Search

Describe driving patterns following moderate-to-severe traumatic brain injury (TBI). Participants: Adults (N = 438) with TBI that required inpatient acute rehabilitation who had resumed driving.Cross-sectional, observational design.Eight TBI Model System sites.A driving survey was completed at phone follow-up.Most respondents reported driving daily, although 41% reported driving less than before their injury. Driving patterns were primarily associated with employment, family income, sex, residence, and time since injury, but not injury severity. Confidence in driving was high for most participants and was associated with a perception that the TBI had not diminished driving ability. Lower confidence and perceived loss of ability were associated with altered driving patterns.Most people with moderate-to-severe TBI resume driving but perhaps not at pre-injury or normal levels compared to healthy drivers. Some driving situations are restricted. The relationship between low confidence/perceived loss of ability and driving patterns/restrictions suggests people with TBI are exhibiting some degree of caution consistent with those perceptions. Careful assessment of driving skills and monitoring during early stages of RTD is warranted, particularly for younger, male, and/or single drivers who express higher levels of confidence.

Rationale: Measuring amyloid and predicting tau status using a single amyloid positron emission tomography (PET) study would be valuable for assessing brain AD pathophysiology. We hypothesized that early-frame amyloid PET (efAP) correlates with the presence of tau pathology because the initial regional brain concentrations of radioactivity are primarily determined by blood flow, which is expected to be decreased in the setting of tau pathology. Methods: 120 participants (63 amyloid-positive/57 amyloid-negative) with dynamic 18F-florbetapir-PET and static 18F-flortaucipir-PET scans obtained within 6 months of each other were included. These subjects were predominantly cognitively intact in both the amyloid positive (63%) and amyloid negative (93%) groups. Parameters for efAP quantification were optimized for stratification of tau PET positivity, assessed by either a tauopathy score or Braak regions. The ability of efAP to stratify tau positivity was measured using receiver operating characteristics (ROC) analysis of area under the curve (AUC). Pearson's r and Spearman's ρ were used for parametric and non-parametric comparisons between efAP and tau PET, respectively. Standardized net benefit was used to evaluate improvement in utilizing efAP as an additional co-predictor over hippocampal volumes in predicting tau PET positivity. Results: Measuring efAP within the hippocampus and summing the first 3 minutes of brain activity post-injection showed the strongest discriminative ability to stratify for tau positivity (AUC 0.67-0.89 across tau PET Braak regions) in amyloid positive individuals. Hippocampal efAP correlated significantly with a global tau-PET tauopathy score in amyloid-positive participants (r = -0.57, P < 0.0001). Compared to hippocampal volumes, hippocampal efAP showed stronger association with tau PET Braak stage (ρ = -0.58 vs. -0.37) and superior stratification of tau PET tauopathy score (AUC: 0.86 vs. 0.66, P = 0.002). Conclusion: Hippocampal efAP can provide additional information to conventional amyloid-PET, including estimation of the likelihood of tau positivity in amyloid-positive individuals.

BACKGROUND: There is an ongoing need for interventions to improve quality of end-of-life care for patients in inpatient settings. OBJECTIVE: To compare two methods for implementing a Comfort Care Education Intervention for Palliative Care Consultation Teams (PCCT) in Veterans Affairs Medical Centers (VAMCs). DESIGN: Cluster randomized implementation trial conducted March 2015–April 2019. PCCTs were assigned to a traditional implementation approach using a teleconference or to an in-person, train-the-champion workshop to prepare PCCTs to be clinical champions at their home sites. PARTICIPANTS: One hundred thirty-two providers from PCCTs at 47 VAMCs. INTERVENTIONS: Both training modalities involved review of educational materials, instruction on using an electronic Comfort Care Order Set, and coaching to deliver the intervention to other providers. MAIN MEASUREMENTS: Several processes of care were identified a priori as quality endpoints for end-of-life care (last 7 days) and abstracted from medical records of veterans who died within 9 months before or after implementation (n = 6,491). The primary endpoint was the presence of an active order for opioid medication at time of death. Secondary endpoints were orders/administration of antipsychotics, benzodiazepines, and scopolamine, do-not-resuscitate orders, advance directives, locations of death, palliative care consultations, nasogastric tubes, intravenous lines, physical restraints, pastoral care visits, and family presence at/near time of death. Generalized estimating equations were conducted adjusting for potential covariates. KEY RESULTS: Eighty-eight providers from 23 VAMCs received teleconference training; 44 providers from 23 VAMCs received in-person workshop training. Analyses found no significant differences between intervention groups in any process-of-care endpoints (primary endpoint AOR (CI) = 1.18 (0.74, 1.89). Furthermore, pre-post changes were not significant for any endpoints (primary endpoint AOR (CI) = 1.16 (0.92, 1.46). Analyses may have been limited by high baseline values on key endpoints with little room for improvement. CONCLUSION: Findings suggest the clinical effectiveness of palliative care educational intervention was not dependent on which of the two implementation methods was used. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02383173

Background: African Americans are at increased risk for Alzheimer’s disease (AD) but barriers to optimal clinical care are unclear. Objective: To comprehensively evaluate potential racial differences in the diagnosis and treatment of AD in an academic medical center. Methods: We used the clinical informatics tool, i2b2, to analyze all patient encounters for AD or mild cognitive impairment (MCI) in the University of Alabama at Birmingham Health System over a three-year period, examining neuroimaging rates and dementia-related medication use by race and clinic site using ratio tests on contingency tables of stratified patient counts. Results: Enterprise-wide, African Americans were not underrepresented among outpatients seen for AD/MCI. However, there were differences in the clinic setting where visits occurred, with African Americans overrepresented in Geriatrics and primary care clinics and underrepresented in Memory Disorders specialty clinics. There were no racial differences in the rates at which any clinic ordered PET neuroimaging tests or dementia-related medications. However, unsurprisingly, specialty clinics ordered both PET neuroimaging and dementia-related medications at a higher rate than primary care clinics, and overall across the medical enterprise, African Americans were statistically less likely to have PET neuroimaging or dementia-related medications ordered. Conclusion: African Americans with AD/MCI were not underrepresented at this academic medical center but were somewhat less likely to have PET neuroimaging or to be on dementia-related medications, potentially in part from underrepresentation in the specialty clinics where these orders are more likely. The reasons for this underrepresentation in specialty clinics are likely multifactorial and important to better understand.

