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To describe a cultural neuropsychological approach to prestatistical harmonization of cognitive data across the United States (U.S.) and Mexico with the Harmonized Cognitive Assessment Protocol (HCAP).We performed a comprehensive review of the administration, scoring, and coding procedures for each cognitive test item administered across the English and Spanish versions of the HCAP in the Health and Retirement Study (HRS) in the U.S. and the Ancillary Study on Cognitive Aging in Mexico (Mex-Cog). For items that were potentially equivalent across studies, we compared each cognitive test item for linguistic and cultural equivalence and classified items as confident or tentative linking items, based on the degree of confidence in their comparability across cohorts and language groups. We evaluated these classifications using differential item functioning techniques.We evaluated 132 test items among 21 cognitive instruments in the HCAP across the HRS and Mex-Cog. We identified 72 confident linking items, 46 tentative linking items, and 14 items that were not comparable across cohorts. Measurement invariance analysis revealed that 64% of the confident linking items and 83% of the tentative linking items showed statistical evidence of measurement differences across cohorts.Prestatistical harmonization of cognitive data, performed by a multidisciplinary and multilingual team including cultural neuropsychologists, can identify differences in cognitive construct measurement across languages and cultures that may not be identified by statistical procedures alone. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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.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.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.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.

Objectives Telephone-administered cognitive assessments are a cost-effective and sometimes necessary alternative to face-to-face assessments. There is limited information in large studies concerning mode effects, or differences in cognition attributable to the assessment method, as a potential measurement threat. We evaluated mode effects on cognitive scores using a population-based sample of community-living older adults. Methods We used data from participants aged 65–79 in the 2014 Health and Retirement Study for whom the interview mode was randomized (n = 6,825). We assessed mode differences in test means, whether mode modifies associations of cognition with criterion variables, and formal measurement invariance testing. Results Relative to face-to-face assessment, telephone assessment was associated with higher scores for memory and calculation (0.06 to 0.013 standard deviations [SD]) and lower scores for nonmemory items (−0.09 to −0.01 SD). Cognition was significantly differentially related to instrumental activities of daily living difficulty depending on assessment mode. Measurement invariance testing identified evidence of mode differences in certain tests as a function of mode: adjusting for underlying cognition, the largest mode differences in memory and attention: immediate noun recall, delayed word recall, and serial-7s scores were higher given telephone administration. Discussion Differences by mode of administration are apparent in cognitive measurement in older adults, albeit to a small degree in our study, and most pronounced for tests of memory and attention. The importance of accounting for mode differences ultimately depends on one’s research question and study sample: not all associations may be affected by mode differences, and such modification may only be apparent among those with lower cognitive functioning.

Objectives: Cognitive abilities have been implicated as predictors of mortality in older adults. This study examines the effects of cognitive training on mortality 20 years post-intervention. Methods: Data come from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) randomized control trial (N = 2802). Participants were cognitively and physically healthy, community-dwelling adults aged 65 and older. Cox proportional hazard models were used to investigate (1) the association between baseline cognition and mortality risk and (2) the effect of ACTIVE cognitive training (memory, reasoning, and speed of processing) on mortality risk 20 years post-intervention. Results: Higher baseline cognition predicted lower mortality risk 20 years post-intervention. No significant effects of ACTIVE cognitive training in memory, reasoning, or speed of processing on mortality risk were observed. Discussion: More work is needed to identify cognitive training interventions that may lead to lower mortality risks in later adulthood.

BACKGROUND: There is a dearth of studies examining the associations of objectively measured dual sensory impairment (DSI) with incident mobility and activities of daily life (ADL) difficulty longitudinally. METHODS: Cox proportional hazards models were used to examine the associations of DSI and single sensory impairment (hearing, vision) with incident mobility difficulty (many problems or inability to walk ¼ mile and/or climb 10 steps) and ADL difficulty up to six years of follow-up among 2,020 participants of the Health, Aging and Body Composition Study, a cohort of older adults aged 70–79 years from Pittsburgh, PA and Memphis, TN. Vision impairment (VI) was defined as impaired visual acuity (20/50 or worse on Bailey-Lovie distance test) and contrast sensitivity (25 decibels. Models were adjusted by age, race, sex, education, diabetes, depressive symptoms, hypertension, gait speed from 20-meter walk, global cognition score, prevalent cardiovascular disease, and body mass index. RESULTS: There were 23% with DSI (n=459). DSI was associated with increased risk of both incident report of mobility (Hazard Ratio [HR]=2.25, 95% Confidence Interval [CI]: 1.47, 3.43) and ADL difficulty (HR=2.26, 95% CI: 1.50, 3.40). Neither VI nor HI alone were associated with risk of either outcome. CONCLUSIONS: DSI is associated with increased risk of incident mobility and ADL difficulty. Rehabilitation and adaptive environmental changes for individuals living with DSI may be important to maximize mobility and daily function.

