Predictors of combined cognitive and physical decline

OBJECTIVES: To determine the incidence and correlates of combined declines in cognitive and physical performance. DESIGN: Cohort study of community-dwelling older women with moderate to severe disability. SETTING: The community surrounding Baltimore, Maryland. PARTICIPANTS: Participants in the Women's Health and Aging Study I with Mini-Mental State Examination (MMSE) score or 24 or greater and walking speed greater than 0.4 m/s at baseline. MEASUREMENTS: Cognitive decline was defined as an MMSE score less than 24 and physical decline as a walking speed of 0.4 m/s or less in at least one of the three annual follow-up visits. Participants were stratified into groups based on cognitive or physical decline or both. Group characteristics were compared, and results were adjusted for age, race, education, and significant covariates. RESULTS: Of 558 women that met the baseline MMSE and walking speed inclusion criteria, 21% developed physical decline, 12% developed cognitive decline, and 11% experienced combined cognitive and physical decline. After adjustment, physical decline was associated with age, nonwhite race, former smoking, baseline walking speed, and instrumental activities of daily living (IADL) impairment. Cognitive decline was associated with age and baseline MMSE score. Combined decline was associated with age, baseline walking speed, MMSE score, IADL impairment, as well as current smoking (odds ratio (OR)=5.66, 95% confidence interval (CI)=1.49-21.54) and hemoglobin level (OR=0.68, 95% CI=0.47-0.98). CONCLUSION: Potential predictors of cognitive and physical performance decline were identified. The association between smoking and lower hemoglobin levels and combined cognitive and physical decline may represent potentially modifiable risk factors and should be confirmed in future studie

Leisure-time physical activity volume, intensity, and duration from mid-to late-life in U.S. subpopulations by race and sex. The Atherosclerosis Risk in communities (ARIC) study

Mitigating age-related disease and disability presents challenges. Physical activity (PA) may be influential for prolonging health and functioning, warranting characterization of its patterns over the life course in population-based data. With the availability of up to three self-reported assessments of past year leisuretime PA (LTPA) over multiple decades in 15,036 participants (26% African American; 55% women; mean baseline age=54; median follow-up=23 years) from the Atherosclerosis Risk in Communities (ARIC) Study sampled from four U.S. communities, race-sex-stratified trajectories of average weekly intensity (metabolic equivalent of task (MET), duration (hours), and energy expenditure or volume (MET-h) of LTPA were developed from age 45 to 90 using joint models to accommodate expected non-ignorable attrition. Declines in weekly LTPA intensity, duration, and volume from age 70 to 90 were observed in white women (2.9 to 1.2 MET; 2.5 to 0.6 h; 11.1 to 2.6 MET-h), white men (2.5 to 1.0 MET; 3.5 to 1.8 h; 15.5 to 6.4 MET-h), African American women (2.5 to 2.4 MET; 0.8 to 0.1 h; 6.7 to 6.0 MET-h), and African American men (2.3 to 1.4 MET; 1.5 to 0.6 h; 8.0 to 2.3 MET-h). These data reveal population-wide shifts towards less active lifestyles in older adulthood

Inflammatory markers and incident mobility limitation in the elderly

OBJECTIVES: To examine the relationship between indicators of inflammation and the incidence of mobility limitation in older persons. DESIGN: Prospective cohort study: the Health, Aging and Body Composition Study. SETTING: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: A total of 2,979 men and women, aged 70 to 79, without mobility limitation at baseline. MEASUREMENTS: Serum levels of interleukin (IL)-6, tumor necrosis factor alpha (TNFα), and C-reactive protein (CRP) and soluble cytokine receptors (IL-2sR, IL-6sR, TNFsR1, TNFsR2) were measured. Mobility limitation was assessed and defined as reporting difficulty or inability to walk one-quarter of a mile or to climb 10 steps during two consecutive semiannual assessments over 30 months. RESULTS: Of the 2,979 participants, 30.1% developed incident mobility limitation. After adjustment for confounders (demographics, prevalent conditions at baseline, body composition), the relative risk (RR) of incident mobility limitation per standard deviation (SD) increase was 1.19 (95% confidence interval (CI) = 1.10-1.28) for IL-6, 1.20 (95% CI = 1.12-1.29) for TNFα and 1.40 (95% CI = 1.18-1.68) for CRP. The association between inflammation and incident mobility limitation was especially strong for the onset of more severe mobility limitation and when the levels of multiple inflammatory markers were high. When persons with baseline or incident cardiovascular disease events or persons who were hospitalized during study follow-up were excluded, findings remained similar. In a subset (n = 499), high levels of the soluble receptors IL2sR and TNFsR1 (per SD increase: RR = 1.23 (95% CI = 1.04-1.46) and RR = 1.28 (95% CI = 1.04-1.57), respectively) were also associated with incident mobility limitation. CONCLUSION: Findings suggest that inflammation is prognostic for incident mobility limitation over 30 months, independent of cardiovascular disease events and incident severe illness

Inflammatory Markers and Onset of Cardiovascular Events: Results from the Health ABC Study