Background Cross-sectional studies suggest self-reported cancer history is associated with decreased risk of Alzheimer's disease (AD). However, little is known about how self-reported cancer affects longitudinal AD progression, the primary outcome in clinical trials and observational studies. Objective To determine self-reported cancer history's effect on longitudinal AD progression in an observational study. Methods We utilized data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to evaluate progression to AD by self-reported all-cancer, breast, prostate, colorectal, or non-melanoma skin cancer history. Linear mixed effects models were used to examine baseline differences and rates of progression on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) by self-reported cancer history. Age at AD onset was examined using consensus clinical diagnoses with Cox proportional hazards regression. Results Among 1,271 participants, models revealed no significant differences in progression over time but did reveal significantly lower baseline ADAS-Cog score, indicating better cognition at a given age in those with self-reported cancer history. Cox models indicated those with self-reported cancer history had significantly later age of AD onset (HR: 0.67, 95% CI: 0.53-0.85) after adjustment for covariates. Conclusion Participants with self-reported cancer history entered ADNI with better cognition and later age of AD onset, but progressed similarly to participants without such history, indicating differences in AD between those with and without self-reported cancer history emerge early in the disease course. Such differences in longitudinal progression by self-reported cancer history could affect AD trials and observational studies, given the current focus on early disease course. Further investigation is warranted with detailed longitudinal assessment of cancer and AD.

Objective To evaluate the ability of persons with metastatic cancer to self‐assess their medical decision‐making capacity (MDC). To investigate this, we compared an objective measure of MDC with self‐ratings and evaluated predictors of agreement. Methods Data were obtained from a cross‐sectional study of metastatic cancer patients at a large academic medical center. Across all standards of MDC, sensitivity, specificity, and reliability using Gwet's AC1 statistic were calculated using the objective measure as the gold standard. Logistic regression was used to evaluate predictors of agreement between the measures across all MDC standards. Results In those with brain metastases, high sensitivity (greater than 0.7), but low specificity was observed for all standards. Poor reliability was observed across all standards. Higher age resulted in higher odds of disagreement for Standard 3 (appreciation) (OR: 1.07, 95% CI: 1.00, 1.15) and Standard 4 (reasoning) (OR: 1.05, 95% CI: 1.00, 1.10). For Standard 3, chemotherapy use and brain metastases compared to other metastases resulted in higher odds of disagreement (Chemotherapy: OR: 5.62, 95% CI: 1.37, 23.09, Brain Metastases: OR: 5.93, 95% CI: 1.28, 27.55). For Standard 5 (understanding), no predictors were associated with disagreement. Conclusions For less cognitively complex standards (e.g., appreciation), self‐report may be more valid and reliable than more cognitively complex standards (e.g., reasoning or understanding). However, overall, MDC self‐report in the current sample is suboptimal. Thus, the need for detailed assessment of MDC, especially when patients are older or used chemotherapy, is indicated. Other studies should be conducted to assess MDC agreement longitudinally.

OBJECTIVE To examine convergent validity of the Brief Test of Adult Cognition by Telephone (BTACT) by determining correlation with established neuropsychological tests, administered an average of 4.4 days apart, in an inpatient traumatic brain injury (TBI) population. SETTING Acute inpatient rehabilitation hospital. PARTICIPANTS Fifty-five patients receiving inpatient rehabilitation for new-onset TBI (69.1% male; mean age = 37 years, SD = 14 years). DESIGN Cross-sectional, secondary data analysis. MAIN MEASURES BTACT; California Verbal Learning Test-second edition (CVLT-2); Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span; Trail Making Test; semantic fluency; phonemic fluency; Symbol Digit Modalities Test; Wisconsin Card Sorting Test. RESULTS The BTACT was significantly associated with established neuropsychological tests across composite scores of overall cognition (r = 0.64, P < .001), episodic verbal memory (r = 0.66, P < .001), and executive function (r = 0.56, P < .001). For BTACT subtests, Word List Immediate Recall and Word List Delayed Recall were correlated with CVLT-2 learning trials total score (r = 0.57, P < .01) and long delay free recall (r = 0.60, P < .001), respectively. BTACT Digits Backward correlated with WAIS-IV Digit Span (r = 0.51, P < .01). BTACT Animal Fluency was associated with semantic fluency (r = 0.65, P < .01), phonemic fluency (r = 0.60, P < .01), and Trail Making Test Part B (r = 0.39, P < .01). CONCLUSION BTACT composite scores of overall cognition, verbal memory, and executive function demonstrate initial convergent validity in a TBI inpatient population. Future research should examine validity in a larger sample of individuals with TBI.

Background Patients living in rural areas experience a variety of unmet needs that result in healthcare disparities. The triple threat of rural geography, racial inequities, and older age hinders access to high-quality palliative care (PC) for a significant proportion of Americans. Rural patients with life-limiting illness are at risk of not receiving appropriate palliative care due to a limited specialty workforce, long distances to treatment centers, and limited PC clinical expertise. Although culture strongly influences people’s response to diagnosis, illness, and treatment preferences, culturally based care models are not currently available for most seriously ill rural patients and their family caregivers. The purpose of this randomized clinical trial (RCT) is to compare a culturally based tele-consult program (that was developed by and for the rural southern African American (AA) and White (W) population) to usual hospital care to determine the impact on symptom burden (primary outcome) and patient and care partner quality of life (QOL), care partner burden, and resource use post-discharge (secondary outcomes) in hospitalized AA and White older adults with a life-limiting illness. Methods Community Tele-pal is a three-site RCT that will test the efficacy of a community-developed, culturally based PC tele-consult program for hospitalized rural AA and W older adults with life-limiting illnesses (n = 352) and a care partner. Half of the participants (n = 176) and a care partner (n = 176) will be randomized to receive the culturally based palliative care consult. The other half of the patient participants (n = 176) and care partners (n = 176) will receive usual hospital care appropriate to their illness. Discussion This is the first community-developed, culturally based PC tele-consult program for rural southern AA and W populations. If effective, the tele-consult palliative program and methods will serve as a model for future culturally based PC programs that can reduce patients’ symptoms and care partner burden. Trial registration ClinicalTrials.gov NCT03767517. Registered on 27 December 2018.

Background Cognitive processing speed is important for performing everyday activities in persons with mild cognitive impairment (MCI). However, its role in daily function has not been examined while simultaneously accounting for contributions of Alzheimer’s disease (AD) risk biomarkers. We examine the relationships of processing speed and genetic and neuroimaging biomarkers to composites of daily function, mobility, and driving. Method We used baseline data from 103 participants on the MCI/mild dementia spectrum from the Applying Programs to Preserve Skills trial. Linear regression models examined relationships of processing speed, structural magnetic resonance imaging (MRI), and genetic risk alleles for AD to composites of performance-based instrumental activities of daily living (IADLs), community mobility, and on-road driving evaluations. Results In multivariable models, processing speed and the brain MRI neurodegeneration biomarker Spatial Pattern of Abnormality for Recognition of Early Alzheimer’s disease (SPARE-AD) were significantly associated with functional and mobility composite performance. Better processing speed and younger age were associated with on-road driving ratings. Genetic risk markers, left hippocampal atrophy, and white matter lesion volumes were not significant correlates of these abilities. Processing speed had a strong positive association with IADL function (p < .001), mobility (p < .001), and driving (p = .002). Conclusions Cognitive processing speed is strongly and consistently associated with critical daily functions in persons with MCI in models including genetic and neuroimaging biomarkers of AD risk. SPARE-AD scores also significantly correlate with IADL performance and mobility. Results highlight the central role of processing speed in everyday task performance among persons with MCI/mild dementia.

