American football is the largest participation sport in US high schools and is a leading cause of concussion among adolescents. Little is known about the long-term cognitive and mental health ...consequences of exposure to football-related head trauma at the high school level.
To estimate the association of playing high school football with cognitive impairment and depression at 65 years of age.
A representative sample of male high school students who graduated from high school in Wisconsin in 1957 was studied. In this cohort study using data from the Wisconsin Longitudinal Study, football players were matched between March 1 and July 1, 2017, with controls along several baseline covariates such as adolescent IQ, family background, and educational level. For robustness, 3 versions of the control condition were considered: all controls, those who played a noncollision sport, and those who did not play any sport.
Athletic participation in high school football.
A composite cognition measure of verbal fluency and memory and attention constructed from results of cognitive assessments administered at 65 years of age. A modified Center for Epidemiological Studies' Depression Scale score was used to measure depression. Secondary outcomes include results of individual cognitive tests, anger, anxiety, hostility, and heavy use of alcohol.
Among the 3904 men (mean SD age, 64.4 0.8 years at time of primary outcome measurement) in the study, after matching and model-based covariate adjustment, compared with each control condition, there was no statistically significant harmful association of playing football with a reduced composite cognition score (-0.04 reduction in cognition vs all controls; 97.5% CI, -0.14 to 0.05) or an increased modified Center for Epidemiological Studies' Depression Scale depression score (-1.75 reduction vs all controls; 97.5% CI, -3.24 to -0.26). After adjustment for multiple testing, playing football did not have a significant adverse association with any of the secondary outcomes, such as the likelihood of heavy alcohol use at 65 years of age (odds ratio, 0.68; 95% CI, 0.32-1.43).
Cognitive and depression outcomes later in life were found to be similar for high school football players and their nonplaying counterparts from mid-1950s in Wisconsin. The risks of playing football today might be different than in the 1950s, but for current athletes, this study provides information on the risk of playing sports today that have a similar risk of head trauma as high school football played in the 1950s.
Large amounts of labeled data are a prerequisite to training accurate and reliable machine learning models. However, in the medical domain in particular, this is also a stumbling block as accurately ...labeled data are hard to obtain. DementiaBank, a publicly available corpus of spontaneous speech samples from a picture description task widely used to study Alzheimer's disease (AD) patients' language characteristics and for training classification models to distinguish patients with AD from healthy controls, is relatively small—a limitation that is further exacerbated when restricting to the balanced subset used in the Alzheimer's Dementia Recognition through Spontaneous Speech (ADReSS) challenge. We build on previous work showing that the performance of traditional machine learning models on DementiaBank can be improved by the addition of normative data from other sources, evaluating the utility of such extrinsic data to further improve the performance of state-of-the-art deep learning based methods on the ADReSS challenge dementia detection task. To this end, we developed a new corpus of professionally transcribed recordings from the Wisconsin Longitudinal Study (WLS), resulting in 1366 additional Cookie Theft Task transcripts, increasing the available training data by an order of magnitude. Using these data in conjunction with DementiaBank is challenging because the WLS metadata corresponding to these transcripts do not contain dementia diagnoses. However, cognitive status of WLS participants can be inferred from results of several cognitive tests including semantic verbal fluency available in WLS data. In this work, we evaluate the utility of using the WLS ‘controls’ (participants without indications of abnormal cognitive status), and these data in conjunction with inferred ‘cases’ (participants with such indications) for training deep learning models to discriminate between language produced by patients with dementia and healthy controls. We find that incorporating WLS data during training a BERT model on ADReSS data improves its performance on the ADReSS dementia detection task, supporting the hypothesis that incorporating WLS data adds value in this context. We also demonstrate that weighted cost functions and additional prediction targets may be effective ways to address issues arising from class imbalance and confounding effects due to data provenance.
Abstract
With over 27,000 analysis variables covering more than 60 years of participants’ lives, the WLS data can be overwhelming to new users who are looking for the measures they need to answer ...their research questions. Core WLS survey data is free and easy to download from our website. As we add new types of measures and new waves of data, we refine our data sharing methods to balance our need to make the data easily available with the need to protect the confidentiality of participants. This presentation will teach users how to access to the data files they need for their research and how to use our online documentation of survey instruments and data files. Symposium attendees will also receive a USB drive with the publicly available data and complete documentation.
Study objective The objective of this study was to evaluate the relationship between self-reported cost-related nonadherence to prescription medications and emergency department (ED) utilization ...among Medicare beneficiaries. We hypothesized that persons who report cost-related medication nonadherence would have subsequent higher ED use. Methods We conducted a retrospective cohort study of continuously enrolled Medicare beneficiaries in 2006 and 2007. We used multivariate logistic regression to evaluate the relationship between ED use and cost-related medication nonadherence. Our principal dependent variable was any ED visit within a 364-day period after an interview assessing cost-related medication nonadherence. Our principal independent variables both denoted cost-related medication nonadherence: mild cost-related medication nonadherence, defined as a reduction in dose or a delay in filling medications because of cost; and severe cost-related medication nonadherence, defined as not filling a medication at all because of cost. Results Our sample consisted of 7,177 Medicare Current Beneficiary Survey respondents. Approximately 7.5% of respondents reported mild cost-related medication nonadherence only (n=541) and another 8.2% reported severe cost-related medication nonadherence (n=581). Disabled Medicare beneficiaries with severe cost-related medication nonadherence were more likely to have at least 1 ED visit (1.53; 95% confidence interval 1.03 to 2.26) compared with both disabled Medicare beneficiaries without cost-related medication nonadherence and elderly Medicare beneficiaries in all cost-related medication nonadherence categories. Conclusion Our results show an association between severe cost-related medication nonadherence and ED use. Disabled beneficiaries younger than 65 years who report severe cost-related medication nonadherence were more likely to have at least 1 ED visit, even when adjusting for other factors that affect utilization.
ObjectivesThis study examined how environmental, health, social, behavioural and genetic factors interact to contribute to myocardial infarction (MI) risk.DesignSurvey data collected by Wisconsin ...Longitudinal Study (WLS), USA, from 1957 to 2011, including 235 environmental, health, social and behavioural factors, and 77 single- nucleotide polymorphisms were analysed for association with MI. To identify associations with MI we utilized recursive partitioning and random forest prior to logistic regression and chi-squared analyses.Participants6198 WLS participants (2938 men; 3260 women) who (1) had a MI before 72 years and (2) had a MI between 65 and 72 years.ResultsIn men, stroke (LR OR: 5.01, 95% CI 3.36 to 7.48), high cholesterol (3.29, 2.59 to 4.18), diabetes (3.24, 2.53 to 4.15) and high blood pressure (2.39, 1.92 to 2.96) were significantly associated with MI up to 72 years of age. For those with high cholesterol, the interaction of smoking and lower alcohol consumption increased prevalence from 23% to 41%, with exposure to dangerous working conditions, a factor not previously linked with MI, further increasing prevalence to 50%. Conversely, MI was reported in <2.5% of men with normal cholesterol and no history of diabetes or depression. Only stroke (4.08, 2.17 to 7.65) and diabetes (2.71, 1.81 to 4.04) by 65 remained significantly associated with MI for men after age 65. For women, diabetes (5.62, 4.08 to 7.75), high blood pressure (3.21, 2.34 to 4.39), high cholesterol (2.03, 1.38 to 3.00) and dissatisfaction with their financial situation (4.00, 1.94 to 8.27) were significantly associated with MI up to 72 years of age. Conversely, often engaging in physical activity alone (0.53, 0.32 to 0.89) or with others (0.34, 0.21 to 0.57) was associated with the largest reduction in odds of MI. Being non-diabetic with normal blood pressure and engaging in physical activity often lowered prevalence of MI to 0.2%. Only diabetes by 65 (4.25, 2.50 to 7.24) and being exposed to dangerous work conditions at 54 (2.24, 1.36 to 3.69) remained significantly associated with MI for women after age 65, while still menstruating at 54 (0.46, 0.23 to 0.91) was associated with reduced odds of MI.ConclusionsTogether these results indicate important differences in factors associated with MI between the sexes, that combinations of factors greatly influence the likelihood of MI, that MI-associated factors change and associations weaken after 65 years of age in both sexes, and that the limited genotypes assessed were secondary to environmental, health, social and behavioral factors.
The Wisconsin Longitudinal Study (WLS) is a longitudinal study of men and women who graduated from Wisconsin high schools in 1957 and one of their randomly selected siblings. Wisconsin is located in ...the upper midwest of the United States and had a population of approximately 14 000 000 in 1957, making it the 14th most populous state at that time. Data spanning almost 60 years allow researchers to link family background, adolescent characteristics, educational experiences, employment experiences, income, wealth, family formation and social and religious engagement to midlife and late-life physical health, mental health, psychological well-being, cognition, end of life planning and mortality. The WLS is one of the few longitudinal data sets that include an administrative measure of cognition from childhood. Further, recently collected saliva samples allow researchers to explore the inter-relationships among genes, behaviours and environment, including genetic determinants of behaviours (e.g. educational attainment); the interactions between genes and environment; and how these interactions predict behaviours. Most panel members were born in 1939, and the sample is broadly representative of White, non-Hispanic American men and women who have completed at least a high school education. Siblings cover several adjoining cohorts: they were born primarily between 1930 and 1948. At each interview, about two-thirds of the sample lived in Wisconsin, and about one-third lived elsewhere in the United States or abroad. The data, along with documentation, are publicly accessible and can be accessed at http://www.ssc.wisc.edu/wlsresearch/. Requests for protected data or assistance should be sent to wls@ssc.wisc.edu.
