. Finally, we demonstrate how we refined and updated the FI-CGA, we provide examples of applications of the FI-CGA across the institution and describe areas of ongoing process improvement and challenges for the use of this tailored yet standardized tool across diverse inpatient and outpatient services. The process outlined can be used by other geriatric departments to introduce and incorporate an FI-CGA.

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

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.