Background/objectives The University of Alabama at Birmingham (UAB) Life-Space Assessment (LSA) is a widely used measure of community mobility. To assist clinicians and researchers with assessing the significance of changes in scores, we determined the minimal important change associated with a change in health status. Setting Homes of community-dwelling older adults. Participants A total of 419 African American and non-Hispanic white adults 75 years and older participating in the UAB Study of Aging II, a longitudinal epidemiological study across the state of Alabama. Intervention None. Measurements Linear mixed models were used to compare change in LSA scores over 1-month intervals (N = 9712) between participants reporting improvement, no change, or decline in activities of daily living walking scores, accounting for the correlation among scores for the same participant over time. Results A decline in walking status was associated with a mean decrease in LSA scores of 2.93 points (95% confidence interval [CI] = 1.69-4.17 points), indicating lower mobility. An improvement in walking status was associated with a mean increase in LSA scores of 2.51 points (95% CI = 1.26-3.77 points), indicating higher mobility. Conclusion A change in LSA scores of five or more is clinically important, exceeding the 95% CI for the change in LSA associated with change in walking status. Changes exceeding this threshold should prompt further investigation by providers with a goal of preserving mobility. J Am Geriatr Soc 67:565-569, 2019.

Physicians have long debated the diagnosis of acute confusional states as delirium or encephalopathy, often based on specialty. Recently, CMS assigned a lower severity to the nonspecific behavioral diagnosis of delirium than for the pathophysiological diagnosis of encephalopathy, potentially exacerbating these disagreements. Therefore, we sought to evaluate trends in these two diagnoses among hospitalized adults. Using 2011-2018 IBM MarketScan datasets, we identified delirium/encephalopathy patients who were ≥ 18 years and enrolled with medical and pharmacy coverage for each calendar year. Delirium/encephalopathy were defined using validated ICD-9/10 codes among hospitalized patients. We identified the physician specialties associated with the hospitalization and comorbidities using ICD9/10 inpatient/outpatient diagnosis codes within one year prior to the diagnosis of delirium or encephalopathy. Log-binomial models were used to evaluate the trends adjusting for age, gender, insurance and comorbidities. We identified 10,418 delirium and 87,393 encephalopathy hospitalized patients in 2011-2018. Of these patients, the total number of patients with either diagnosis increased, but the proportion of patients with delirium for each year decreased from 20% in 2011 to 9% in 2018. During the 8 years, neurologists and internists increased their use of both diagnoses, whereas psychiatrists only increased for delirium. Patients with encephalopathy are more likely to be older, female, and have more comorbidities. These shifts in diagnosis complicate the study of delirium and encephalopathy, and can lead to erroneous conclusions about trends in the incidence and prevalence of these disorders unless properly understood.

Metastatic cancer patients undergo numerous treatment strategies with known cognitive side effects. It is unclear how medical decision-making capacity (MDC) is impacted by cognitive deficits in metastatic cancer. This study examines reliability of an objective measure of MDC compared with self-report. Participants with newly diagnosed metastasis to the brain and other sites were enrolled at the University of Alabama at Birmingham over seven years. At the study visit, participants completed a comprehensive neuropsychological battery including memory and executive functioning, and the Capacity to Consent to Treatment Instrument (CCTI) assessing medico-legal domains of MDC. The CCTI is a reliable and valid instrument containing two vignettes of hypothetical medical situations assessing four standards of consent. We examined reliability between the CCTI and self-reported MDC using Gwet’s AC1 statistic. Participants with brain metastasis with impairment on the CCTI demonstrated significantly lower executive functioning and memory skills than those without impairment (Trails B Raw: 158.20±86.82 vs. 118.90±77.98 p: 0.0248; Digit-Span Raw Forward: 9.13±2.30 vs. 10.12±2.03 p: 0.0254). There were no significant differences between intact and impaired participants with other metastases. Low reliability was observed between self-report and all medico-legal standards on the CCTI across both metastatic groups [Gwet’s AC1 Appreciation: 0.70 (0.58, 0.81); Reasoning: 0.34 (0.16, 0.52); Understanding: 0.44, (0.27, 0.60)]. Self-rating of MDC is unreliable in metastatic cancer patients. Patients with metastases (particularly brain metastases) may lack awareness of deficits in their MDC, so providers must affirm proper autonomy in their decisions.

BACKGROUND: Post-traumatic stress disorder (PTSD) can be exacerbated by subsequent trauma, but it is unclear if symptoms are worsened by impending death. PTSD symptoms, including hyperarousal, negative mood and thoughts, and traumatic re-experiencing, can impact end-of-life symptoms, including pain, mood, and poor sleep. Thus, increased symptoms may lead to increased end-of-life healthcare utilization. OBJECTIVES: To determine if veterans with PTSD have increased end-of-life healthcare utilization or medication use and to examine predictors of medication administration. DESIGN: Secondary analysis of a stepped-wedge design implementation trial to improve end-of-life care for Veterans Affairs (VA) inpatients. Outcome variables were collected via direct chart review. Analyses included hierarchical, generalized estimating equation models, clustered by medical center. SUBJECTS: Veterans, inpatient at one of six VA facilities, dying between 2005 and 2011. MAIN MEASURES: Emergency room (ER) visits, hospitalizations, and medication administration in the last 7 days of life. KEY RESULTS: Of 5341 veterans, 468 (8.76%) had PTSD. Of those, 21.4% (100/468) had major depression and 36.5% (171/468) had anxiety. Veterans with PTSD were younger (mean age 65.4 PTSD, 70.5 no PTSD, p < 0.0001) and had more VA hospitalizations and ER visits in the last 12 months of life (admissions: PTSD 2.8, no PTSD 2.4, p < 0.0001; ER visits: 3.2 vs 2.5, p < 0.0001). PTSD was associated with antipsychotic administration (OR 1.52, 95% CI 1.06–2.18). Major depression (333/5341, 6.2%) was associated with opioid administration (OR 1.348, 95% CI 1.129–1.609) and benzodiazepines (OR 1.489, 95% CI 1.141–1.943). Anxiety disorders (778/5341, 14.6%) were only associated with benzodiazepines (OR 1.598, 95% CI 1.194–2.138). CONCLUSIONS: PTSD’s association with increased end-of-life healthcare utilization and increased antipsychotic administration in the final days of life suggests increased symptom burden and potential for terminal delirium in individuals with PTSD. Understanding the burden of psychiatric illness and potential risks for delirium may facilitate the end-of-life care for these patients. TRIAL REGISTRATION: NCT00234286 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-019-05538-x) contains supplementary material, which is available to authorized users.

OBJECTIVES: Hospital-associated disability (HAD), defined as loss of independence in activities of daily living (ADL) following acute hospitalization, is observed among older adults. The study objective is to determine overall prevalence of HAD among older adults hospitalized in acute care, and to assess the impact of study initiation year in moderation of prevalence. DESIGN: Meta-analysis of data collected from randomized trials, quasi-experimental and prospective cohort studies. English-language searches to identify included studies were completed February 2018 and updated May 2018 of electronic databases and reference lists of studies and reviews. Included studies were human subjects investigations that measured ADL ≥ 2 time points before/during and after hospitalization and reported prevalence of ADL decline among older adults. SETTING: Acute care hospital units. PARTICIPANTS: Adults aged ≥ 65 years hospitalized in medical-surgical acute care. Total sample size across all included studies was 7,375. METHODS: Independence in ADL was assessed using the Katz Index of Independence in Activities of Daily Living and Barthel Index of Independence in Activities of Daily Living. RESULTS: Random effects meta-analysis across included studies identified combined prevalence of HAD as 30% (95% CI: 24%, 33%; p < 0.001). The effect of study initiation year on prevalence rate was minimal. A large amount of heterogeneity was observed between studies, which may be due in part to non-standardized measurement of ADL impairment or other methodological differences. CONCLUSIONS AND IMPLICATIONS: Hospitalization in acute care poses a significant risk to functional independence of older adults and this risk is unchanged despite shorter lengths of stay. The evidence supports the continued need for hospital-based programs that provide assessment of functional ability and identification of at risk older adults in order to better treat and prevent HAD.

Performance of instrumental activities of daily living (IADLs) can become compromised in older adults with mild cognitive impairment (MCI). Patients’ level of insight into their everyday functioning varies both amongst individuals and across domains assessed, with some individuals exhibiting complete unawareness of deficits. The current cross-sectional study examined the neuroanatomical substrates of self-awareness in order to help explain the variability in this phenomenon in older adults across a continuum of cognitive impairment. Eighty-five participants (ages 54–88, mean age = 73 years, 57% female, 89% Caucasian) diagnosed with MCI or mild probable dementia underwent structural magnetic resonance imaging. Level of self-awareness was assessed by calculating the discrepancy between objective and subjective performance across six IADLs (Financial Management, Driving, Grocery Shopping, Nutrition Evaluation, Medication Management, and Telephone Use). Over-estimation of current abilities occurred in 13–31% of the sample depending on which IADL was evaluated. Poor awareness was significantly related to reduced volume in the bilateral medial prefrontal cortex, middle and posterior cingulate cortex, right insular cortex, and cerebellum. No associations were found with total white matter lesion load. These findings were broadly consistent across all functional domains assessed, supporting the theory that cortical midline and cerebellar structures are involved in self-referential processing across a variety of different cognitive and behavioral skills. Longitudinal studies are needed to confirm this association.

Objective To describe the presence of practice effects in persons with Alzheimer disease (AD) or mild cognitive impairment (MCI) and to evaluate how practice effects affect cognitive progression and the outcome of clinical trials. Methods Using data from a meta-database consisting of 18 studies including participants from the Alzheimer disease Cooperative Study (ADCS) and the Alzheimer Disease Neuroimaging Initiative (ADNI) with ADAS-Cog11 as the primary outcome, we defined practice effects based on the improvement in the first two ADAS-Cog11 scores and then estimated the presence of practice effects and compared the cognitive progression between participants with and without practice effects. The robustness of practice effects was investigated using CDR SB, an outcome independent the definition itself. Furthermore, we evaluated how practice effects can affect sample size estimation. Results The overall percent of practice effects for AD participants was 39.0% and 53.3% for MCI participants. For AD studies, the mean change from baseline to 2 years was 12.8 points for the non-practice effects group vs 7.4 for the practice effects group; whereas for MCI studies, it was 4.1 for non-practice effects group vs 0.2 for the practice effects group. AD participants without practice effects progressed 0.9 points faster than those with practice effects over a period of 2 years in CDR-SB; whereas for MCI participants, the difference is 0.7 points. The sample sizes can be different by over 35% when estimated based on participants with/without practice effects. Conclusion Practice effects were prevalent and robust in persons with AD or MCI and affected the cognitive progression and sample size estimation. Planning of future AD or MCI clinical trials should account for practice effects to avoid underpower or considers target trials or stratification analysis based on practice effects.

The Acute Care for Elders (ACE) Unit model improves cognitive and functional outcomes for hospitalized elders but reaches a small proportion of patients. To disseminate ACE Unit principles, we piloted the "Virtual ACE Intervention" that standardizes care processes for cognition and function without daily geriatrician oversight on two non-ACE units. The Virtual ACE Intervention includes staff training on geriatric assessments for cognition and function and on nurse-driven care algorithms. Completion of the geriatric assessments by nursing staff in patients aged 65 years and older and measures of patient mobility and prevalence of an abnormal delirium screening score were compared preintervention and postintervention. Postintervention, the completion of the assessments for current functional status and delirium improved (62.5% vs. 88.5%, p < .001) and (4.2% vs. 96.5%, p < .001). In a subsample analysis, in the postintervention period, more patients were up to the chair in the past day (36.4% vs. 63.5%, p = .04) and the prevalence of an abnormal delirium screening score was lower (13.6% vs. 4.8%, p = .16). The Virtual ACE Intervention is a feasible model for disseminating ACE Unit principles to non-ACE Units and may lead to increased adherence to care processes and improved clinical outcomes.

Delirium, or acute confusional state, affects up to 7 million hospitalized older adults annually, and is associated with increased risk of mortality, institutionalization, and cognitive and functional impairment. There has been a proliferation of both pharmacological and nonpharmacological clinical trials to reduce the incidence and sequelae of delirium. In other neuropsychiatric disorders, exclusion criteria prevent up to 75% of individuals with the condition under study from participating. It is unclear how well these trial samples represent the population of older adults with delirium. We selected all intervention trials registered at ClinicalTrials.gov containing the keyword “delirium” (N=131), regardless of type of intervention. We manually examined study descriptions to restrict analysis to studies with delirium as a primary or secondary outcome (N=92). Of these 92 studies, 76% enrolled only adults, with 45% enrolling only older adults. 38% of studies were restricted to surgical units, 27% to intensive care units, and 7.6% to medical units. Only 1 study examined nursing homes and 4 studies examined palliative care. 50% of studies excluded individuals with pre-existing dementia, 28% excluded individuals with psychiatric disorders, and 30% excluded individuals with neurological disorders. 34% of studies excluded individuals with alcohol or drug abuse. Overall, many intervention studies for delirium are limited to the surgical and ICU populations, and they exclude individuals with common comorbidities associated with an increased risk of delirium. Similar to other neuropsychiatric disorders, these findings raise significant concerns about the generalizability of clinical trials in delirium to the hospitalized older adult population.

Background Life-space is associated with adverse health outcomes in older adults, but its role in health care utilization among individuals with heart failure is not well understood. We examined the relationship between life-space and both emergency department (ED) utilization and hospitalization. Methods Participants were community-dwelling older adults with a verified diagnosis of heart failure who completed a baseline in-home assessment and at least one follow-up telephone interview. Life-space was measured at baseline and at follow-up every 6 months for 8.5 years. Poisson models were used to determine the association between life-space, measured at the beginning of each 6-month interval, and health care utilization, defined as ED utilization or hospitalization in the immediate ensuing 6 months, adjusting for sociodemographic and clinical confounders. Results A total of 147 participants contributed 259 total health care utilization events involving an ED visit or a hospital admission. Multivariate analysis demonstrated an inverse association between life-space and health care utilization, where a clinically significant 10-point difference in life-space was independently associated with a 14% higher rate of ED utilization or hospitalization (incidence rate ratio 1.14, 95% CI 1.04-1.26, p = .004). Conclusions Life-space may be a useful identifier of community-dwelling older adults with heart failure at increased risk of ED visits or hospital admissions in the ensuing 6 months. Life-space may therefore be a potentially important component of intervention programs to reduce health care utilization.

Introduction The sample size re-estimation (SSR) adaptive design allows interim analyses and resultant modifications of the ongoing trial to preserve or increase power. We investigated the applicability of SSR in Alzheimer's disease (AD) trials using a meta-database of clinical studies. Methods Based on six studies, we simulated clinical trials using Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) as primary outcome. A single SSR based on effect sizes or based on variances was conducted at 6 months and 12 months. Resultant power improvement and sample size adjustments were evaluated. Results SSR resulted in highly variable outcomes for both sample size increases and power improvement. The gain in power after SSR varies by initial sample sizes, trial durations, and effect sizes. Conclusions SSR adaptive designs can be effective for trials in AD and mild cognitive impairment with small or medium initial sample sizes. However, SSR in larger trials (>200 subjects per arm) generates no major advantages over the typical randomized trials.

To identify approximately 500 cases of incident cognitive impairment (ICI) in a large, national sample adapting an existing cognitive test-based case definition and to examine relationships of vascular risk factors with ICI.Participants were from the REGARDS study, a national sample of 30,239 African-American and White Americans. Participants included in this analysis had normal cognitive screening and no history of stroke at baseline, and at least one follow-up cognitive assessment with a three-test battery (TTB). Regression-based norms were applied to TTB scores to identify cases of ICI. Logistic regression was used to model associations with baseline vascular risk factors.We identified 495 participants with ICI of 17,630 eligible participants. In multivariable modeling, income (OR 1.83 CI 1.27,2.62), stroke belt residence (OR 1.45 CI 1.18,1.78), history of transient ischemic attack (OR 1.90 CI 1.29,2.81), coronary artery disease(OR 1.32 CI 1.02,1.70), diabetes (OR 1.48 CI 1.17,1.87), obesity (OR 1.40 CI 1.05,1.86), and incident stroke (OR 2.73 CI 1.52,4.90) were associated with ICI.We adapted a previously validated cognitive test-based case definition to identify cases of ICI. Many previously identified risk factors were associated with ICI, supporting the criterion-related validity of our definition.

BackgroundPost hoc analyses from clinical trials in Alzheimer's disease (AD) suggest that more cognitively impaired participants respond differently from less impaired on cognitive outcomes. We examined pooled clinical trials data to assess the utility of enriching trials using baseline cognition.MethodsWe included 2882 participants with mild to moderate AD in seven studies from a meta-database. We used mixed effects models to estimate the rate of decline in Alzheimer's disease Assessment Scale-cognitive (ADAS-Cog) scores among Mini-Mental State Examination (MMSE) groups.FindingsBaseline MMSE category was associated with baseline scores and rate of decline on the ADAS-Cog, adjusting for age and education (both P

Background Given the complex and progressive nature of Alzheimer’s disease (AD), a precision medicine approach for diagnosis and treatment requires the identification of patient subgroups with biomedically distinct and actionable phenotype definitions. Methods Longitudinal patient-level data for 1160 AD patients receiving placebo or no treatment with a follow-up of up to 18 months were extracted from an integrated clinical trials dataset. We used latent class mixed modelling (LCMM) to identify patient subgroups demonstrating distinct patterns of change over time in disease severity, as measured by the Alzheimer’s Disease Assessment Scale—cognitive subscale score. The optimal number of subgroups (classes) was selected by the model which had the lowest Bayesian Information Criterion. Other patient-level variables were used to define these subgroups’ distinguishing characteristics and to investigate the interactions between patient characteristics and patterns of disease progression. Results The LCMM resulted in three distinct subgroups of patients, with 10.3% in Class 1, 76.5% in Class 2 and 13.2% in Class 3. While all classes demonstrated some degree of cognitive decline, each demonstrated a different pattern of change in cognitive scores, potentially reflecting different subtypes of AD patients. Class 1 represents rapid decliners with a steep decline in cognition over time, and who tended to be younger and better educated. Class 2 represents slow decliners, while Class 3 represents severely impaired slow decliners: patients with a similar rate of decline to Class 2 but with worse baseline cognitive scores. Class 2 demonstrated a significantly higher proportion of patients with a history of statins use; Class 3 showed lower levels of blood monocytes and serum calcium, and higher blood glucose levels. Conclusions Our results, ‘learned’ from clinical data, indicate the existence of at least three subgroups of Alzheimer’s patients, each demonstrating a different trajectory of disease progression. This hypothesis-generating approach has detected distinct AD subgroups that may prove to be discrete endophenotypes linked to specific aetiologies. These findings could enable stratification within a clinical trial or study context, which may help identify new targets for intervention and guide better care. Electronic supplementary material The online version of this article (10.1186/s13195-017-0332-0) contains supplementary material, which is available to authorized users.

