Association Between High School Personality Phenotype and Dementia 54 Years Later in Results From a National US Sample.

Importance: Personality phenotype has been associated with subsequent dementia in studies of older adults. However, neuropathologic changes often precede cognitive symptoms by many years and may affect personality itself. Therefore, it is unclear whether supposed dementia-prone personality profiles (high neuroticism and low conscientiousness) are true risk factors or merely reflections of preexisting disease. Objectives: To examine whether personality during adolescence-a time when preclinical dementia pathology is unlikely to be present-confers risk of dementia in later life and to test whether associations could be accounted for by health factors in adolescence or differed across socioeconomic status (SES). Design, Setting, and Participants: Cohort study in the United States. Participants were members of Project Talent, a national sample of high school students in 1960. Individuals were identified who received a dementia-associated International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code during any year between 2011 and 2013. The dates of our analysis were March 2018 to May 2019. Exposures: Ten personality traits were measured by the 150-item Project Talent Personality Inventory. Socioeconomic status was measured by a composite based on parental educational level, income, occupation, and property ownership. Participants were also surveyed on demographic factors and height and weight. Main Outcomes and Measures: Medicare records were collected, with dementia diagnoses in the period of 2011 to 2013 classified according to the US Centers for Medicare & Medicaid Services ICD-9-based algorithm. Cox proportional hazards regression models estimated the relative risk of dementia based on the 10 personality traits, testing interactions with SES and adjusting for demographic confounders. Results: The sample of 82 232 participants was 50.1% female, with a mean (SD) age of 15.8 (1.7) years at baseline and 69.5 (1.2) years at follow-up. Lower risk of dementia was associated with higher levels of vigor (hazard ratio for 1 SD, 0.93; 95% CI, 0.90-0.97; P < .001). Calm and maturity showed protective associations with later dementia that increased with SES. At 1 SD of SES, calm showed a hazard ratio of 0.89 (95% CI, 0.84-0.95; P < .001 for the interaction) and maturity showed a hazard ratio of 0.90 (95% CI, 0.85-0.96; P = .001 for the interaction). Conclusions and Relevance: This study's findings suggest that the adolescent personality traits associated with later-life dementia are similar to those observed in studies of older persons. Moreover, the reduction in dementia risk associated with a calm and mature adolescent phenotype may be greater at higher levels of SES. Personality phenotype may be a true independent risk factor for dementia by age 70 years, preceding it by almost 5 decades and interacting with adolescent socioeconomic conditions.

High school personality traits and 48-year all-cause mortality risk: results from a national sample of 26 845 baby boomers.

BACKGROUND: It is unclear if adolescent personality predicts mortality into late life, independent of adolescent socioeconomic status (SES). METHODS: Over 26 000 members of Project Talent, a US population cohort of high school students, completed a survey including 10 personality scales and SES in 1960. Multi-source mortality follow-up obtained vital status data through an average 48-year period ending in 2009. Cox proportional hazard models examined the relative risk associated with personality traits, as well as confounding by both a measure of SES and by race/ethnicity. RESULTS: Adjusted for sex and grade, higher levels of vigour, calm, culture, maturity and social sensitivity in high school were associated with reduced mortality risk (HRs=0.92 to. 96), while higher levels of impulsivity were associated with greater mortality risk. Further adjustment for SES and school racial/ethnic composition mildly attenuated (eg, 12%), but did not eliminate these associations. Final HRs for a 1 SD change in personality traits were similar to that for a 1 SD change in SES. CONCLUSIONS: Adaptive personality traits in high school are associated with all-cause mortality in the USA as far into the future as the seventh decade, and to a degree similar to high school socioeconomic disadvantage.

Investigating the Early Life Determinants of Type-II Diabetes Using a Project Talent-Medicare Linked Data-set.

The increasing prevalence of Type II Diabetes (T2D) presents a serious health and financial public crisis. Our study examines the hypothesis that adolescents' perceptions of economic insecurity, along with absolute and relative socioeconomic status (SES), can contribute to T2D prevalence later in life. Project Talent (PT) Survey data, collected on high school students in 1960, have been linked to Medicare records from 2012, presenting a unique opportunity to examine measures gathered in adolescence and T2D prevalence later-in-life among a large, national, and diverse sample (n=88,849). Our results provide compelling evidence that real, perceived, and relative SES in adolescence have persistent impacts on later-in-life diabetes risk, even when controlling for possible confounders such as cognitive ability, conscientiousness, and early-adulthood educational attainment.

Adolescent Cognitive Aptitudes and Later-in-Life Alzheimer Disease and Related Disorders.