BACKGROUND. The ability to rate delirium severity is key to providing optimal care for persons with Alzheimer’s Disease and Related Dementias (ADRD). Such ratings would allow clinicians to assess response to treatment, recovery time and prognosis, nursing burden and staffing needs, and to provide nuanced, appropriate patient-centered care. Given the lack of existing tools, we defined content domains for a new delirium severity instrument for use in individuals with mild to moderate ADRD, the DEL-S-AD. METHODS. We built upon our previous study in which we created a content domain framework to inform development of a general delirium severity instrument, the DEL-S. We engaged a new expert panel to discuss issues of measurement in delirium and dementia and to determine which content domains from the prior framework were useful in characterizing delirium severity in ADRD. We also asked panelists to identify new domains. Our panel included eight interdisciplinary members with expertise in delirium and dementia. Panelists participated in two rounds of review followed by two surveys over two months. RESULTS. Panelists endorsed the same content domains as for general delirium severity, including Cognitive, Level of Consciousness, Inattention, Psychiatric-Behavioral, Emotional Dysregulation, Psychomotor Features, and Functional; however, they excluded six of the original subdomains which they considered unhelpful in the context of ADRD: cognitive impairment; anxiety; fear/sense of unease; depression; gait/walking; and incontinence. Debated measurement challenges included assessment at one point in time versus over time, accounting for differences in clinical settings, and accurate assessment of symptoms related to delirium versus dementia. CONCLUSIONS. By capturing a range of characteristics of delirium severity potentially present in patients with ADRD, a population that may already have attention, functional, and emotional changes at baseline, the DEL-S-AD provides a novel rating tool that will be useful for clinical and research purposes to improve patient care.

Advanced parental age at offspring birth has been associated with autism spectrum disorder (ASD). The objective of the current study was to investigate associations between parental age at birth and autism severity. The Rhode Island Consortium for Autism Research and Treatment (RI-CART) study represents a community-based sample with a range of autism severity, including participants with and without ASD. This study involved participants (n = 1178) enrolled in RI-CART with available mother and father ages at birth. Primary data points included the age of mother and father at the participant's birth and results from the Autism Diagnostic Observation Schedule - Second Edition (ADOS-2). Mothers were 1.7 years older at the time of birth of the child with ASD, as compared to mothers of offspring without ASD. Fathers of children with ASD were 1.6 years older at the time of birth than fathers of children without ASD. The age of both parents at offspring birth displayed a positive, statistically significant association with overall ASD severity and the severity of restricted/repetitive behaviors. This finding was driven by the association between parental age and the severity of compulsions or rituals. Intelligence and adaptive functioning did not moderate the relationship between parental age and ASD severity. This study extends prior research to show that advanced parental age at birth is associated with the severity as well as the presence of ASD in offspring.

Delirium is a debilitating medical condition that disproportionately affects hospitalized older adults(1) and is associated with adverse health outcomes, increased mortality, and high medical costs.(2) Efforts to understand delirium risk in hospitalized older adults have focused on examining medical comorbidities, pre-existing cognitive deficits, and other clinical and demographic factors present in the period proximate to the hospitalization.(3,4) The contribution of social determinants of health (SDOH), including social circumstances, environmental characteristics, and early-life exposures, referred as the social exposome,(5) to delirium risk are poorly understood. Increased knowledge about the influence of SDOH will offer a more comprehensive understanding of factors that may increase vulnerability to delirium and poor outcomes. Clinically, these efforts can guide the development and implementation of holistic preventive strategies to improve clinical outcomes. We propose a social determinants of health (SDOH) framework for delirium tailored to older adults. We provide the definition, description, and rationale for the domains and variables in our proposed model.