OBJECTIVE To examine whether cognitive reserve (CR) attenuates the initial impact of traumatic brain injury (TBI) on cognitive performance (neural reserve) and results in faster cognitive recovery rates in the first year postinjury (neural compensation), and whether the advantage of CR differs on the basis of the severity of TBI. SETTING Inpatient/outpatient clinics at an academic medical center. PARTICIPANTS Adults with mild TBI (mTBI; n = 28), complicated mild TBI (cmTBI; n = 24), and moderate to severe TBI (msevTBI; n = 57), and demographically matched controls (n = 66). DESIGN Retrospective, longitudinal cohort assessed at 1, 6, and 12 months postinjury. MAIN MEASURES Outcomes were 3 cognitive domains: processing speed/executive function, verbal fluency, and memory. Premorbid IQ, estimated with the Wechsler Test of Adult Reading, served as CR proxy. RESULTS Higher premorbid IQ was associated with better performance on cognitive domains at 1 month postinjury, and the effect of IQ was similarly beneficial for all groups. Cognitive recovery rate was moderated only by TBI severity; those with more severe TBI had faster recovery in the first year. CONCLUSION Results support only the neural reserve theory of CR within a TBI population and indicate that CR is neuroprotective, regardless of the degree of TBI. Higher premorbid CR does not allow for more rapid adaptation and recovery from injury.

BackgroundDespite substantial research and development investment in Alzheimer’s disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, β-amyloid and AD, and several studies have shown a reduced risk for AD and dementia in populations treated with statins. However, while some clinical trials evaluating statins in general AD populations have been conducted, these resulted in no significant therapeutic benefit. By focusing on subgroups of the AD population, it may be possible to detect endotypes responsive to statin therapy.MethodsHere we investigate the possible protective and therapeutic effect of statins in AD through the analysis of datasets of integrated clinical trials, and prospective observational studies.ResultsRe-analysis of AD patient-level data from failed clinical trials suggested by trend that use of simvastatin may slow the progression of cognitive decline, and to a greater extent in ApoE4 homozygotes. Evaluation of continual long-term use of various statins, in participants from multiple studies at baseline, revealed better cognitive performance in statin users. These findings were supported in an additional, observational cohort where the incidence of AD was significantly lower in statin users, and ApoE4/ApoE4-genotyped AD patients treated with statins showed better cognitive function over the course of 10-year follow-up.ConclusionsThese results indicate that the use of statins may benefit all AD patients with potentially greater therapeutic efficacy in those homozygous for ApoE4.

Poor nutritional status is associated with adverse health outcomes across the life course, affecting older adults’ ability to maintain overall well-being, limiting physical strength, and affecting mobility. International research has demonstrated associations between nutritional risk and general musculoskeletal pain; however, no research has explored relationships between nutritional risk and low back pain. Using the University of Alabama-Birmingham Study of Aging, we examined this relationship among 1000 community-dwelling older Alabamians (65+years). We used the DETERMINE Checklist, a well-validated nutritional risk assessment and assessed presence and severity of low back pain over the past 4 weeks. We completed univariate and bivariate analysis and multivariate logistic regression, adjusting for factors significant in the bivariate analyses: sex, body mass index, depression, and co-morbidities. More than half of the participants were at nutritional risk (55.2%). In multivariate analyses, one point increases in nutritional risk were associated with a 14% increase in the likelihood of low back pain 95% CI (1.087,1.213); in categorical analyses, moderate nutritional risk and high nutritional risk were associated with an increase in likelihood of low back pain [46% (95% CI 1.07,2.02) and 164% (95% CI 1.80,3.94), respectively]. While this cross-sectional analysis should be interpreted cautiously, it further emphasizes the importance of nutritional health for older adults. Clinicians treating patients with low back pain or nutritional risk may consider assessing for the other condition. When nutritional risk is detected, clinicians should refer to services such as counseling with a registered dietitian or to a social worker for assistance identifying community-based nutritional supports.

Summary Background Asymmetry of hippocampal internal architecture (HIA) has been reported to be a frequent imaging finding in epilepsy patients with temporal lobe epilepsy (TLE) who exhibit other signs of hippocampal sclerosis. HIA asymmetry may also be an independent predictor of the side of seizure onset in patients with otherwise normal MRI scans. The study of HIA asymmetry and its relationship to the laterality of TLE would benefit from a reliable method of assessing the clarity of HIA in MRI scans. We propose a visual scoring system that rates HIA clarity from 1 (imperceptible) to 4 (excellent) and report the inter-rater reliability (IRR) of this system. Methods In the initial preliminary phase of this study we examined IRR using a kappa statistic ( κ ) among a mixed group of expert and non-expert reviewers using only a brief description of the scoring system to score single images from a series of patients. In the second phase we explored the effect of training on the use of our HIA scoring system by assessing IRR among neuroimaging experts before and after a brief interactive training session. In this phase, multiple slices from each patient were scored. Separate κ values and intraclass correlation coefficients (ICC) were calculated from the scores given to each hippocampal image and from the asymmetry of scores between left and right for each slice. In the third phase the effect of training on non-expert reviewers was explored using a similar approach as with the expert reviewers. Results In the preliminary phase of the study, HIA scoring of single images showed substantial agreement among expert reviewers ( κ HIA =0.65), fair agreement among non-expert reviewers ( κ HIA =0.27), and a fair to moderate degree of agreement among all the reviewers as a whole ( κ HIA =0.40). In the second phase, prior to training there was substantial agreement among expert reviewers in regard to the individual HIA scores ( κ HIA =0.62; ICC HIA =0.81) but only moderate agreement on the degree of asymmetry ( κ Asym =0.47; ICC Asym =0.71). Training improved agreement on the individual HIA scores ( κ HIA =0.58–0.72; ICC HIA =0.76–0.84) and on the degree of asymmetry ( κ Asym =0.61–0.67; ICC Asym =0.81–0.85). Among non-expert reviewers, scores improved from only a fair degree of agreement pre-training ( κ HIA =0.25, κ Asym =0.25; ICC HIA =0.68, ICC Asym =0.66) to a moderate level of agreement after training ( κ HIA =0.54, κ Asym =0.52; ICC HIA =0.78, ICC Asym =0.81). Conclusions The proposed HIA scoring system has a substantial degree of inter-rater reliability among experienced neuroimaging reviewers. Training improves the detection of asymmetries in HIA score in particular. Non-expert reviewers can employ the system with a moderate degree of reliability, and training has an even greater impact on the improvement of scoring reliability.

