Faculty Bibliography
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Department/Unit:Population Health
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13264
Interrelationships between cognitive and physical impairment [Meeting Abstract]
Background: Cognitive and physical impairments are common, coexisting chronic conditions that have complex, and often bidirectional relationships in which presence of one has the potential to initiate, synergize, or result from the other. Understanding how the processes that lead to dementia and physical disability interrelate at early stages of dysfunction affords the opportunity for preventative or restorative interventions. We evaluated both crosssectional and longitudinal associations between cognitive and physical function to better understand the directionality of the relationships. Methods: Data from 2 studies of cognitive and functional aging were used: a longitudinal study conducted at the Knight ADRC at Washington University in St. Louis (766 individuals followed up for up to 8 years) and a cross-sectional study conducted at NYU (272 individuals). Both studies enrolled community-dwelling individuals over the age of 50 who underwent cognitive and physical assessments tapping into global (e.g., CDR-SB, MoCA, AD8) and individual cognitive domains (e.g., Naming, Trailmaking) and physical performance (PP) measures (e.g., grip-strength (GS), muscle mass (MM)). Formal diagnoses were available in the longitudinal study, while the cross-sectional studies established impaired vs. non-impaired. Associations were investigated with regression analysis techniques. Results: GS impairment was associated with lower MoCA (B=-2.0, p=0.011); when combined with low MM the likelihood of dual cognitive-physical impairment increased. The effect of low GS on global cognition doubled when poor PP was also present (indicator of later stage physical impairment; B=-3.77, p<0.001). However, while the rate of decline in cognitive (various measures; p<0.001) and physical (slope=-1.22, p<0.001) performance was sharper in those with baseline cognitive impairment, baseline physical impairment had no significant impact on either cognitive or physical decline. Cross-sectionally, GS impacted MoCA through poor PP (indirect effect=0.018, p<0.01). When type of dementia was considered, vascular dementia declined faster than controls (slope=-2.70, p<0.001) or AD (slope=-2.18, p<0.001). Conclusions: Earlier indicators of physical dysfunction (i.e. low GS) are associated with cognitive impairment with evidence for a dose-response operating in the direction of cognitive-to-physical impairment (although the reverse cannot be ruled out). Targeted interventions to maintain physical functionality and strength in individuals with dementia, particularly vascular dementia may mitigate future decline and disability
EMBASE:72125607
ISSN: 1552-5260
CID: 1924852
The role of isolation in dementia caregiver grief [Meeting Abstract]
Background: Approximately 5.2 million Americans are affected by Alzheimer's disease (AD), with another 1.3 million individuals affected by Lewy Body Dementia (LBD), the second most common cause. Nearly 60% of dementia caregivers rate emotional stress of caregiving as high or very high, and this will only increase as more resources are required with dementia progression. As such, the grieving process for caregivers likely begins early, as adult children and spouses often take on a multitude of new responsibilities previously managed by the patient, often prior to the formal diagnosis. Adverse outcomes for the caregiver (e.g., stress, depression and poor health) directly lead to declines in quality of life for both the patient and the caregiver. Improved understanding of caregiver grief will provide important information to develop interventions for the early identification of caregiver grief. We examine the sensitivity of the underlying constructs measured by the Marwit-Meuser Caregiver Grief Inventory Short Form (MMCGI-SF), a common self-reported measure of caregiver grief. Methods: An online survey of dementia caregivers [AD (n=64), LBD (n=350)] was completed including the MMCGI-SF. The MMCGI-SF contains three constructs: Personal Sacrifice Burden, Heartfelt Sadness, and Worry and Felt Isolation. We conducted confirmatory factor analyses to determine goodness of fit testing whether this model of grief holds for spouse and child primary caregivers for patients with AD and LBD. Results: Caregiver ages were equivalent (M=62.0(610.5) as were patient dementia stage (CDR Box Scores; M=10.4(64.4). Confirmatory factor analysis rejected the current MMCGI-SF model for both groups. The model was improved by separating the construct of "Worry and Felt Isolation" into separate categories in both AD: CFI = .88, NFI = .89, RMSEA = .091 (.062-.117) and LBD: CFI = .93, NFI = .92, RMSEA = .072 (.063-.080). Conclusions: Isolation was shown to be an important component of grief state for spouse and adult child caregivers, particularly caregivers of LBD. This may be due to constellation of cognitive, motor, behavioral, and autonomic features that distinguish LBD from AD. We believe that changes in healthcare and the extended lifespan of patients have led to the need for caregiver interventions that specifically targeting isolation
EMBASE:72125151
ISSN: 1552-5260
CID: 1924882
Perception differences in health status, medical care access, and alzheimer disease between caucasians and african americans [Meeting Abstract]
Background: There are significant cultural differences regarding knowledge and perceptions of Alzheimer disease (AD) potentially leading to delays in diagnosis and treatment. There is a need to better understand differences between Caucasian and African American older adults regarding their knowledge of AD, perceived access to care, health beliefs, and willingness to discuss memory problems with providers. Methods: A population-based survey of 1,039 non-demented older adults across three counties (urban, suburban, rural) had a mean age of 62.7+10.2 (range, 50-97); 94% high school education; 67% women, 86% white, mean Short Blessed Test = 1.7+2.2. Constructs from behavioral models including Health Belief Model, Self-efficacy, and Social Support were compared between White (n=863) and Black (n=121) respondents attitudes and perceptions regarding dementia screening. Results: African American older adults were less likely to use the internet for health information (p=.005) and more dependent on public transportation (p<.001) for doctor visits. Black older adults were more likely to believe memory loss a part of normal aging (p=.01), had less knowledge about dementia (p=.003) and its consequences (p=.002), were less likely to know their healthcare provider could test for dementia (p=.004), had lower perceived accessibility of dementia-related services (p=.001), and reported lower self-efficacy to discuss memory problems with their providers (p=.006). Health Belief model constructs differed with African Americans reporting higher perceived barriers (p=.003) and lower perceived severity (p=.03). Logistic regression models showed that intention for screening is predicted by white race (OR 4.28); male gender (OR 2.10), self-reported anxiety (OR 1.44), self-efficacy to discuss memory problems (OR 2.72), knowledge their MD can test memory (OR 1.70), and social support (OR 1.23). Conclusions: We found significant differences in socioeconomic factors, utilization and accessibility to medical services, and knowledge of dementia between Caucasians and African- Americans. Although older African-Americans reported intention to have their memory evaluated, actual screening behaviors were more likely to occur in individuals with high self-efficacy for discussing memory problems, perceived accessibility to dementia services, already present preventive health behaviors, and a social support system. These constructs can be used to develop interventions to evaluate and improve cognitive health in African Americans
EMBASE:72124388
ISSN: 1552-5260
CID: 1924932
Advancing Patient-centered Outcomes in Emergency Diagnostic Imaging: A Research Agenda
Diagnostic imaging is integral to the evaluation of many emergency department (ED) patients. However, relatively little effort has been devoted to patient-centered outcomes research (PCOR) in emergency diagnostic imaging. This article provides background on this topic and the conclusions of the 2015 Academic Emergency Medicine consensus conference PCOR work group regarding "Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization." The goal was to determine a prioritized research agenda to establish which outcomes related to emergency diagnostic imaging are most important to patients, caregivers, and other key stakeholders and which methods will most optimally engage patients in the decision to undergo imaging. Case vignettes are used to emphasize these concepts as they relate to a patient's decision to seek care at an ED and the care received there. The authors discuss applicable research methods and approaches such as shared decision-making that could facilitate better integration of patient-centered outcomes and patient-reported outcomes into decisions regarding emergency diagnostic imaging. Finally, based on a modified Delphi process involving members of the PCOR work group, prioritized research questions are proposed to advance the science of patient-centered outcomes in ED diagnostic imaging.
PMID: 26574729
ISSN: 1553-2712
CID: 1921172
Melamine Nephrotoxicity is Mediated by Hyperuricemia
OBJECTIVE: We tested whether melamine nephrotoxicity was exacerbated by urate (a typical component of renal stones in humans) in rats with hyperuricemiainduced by the uricase inhibitor, potassium oxonate (Oxo). METHODS: Rats were exposed to melamine or Oxo alone or combinations of melamine (200-400 mg/kg) and Oxo (200-600 mg/kg) for 3 consecutive days. Kidney injury was evaluated by renal biochemical functions, histomorphology, and lipid peroxidation. Kidney crystals were analyzed for their composition. RESULTS: Nephrotoxicity was minimal in animals administered melamine or Oxo alone, but it was demonstrable in animals administered at least 800 mg/kg of the two compounds combined. All rats in the 400+600 (melamine+Oxo) and 400+400 mg/kg groups and 4 out of 6 in the 200+600 mg/kg group died within 3 days; no rat died in the 200+400 or 200+200 mg/kg group. Dose-dependent renal damage resembling clinical findings in affected patients was observed in rats administered the two compounds. Crystal composition determination revealed the existence of melamine and uric acid in the affected kidneys, resembling human stones. CONCLUSION: Our findings suggest that uric acid plays a key role in melamine-related kidney injury in humans. Future studies should consider uric acid together with melamine when examining adverse effects in humans.