Background - Inflammation plays an important role in cardiovascular disease. The aim of this study is to investigate the predictive value of several inflammatory markers on the incidence of cardiovascular events in well-functioning older persons. Methods and Results - The subjects were 2225 participants 70 to 79 years old, without baseline cardiovascular disease, who were enrolled in the Health, Aging, and Body Composition study. Incident coronary heart disease (CHD), stroke, and congestive heart failure (CHF) events were detected during an average follow-up of 3.6 years. Blood levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-\uce\ub1 (TNF-\uce\ub1) were assessed. After adjustment for potential confounders, IL-6 was significantly associated with all outcomes (CHD events, per IL-6 SD increase: RR, 1.27; 95% CI, 1.10 to 1.48; stroke events, per IL-6 SD increase: RR, 1.45; 95% CI, 1.12 to 1.86; CHF events, per IL-6 SD increase: RR, 1.72; 95% CI, 1.40 to 2.12). TNF-\uce\ub1 showed significant associations with CHD (per TNF-\uce\ub1 SD increase: RR, 1.22; 95% CI, 1.04 to 1.43) and CHF (per TNF-\uce\ub1 SD increase: RR, 1.59; 95% CI, 1.30 to 1.95) events. CRP was significantly associated with CHF events (per CRP SD increase: RR, 1.48; 95% CI, 1.23 to 1.78). A composite summary indicator of inflammation showed a strong association with incident cardiovascular events, with an especially high risk if all 3 inflammatory markers were in the highest tertile. Conclusions - Findings suggest that inflammatory markers are independent predictors of cardiovascular events in older persons

Is an MRI-derived anatomical measure of dementia risk also a measure of brain aging?

Machine learning methods have been applied to estimate measures of brain aging from neuroimages. However, only rarely have these measures been examined in the context of biologic age. Here, we investigated associations of an MRI-based measure of dementia risk, the Alzheimer’s disease pattern similarity (AD-PS) scores, with measures used to calculate biological age. Participants were those from visit 5 of the Atherosclerosis Risk in Communities Study with cognitive status adjudication, proteomic data, and AD-PS scores available. The AD-PS score estimation is based on previously reported machine learning methods. We evaluated associations of the AD-PS score with all-cause mortality. Sensitivity analyses using only cognitively normal (CN) individuals were performed treating CNS-related causes of death as competing risk. AD-PS score was examined in association with 32 proteins measured, using a Somalogic platform, previously reported to be associated with age. Finally, associations with a deficit accumulation index (DAI) based on a count of 38 health conditions were investigated. All analyses were adjusted for age, race, sex, education, smoking, hypertension, and diabetes. The AD-PS score was significantly associated with all-cause mortality and with levels of 9 of the 32 proteins. Growth/differentiation factor 15 (GDF-15) and pleiotrophin remained significant after accounting for multiple-testing and when restricting the analysis to CN participants. A linear regression model showed a significant association between DAI and AD-PS scores overall. While the AD-PS scores were created as a measure of dementia risk, our analyses suggest that they could also be capturing brain aging

Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure

Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinant

Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts

Background: Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. Objective: To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. Design: We conducted genome-wide association (GWA) meta-analysis of fish (n = 86, 467) and EPA +DHA (n = 62, 265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. Results: Heritability estimates for fish and EPA+DHA consumption ranged from 0.13

Associations between drug and alcohol use, smoking, and frailty among people with HIV across the United States in the current era of antiretroviral treatment

Objective: To examine associations between frailty and drug, alcohol, and tobacco use among a large diverse cohort of people with HIV (PWH) in clinical care in the current era. Methods: PWH at 7 sites across the United States completed clinical assessments of patient-reported measures and outcomes between 2016 and 2019 as part of routine care including drug and alcohol use, smoking, and other domains. Frailty was assessed using 4 of the 5 components of the Fried frailty phenotype and PWH were categorized as not frail, pre-frail, or frail. Associations of substance use with frailty were assessed with multivariate Poisson regression. Results: Among 9336 PWH, 43% were not frail, 44% were prefrail, and 13% were frail. Frailty was more prevalent among women, older PWH, and those reporting current use of drugs or cigarettes. Current methamphetamine use (1.26: 95% CI 1.07–1.48), current (1.65: 95% CI 1.39–1.97) and former (1.21:95% CI 1.06–1.36) illicit opioid use, and former cocaine/crack use (1.17: 95% CI 1.01–1.35) were associated with greater risk of being frail in adjusted analyses. Current smoking was associated with a 61% higher risk of being frail vs. not frail (1.61: 95% CI 1.41–1.85) in adjusted analyses. Conclusions: We found a high prevalence of prefrailty and frailty among a nationally distributed cohort of PWH in care. This study identified distinct risk factors that may be associated with frailty among PWH, many of which, such as cigarette smoking and drug use, are potentially modifiable

Gene × dietary pattern interactions in obesity: Analysis of up to 68 317 adults of European ancestry

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GR

Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium

Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stageGWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10-6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with totalmortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5×10-6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10-3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10-9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10-3). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders