O5‐08‐01: Trends In Racial And Ethnic Differences In Dementia Prevalence Rates And Disease Awareness

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153266/1/alzjjalz2019064876.pd

Racial and Ethnic Differences in Knowledge About One’s Dementia Status

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156478/1/jgs16442.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156478/3/jgs16442_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156478/2/jgs16442-sup-0001-supinfo.pd

Speed accuracy tradeoff? Not so fast: Marginal changes in speed have inconsistent relationships with accuracy in real-world settings

The speed-accuracy tradeoff suggests that responses generated under time constraints will be less accurate. While it has undergone extensive experimental verification, it is less clear whether it applies in settings where time pressures are not being experimentally manipulated (but where respondents still vary in their utilization of time). Using a large corpus of 29 response time datasets containing data from cognitive tasks without experimental manipulation of time pressure, we probe whether the speed-accuracy tradeoff holds across a variety of tasks using idiosyncratic within-person variation in speed. We find inconsistent relationships between marginal increases in time spent responding and accuracy; in many cases, marginal increases in time do not predict increases in accuracy. However, we do observe time pressures (in the form of time limits) to consistently reduce accuracy and for rapid responses to typically show the anticipated relationship (i.e., they are more accurate if they are slower). We also consider analysis of items and individuals. We find substantial variation in the item-level associations between speed and accuracy. On the person side, respondents who exhibit more within-person variation in response speed are typically of lower ability. Finally, we consider the predictive power of a person's response time in predicting out-of-sample responses; it is generally a weak predictor. Collectively, our findings suggest the speed-accuracy tradeoff may be limited as a conceptual model in its application in non-experimental settings and, more generally, offer empirical results and an analytic approach that will be useful as more response time data is collected

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

The complex genetics of gait speed:Genome-wide meta-analysis approach

Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Publisher Correction:Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals (Nature Genetics, (2020), 52, 12, (1314-1332), 10.1038/s41588-020-00713-x)

In the version of this article originally published, the e-mail address of corresponding author Patricia B. Munroe was incorrect. The error has been corrected in the HTML and PDF versions of the article

GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity.In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)).We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011 911-03-012 Research Institute for Diseases in the Elderly 014-93-015 RIDE2 Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) 050-060-810 Erasmus Medical Center Erasmus University, Rotterdam Netherlands Organization for the Health Research and Development (ZonMw) Research Institute for Diseases in the Elderly (RIDE) Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports European Commission (DG XII) Municipality of Rotterdam National Institutes of Health National Institute on Aging (NIA) R01 AG005407 R01 AR35582 R01 AR35583 R01 AR35584 R01 AG005394 R01 AG027574 R01 AG027576 AG023629 R01AG29451 U01AG009740 RC2 AG036495 RC4 AG039029 P30AG10161 R01AG17917 R01AG15819 R01AG30146 U01-AG023755 U19-AG023122 NHLBI HHSN 268201200036C HHSN268200800007C N01HC55222 N01HC85079 N01HC85080 N01HC85081 N01HC85082 N01HC85083 N01HC 85086 HL080295 HL087652 HL105756 National Institute of Neurological Disorders and Stroke (NINDS) National Center for Advancing Translational Sciences, CTSI UL1TR000124 National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) DK063491 National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) National Center for Research Resources (NCRR) NIH Roadmap for Medical Research U01 AR45580 U01 AR45614 U01 AR45632 U01 AR45647 U01 AR45654 U01 AR45583 U01 AG18197 U01-AG027810 UL1 RR024140 NIAMS R01-AR051124 RC2ARO58973 National Heart, Lung and Blood Institute's Framingham Heart Study N01-HC-25195 Affymetrix, Inc N02-HL-6-4278 Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine Boston Medical Center National Institute of Arthritis, Musculoskeletal and Skin Diseases NIA R01 AR/AG 41398 NIH N01-AG-12100 NIA Intramural Research Program Hjartavernd (the Icelandic Heart Association) Althingi (the Icelandic Parliament) Illinois Department of Public Health Translational Genomics Research Institute Italian Ministry of Health ICS110.1/RF97.71 U.S. National Institute on Aging 263 MD 9164 263 MD 821336 Intramural Research Program of the NIH, National Institute on Aging 1R01AG028321 1R01HL09257

Non-pharmacological care for patients with generalized osteoarthritis: design of a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Non-pharmacological treatment (NPT) is a useful treatment option in the management of hip or knee osteoarthritis. To our knowledge however, no studies have investigated the effect of NPT in patients with generalized osteoarthritis (GOA). The primary aim of this study is to compare the effectiveness of two currently existing health care programs with different intensity and mode of delivery on daily functioning in patients with GOA. The secondary objective is to compare the cost-effectiveness of both interventions.</p> <p>Methods/Design</p> <p>In this randomized, single blind, clinical trial with active controls, we aim to include 170 patients with GOA. The experimental intervention consist of six self-management group sessions provided by a multi-disciplinary team (occupational therapist, physiotherapist, dietician and specialized nurse). The active control group consists of two group sessions and four sessions by telephone, provided by a specialized nurse and physiotherapist. Both therapies last six weeks. Main study outcome is daily functioning during the first year after the treatment, assessed on the Health Assessment Questionnaire. Secondary outcomes are health related quality of life, specific complaints, fatigue, and costs. Illness cognitions, global perceived effect and self-efficacy, will also be assessed for a responder analysis. Outcome assessments are performed directly after the intervention, after 26 weeks and after 52 weeks.</p> <p>Discussion</p> <p>This article describes the design of a randomized, single blind, clinical trial with a one year follow up to compare the costs and effectiveness of two non-pharmacological interventions with different modes of delivery for patients with GOA.</p> <p>Trial registration</p> <p>Dutch Trial Register NTR2137</p