Importance: Low early-life cognitive ability is a potential early marker of dementia risk in later life. Previous studies use only global measures of general intelligence and/or study this relationship in gender-specific samples. The contribution of early-life performance on specific cognitive abilities, such as language, reasoning, and visualization aptitudes, to indicating future dementia risk is unknown. Objectives: To investigate the association between adolescent cognitive ability and Medicare-recorded Alzheimer disease and related disorders (ADRD) using both general and specific measures of cognitive ability and to explore these associations separately in men and women. Design, Setting, and Participants: Population-based cohort study from the Project Talent-Medicare linked data set, a linkage of adolescent sociobehavioral data collected from high school students in 1960 to participants' 2012 to 2013 Medicare Claims and expenditures data. The association between adolescent cognitive ability and risk of ADRD in later life was assessed in a diverse sample of 43 014 men and 42 749 women aged 66 to 73 years using a series of logistic regressions stratified by sex, accounting for demographic characteristics, adolescent socioeconomic status, and regional effects. Data analysis was conducted from November 2017 to March 2018. Main Outcomes and Measures: Presence of Medicare-reported ADRD. Results: Overall, 1239 men (2.9%) and 1416 women (3.3%) developed ADRD. Lower mechanical reasoning was associated with increased odds of ADRD in men (odds ratio, 1.17; 95% CI, 1.05-1.29), and lower memory for words in adolescence was associated with increased odds of ADRD in women (odds ratio, 1.16; 95% CI, 1.05-1.28). Lower performance on several other language, reasoning, visualization, and mathematic aptitudes in adolescence showed prominent, but weaker, associations with odds of ADRD. Conclusions and Relevance: This work contributes to the understanding of early-life origins of ADRD risk. The results suggest specific measures of cognitive ability may contribute to very early identification of at-risk subgroups who may benefit from prevention or intervention efforts.

The impact of retirement on health: quasi-experimental methods using administrative data.

BACKGROUND: Is retirement good or bad for health? Disentangling causality is difficult. Much of the previous quasi-experimental research on the effect of health on retirement used self-reported health and relied upon discontinuities in public retirement incentives across Europe. The current study investigated the effect of retirement on health by exploiting discontinuities in private retirement incentives to test the effect of retirement on health using a quasi-experimental study design. METHODS: Secondary data (1997-2009) on a cohort of male manufacturing workers in a United States setting. Health status was determined using claims data from private insurance and Medicare. Analyses used employer-based administrative and claims data and claim data from Medicare. RESULTS: Widely used selection on observables models overstate the negative impact of retirement due to the endogeneity of the decision to retire. In addition, health status as measured by administrative claims data provide some advantages over the more commonly used survey items. Using an instrument and administrative health records, we find null to positive effects from retirement on all fronts, with a possible exception of increased risk for diabetes. CONCLUSIONS: This study provides evidence that retirement is not detrimental and may be beneficial to health for a sample of manufacturing workers. In addition, it supports previous research indicating that quasi-experimental methodologies are necessary to evaluate the relationship between retirement and health, as any selection on observable model will overstate the negative relationship of retirement on health. Further, it provides a model for how such research could be implemented in countries like the United States that do not have a strong public pension program. Finally, it demonstrates that such research need-not rely upon survey data, which has certain shortcomings and is not always available for homogenous samples.

Linking individual medicare health claims data with work-life claims and other administrative data.

BACKGROUND: Researchers investigating health outcomes for populations over age 65 can utilize Medicare claims data, but these data include no direct information about individuals' health prior to age 65 and are not typically linkable to files containing data on exposures and behaviors during their worklives. The current paper is a proof-of-concept, of merging employers' administrative data and private, employment-based health claims with Medicare data. Characteristics of the linked data, including sensitivity and specificity, are evaluated with an eye toward potential uses of such linked data. This paper uses a sample of former manufacturing workers from an industrial cohort as a test case. The dataset created by this integration could be useful to research in areas such as social epidemiology and occupational health. METHODS: Medicare and employment administrative data were linked for a large cohort of manufacturing workers (employed at some point during 1996-2008) who transitioned onto Medicare between 2001-2009. Data on work-life health, including biometric indicators, were used to predict health at age 65 and to investigate the concordance of employment-based insurance claims with subsequent Medicare insurance claims. RESULTS: Chronic diseases were found to have relatively high levels of concordance between employment-based private insurance and subsequent Medicare insurance. Information about patient health prior to receipt of Medicare, including biometric indicators, were found to predict health at age 65. CONCLUSIONS: Combining these data allows for evaluation of continuous health trajectories, as well as modeling later-life health as a function of work-life behaviors and exposures. It also provides a potential endpoint for occupational health research. This is the first harmonization of its kind, providing a proof-of-concept. The dataset created by this integration could be useful for research in areas such as social epidemiology and occupational health.

Early-Life State-of-Residence Characteristics and Later Life Hypertension, Diabetes, and Ischemic Heart Disease.

OBJECTIVES: We examined how state characteristics in early life are associated with individual chronic disease later in life. METHODS: We assessed early-life state of residence using the first 3 digits of social security numbers from blue- and white-collar workers from a US manufacturing company. Longitudinal data were available from 1997 to 2012, with 305 936 person-years of observation. Disease was assessed using medical claims. We modeled associations using pooled logistic regression with inverse probability of censoring weights. RESULTS: We found small but statistically significant associations between early-state-of-residence characteristics and later life hypertension, diabetes, and ischemic heart disease. The most consistent associations were with income inequality, percentage non-White, and education. These associations were similar after statistically controlling for individual socioeconomic and demographic characteristics and current state characteristics. CONCLUSIONS: Characteristics of the state in which an individual lives early in life are associated with prevalence of chronic disease later in life, with a strength of association equivalent to genetic associations found for these same health outcomes.

Multiplexing immunoassays for cytokine detection in the serum of patients with rheumatoid arthritis: lack of sensitivity and interference by rheumatoid factor.

OBJECTIVES: Accurately measuring cytokines in clinical material remains an important challenge in the development of biomarkers. Enzyme-linked immunoabsorbent assays (ELISAs) are considered 'gold standard'; however, their use is limited by the relatively large sample volume required for multiple analyte testing. Several alternatives (including membrane or bead-ELISA) have been developed particularly to enable multiplexing. Concerns were raised regarding their use in rheumatology due to interference by heterophilic antibodies, notably rheumatoid factor (RF). In this report, we compared several multiplex assays using serum from rheumatoid arthritis (RA) patients with respect to the presence of residual RF following attempted removal employing commonly used procedures. METHODS: Healthy control and RF-positive/negative RA sera were used to compare 4 multiplex assays with ELISA: bead-based 'Luminex' immunoassay, cytometric bead assays (CBAs), membrane-based and Mosaic™ ELISAs. Sera were tested following Ig blockade (mixed species serum) or removal (using PEG6000 or sepharose-L). RESULTS: Ig removal was only partially efficient and residual RF was detected in most sera. RF had no impact on cytokine measurement by ELISA. In single and multiplex Luminex, cytokine levels associated with false positive results correlated directly with RF titres. Following Ig-blockade/removal, these relationship remained suggesting false positivity was still associated with the presence of residual RF. Conversely, detection of cytokines in multiplex membrane-based or Mosaic- ELISA were not affected by the presence of RF; however, levels of cytokines readily detected by ELISA were often below the detection threshold of these assays. CBA assays were also low on sensitivity but unaffected by RF. CONCLUSIONS: False positivity, due to the presence of heterophilic antibodies, mainly affected Luminex assays. Other assays however remained limited in their sensitivity. Multiplexing of cytokine measurement remains a challenge, particularly in rheumatological pathologies, until assays of adequate sensitivity are developed. ELISA remains the gold standard.

Bilingual language assessment: a meta-analysis of diagnostic accuracy.

PURPOSE: To describe quality indicators for appraising studies of diagnostic accuracy and to report a meta-analysis of measures for diagnosing language impairment (LI) in bilingual Spanish-English U.S. children. METHOD: The authors searched electronically and by hand to locate peer-reviewed English-language publications meeting inclusion criteria; the authors rated quality features, calculated accuracy metrics and confidence intervals, and generated forest plots. RESULTS: Of 771 citations (86 unique) located initially, accuracy metrics could be calculated for 17 index measures studied in a total of 100 children with LI and 109 with typical language. Most studies lacked clear descriptions of reference standards, procedures, and controls for subjective bias, making it difficult to rate specific quality features with confidence. Positive likelihood ratios (LR+) for most measures were at least diagnostically suggestive (pooled LR+ = 4.12; 95% CI [2.94, 5.78]). Negative likelihood ratios (LR-) were also generally suggestive, but heterogeneity precluded averaging. For every measure, confidence intervals for LR+ and LR- included diagnostically uninformative values. CONCLUSIONS: The available evidence does not support strong claims concerning the diagnostic accuracy of these measures, but a number appear promising. Several steps are suggested for strengthening future investigations of diagnostic accuracy.

Long bone defect models for tissue engineering applications: criteria for choice.

The replacement and repair of bone lost due to trauma, cancer, or congenital defects is a major clinical challenge. Skeletal tissue engineering is a potentially powerful strategy in modern regenerative medicine, and research in this field has increased greatly in recent years. Tissue engineering strategies seek to translate research findings in the fields of materials science, stem cell biology, and biomineralization into clinical applications, demanding the use of appropriate in vivo models to investigate bone regeneration of the long bone. However, identification of the optimal in vivo segmental bone defect model from the literature is difficult due to the use of different animal species (large and small mammals), different bones (weight-bearing and nonweight bearing), and multiple protocols, including the use of various scaffolds, cells, and bioactives. The aim of this review is to summarize the available animal models for evaluating long bone regeneration in vivo. We highlight the differences not only in species and sites but also in defect size, means of defect creation, duration of study, and fixation method. A critical evaluation of the most clinically relevant models is addressed to guide the researcher in his/her choice of the most appropriate model to use in future hypothesis-driven investigations.