In an influential body of work extending across more than three decades and drawing on data from the United States, Poland, Japan and the Ukraine, Melvin Kohn, Carmi Schooler and their associates ...have found that cognitive capacities are affected by experiences on the job; specifically, that working at a complex job improves cognitive functioning. These findings anticipate and parallel research on the relationships among social integration, leisure-time activities and cognitive functioning among the elderly. This paper tests the Kohn–Schooler hypothesis using different measures, models and data. Specifically, we estimate models of the reciprocal influence of work complexity and cognitive functioning at ages 53 to 54 and 64 to 65 among women and men who graduated from Wisconsin high schools in 1957. Even when adolescent academic ability test scores and high school rank have been controlled, we find moderate effects of the complexity of work on abstract reasoning ability at ages 53 to 54 (in 1993). These effects are similar among women and men and are robust to reasonable assumptions about the unreliability of measurement of adolescent academic ability. However, there were no such effects, either in 1993 or in 2004, among individuals who were still working at ages 64 to 65. Thus, the full set of findings provides only limited support for the Kohn–Schooler hypothesis.
ObjectivesSingle genetic loci offer little predictive power for the identification of depression. This study examined whether an analysis of gene–gene (G × G) interactions of 78 single nucleotide ...polymorphisms (SNPs) in genes associated with depression and age-related diseases would identify significant interactions with increased predictive power for depression.DesignA retrospective cohort study.SettingA survey of participants in the Wisconsin Longitudinal Study.ParticipantsA total of 4811 persons (2464 women and 2347 men) who provided saliva for genotyping; the group comes from a randomly selected sample of Wisconsin high school graduates from the class of 1957 as well as a randomly selected sibling, almost all of whom are non-Hispanic white.Primary outcome measureDepression as determine by the Composite International Diagnostic Interview–Short-Form.ResultsUsing a classification tree approach (recursive partitioning (RP)), the authors identified a number of candidate G × G interactions associated with depression. The primary SNP splits revealed by RP (ANKK1 rs1800497 (also known as DRD2 Taq1A) in men and DRD2 rs224592 in women) were found to be significant as single factors by logistic regression (LR) after controlling for multiple testing (p=0.001 for both). Without considering interaction effects, only one of the five subsequent RP splits reached nominal significance in LR (FTO rs1421085 in women, p=0.008). However, after controlling for G × G interactions by running LR on RP-specific subsets, every split became significant and grew larger in magnitude (OR (before) → (after): men: GNRH1 novel SNP: (1.43 → 1.57); women: APOC3 rs2854116: (1.28 → 1.55), ACVR2B rs3749386: (1.11 → 2.17), FTO rs1421085: (1.32 → 1.65), IL6 rs1800795: (1.12 → 1.85)).ConclusionsThe results suggest that examining G × G interactions improves the identification of genetic associations predictive of depression. 4 of the SNPs identified in these interactions were located in two pathways well known to impact depression: neurotransmitter (ANKK1 and DRD2) and neuroendocrine (GNRH1 and ACVR2B) signalling. This study demonstrates the utility of RP analysis as an efficient and powerful exploratory analysis technique for uncovering genetic and molecular pathway interactions associated with disease aetiology.
Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury
. These substances are used ...across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries
. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.
Abstract
Objective
To test the feasibility of collecting and integrating data on the gut microbiome into one of the most comprehensive longitudinal studies of aging and health, the Wisconsin ...Longitudinal Study (WLS). The long-term goal of this integration is to clarify the contribution of social conditions in shaping the composition of the gut microbiota late in life. Research on the microbiome, which is considered to be of parallel importance to human health as the human genome, has been hindered by human studies with nonrandomly selected samples and with limited data on social conditions over the life course.
Methods
No existing population-based longitudinal study had collected fecal specimens. Consequently, we created an in-person protocol to collect stool specimens from a subgroup of WLS participants.
Results
We collected 429 stool specimens, yielding a 74% response rate and one of the largest human samples to date.
Discussion
The addition of data on the gut microbiome to the WLS—and to other population based longitudinal studies of aging—is feasible, under the right conditions, and can generate innovative research on the relationship between social conditions and the gut microbiome.