Approximately 30% of autistic children are considered minimally verbal. The field lacks an efficient and reliable measure of communicative capacity among minimally verbal autistic children. Improved methods are needed to determine which children are at greatest risk for minimally verbal outcomes to better target interventions. Here, we present the Low Verbal Investigatory Survey (LVIS), a brief parent-report measure designed to assess communicative capacity among minimally verbal autistic children. The 36-item easy-to-complete LVIS was developed to capture the atypical language trajectories associated specifically with autism. We report pilot results from a sample of 147 children (1–8 years) whose caregivers completed the LVIS as part of other studies. Principal components analysis was used to assess dimensionality of the LVIS; composite scores were compared with existing measures of communicative capacity, all of which take significantly more time and training to administer and score. Scores on the LVIS were strongly correlated with existing gold-standard measures of communication. Presence of atypical vocalizations was determined to be particularly relevant for symptoms of autism as well as language and cognitive abilities. These findings provide initial validation of a tool designed to capture multiple dimensions of communicative capacity in children with minimal or low verbal skills. Lay abstract Approximately one in three autistic children is unable to communicate with language; this state is often described as minimally verbal. Despite the tremendous clinical implications, we cannot predict whether a minimally verbal child is simply delayed (but will eventually develop spoken language) or will continue to struggle with verbal language, and might therefore benefit from learning an alternative form of communication. This is important for clinicians to know, to be able to choose the most helpful interventions, such as alternative forms of communication. In addition, the field lacks a standard definition of “minimally verbal.” Even when we do agree on what the term means (e.g. fewer than 20 words), describing a child based on their lack of words does not tell us whether that child is communicating in other ways or how they are using those 20 words. To address these concerns, we developed the Low Verbal Investigatory Survey (LVIS), a one-page parent-report measure designed to help us characterize how minimally verbal autistic children are communicating. Parents of 147 children (aged 1–8 years) completed the LVIS. Here, we ask (1) whether the survey measures what it was designed to measure, that is, communicative ability in children without much spoken language, and (2) how the LVIS relates to cognitive and language ability, and symptoms of autism. Results suggest that this survey, which takes only 5 min to complete, is a good estimate of the child’s communication skills. Furthermore, LVIS survey scores are correlated with other measures of language and cognitive abilities as well as autism symptomatology. The LVIS has the potential to save time and money in both clinical and research efforts to assess communication skills in minimally verbal autistic children.

Evidence-based treatment for Latinx/Hispanic (L/H) with suicidal behaviors (SB) is scarce. This study evaluated the acceptability and preliminary efficacy of a socio-cognitive-behavioral therapy protocol for SB (SCBT-SB) with L/H adolescents and the feasibility of conducting a randomized controlled trial (RCT) of SCBT-SB compared to treatment-as-usual (TAU). A pilot RCT was conducted with 46 L/H teens. The target outcomes included suicidal ideation (SI), suicide attempts (SAs), and depressive/internalizing symptoms. Results indicated that the SCBT-SB was acceptable and an RCT with diverse L/H families is feasible to implement. Within group analyses showed reductions over time for each group in SI and depressive/internalizing symptoms. Intent-to-treat between-group analyses showed a medium effect for the SCBT-SB at the twelve-month follow-up for depressive/internalizing symptoms and a large effect for SA. Although results must be interpreted cautiously given the small sample size, outcomes suggest that SCBT-SB may be a promising psychosocial treatment for depressive/internalizing symptoms, and SAs in L/H youth.

Background and ObjectivesAndexanet alfa was recently approved as a reversal agent for the factor Xa inhibitors (FXais) apixaban and rivaroxaban, but its impact on long-term outcomes in FXai-associated intracerebral hemorrhage (ICH) is unknown. We aimed to explore potential clinical implications of andexanet alfa in FXai-associated ICH in this simulation study.MethodsWe simulated potential downstream implications of andexanet alfa across a range of possible hemostatic effects using data from a single center that treats FXai-associated ICH with prothrombin complex concentrate (PCC). We determined baseline probabilities of inadequate hemostasis across patients taking FXai and those not taking FXai via multivariable regression models and then determined the probabilities of unfavorable 3-month outcome (modified Rankin Scale score 4–6) using models comprising established predictors and each patient's calculated probability of inadequate hemostasis. We applied bootstrapping with model parameters from this derivation cohort to simulate a range of hemostatic improvements and corresponding outcomes and then calculated absolute risk reduction (relative to PCC) and projected number needed to treat (NNT) to prevent 1 unfavorable outcome.ResultsTraining models using real-world patients (n = 603 total, 55 on FXai) had good accuracy in predicting inadequate hemostasis (area under the curve [AUC] 0.78) and unfavorable outcome (AUC 0.78). Inadequate hemostasis was strongly associated with unfavorable outcome (odds ratio 4.5, 95% confidence interval [CI] 2.0–9.9) and occurred in 11.4% of patients taking FXai. Across simulated patients taking FXai comparable to those in A Study in Participants With Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors (ANNEXA-4) study, predicted absolute risk reduction of unfavorable outcome was 4.9% (95% CI 1.3%–7.8%) when the probability of inadequate hemostasis was reduced by 33% and 7.4% (95% CI 2.0%–11.9%) at 50% reduction, translating to projected NNT of 21 (cumulative cost $519,750) and 14 ($346,500), respectively.DiscussionEven optimistic simulated hemostatic effects suggest that the costs and potential benefits of andexanet alfa should be carefully considered. Placebo-controlled randomized trials are needed before its use can definitively be recommended.

