Search

IMPORTANCE: Previous estimates suggested that 1 in 3 cases of Alzheimer disease and related dementia (ADRDs) in the US are associated with modifiable risk factors, the most prominent being physical inactivity, depression, and smoking. However, these estimates do not account for changes in risk factor prevalence over the past decade and do not consider potential differences by sex or race and ethnicity. OBJECTIVE: To update estimates of the proportion of ADRDs in the US that are associated with modifiable risk factors and to assess for differences by sex and race and ethnicity. DESIGN, SETTING, AND PARTICIPANTS: For this cross-sectional study, risk factor prevalence and communality were obtained from the nationally representative US Behavioral Risk Factor Surveillance Survey data from January 2018 to December 2018, and relative risks for each risk factor were extracted from meta-analyses. Data were analyzed from December 2020 to August 2021. Respondents included 378 615 noninstitutionalized adults older than 18 years. The number before exclusion was 402 410. Approximately 23 795 (~6%) had missing values on at least 1 of the variables of interest. EXPOSURES: Physical inactivity, current smoking, depression, low education, diabetes, midlife obesity, midlife hypertension, and hearing loss. MAIN OUTCOMES AND MEASURES: Individual and combined population-attributable risks (PARs) associated with ADRDs, accounting for nonindependence between risk factors. RESULTS: Among 378 615 individuals, 171 161 (weighted 48.7%) were male, and 134 693 (weighted 21.1%) were 65 years and older. Race and ethnicity data were self-reported and defined by the US Behavioral Risk Factor Surveillance System Data; 6671 participants (weighted 0.9%) were American Indian and Alaska Native, 8043 (weighted 5.1%) were Asian, 29 956 (weighted 11.7%) were Black, 28 042 (weighted 16.0%) were Hispanic (any race), and 294 394 (weighted 64.3%) were White. Approximately 1 in 3 of ADRD cases (36.9%) in the US were associated with 8 modifiable risk factors, the most prominent of which were midlife obesity (17.7%; 95% CI, 17.5-18.0), physical inactivity (11.8%; 95% CI, 11.7-11.9), and low educational attainment (11.7%; 95% CI, 11.5-12.0). Combined PARs were higher in men (35.9%) than women (30.1%) and differed by race and ethnicity: American Indian and Alaska Native individuals, 39%; Asian individuals, 16%; Black individuals, 40%; Hispanic individuals (any race), 34%; and White individuals, 29%. The most prominent modifiable risk factors regardless of sex were midlife obesity for American Indian and Alaska Native individuals, Black individuals, and White individuals; low education for Hispanic individuals; and physical inactivity for Asian individuals. CONCLUSIONS AND RELEVANCE: The findings suggest that risk factors associated with ADRDs have changed over the past decade and differ based on sex and race and ethnicity. Alzheimer risk reduction strategies may be more effective if they target higher-risk groups and consider current risk factor profiles.

Background: We recently estimated that 36.9% of Alzheimer’s disease and related dementias (ADRD) cases in the US may be attributable to modifiable risk factors, but it is not known whether national estimates generalize to specific states or regions. Objective: To compare national estimates of modifiable risk factors of ADRD to California, overall and by sex and race/ethnicity, and to estimate number of cases potentially preventable by reducing the prevalence of key risk factors by 25%. Methods: Adults ≥18 years who participated in the Behavioral Risk Factor Surveillance Survey in California (n = 9,836) and the US (n = 378,615). We calculated population attributable risks (PARs) for eight risk factors (physical inactivity, current smoking, depression, low education, diabetes mellitus, midlife obesity, midlife hypertension, and hearing loss) and compared estimates in California and the U.S. Results: In California, overall, 28.9% of ADRD cases were potentially attributable to the combination of risk factors, compared to 36.9% in the U.S. The top three risk factors were the same in California and the U.S., although their relative importance differed (low education [CA:14.9%; U.S.:11.7% ], midlife obesity [CA:14.9%; U.S.:17.7% ], and physical inactivity [CA:10.3%; U.S.:11.8% ]). The number of ADRD cases attributable to the combined risk factors was 199,246 in California and 2,287,683 in the U.S. If the combined risk factors were reduced by 25%, we could potentially prevent more than 40,000 cases in California and 445,000 cases in the U.S. Conclusion: Our findings highlight the importance of examining risk factors of ADRD regionally, and within sex and race/ethnic groups to tailor dementia risk reduction strategies.

