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Measuring amyloid and predicting tau status using a single amyloid 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 determined primarily by blood flow, which is expected to be decreased in the setting of tau pathology. Methods: The study included 120 participants (63 amyloid-positive and 57 amyloid-negative) with dynamic (18)F-florbetapir PET and static (18)F-flortaucipir PET scans obtained within 6 mo of each other. These subjects were predominantly cognitively intact in both the amyloid-positive (63%) and the 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-characteristic analysis of area under the curve (AUC). Pearson r and Spearman ρ were used for parametric and nonparametric comparisons between efAP and tau PET, respectively. Standardized net benefit was used to evaluate improvement in using efAP as an additional copredictor over hippocampal volume in predicting tau PET positivity. Results: Measuring efAP within the hippocampus and summing the first 3 min of brain activity after 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

Disadvantaged neighborhood environments may have low access to healthcare, perpetuating health disparities. Previous research has reported on associations between neighborhood disadvantage (ND) and depressive symptomology but not depression diagnoses, which may indicate access to healthcare. This study tested how ND relates to depressive symptomology and diagnosis to assess for neighborhood disparities in mental health care cross-sectionally. Data from 998 community-dwelling, Black and White individuals aged 65+ included in the University of Alabama at Birmingham Study of Aging were analyzed. We obtained participants&rsquo, depressive symptomology from the Geriatric Depression Scale (n = 100) and a verified depression diagnosis from self-report and review of medication, physician-report, and/or hospital discharge summaries (n = 84). We assessed ND from US Census data, divided the sample into tertiles of ND and fit models with Generalized Estimating Equations covarying for various other variables (e.g., sex, race, physical performance, socioeconomic status, etc.). We found living in the high and mid-ND tertiles to be associated with depressive symptomology, yet ND had no significant relation to depression diagnosis. Therefore, older adults living in high and mid-disadvantaged neighborhoods may be more likely to experience depressive symptomology but not receive a diagnosis, indicating a possible disparity in mental health care.

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.

This study aimed to determine the proportion of older adults who recovered community mobility after hospitalization and identify factors associated with recovery. Using a random sample of 1,000 Medicare beneficiaries ≥65 years of age, we identified individuals with at least one hospitalization over 8.5 years of follow-up. Data were collected at baseline and every 6 months, including demographics, function, social support, community mobility measured by the UAB Life-Space Assessment (LSA), and overnight hospital admissions. Recovery was defined as a LSA score no more than five points lower than the prehospitalization LSA score at last follow-up. Overall, 339 participants ( M age = 75.4 [ SD = 6.6] years, 44% African American, 48% female) had at least one hospitalization. In the full logistic regression model, younger age ( p = .007) and religious service attendance ( p = .001) remained independently associated with recovery. An understanding of factors associated with recovery after hospitalization may provide a target for future interventions.

Social factors may disparately affect access to food and nutritional risk among older adults by race and gender. This study assesses these associations using the Mini Nutritional Assessment among 414 community-dwelling persons 75+ years of age in Alabama. Descriptive analyses on the full sample and by African American men, African American women, white men, and white women showed that mean scores for the full Mini Nutritional Assessment differed by groups, with African American men and African American women having the highest nutritional risk. Multivariable analyses indicated that social factors affect nutritional risk differently by race and gender. Nutritional risk interventions are warranted for older adults.

Research Objectives To determine anxiety trajectories across the first 10 years after traumatic brain injury (TBI), and to identify predictors of the longitudinal course of anxiety. Design Longitudinal cohort study. Setting Community. Participants 2836 participants with moderate to severe TBI enrolled in the Traumatic Brain Injury Model Systems (TBIMS) National Database who had anxiety outcomes for ≥2 data collection points over a 10-year follow-up period. Interventions N/A. Main Outcome Measures Generalized Anxiety Disorder-7 (GAD-7) at 1, 2, 5, and 10-year follow-ups. Relationships were examined with demographic variables, indicators of TBI severity, number of TBIs in addition to the index TBI, pre-morbid mental health, and substance abuse history. Results A latent class mixed model identified three anxiety trajectories: low-stable (n=2195), increasing (n=289), and decreasing (n=352). Higher GAD-7 scores were significantly associated with Black race, having public insurance, premorbid mental health problems, experiencing ≥2 additional TBIs with loss of consciousness (LOC), and increased years post-TBI. An interaction between follow-up year and age was also related to GAD-7 scores (p=.001). Conclusions Most individuals in the sample had low anxiety that was stable over time (77%). Smaller percentages of individuals had higher levels of anxiety, that either increased (10%) or decreased (13%) as time progressed. Multiple TBI's with LOC were related to greater anxiety up to 10 years after injury. Systemic economic and racial inequities likely contribute to long-term anxiety, as evidenced by greater anxiety in those who had public insurance and/or identified as Black. Younger individuals were more likely to experience an increase in their anxiety over time, suggesting a need for long-term anxiety surveillance, particularly for patients whose TBI occurred at an earlier stage in life. Author(s) Disclosures None.

Objective The authors investigated potential effects of increased African American participation in Alzheimer disease (AD) and mild cognitive impairment (MCI) clinical trials by examining differences in comorbid conditions and treatment outcome affecting trial design. Methods Using a meta-database of 18 studies from the Alzheimer's Disease Cooperative Study and the Alzheimer's Disease Neuroimaging Initiative, a cohort of 5,164 subjects were included for whom there were baseline demographic data and information on comorbid disorders, grouped by organ system. Meta-analysis was used to compare prevalence of comorbidities, dropouts, and rates of change on the cognitive subscale of the Alzheimer's Disease Assessment Scale by race. Clinical trial scenarios similar to recent therapeutic trials were simulated to determine effects of increased African American participation on statistical power. Results Approximately 7% of AD, 4% of MCI, and 11% of normal participants were African American. African American subjects had higher prevalence of cardiovascular disorders (odds ratio: 2.10; 95% confidence interval [CI]: 1.71–2.57) and higher rate of dropouts (odds ratio: 1.60; 95% CI: 1.15–2.21) compared with whites but lower rates of other disorders. There were no significant differences in rate of progression (–0.862 points/year; 95% CI: −1.89 to 0.162) by race and little effect on power in simulated trials with sample sizes similar to current AD trial designs. Conclusion Increasing African American participation in AD clinical trials will require adaptation of trial protocols to address comorbidities and dropouts. However, increased diversity is unlikely to negatively affect trial outcomes and should be encouraged to promote generalizability of trial results.

Objective: To determine whether decline in life-space mobility predicts increased health care utilization among community-dwelling older adults. Method: Health care utilization (number of emergency department [ED] visits and hospitalizations) was self-reported during monthly interviews among 419 community-dwelling African American and non-Hispanic White adults aged 75 years and older in The University of Alabama at Birmingham (UAB) Study of Aging II. Life-space was measured using the UAB Life-Space Assessment. Generalized estimating equations were used to examine associations of life-space at the beginning of each interval with health care utilization over the 1-month interval. Results: Overall, 400 participants were followed for 36 months. A 10-point decrease in life-space was associated with 14% increased odds of an ED visit and/or hospitalization over the next month, adjusting for demographics, transportation difficulty, comorbidity, and having a doctor visit in the last month. Discussion: Life-space is a practical alternative in predicting future health care utilization to performance-based measures, which can be difficult to incorporate into clinical or public health practice.

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.

Objective To examine the neuropsychological correlates of anosognosia for instrumental activities of daily living (IADLs) in older adults with mild cognitive impairment (MCI) and mild dementia. Method Participants (n = 103; age range = 54–88, 52% female) with MCI and mild dementia were recruited from neurology and geriatrics clinics for cross-sectional analysis. They completed neuropsychological tests along with subjective and performance-based assessments of six IADLs: financial management, driving, grocery shopping, nutrition evaluation, telephone use, and medication management. For each IADL, participants were classified as having anosognosia when there was objective difficulty but no subjective complaints. Results Depending on functional domain, 13–39% of the sample had objective IADL difficulty, and of those, 65–93% lacked insight into these deficits. Binomial logistic regression models controlling for demographic variables revealed that measures of global cognition, executive function, visual attention, and verbal memory predicted classification of anosognosia, and these relationships varied across IADLs. In contrast, basic auditory attention, working memory, depressive symptoms, nor cognitive reserve were significantly related to anosognosia for any IADL. Conclusion Results support the Conscious Awareness Model, which theorizes that accurate metacognitive output is reliant on attentional, memory, and executive functioning systems. Findings from this study suggest that anosognosia for different IADLs may arise from breakdowns at varying points in this model, explaining both inter- and intra-patient variability in self-awareness of functional deficits.

ObjectiveThere is a need for tools enabling efficient evaluation of amyloid- and tau-PET images suited for both clinical and research settings. The purpose of this study was to assess and validate a semi-automated imaging workflow, called Biomarker Localization, Analysis, Visualization, Extraction, and Registration (BLAzER). We tested BLAzER using two different segmentation platforms, FreeSurfer (FS) and Neuroreader (NR), for regional brain PET quantification in images from participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset.Methods127 amyloid-PET and 55 tau-PET studies along with corresponding volumetric MRI were obtained from ADNI. The BLAzER workflow utilizes segmentation of MR images by FS or NR, then visualizes and quantifies regional brain PET data using FDA-cleared software (MIM), enabling quality control to ensure optimal registration and detect segmentation errors.ResultsBLAzER analysis required only ∼5 min plus segmentation time. BLAzER using FS segmentation showed strong agreement with ADNI for global amyloid-PET standardized uptake value ratios (SUVRs) (r = 0.9922, p < 0.001) and regional tau-PET SUVRs across all Braak staging regions (r > 0.97, p < 0.001) with high inter-operator reproducibility for both (ICC > 0.97) and nearly identical dichotomization as amyloid-positive or -negative (2 discrepant cases out of 127). Comparing FS vs. NR segmentation with BLAzER, the global SUVRs were strongly correlated for global amyloid-PET (r = 0.9841, p < 0.001), but were systematically higher (4% on average) with NR, likely due to more inclusion of white matter, which has high florbetapir binding.ConclusionsBLAzER provides an efficient workflow for regional brain PET quantification. FDA-cleared components and the ability to visualize registration reduce barriers between research and clinical applications.

This study examined the relationship between cognitive change and instrumental activities of daily living (IADL) in a large, national, population-based sample. Cognitive change was assessed via verbal fluency, word list learning (WLL), and word list delayed recall (WLD). Incident cognitive impairment was defined by change in Six-Item Screener (SIS) status over a period of 10 years. Impaired IADL was defined as self-reported difficulty or needing assistance performing any IADL at Year 10. A one-word decrease in WLL over a 10-year span increased the odds of impaired IADL by 16% (95% CI 1.08-1.24) and incident cognitive impairment increased the odds of impaired IADL by 59% (95% CI 1.36-1.85) when adjusting for demographic factors, health-related behaviors, vascular risk factors and disease, and depressive symptoms. Cognitive change most strongly predicted impairment in managing finances (OR 2.47, 95% CI 2.04-3.00) and driving (OR 2.06, 95% CI 1.73-2.44).

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.

BACKGROUND: Tools for efficient evaluation of amyloid-and tau-PET images are needed in both clinical and research settings. OBJECTIVE: This study was designed to validate a semi-automated image analysis methodology, called Biomarker Localization, Analysis, Visualization, Extraction, and Registration (BLAzER). We tested BLAzER using two different segmentation platforms, FreeSurfer (FS) and Neuroreader (NR), for regional brain PET quantification in participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. METHODS: 127 amyloid-PET and 55 tau-PET studies with volumetric MRIs were obtained from ADNI. The BLAzER methodology utilizes segmentation of MR images by FS or NR, then visualizes and quantifies regional brain PET data using FDA-cleared software (MIM), enabling quality control to ensure optimal registration and to detect segmentation errors. RESULTS: BLAzER analysis required ~5 min plus segmentation time. BLAzER using FS segmentation showed strong agreement with ADNI for global amyloid-PET standardized uptake value ratios (SUVRs) (r = 0.9922, p 0.97, p 0.97) and nearly identical dichotomization as amyloid-positive or -negative (2 discrepant cases out of 127). Comparing FS versus NR segmentation with BLAzER, global SUVRs were strongly correlated for amyloid-PET (r = 0.9841, p