Purpose To examine associations between physiologic stress and delirium in the setting of a direct neurologic injury. Materials and methods We obtained initial neutrophil-to-lymphocyte ratio (NLR), glucose, and troponin in consecutive non-comatose patients with non-traumatic intracerebral hemorrhage (ICH) over 1 year, then used multivariable regression models to determine associations between each biomarker and incident delirium. Delirium diagnoses were established using DSM-5-based methods, with exploratory analyses further categorizing delirium as first occurring 24 h after presentation (“later-onset”). Results Of 284 patients, delirium occurred in 55% (early-onset: 39% [n = 111]; later-onset: 16% [n = 46]). Patients with delirium had higher NLR (mean 9.0 ± 10.4 vs. 6.4 ± 5.5; p = 0.01), glucose (mean 146.5 ± 59.6 vs. 129.9 ± 41.4 mg/dL; p = 0.008), and a higher frequency of elevated troponin (>0.05 ng/mL; 21% vs. 10%, p = 0.02). In adjusted models, elevated NLR (highest quartile: OR 3.4 [95% CI 1.5–7.8]), glucose (>180 mg/dL: OR 3.1 [95% CI 1.1–8.2]), and troponin (OR 3.0 [95% CI 1.2–7.2]) were each associated with delirium, but only initial NLR was specifically associated with later-onset delirium and with delirium in non-mechanically ventilated patients. Conclusions Stress-related biomarkers corresponding to multiple organ systems are associated with ICH-related delirium. Early NLR elevation may also predict delayed-onset delirium, potentially implicating systemic inflammation as a contributory delirium mechanism.

Several methods used to examine differential item functioning (DIF) in Patient-Reported Outcomes Measurement Information System (PROMIS®) measures are presented, including effect size estimation. A summary of factors that may affect DIF detection and challenges encountered in PROMIS DIF analyses, e.g., anchor item selection, is provided. An issue in PROMIS was the potential for inadequately modeled multidimensionality to result in false DIF detection. Section 1 is a presentation of the unidimensional models used by most PROMIS investigators for DIF detection, as well as their multidimensional expansions. Section 2 is an illustration that builds on previous unidimensional analyses of depression and anxiety short-forms to examine DIF detection using a multidimensional item response theory (MIRT) model. The Item Response Theory-Log-likelihood Ratio Test (IRT-LRT) method was used for a real data illustration with gender as the grouping variable. The IRT-LRT DIF detection method is a flexible approach to handle group differences in trait distributions, known as impact in the DIF literature, and was studied with both real data and in simulations to compare the performance of the IRT-LRT method within the unidimensional IRT (UIRT) and MIRT contexts. Additionally, different effect size measures were compared for the data presented in Section 2. A finding from the real data illustration was that using the IRT-LRT method within a MIRT context resulted in more flagged items as compared to using the IRT-LRT method within a UIRT context. The simulations provided some evidence that while unidimensional and multidimensional approaches were similar in terms of Type I error rates, power for DIF detection was greater for the multidimensional approach. Effect size measures presented in Section 1 and applied in Section 2 varied in terms of estimation methods, choice of density function, methods of equating, and anchor item selection. Despite these differences, there was considerable consistency in results, especially for the items showing the largest values. Future work is needed to examine DIF detection in the context of polytomous, multidimensional data. PROMIS standards included incorporation of effect size measures in determining salient DIF. Integrated methods for examining effect size measures in the context of IRT-based DIF detection procedures are still in early stages of development.