Asymmetry of hippocampal internal architecture (HIA) clarity has been suggested to be a sign of hippocampal sclerosis (HS) and is frequently associated with other MRI findings of HS. The goal of this work is to use a previously developed HIA visual scoring system (Ver Hoef et al., 2013) to quantify HIA asymmetry in a retrospective series of consecutive temporal lobe epilepsy (TLE) patients and evaluate its value in predicting laterality of seizure onset both in patients with other signs of HS (HS+) and those without (HS-).The HIA scoring system was used to rate hippocampal asymmetry and to assess the agreement between HIA and seizure lateralization. The median values of the average HIA scores for each hippocampus were compared for HS+ epileptogenic hippocampi, HS- epileptogenic hippocampi, and non-epileptogenic hippocampi with a Kruskal-Wallis one-way analysis of variance by ranks. Pair-wise differences between groups were evaluated with the two-tailed Mann-Whitney U test. A logistic regression model examined the utility of average HIA asymmetry score in predicting the true laterality of seizure onset as determined by video-EEG. Sensitivity and specificity are calculated using various asymmetry thresholds in each patient group.Fifty-five patients were identified who met inclusion criteria. Thirteen patients (24%) were found to have hippocampal atrophy and/or signal abnormality indicative of HS (HS+) and 42 did not (HS-). Significant differences were observed in the distribution of individual and average HIA scores between each of the groups of hippocampi, with HS+ hippocampi having the lowest HIA scores and non-epileptogenic hippocampi having the highest. Logistic regression analysis showed that the average HIA asymmetry score was a strong predictor of the laterality of seizure onset (β=3.93508, p0.001). HIA asymmetry remained significant even after adjustment for HS+/HS- status (β=3.8854, p0.001). Among HS- patients, when the average HIA asymmetry score was equal to or exceeded a threshold value of 0.5, the specificity for correctly predicting the side of seizure onset was between 95% and 100% with a sensitivity of 40-45%. Among HS+ patients, a threshold of 0.3 yielded a sensitivity of 85% and specificity of 100%.In this report we show for the first time that HIA asymmetry is a significant predictor of the laterality of seizure onset in TLE patients with otherwise normal MRI findings, and that the proposed HIA scoring system has high specificity and moderate sensitivity for lateralizing seizure onset in patients with TLE.

Objective: To investigate recovery of medical decision-making capacity (MDC) over the first year following traumatic brain injury (TBI). Methods: A total of 177 participants (111 persons with TBI and 66 healthy controls) were recruited from an inpatient/outpatient TBI rehabilitation unit and outpatient neurology department. Participants with TBI were classified by injury severity into subgroups: mild TBI (mTBI; n = 28), complicated mild TBI (cmTBI; n = 23), and moderate/severe TBI (msevTBI; n = 60). Control and TBI groups were compared at 1 month (t1), 6 months (t2), and 12 months (t3) postinjury using the Capacity to Consent to Treatment Instrument (CCTI), which evaluates MDC using 5 consent standards: expressing choice, reasonable choice, appreciation, reasoning, and understanding. Results: Relative to controls, no TBI group displayed impairment on CCTI expressing choice or reasonable choice at any timepoint. Those with mTBI had reduced appreciation and understanding at t1, which resolved by t2. The cmTBI and msevTBI groups were impaired on all 3 complex consent standards at t1. While patients with cmTBI improved to a level similar to controls by t3, those with msevTBI remained impaired on reasoning and understanding. Across all TBI groups, notable MDC improvement only occurred over the first 6 months postinjury. Conclusions: Over 1 year, most individuals with mTBI or cmTBI regain MDC, while many individuals with msevTBI have lingering deficits in reasoning and comprehension of treatment information. Clinical recovery of MDC occurs primarily during the first 6 months post-TBI regardless of injury severity. Clinicians can therefore identify MDC outcomes in TBI at 6 months postinjury.

OBJECTIVE: The current study sought to determine whether the Wechsler Test of Adult Reading (WTAR) provides a stable estimate of premorbid intellectual ability in acutely injured patients recovering from traumatic brain injury (TBI). METHOD: A total of 135 participants (43 mild TBI [mTBI], 40 moderate/severe TBI [msevTBI], 52 healthy controls) were administered the WTAR at 1 and 12 months post-injury. RESULTS: Despite similar demographic profiles, participants with msevTBI performed significantly worse than controls on the WTAR at both time points. Moreover, the msevTBI group had a significant improvement in WTAR performance over the 1-year period. In contrast, those participants with mTBI did not significantly differ from healthy controls and both the mTBI and control groups demonstrated stability on the WTAR over time. CONCLUSIONS: Results indicate that word-reading tests may underestimate premorbid intelligence during the immediate recovery period for patients with msevTBI. Clinicians should consider alternative estimation measures in this TBI subpopulation.© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]/* */ Language: en

The study purpose was to assess the effects of emergency department visits on mobility as measured by Life-Space Assessment (LSA) scores and to compare life-space trajectories associated with emergency department visit only, hospitalization, and no event.A total of 410 community-dwelling adults aged ≥75 years who were living in the community, were able to communicate by telephone, could schedule an in-home interview, and could answer questions independently were followed from June 2010 to August 2014. In-home baseline and monthly telephone follow-up interviews collected data on LSA scores, emergency department use, and hospitalizations. Life-space is measured using a validated patient-reported tool reflecting community mobility and quality of life. Trajectories of LSA before and after an emergency department visit or hospitalization were compared with no event occurrence.Mean age of participants was 81.7 years (standard deviation, 4.8); 57% were female, and 35% were African American. During 3 years of follow-up, 83 persons (20%) had an emergency department visit without subsequent hospitalization and 164 persons (40%) were hospitalized. Although baseline LSA scores were similar, in the month after an emergency department visit, adjusted LSA scores decreased by 6.1 points (P = .01) in comparison with hospitalized participants who experienced an average decrease of 18.0 points (P.0001). Neither those with an emergency department visit only nor those with hospitalization recovered to their prior level of community mobility. Moreover, those with an emergency department visit showed no significant improvement in LSA scores up to 1 year later.Older adults who experienced an emergency department visit or hospitalization had an associated decrease in community mobility without significant recovery.

Background Many post hoc analyses of clinical trials in Alzheimer's disease (AD) and mild cognitive impairment (MCI) are in small Phase 2 trials. Subject heterogeneity may lead to statistically significant post hoc results that cannot be replicated in larger follow-up studies. Objective We investigated the extent of this problem using simulation studies mimicking current trial methods with post hoc analyses based on ApoE4 carrier status. Methods We used a meta-database of 24 studies, including 3,574 subjects with mild AD and 1,171 subjects with MCI/prodromal AD, to simulate clinical trial scenarios. Post hoc analyses examined if rates of progression on the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) differed between ApoE4 carriers and non-carriers. Results Across studies, ApoE4 carriers were younger and had lower baseline scores, greater rates of progression, and greater variability on the ADAS-cog. Up to 18% of post hoc analyses for 18-month trials in AD showed greater rates of progression for ApoE4 non-carriers that were statistically significant but unlikely to be confirmed in follow-up studies. The frequency of erroneous conclusions dropped below 3% with trials of 100 subjects per arm. In MCI, rates of statistically significant differences with greater progression in ApoE4 non-carriers remained below 3% unless sample sizes were below 25 subjects per arm. Conclusions Statistically significant differences for ApoE4 in post hoc analyses often reflect heterogeneity among small samples rather than true differential effect among ApoE4 subtypes. Such analyses must be viewed cautiously. ApoE genotype should be incorporated into the design stage to minimize erroneous conclusions.