PMID: 26777910
ISSN: 0895-3988
CID: 1921332
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types
BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. METHODS: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. RESULTS: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE =0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. CONCLUSION: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
PMCID:4806328
PMID: 26464424
ISSN: 1460-2105
CID: 1909402
Older Adults Reporting More Diabetes Mellitus Care Have Greater 9-Year Survival
OBJECTIVES: To determine whether receiving more recommended diabetes mellitus (DM) care processes (tests and screenings) would translate into better 9-year survival for middle-aged and older adults. DESIGN: Longitudinal mortality analysis using the Health and Retirement Study Diabetes Mailout Survey. SETTING: Health and Retirement Study (HRS). PARTICIPANTS: Individuals aged 51 and older (n = 1,879; mean age 68.8 +/- 8.7, 26.5% aged >/=75) with self-reported DM who completed the Diabetes Mailout Survey and the core 2002 HRS survey. MEASUREMENTS: A composite measure of five self-reported diabetes mellitus care process measures were dichotomized as greater (3-5 processes) versus fewer (0-2 processes) care processes provided. Cox proportional hazards models were used to test relationships between reported measures and mortality, controlling for sociodemographic characteristics, function, comorbidities, geriatric conditions, and insulin use. RESULTS: Prevalence of self-reported care processes was 80.1% for glycosylated hemoglobin test, 75.9% for urine test, 67.5% for eye examination, 67.7% for aspirin counseling, and 48.2% for diabetes education. In 9 years, 32.1% respondents died. Greater care correlated with 24% lower risk of dying (adjusted hazard ratio = 0.76, 95% confidence interval = 0.64-0.91) at 9-year follow up. When respondents were age-stratified (>/=75 vs <75) longer survival was statistically significant only in the older age group. CONCLUSION: Although it is not possible to account for differences in adherence to care that may also affect survival, this study demonstrates that monitoring of and counseling about types of DM care processes are associated with long-term survival benefit even in individuals aged 75 and older with DM.
PMCID:4688231
PMID: 26659115
ISSN: 1532-5415
CID: 1907582
Efficacy for remyelination and safety of anti-lingo-1 monoclonal antibody (biib033) in acute optic neuritis: Results from the renew study [Meeting Abstract]
Background: Anti-LINGO-1 is a monoclonal antibody antagonist of LINGO-1, an oligodendrocyte differentiation and myelination suppressor. Objective: To determine the efficacy/safety of anti-LINGO-1 for CNS remyelination. Methods: Subjects with a first unilateral acute optic neuritis episode were treated with high-dose steroids and randomized to 100mg/kg anti-LINGO-1 IV or placebo every 4 weeks (NCT01721161). Subject and IRB approval were obtained. Nerve conduction latency recovery using full-field visual evoked potential (FF-VEP) in the affected eye over time versus unaffected eye at baseline assessed remyelination (pre-specified primary endpoint). Between-treatment comparisons were evaluated by ANCOVA and mixed-effect model repeated measure (MMRM) in subjects who completed the study and did not miss >1 study dose or receive MS modifying therapy (prespecified per-protocol population). Safety/tolerability was evaluated in those who received >1 study dose and included adverse event (AE) and clinical laboratory result assessments. Results: Anti-LINGO-1-treated subjects (n =33) showed improved latency recovery versus placebo (n=36): mean (95% confidence interval) -7.55ms (-15.12 to 0.01) at Week 24 (P=0.05); -9.13ms (-16.11 to -2.14; P=0.01) at Week 32. 54% of anti-LINGO-1 subjects had no/mild latency delay at Week 24 (affected eye FF-VEP latency <10% worse than baseline fellow eye) versus 27% of the placebo group (P=0.036). Additional subgroup analyses will be presented. 34/41 in each group experienced any AE, serious AEs occurred in 2 placebo and 5 anti-LINGO-1 subjects, and there were 3 treatment-related serious AEs. Conclusions: Improvement in FF-VEP latency is consistent with the first evidence of remyelination in a Phase 2 trial. Anti-LINGO-1 was generally well tolerated
EMBASE:72091400
ISSN: 0022-510x
CID: 1904622
Screening early childhood social emotional and mental health functioning in a low-income country context [Meeting Abstract]
Background: Increased attention has been paid to identifying and responding to the mental health and social emotional needs of young children in low income countries. There is lack of brief screening scales and assessment tools to characterize child mental health burden or to evaluate impact of early intervention in Sub-Saharan African (SSA) countries. This study sought to determine reliability and validity of three different parent/caregiver brief screening tools in a SSA country - Uganda. The Pediatric Symptom Checklist (14 item Pictorial Scale) (Gardner et al., 2007), assesses child behavioral problems using a pictorial format that takes into account the low literacy rates in SSA countries. The Social Competence Scale (12 items) (Gouley, et al., 2007) utilizes a strength-based evaluation approach to assess children's emotional regulation and prosocial/communication competence. The Strength and Difficult Questionnaire (SDQ; 25 items) (Goodman, et al., 1997, 2009), is available in 80 languages, focuses on psychiatric symptoms and assesses hyperactivity, emotional symptoms, peer problems and conduct problems. Methods: Parents of 303 Ugandan 4-9 year-old children from the community were recruited and interviewed, and 103 of these who were also part of an ongoing school-based mental health intervention trial were interviewed a 2nd time (about 5 months after 1st assessment). Data from both time points were utilized to establish reliability and validity. Data from the control sample (n=42) were used for evaluating test-retest reliability. The mean age of participating parents was 35.92 years (SD = 9.80 years). About one third of parents (32%) were single, and 48% had primary or less education. Study children were an average 6.51 years old (SD = 1.08 years) and all were enrolled in Nursery to Primary 3 in Kampala, Uganda. For the purpose of validation measurement, we also included Patient Health Questionnaire (assessing parental depression; Kroenke et al., 2001; alpha=.83) and Parenting Stress Scale (PSI, Abidin, 1995; 5 items, alpha= .63). Findings: Consistent with developers' conceptual frameworks, two factors emerged from the Pictorial Scale (Internalizing and Externalizing problems) and Social Competence Scales (Emotion regulation and Prosocial/Communication skills). However, for the SDQ scale, only one-factor emerged, with estimated 21-27% of children having abnormal level of problem behaviors. All three brief screening tools applied in this study had adequate reliability and validity. Reliability (assessed by Chronbach's alpha) ranged from .61-.68 for Pictorial scale, .61-.63 for SDQ, and .71-.87 for Social Competence Scale. All social emotional and mental health scales included were related in expected ways. The strength-based Social Competence scale is also sensitive to intervention evaluation. Interpretation: Our findings suggest that selection of instruments needs to include parent literacy levels and cultural contexts. A strength-based measure may be more relevant than pathology-based measures in SSA context
EMBASE:72073685
ISSN: 2214-9996
CID: 1904882
Incidence and determinants of fall-related major bleeding among older adults with atrial fibrillation [Meeting Abstract]
Background: Fall-related major bleeding is a concern among clinicians who are hesitant to prescribe oral anticoagulation to older adults with atrial fibrillation. Objectives: The aim of this study was to describe the incidence and risk factors of this outcome in large datasets. Methods: We created a retrospective cohort of 33 732 veterans with atrial fibrillation aged >75 years who were new referrals to VA anticoagulation clinics (warfarin therapy) between 1 January 2001 and 31 December 2012. Patients with comorbid conditions requiring warfarin (mechanical heart valve, pulmonary embolus) were excluded. Clinical characteristics, laboratory, and pharmacy data were extracted from the VA electronic medical record. We then linked VA data with Medicare claims data for subsequent hospitalizations. The primary outcome (fall-related major bleeding) was defined as any hospitalization for traumatic intracranial bleeding, hemarthrosis, or fracture-related bleeding. Cox proportional hazards regression was used to determine predictors of interest selected a priori based on prior known associations. Results: Mean patient age was 81.1+/-4.1 years, and comorbidities were common (hypertension 82.2%, coronary artery disease 42.8%, diabetes 33.6%). Over the study period, the incidence rate of fall-related major bleeding was 4.60 per 1000 person-years, and nearly all of these events (99.0%) resulted in traumatic intracranial hemorrhages. In unadjusted models, significant predictors for fall-related major bleeding included dementia (HR 1.84, 95%CI 1.31-2.58), fall within the past year (HR 1.60, 95%CI 1.11-2.29), depression (HR 1.48, 95%CI 1.21-1.80), hypertension (HR 1.24, 95%CI 1.00-1.54), abnormal renal/liver function (HR 1.50, 95%CI 1.06-2.11), prior stroke (HR 1.49, 95%CI 1.13-1.96), and labile international normalized ratio (INR) (HR 1.90, 95%CI 1.12-3.24). After adjusting for potential confounders, labile INR, dementia, depression, and stroke and remained significant predictors. Conclusions: Fall-related major bleeding is a relatively uncommon event among older adults receiving anticoagulation for AF. However, several factors place patients at increased risk, and optimal management for this high-risk phenotype deserves further study
EMBASE:72098831
ISSN: 1053-8569
CID: 1905652