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.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.Seventy-six (24%) patients had ADRD and were more likely to develop delirium (51% vs. 24%, P0.001) 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.Our findings highlight the complexity of health-care costs for ADRD patients who develop delirium, a potentially preventable source of expenditures.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.

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.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.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.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.

Efforts to conceptualize risk factors for postoperative delirium in older adults have focused on the time proximate to the episode, but how early-life exposures influence delirium risk is poorly understood.An observational cohort of 547 patients aged 70+undergoing major non-cardiac surgery at two academic medical centers in Boston. Demographic characteristics, cognition, parental education, health, and participation in cognitively stimulating activities were assessed prior to surgery. Delirium incidence and severity were measured daily during hospitalization.Higher paternal education was associated with significantly lower incidence of delirium (Examining early-life exposures may yield unique insights into the risks and pathogenesis of delirium.Evaluating long-term factors that increase vulnerability to delirium may improve our ability to calculate risk. It may guide clinical decision-making and inform pre- and post-operative recommendations.

ImportanceThe study results suggest that delirium is the most common postoperative complication in older adults and is associated with poor outcomes, including long-term cognitive decline and incident dementia.ObjectiveTo examine the patterns and pace of cognitive decline up to 72 months (6 years) in a cohort of older adults following delirium.Design, Setting, and ParticipantsThis was a prospective, observational cohort study with long-term follow-up including 560 community-dwelling older adults (older than 70 years) in the ongoing Successful Aging after Elective Surgery study that began in 2010. The data were analyzed from 2021 to 2022.ExposureDevelopment of incident delirium following major elective surgery.Main Outcomes and MeasuresDelirium was assessed daily during hospitalization using the Confusion Assessment Method, which was supplemented with medical record review. Cognitive performance using a comprehensive battery of neuropsychological tests was assessed preoperatively and across multiple points postoperatively to 72 months of follow-up. We evaluated longitudinal cognitive change using a composite measure of neuropsychological performance called the general cognitive performance (GCP), which is scaled so that 10 points on the GCP is equivalent to 1 population SD. Retest effects were adjusted using cognitive test results in a nonsurgical comparison group.ResultsThe 560 participants (326 women [58%]; mean [SD] age, 76.7 [5.2] years) provided a total of 2637 person-years of follow-up. One hundred thirty-four participants (24%) developed postoperative delirium. Cognitive change following surgery was complex: we found evidence for differences in acute, post–short-term, intermediate, and longer-term change from the time of surgery that were associated with the development of postoperative delirium. Long-term cognitive change, which was adjusted for practice and recovery effects, occurred at a pace of about −1.0 GCP units (95% CI, −1.1 to −0.9) per year (about 0.10 population SD units per year). Participants with delirium showed significantly faster long-term cognitive change with an additional −0.4 GCP units (95% CI, −0.1 to −0.7) or −1.4 units per year (about 0.14 population SD units per year).Conclusions and RelevanceThis cohort study found that delirium was associated with a 40% acceleration in the slope of cognitive decline out to 72 months following elective surgery. Because this is an observational study, we cannot be sure whether delirium directly causes subsequent cognitive decline, or whether patients with preclinical brain disease are more likely to develop delirium. Future research is needed to understand the causal pathway between delirium and cognitive decline.

The objective of this study was to determine the clinical features that moderate a later age at ASD diagnosis in females in a large sample of females with ASD. Within two large and independent ASD datasets (> 20,000 females), females were first diagnosed with ASD 14-months later relative to males. This later age at diagnosis was moderated by a mild or atypical presentation, wherein repetitive behaviors were limited, IQ and language were broadly intact, and recognized symptoms emerged later in development. Females are at risk for a later age at ASD diagnosis and treatment implementation, and modification of early childhood ASD screening methods for females may be warranted.

Objectives To characterize the extent to which brief cognitive assessments administered in the population-representative U.S. Health and Retirement Study (HRS) and its International Partner Studies can be considered to be measuring a single, unidimensional latent cognitive function construct. Methods Cognitive function assessments were administered in face-to-face interviews in 12 studies in 26 countries (N = 155,690), including the U.S. HRS and selected International Partner Studies. We used the time point of the first cognitive assessment for each study to minimize differential practice effects across studies and documented cognitive test item coverage across studies. Using confirmatory factor analysis models, we estimated single-factor general cognitive function models and bifactor models representing memory-specific and nonmemory-specific cognitive domains for each study. We evaluated model fits and factor loadings across studies. Results Despite relatively sparse and inconsistent cognitive item coverage across studies, all studies had some cognitive test items in common with other studies. In all studies, the bifactor models with a memory-specific domain fit better than single-factor general cognitive function models. The data fit the models at reasonable thresholds for single-factor models in 6 of the 12 studies and for the bifactor models in all 12 of the 12 studies. Discussion The cognitive assessments in the U.S. HRS and its International Partner Studies reflect comparable underlying cognitive constructs. We discuss the assumptions underlying our methods, present alternatives, and future directions for cross-national harmonization of cognitive aging data.

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.

OBJECTIVES: Over 30 instruments are in current, active use for delirium identification. In a recent systematic review, we recommended 4 commonly used and well-validated instruments for clinical and research use. The goal of this study is to harmonize the four instruments on the same metric using modern methods in psychometrics. DESIGN: Secondary data analysis from 3 studies, and a simulation study based on the observed data. SETTING: Hospitalized (non-ICU) adults over 65 years old in the United States, Ireland, and Belgium. PARTICIPANTS: The total sample comprised 600 participants, contributing 1,623 assessments. MEASUREMENTS: Confusion Assessment Method (long-form and short-form), Delirium Observation Screening Scale, Delirium Rating Scale-Revised-98 (DRS-R-98) (total and severity scores), and Memorial Delirium Assessment Scale. RESULTS: Using item response theory, we linked scores across instruments, placing all four instruments and their separate scorings on the same metric (the propensity to delirium). Kappa statistics comparing agreement in delirium identification among the instruments ranged from 0.37 to 0.75, with the highest agreement between the DRS-R-98 total score and MDAS. After linking scores, we created a harmonized item bank, called the Delirium Item Bank (DEL-IB), consisting of 50 items. The DEL-IB allowed us to create six crosswalks, to allow scores to be translated across instruments. CONCLUSIONS: With our results, individual instrument scores can be directly compared to aid in clinical decision-making, and quantitatively combined in meta-analyses. ispartof: AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY vol:30 issue:3 pages:284-294 ispartof: location:England status: published

Background Evaluating the long-term health consequences of migration requires longitudinal data on migrants and non-migrants to facilitate adjustment for time-varying confounder-mediators of the effect of migration on health. Methods We merged harmonized data on subjects aged 50+ from the US-based Health and Retirement Study (HRS) and the Mexican Health and Aging Study (MHAS). Our exposed group includes MHAS-return migrants (n = 1555) and HRS Mexican-born migrants (n = 924). Our unexposed group includes MHAS-never migrants (n = 16,954). We constructed a lifecourse data set from birth (age 0) until either age at migration to the United States or age at study entry. To account for confounding via inverse probability of treatment weights (IPTW), we modeled the probability of migration at each year of life using time-varying pre-migration characteristics. We then evaluated the effect of migration on mortality hazard estimated with and without IPTW. Results Mexico to the United States migration was predicted by time-varying factors that occurred before migration. Using measured covariates at time of enrollment to account for selective migration, we estimated that, for women, migrating reduces mortality risk by 13%, although this estimate was imprecise and results were compatible with either large protective or deleterious associations (hazard ratio [HR] =0.87, 95% confidence interval [CI]: 0.60, 1.27). When instead using IPTWs, the estimated effect on mortality was similarly imprecise (HR = 0.98, 95% CI: 0.77, 1.25). The relationship among men was similarly uncertain in both models. Conclusions Although time-varying social factors predicted migration, IPTW weighting did not affect our estimates. Larger samples are needed to precisely estimate the health effects of migration.