Hart T, Hoffman JM, Pretz C, Kennedy R, Clark AN, Brenner LA. A longitudinal study of major and minor depression following traumatic brain injury. Objective To examine patterns of change and factors associated with change in depression, both major (major depressive disorder [MDD]) and minor, between 1 and 2 years after traumatic brain injury (TBI). Design Observational prospective longitudinal study. Setting Inpatient rehabilitation centers, with 1- and 2-year follow-up conducted primarily by telephone. Participants Persons with TBI (N=1089) enrolled in the Traumatic Brain Injury Model Systems database, followed at 1 and 2 years postinjury. Interventions Not applicable. Main Outcome Measure Patient Health Questionnaire-9. Results Among participants not depressed at 1 year, close to three fourths remained so at 2-year follow-up. However, 26% developed MDD or minor depression between the first and second years postinjury. Over half of participants with MDD at year 1 also reported MDD the following year, with another 22% reporting minor depression; thus three fourths of those with MDD at year 1 experienced clinically significant symptoms at year 2. Almost one third of those with minor depression at year 1 traversed to MDD at year 2. Polytomous logistic regression confirmed that worse depression at year 1 was associated with higher odds of depression a year later. For those without depression at year 1, symptom worsening over time was related to year 2 problematic substance use and lower FIM motor and cognitive scores. For those with depression at year 1, worsening was associated with lower cognitive FIM, poor social support, and preinjury mental health issues including substance abuse. Conclusions Major and minor depression exist on a continuum along which individuals with TBI may traverse over time. Predictors of change differ according to symptom onset. Results highlight importance of long-term monitoring for depression, treating minor as well as major depression, and developing interventions for comorbid depression and substance abuse.

Importance Clinical trials in Alzheimer disease (AD) generally allow participants to continue receiving concomitant medications, including cholinesterase inhibitors (ChEIs) and memantine, if the dose is stable. Previous analysis of observational studies indicates such individuals experience greater rate of decline on cognitive testing than those not receiving such medications. Objective To investigate whether concomitant use of ChEIs or memantine is associated with cognitive outcomes in AD clinical trials. Data Sources Meta-database of 18 studies from the Alzheimer Disease Cooperative Study and Alzheimer Disease Neuroimaging Initiative. Study Selection All studies with data on ChEI and memantine use that included assessment of specified outcome measures. Data Extraction and Synthesis The analysis estimated annual rate of decline on the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog) using linear mixed-effects models, and compared rates for participants receiving ChEIs and memantine, alone and combined, with participants not receiving either medication using random-effects meta-analysis. Main Outcomes and Measures Annual rate of change on the ADAS-cog. Results Across 10 studies, of 2714 participants, the mean (SD) age was 75.0 (8.2) years, 58% were female, and 9% were racial/ethnic minorities. There were 906 participants (33.4%) receiving ChEIs, 143 (5.3%) receiving memantine, 923 (34.0%) receiving both, and 742 (27.3%) receiving neither. Meta-analysis showed those receiving ChEIs or memantine were associated with significantly greater annual rate of decline on the ADAS-cog than those receiving neither medication (1.4 points/y; 95% CI, 0.1-2.7). Conclusions and Relevance Similar to observational studies, many participants in AD clinical trials receiving ChEIs or memantine experience greater cognitive decline. This difference is nearly as large as the hypothesized effect sizes of the treatments investigated in the trials. Concomitant use of ChEIs or memantine may be confounded with outcomes on the ADAS-cog and should be considered in design of clinical trials of potential therapeutic agents for AD. Post hoc analyses stratifying by ChEIs or memantine must be interpreted cautiously given the potential for confounding.

Objective: To determine predictors of family caregiver life satisfaction at one and two years after traumatic brain injury (TBI). Methods: Prospective collaborative longitudinal study of 336 family members caring for individuals with TBI participating in the National Institute on Disability and Rehabilitation Research (NIDRR) designated TBI Model Systems of Care (TBIMS). Survivors' medical and demographic information was obtained from the TBIMS database. Follow-up interviews were completed with both survivors and family caregivers at 1 year and 2 years post injury. The primary outcome variable, caregiver life satisfaction, was measured with the Satisfaction with Life Scale (SWLS). Results: Repeated measures ordinal logistic regression showed that survivors' functional status at discharge, drug use, and neurobehavioral problems were significant predictors of family caregivers' life satisfaction at 1 and 2 years post injury. Conclusions: Family members of individuals with TBI often experience reduced life satisfaction in the first 2 years following their relatives' TBI. Psychiatric and neurobehavioral problems, such as drug use and depression, as well as motor dysfunction in survivors may be important contributors to decreased life satisfaction among their caregivers.

The authors studied factors associated with referral of delirium patients to psychiatry consultation and its outcome implications. Characteristics and treatment outcomes of delirium patients referred to psychiatry were compared with those not referred. Referred patients were younger, had a more hyperactive subtype, greater substance abuse, less comorbid dementia, were more likely to be recognized as having delirium, and be prescribed medications. Improvement in referred patients was indicated by lower readmission rate postdischarge. No differences were noted in length of stay, discharge status, or mortality within 1 year of the index episode. Psychiatric interventions were moderately helpful. Patients' characteristics and delirium subtypes may influence referral and should inform future liaison efforts.

Objective To determine characteristics of patients with complicated mild traumatic brain injury (CMTBI) on the inpatient rehabilitation unit and to accentuate limits of current classification systems for patients with mild TBI. Design Multicenter analysis of individuals with a Glasgow Coma Scale (GCS) score of 13 to 15 (lowest score in 24 h) and positive computed tomography findings admitted to inpatient rehabilitation for TBI. Setting 16 TBI Model System centers funded by the National Institute on Disability and Rehabilitation Research. Participants 373 adults with CMTBI. Main outcome measures Functional Independence Measure (FIM) and Disability Rating Scale (DRS) scores, length of stay, and medical complications. Results 16% of the sample experienced serious cranial complications (eg, cerebrospinal fluid leak, intracranial hypertension), with seizures being the most common during the course of inpatient rehabilitation. Most patients demonstrated substantial improvements on functional outcome measures during rehabilitation (mean admission FIM 68.2, discharge FIM 100.6; admission DRS 9.1, discharge DRS 4.8). Age, acute length of stay, and FIM score on rehabilitation admission were significant predictors of rehabilitation length of stay. Factors not predictive of rehabilitation duration were GCS score, ethnicity, gender, incidence of fractures, and incidence of cranial/noncranial complications. Conclusion Despite favorable GCS scores, some patients with CMTBI suffer a variety of serious cranial and noncranial complications. Such patients appear to benefit from additional brain injury services offered in inpatient rehabilitation. Further study of the unique treatment needs of these patients is warranted.