In chronic infection, inflammation and cancer, the tissue microenvironment controls how local immune cells behave, with tissue-resident fibroblasts emerging as a key cell type in regulating activation or suppression of an immune response. Fibroblasts are heterogeneous cells, encompassing functionally distinct populations, the phenotypes of which differ according to their tissue of origin and type of inciting disease. Their immunological properties are also diverse, ranging from the maintenance of a potent inflammatory environment in chronic inflammation to promoting immunosuppression in malignancy, and encapsulating and incarcerating infectious agents within tissues. In this Review, we compare the mechanisms by which fibroblasts control local immune responses, as well as the factors regulating their inflammatory and suppressive profiles, in different tissues and pathological settings. This cross-disease perspective highlights the importance of tissue context in determining fibroblast–immune cell interactions, as well as potential therapeutic avenues to exploit this knowledge for the benefit of patients with chronic infection, inflammation and cancer. © 2021, Springer Nature Limited.

OBJECTIVES: Short and long sleep duration are associated with poor health outcomes and are most prevalent among racial/ethnic minorities. Few studies have investigated the intersection of other sociodemographic characteristics with race/ethnicity on sleep duration prevalence. DESIGN: Longitudinal retrospective analysis of continental U.S. cohort, the REasons for Geographic And Racial Differences in Stroke (REGARDS) PARTICIPANTS: Black (n = 7,547) and white (n = 12,341) adults, 56% women, ≥45 years MEASUREMENTS: At baseline (2003–07), participants reported age, sex, race, education, income, marital status, U.S. region, and employment status. The weighted average of reported sleep duration on weekdays and weekends, assessed at follow-up (2008–10), was categorized as

© 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited., The application of computational and mathematical modelling to explore the mechanics of biological systems is becoming prevalent. To significantly impact biological research, notably in developing novel therapeutics, it is critical that the model adequately represents the captured system. Confidence in adopting in silico approaches can be improved by applying a structured argumentation approach, alongside model development and results analysis. We propose an approach based on argumentation from safety-critical systems engineering, where a system is subjected to a stringent analysis of compliance against identified criteria. We show its use in examining the biological information upon which a model is based, identifying model strengths, highlighting areas requiring additional biological experimentation and providing documentation to support model publication. We demonstrate our use of structured argumentation in the development of a model of lymphoid tissue formation, specifically Peyer's Patches. The argumentation structure is captured using Artoo (www.york.ac.uk/ycil/software/artoo), our Web-based tool for constructing fitness-for-purpose arguments, using a notation based on the safety-critical goal structuring notation. We show how argumentation helps in making the design and structured analysis of a model transparent, capturing the reasoning behind the inclusion or exclusion of each biological feature and recording assumptions, as well as pointing to evidence supporting model-derived conclusions., This work was part funded by the Wellcome Trust (ref: 097829) through the Centre for Chronic Diseases and Disorders (C2D2) at the University of York and the Medical Research Council (G0601156) to M.C. P.A. was funded by EPSRC grant no. EP/I005943/1 ‘Resilient Futures'. Part of F.A.C.P.'s contribution was supported by the CoSMoS project, EPSRC grant EP/E053505/1. J.T. is part funded by the Royal Society and the Royal Academy of Engineering. H.V.-F. was funded by the FCT Portugal (PTDC/SAU-MII/100016/2008), European Molecular Biology Organisation (Project 1648) and European Research Council (Project 207057).

Highlights • Aerobic physical activity interventions had a large effect on memory. • Aerobic physical activity interventions had a small effect on executive function. • Meeting U.S. physical activity guidelines resulted in a large effect on memory. • Studies with a no treatment control had a large effect on memory., The worldwide population of adults ages 50 and older continues to increase and is projected to reach over 2.3 billion by 2030. Aging is the biggest risk factor for cognitive impairment and dementia. Aerobic physical activity may improve cognitive functioning, thus delaying aging-related cognitive decline. The purpose of this review was to examine the effect of aerobic physical activity on memory and executive function in sedentary adults with no known cognitive impairment. PubMed, CINAHL, Psycinfo, and Cochrane Library databases were systematically searched for peer-reviewed articles up to July 2019. Randomized controlled trials of sedentary adults, aged 50 and older, that compared an aerobic physical activity intervention to either no treatment or alternative active comparator and reported outcome measures of memory and/or executive function were included. A random effects meta-analysis was performed to examine the separate effect sizes for memory and executive function. Nine studies met inclusion criteria and contributed either memory and/or executive function effect sizes (n = 547). Results from the random effects meta-analysis suggested, by post-intervention, a large effect size for the aerobic physical activity interventions on memory (g = 0.80, 95%CI: 0.14–1.47; n = 7; p = 0.02) and a small effect on executive function (g = 0.37, 95%CI: 0.04–0.69; n = 6; p = 0.03). Aerobic physical activity may improve memory and executive function in sedentary adults without cognitive impairment. Policymakers and providers should promote aerobic physical activity in this population, and further research should investigate the most effective ways to promote aerobic physical activity in mid-life to older adults.