Rationale: Delirium severity and duration are independently associated with higher mortality and morbidity. No studies to date have described a delirium trajectory by integrating both severity and duration. Objectives: The primary aim was to develop delirium trajectories by integrating symptom severity and duration. The secondary aim was to investigate the association among trajectory membership, clinical characteristics, and 30-day mortality. Methods: A secondary analysis of the PMD (Pharmacologic Management of Delirium) randomized control trial (ClinicalTrials.gov Identifier: NCT00842608; N = 531) was conducted. The presence of delirium and symptom severity were measured at least daily for 7 days using the Confusion Assessment Method for the intensive care unit (CAM-ICU) and CAM-ICU-7 (on a scale of 0–7, with 7 being the most severe). Delirium trajectories were defined using an innovative, data-driven statistical method (group-based trajectory modeling [GBTM]) and SAS v9.4. Results: A total of 531 delirious participants (mean age 60 yr [standard deviation = 16], 55% female, and 46% African American) were analyzed. Five distinct delirium trajectories were described (CAM-ICU-7: mean [standard deviation]); mild-brief (CAM-ICU-7: 0.5 [0.5]), severe-rapid recovers (CAM-ICU-7: 2.1 [1.0]), mild-accelerating (CAM-ICU-7: 2.2 [0.9]), severe-slow recovers (CAM-ICU-7: 3.9 [0.9]), and severe-nonrecovers (CAM-ICU-7: 5.9 [1.0]). Baseline cognition and race were associated with trajectory membership. Trajectory membership independently predicted 30-day mortality while controlling for age, sex, race, cognition, illness severity, and comorbidities. Conclusions: This secondary analysis described five distinct delirium trajectories based on delirium symptom severity and duration using group-based trajectory modeling. Trajectory membership predicted 30-day mortality.

Objectives Compare longitudinal trajectories of youth with Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Bipolar Disorder (BD), grouped at baseline by presence/absence of increased energy during their worst lifetime mood episode (required for DSM-5). Methods Participants from the parent Course and Outcome of Bipolar Youth study (N = 446) were assessed utilizing The Schedule for Affective Disorders and Schizophrenia for School-Age Children (KSADS), KSADS Mania Rating Scale (KMRS), and KSADS Depression Rating Scale (KDRS). Youth were grouped at baseline into those with increased energy (meeting DSM-5 Criteria A for mania) vs. without increased energy (meeting DSM-IV, but not DSM-5, Criteria A for mania), for those who had worst lifetime mood episode recorded (n = 430). Youth with available longitudinal data had the presence/absence of increased energy measured, as well as psychiatric symptomatology/clinical outcomes (evaluated via the Adolescent Longitudinal Interval Follow-Up Evaluation), at each follow-up for 12.5 years (n = 398). Results At baseline, the increased energy group (based on endorsed increased energy during worst lifetime mood episode; 86% of participants) vs. the without increased energy group, were more likely to meet criteria for BD-I and BD Not Otherwise Specified, had higher KMRS/KDRS total scores, and displayed poorer family/global psychosocial functioning. However, frequency of increased energy between groups was comparable after 5 years, and no significant group differences were found on clinical/psychosocial functioning outcomes after 12.5 years. Limitations Secondary data limited study design; groupings were based on one time point. Conclusions Results indicate no clinically relevant longitudinal group differences.

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

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.

Rhythmic neural activity has been proposed to play a fundamental role in cognition. Both healthy and pathological aging are characterized by frequency-specific changes in oscillatory activity. However, the cognitive relevance of these changes across the spectrum from normal to pathological aging remains unknown. We examined electroencephalography (EEG) correlates of cognitive function in healthy aging and 2 of the most prominent and debilitating age-related disorders: type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). Relative to healthy controls (HC), patients with AD were impaired on nearly every cognitive measure, whereas patients with T2DM performed worse mainly on learning and memory tests. A continuum of alterations in resting-state EEG was associated with pathological aging, generally characterized by reduced alpha (α) and beta (β) power (ADT2DMHC) and increased delta (δ) and theta (θ) power (ADT2DMHC), with some variations across different brain regions. There were also reductions in the frequency and power density of the posterior dominant rhythm in AD. The ratio of (α + β)/(δ + θ) was specifically associated with cognitive function in a domain- and diagnosis-specific manner. The results thus captured both similarities and differences in the pathophysiology of cerebral oscillations in T2DM and AD. Overall, pathological brain aging is marked by a shift in oscillatory power from higher to lower frequencies, which can be captured by a single cognitively relevant measure of the ratio of (α + β) over (δ + θ) power.

Posttraumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder associated with disruption in social and occupational function. Transcranial magnetic stimulation (TMS) represents a novel approach to PTSD, and intermittent theta-burst stimulation (iTBS) is a new, more rapid administration protocol with data supporting efficacy in depression. The authors conducted a sham-controlled study of iTBS for PTSD.Fifty veterans with PTSD received 10 days of sham-controlled iTBS (1,800 pulses/day), followed by 10 unblinded sessions. Primary outcome measures included acceptability (retention rates), changes in PTSD symptoms (clinician- and self-rated), quality of life, social and occupational function, and depression, obtained at the end of 2 weeks; analysis of variance was used to compare active with sham stimulation. Secondary outcomes were evaluated 1 month after treatment, using mixed-model analyses. Resting-state functional MRI was acquired at pretreatment baseline on an eligible subset of participants (N=26) to identify response predictors.Retention was high, side effects were consistent with standard TMS, and blinding was successful. At 2 weeks, active iTBS was significantly associated with improved social and occupational function (Cohen's d=0.39); depression was improved with iTBS compared with the sham treatment (d=-0.45), but the difference fell short of significance, and moderate nonsignificant effect sizes were observed on self-reported PTSD symptoms (d=-0.34). One-month outcomes, which incorporated data from the unblinded phase of the study, indicated superiority of active iTBS on clinician- and self-rated PTSD symptoms (d=-0.74 and -0.63, respectively), depression (d=-0.47), and social and occupational function (d=0.93) (all significant). Neuroimaging indicated that clinical improvement was significantly predicted by stronger (greater positive) connectivity within the default mode network and by anticorrelated (greater negative) cross-network connectivity.iTBS appears to be a promising new treatment for PTSD. Most clinical improvements from stimulation occurred early, which suggests a need for further investigation of optimal iTBS time course and duration. Consistent with previous neuroimaging studies of TMS, default mode network connectivity played an important role in response prediction.

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

The early detection of cognitive impairment is one of the most important challenges in Alzheimer's disease (AD) research. The use of brief, short-term repeated test sessions via mobile app has demonstrated similar or better reliability and validity compared to standard in-clinic assessments in adult samples. The present study examined adherence, acceptability, and reliability for a remote, app-based cognitive screening protocol in healthy older adults.Cognitively unimpaired older adults (Participants completed an average of 93% (M = 22.3 sessions, standard deviation = 10.2) of the 24 assigned sessions within 8 to 9 days. Average daily adherence ranged from 95% of sessions completed on day 2 to 88% of sessions completed on day 8. There was a statistically significant effect of session time on adherence between the morning and afternoon sessions only These findings suggests that remote, mobile app-based cognitive testing in short bursts is both highly feasible and reliable in a motivated sample of cognitively normal older adults. Limitations include the limited diversity and generalizability of the sample; this was a largely White, highly educated, and motivated sample self-selected for AD research.

Introduction: The large number of heterogeneous instruments in active use for identification of delirium prevents direct comparison of studies and the ability to combine results. In a recent systematic review we performed, we recommended four commonly used and well-validated instruments and subsequently harmonized them using advanced psychometric methods to develop an item bank, the Delirium Item Bank (DEL-IB). The goal of the present study was to find optimal cut-points on four existing instruments and to demonstrate use of the DEL-IB to create new instruments. Methods: We used a secondary analysis and simulation study based on data from three previous studies of hospitalized older adults (age 65+ years) in the USA, Ireland, and Belgium. The combined dataset included 600 participants, contributing 1,623 delirium assessments, and an overall incidence of delirium of about 22%. The measurements included the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnostic criteria for delirium, Confusion Assessment Method (long form and short form), Delirium Observation Screening Scale, Delirium Rating Scale-Revised-98 (total and severity scores), and Memorial Delirium Assessment Scale (MDAS). Results: We identified different cut-points for each existing instrument to optimize sensitivity or specificity, and compared instrument performance at each cut-point to the author-defined cut-point. For instance, the cut-point on the MDAS that maximizes both sensitivity and specificity was at a sum score of 6 yielding 89% sensitivity and 79% specificity. We then created four new example instruments (two short forms and two long forms) and evaluated their performance characteristics. In the first example short form instrument, the cut-point that maximizes sensitivity and specificity was at a sum score of 3 yielding 90% sensitivity, 81% specificity, 30% positive predictive value, and 99% negative predictive value. Discussion/Conclusion: We used the DEL-IB to better understand the psychometric performance of widely used delirium identification instruments and scorings, and also demonstrated its use to create new instruments. Ultimately, we hope that the DEL-IB might be used to create optimized delirium identification instruments and to spur the development of a unified approach to identify delirium.