OBJECTIVE: To identify neurocognitive predictors of medical decision-making capacity (MDC) in participants with mild and moderate/severe traumatic brain injury (TBI). SETTING: Academic medical center. PARTICIPANTS: Sixty adult controls and 104 adults with TBI (49 mild, 55 moderate/severe) evaluated within 6 weeks of injury. DESIGN: Prospective cross-sectional study. MAIN MEASURES: Participants completed the Capacity to Consent to Treatment Instrument to assess MDC and a neuropsychological test battery. We used factor analysis to reduce the battery test measures into 4 cognitive composite scores (verbal memory, verbal fluency, academic skills, and processing speed/executive function). We identified cognitive predictors of the 3 most clinically relevant Capacity to Consent to Treatment Instrument consent standards (appreciation, reasoning, and understanding). RESULTS: In controls, academic skills (word reading, arithmetic) and verbal memory predicted understanding; verbal fluency predicted reasoning; and no predictors emerged for appreciation. In the mild TBI group, verbal memory predicted understanding and reasoning, whereas academic skills predicted appreciation. In the moderate/severe TBI group, verbal memory and academic skills predicted understanding; academic skills predicted reasoning; and academic skills and verbal fluency predicted appreciation. CONCLUSIONS: Verbal memory was a predictor of MDC in controls and persons with mild and moderate/severe TBI. In clinical practice, impaired verbal memory could serve as a "red flag" for diminished consent capacity in persons with recent TBI. Language: en

The purpose of this study was to examine the trajectories of life-space before and after the transition to driving cessation among a diverse sample of community-dwelling older adults. Life-space scores and self-reported driving cessation were assessed at annual visits from baseline through Year 6 among participants in the University of Alabama at Birmingham Study of Aging. Approximately 58% of older adults reported having stopped driving during the 6 years of follow-up. After adjusting for potential confounders, results from a random intercept model indicate that mean life-space scores decreased about 1 to 2 points every year ( p = .0011) and approximately 28 points at the time of driving cessation ( p < .0001). The rate of life-space decline post driving cessation was not significantly different from the rate of decline prior to driving cessation. Driving cessation was associated with a precipitous decline in life-space score; however, the driving cessation event did not accelerate the rate of life-space decline.

The University of Alabama at Birmingham Life-Space Assessment (LSA) is a self-reported measure for assessing community mobility. Restricted mobility is correlated with a number of adverse health outcomes, including mortality, frailty, cognitive decline, and nursing home admissions. Thus, it is important for providers to understand how the LSA score of a patient compares to the general population. To facilitate such comparisons, we developed demographically adjusted norms for the LSA and its correlation with other functional measures. Norms were based on 15,390 participants age 45 and older in the National Institutes of Health-funded REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national, population-based, longitudinal study investigating the causes of excess stroke mortality among African Americans and individuals living in the Southeastern US stroke belt region. LSA scores declined from a median of 100 in the 45-54 age range to a median of 59.7 in the 85 and older age range, with higher median scores in males. LSA scores showed modest but significant positive correlations with SF-12 Physical Component and Mental Component, Center for Epidemiologic Studies Depression Scale, and Six Item Screener cognitive scores, as well as modest but significant negative correlations with AD8 Dementia Screening, Katz Activities of Daily Living, and Timed Walk scores. The LSA is a brief, easily administered measure that offers a valid method of assessing community mobility in the older adult population.

Objective Examine the correlation of the Brief Test of Adult Cognition by Telephone (BTACT) with established neuropsychological tests in an inpatient traumatic brain injury (TBI) population. Method Participants were 55 patients aged 18–76 years (M age = 37 years; 69% male) receiving inpatient rehabilitation for new-onset TBI at a level I trauma center, acute inpatient rehabilitation hospital. The BTACT is a brief cognitive test battery consisting of the following subtests: Word List Immediate and Delayed Recall (episodic verbal memory), Digits Backward (working memory), Number Series (inductive reasoning), Animal Fluency (verbal fluency), and Backward Counting (processing speed). With the intention of mirroring cognitive functions measured by the BTACT, the neuropsychological battery was comprised of the California Verbal Learning Test-2 (CVLT-2), Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span, Trail Making Test (TMT), semantic fluency, phonemic fluency, Symbol Digit Modalities Test, and Wisconsin Card Sorting Test. Results The BTACT was related to established neuropsychological tests across composite scores of overall cognition (r = .64, p Conclusion BTACT composite scores of overall cognition, verbal memory, and executive function are valid measures in a TBI inpatient population.

Symptomatic peripheral artery disease (PAD) impairs walking, but data on the impact of PAD on community mobility is limited. Life-space mobility measures the distance, frequency, and assistance needed as older adults move through geographic areas extending from their bedroom (life-space mobility score: 0) to beyond their town (life-space mobility score: 120). We evaluated the association of PAD with longitudinal life-space mobility trajectory.Participants were part of the University of Alabama at Birmingham Study of Aging, a longitudinal study of community-dwelling older adults who were observed from 2001 to 2009. We limited our analysis to those who survived at least 6 months (N = 981). PAD was based on self-report with verification by physician report and hospital records. Our primary outcome was life-space mobility score assessed every 6 months. A multilevel change model (mixed model) was used to determine the association between PAD and life-space mobility trajectory during a median 7.9 years of follow-up.Participants had a mean age of 75.7 (standard deviation, 6.7) years; 50.5% were female, and 50.4% were African American. PAD prevalence was 10.1%, and 57.1% of participants with PAD died. In participants with both PAD and life-space restriction, defined as life-space mobility score 60, we observed the highest mortality (73.1%). In a multivariable adjusted mixed effects model, participants with PAD had a more rapid decline in life-space mobility by -1.1 (95% confidence interval [CI], -1.9 to -0.24) points per year compared with those without PAD. At 5-year follow-up, model-adjusted mean life-space mobility was 48.1 (95% CI, 43.5-52.7) and 52.4 (95% CI, 50.9-53.8) among those with and without PAD, respectively, corresponding to a restriction in independent life-space mobility at the level of one's neighborhood.Life-space mobility is a novel patient-centered measure of community mobility, and PAD is associated with significant life-space mobility decline among community-dwelling older adults. Further study is needed to mechanistically confirm these findings and to determine whether better recognition and treatment of PAD alter the trajectory of life-space mobility.

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.

A Nomarski polarizing prism has been used in conjunction with a focused laser differential interferometer to measure the phase velocity of a density disturbance at sampling frequencies ≥ 10 M H z . Use of this prism enables the simultaneous measurement of density disturbances at two closely spaced points that can be arbitrarily oriented about the instrument’s optical axis. The orientation is prescribed by rotating the prism about this axis. Since all four beams (one beam pair at each measurement point) propagate parallel to one another within the test volume, any bias imparted by density fluctuations away from the measurement plane on the disturbance phase velocity is minimized. A laboratory measurement of a spark-generated shock wave and a wind tunnel measurement of a second-mode instability wave on a cone model in a Mach 6 flow are presented to demonstrate the performance of the instrument. High-speed schlieren imaging is used in both cases to verify the results obtained with the instrument.

Previous studies have suggested that Mild Cognitive Impairment (MCI) due to AD represents a continuum of progression from preclinical disease to amnestic single-domain (ASD) to multiple-domain (AMD) and subsequent dementia. This study will examine deficits in driving performance, financial abilities, and processing speed across the continuum of MCI. Eighty-eight clinically referred adults aged 54–88 were evaluated through a comprehensive neuropsychological battery, informant questionnaire, and medical history, and classified by investigators as possible MCI (no objective impairment), MCI-ASD, MCI-AMD, or mild dementia. Separate from the adjudication of diagnosis, participants were administered the Financial Capacity Instrument – Short Form (FCI-SF), the Useful Field of View (UFOV), and an on-road driving test administered by a Certified Driving Rehabilitation Specialist masked to diagnosis. Group differences between global driving rating, UFOV crash risk index and total score, and FCI-SF total scores were examined using one-way ANOVA and planned comparisons. We hypothesized that participants with possible MCI and MCI-ASD would not differ due to a presumed lack of deficits in processing speed, but the remaining groups would differ due to further cognitive decline. We found group differences in global driving rating, UFOV score and risk index, and FCI-SF score (p

The Useful Field of View (UFOV) involves four computer-based tasks of increasing attentional complexity and decreasing display duration. Performance is related to driving skills in Mild Cognitive Impairment (MCI), but less is known about its relationship to other functional domains. We hypothesized that better UFOV scores would be associated with better performance on functional tasks requiring efficient information processing. We analyzed data of 119 adults with diagnoses of MCI due to AD. The mean age of the sample was 74 and 50% were women. UFOV scores represent the briefest duration (16 – 500 ms) at which a person reliably performs each task; these 4 scores (16ms - 500ms) are summed to form a total score. Lower scores are better. We divided the sample by UFOV scores < 1000 (n = 50) vs. > 1000 (n = 69) and used t-tests to examine differences in total scores on the Timed IADL (TIADL) and Financial Capacity Instrument-Short Form (FCI-SF). Each instrument measures efficiency and accuracy in multiple domains, with tasks such as medication management and finding phone numbers (TIADL), and simple money calculations, check writing, and applying medical insurance information (FCI-SF), among others. TIADL and FCI-SF scores differed by UFOV group. Those with UFOV > 1000 had far worse performance on summary scores (p values < .001) and on virtually all domain and time scores of both functional measures. Results emphasize the relationship of processing speed—which can be improved with training—to performance of everyday tasks related to independent functioning in MCI.

Healthy nutritional status is found to be associated with health outcomes across the life course. As people age, nutritional status becomes more important; nutritional risk and malnutrition may impede older adults’ ability to maintain overall well-being, limit their physical strength, and ultimately impact their mobility within their environment. However, the relationship between nutritional risk and declines in life-space mobility is unknown. Using the University of Alabama-Birmingham (UAB) Study of Aging II, we examined the effects of nutritional risk on life-space mobility among 412 community-dwelling older adults age 75+ in Alabama. We used the Mini Nutritional Assessment (MNA®), a well-validated assessment tool for nutritional risk. Life-space mobility scores range from 0 (“totally bed-bound”) to 120 (“traveled out of town every day without assistance”). We employed multivariate regression models that adjusted for demographic factors, baseline life-space mobility, and other measures of health. We found that the life-space mobility scores declined by 4.3 (p

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.

The objective of this study was to determine the effect of self-reported leisure-time physical activity, converted to kilocalorie expenditure and expressed as average daily expenditure, on all-cause mortality among older males 65 years of age and older in the University of Alabama at Birmingham (UAB) Study of Aging (SOA). Mean age of participants was 75.4 years. Multivariable Cox proportional hazard models evaluated the predictors of overall survival. Kilocalorie expenditure (p = .01), Black race (p = .02), young age (p

Second-mode wave growth within the hypersonic boundary layer of a slender cone is investigated experimentally using high-speed schlieren visualizations. Experiments were performed in AEDC Tunnel 9 over a range of unit Reynolds number conditions at a Mach number of approximately 14. A thin lens with a known density profile placed within the field of view enables calibration of the schlieren set-up, and the relatively high camera frame rates employed allow for the reconstruction of time-resolved pixel intensities at discrete streamwise locations. The calibration in conjunction with the reconstructed signals enables integrated spatial amplification rates ($N$ factors) to be calculated for each unit Reynolds number condition and compared to $N$ factors computed from both pressure transducer measurements and linear parabolized stability equation (PSE) solutions. Good agreement is observed between $N$ factors computed from the schlieren measurements and those computed from the PSE solutions for the most-amplified second-mode frequencies. The streamwise development of $N$ factors calculated from the schlieren measurements compares favourably to that calculated from the pressure measurements with slight variations in the $N$ factor magnitudes calculated for harmonic frequencies. Finally, a bispectral analysis is carried out to identify nonlinear phase-coupled quadratic interactions present within the boundary layer. Multiple interactions are identified and revealed to be associated with the growth of disturbances at higher harmonic frequencies.

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.