Social vulnerability index and inflammation: a proteomic analysis linking social context to biological risk in older black adults.

Social Adversity, Systemic Inflammation, and the Ticking of the Biological Aging Clocks in Men and Women

It is found that socioeconomic adversity influences not only inflammatory pathways but also distinct biological aging processes, including metabolomic aging, and that socioeconomic adversity influences not only inflammatory pathways but also distinct biological aging processes.

Exploratory factor and network analysis of 43 inflammatory plasma biomarkers and cognitive performance in Black adults.

BackgroundSystemic inflammation has been implicated in cognitive aging and neurodegeneration; however, inflammatory biomarkers are expressed in coordinated patterns rather than as isolated markers.ObjectiveTo identify latent inflammatory biomarker groupings and evaluate their associations with cognitive performance among midlife and older adults.MethodsThis cross-sectional study included 334 participants from the Aging Research Characterizing Health Exposome via Social Drivers (ARCHES) study. Cognitive performance was assessed using the Preclinical Alzheimer Cognitive Composite (PACC). Plasma inflammatory biomarkers were quantified using the NuLISA™ multiplex immunoassay platform. Exploratory factor analysis (EFA) (minimum residual extraction, oblimin rotation) identified latent inflammatory factors, retaining biomarkers with loadings ≥0.40. Factor scores were evaluated in multivariable linear regression models adjusted for age, sex, education, and genotype status; sensitivity analyses adjusted for socioeconomic context, medication use, BMI, lifestyle factors, and clinical diagnoses. Age-stratified and nonlinear spline analyses were conducted.Results27 of 43 biomarkers formed an eight-factor structure explaining 43% of variance. Two factors were significantly associated with cognitive performance after FDR correction. Factor 4 (CCL4, CXCL1, S100A12) and Factor 5 (IL2, IL5, IL13, IL10, CSF2) were inversely associated with PACC scores. These associations remained consistent across sensitivity analyses. Age-stratified analyses showed that several inflammatory factors were associated with cognitive performance among participants aged 45-<65 years, whereas no factors remained significant among participants aged ≥65 years after FDR correction. Nonlinear modeling indicated a non-linear age-cognitive performance relationship.ConclusionsEFA identified clusters of correlated inflammatory biomarkers associated with cognitive performance in this cohort of midlife and older adults.

Aging with HIV: The Interplay of Neighborhood-Level Social Vulnerability, Social Support, and Physical Activity.

Differential associations of individual- and neighborhood-level socioeconomic status with mortality in dementia: Findings from the Mayo Clinic Study of Aging.

BackgroundAlzheimer's disease (AD) and related dementias are leading causes of death worldwide. While socioeconomic status (SES) is a critical determinant, its impact on mortality after diagnosis remains understudied.ObjectiveTo investigate the roles of neighborhood-level and individual-level SES in predicting mortality risk among older adults with incident dementia.MethodsWe analyzed data from 924 participants with incident dementia from the Mayo Clinic Study of Aging (N = 6909), a cohort with clinical follow-up visits every 15 months. We assessed mortality risk using Cox's time-varying survival regression, adjusting for time-fixed and time-varying covariates. Primary predictors were neighborhood-level SES (Area Deprivation Index [ADI]) and individual-level SES (housing-based SES index [HOUSES], education, and occupation). We also applied a random survival forest model to assess the predictive contribution of SES indicators and identify influential predictors.Results857 participants (92.7%) died, with a median time from dementia diagnosis to death of 29 months (IQR: 12-54). Lower SES measured by HOUSES was associated with increased mortality risk (HR 1.28, 95% CI 1.07-1.52). Conversely, ADI, education, and occupation were not associated with mortality. Male sex, older age, congestive heart failure and diabetes were associated with higher mortality risk. In predictive analysis, HOUSES ranked among the top 10 contributors to mortality risk.ConclusionsAmong older adults with dementia, lower HOUSES was associated with higher mortality risk beyond neighborhood-level deprivation, education, and occupation. Integrating this housing-based individual-level SES measure into dementia care planning may help identify patients with greater socioeconomic vulnerability and inform mortality risk stratification.

Large-scale proteomics to identify novel biomarkers linking social determinants of health to heart failure risk

Adverse social determinants of health (SDOH) associate with greater heart failure (HF) risk. Among 9879 community-based participants of the Atherosclerosis Risk in Communities (ARIC) cohort study, we assessed 4955 plasma proteins using an aptamer-based platform (SomaLogic). We derived an SDOH factor comprising income, education, and area deprivation index (ADI) in Black and white participants. Proteins associated with this factor at Bonferroni significance were tested for associations with incident HF using multivariable Cox proportional hazard models. Among Black participants, 36 proteins were associated with both the SDOH factor and incident HF, 126 were among white participants, and 12 were shared between race strata. Eight of these demonstrated significant mediation effect in causal mediation models. Key results were replicated in 49,396 participants in UK Biobank. Mendelian randomization and colocalization suggested a potentially causal effect of C1q tumor necrosis factor–related protein 1 (C1QTNF1), an adiponectin paralog, on HF. We demonstrate protein biomarkers associated with SDOH burden and HF risk.

Social isolation, loneliness, and blood-based AD/ADRD biomarkers in a nationally-representative study of middle-aged and older adults

ABSTRACT Importance: The biological mechanisms underlying the associations of social isolation and loneliness with dementia risk are not well understood. Objective: To evaluate the relationship of prospectively measured social isolation and loneliness with AD/ADRD blood-based biomarkers. Design: Observational study using the U.S. Health and Retirement Study (2010-2016). Venous blood draws were conducted in 2016 and AD/ADRD biomarkers were released in 2025. We estimated associations of social isolation and loneliness patterns between 2012 and 2014 with continuous biomarkers using linear regressions, accounting for socio-demographic and health covariates. We evaluated effect modification by sex and APOE {varepsilon}4 carrier status. Setting: Population-based Participants: Community-dwelling HRS participants aged 50 years or older (n = 3862). Exposures: Primary exposures were four-category multi-wave variables of persistent, resolving, new-onset, or no social isolation/loneliness across the two exposure waves. Social isolation was classified as "severe" and "moderate-to-severe" based on a 5-item scale including marital status, household size, proximity to children, religious service attendance, and volunteering. Past-week loneliness was measured with a single-item question (yes/no). Main Outcomes and Measures: Neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and the ratio of amyloid beta 42 to amyloid beta 40 (A{beta}42/40), measured in plasma via a Multiplex Simoa Assay and phosphorylated tau (p-tau181), measured in serum via a Simoa Assay. Results: At the analytic baseline, respondents were a mean age of 64 (9.5) years, 59% female, and 25% APOE {varepsilon}4 carriers. Across the two exposure waves, 4% experienced persistent severe social isolation, 16% experienced persistent moderate-to-severe social isolation, and 8% reported persistent loneliness. Multiple patterns of social isolation (vs. no social isolation) were associated with higher NfL, including persistent severe social isolation ({beta}: 0.31), new-onset moderate-to-severe social isolation ({beta}: 0.14), and resolving moderate-to-severe social isolation ({beta}: 0.20). Persistent severe social isolation was associated with lower GFAP ({beta}: -0.31) while persistent loneliness and, for men, new-onset loneliness were associated with higher GFAP ({beta}_persistent: 0.16; {beta}_(new onset_men): 0.25). New-onset severe social isolation was associated with a lower A{beta}42/40 ratio ({beta}: -0.25) while resolving moderate-to-severe social isolation and, for men, persistent severe social isolation were each associated with higher p-tau181 ({beta}_resolving: 0 .11; {beta}_(persistent_men): 0.41). There was some additional variation by APOE {varepsilon}4 carriership, although selective survival is a concern. Conclusions: Social isolation was associated with elevated blood-based biomarkers of neuronal injury, with variation by patterns of exposure over time. Associations between social isolation and loneliness with biomarkers related to astrocyte damage and Alzheimer's disease were less consistent, and varied in sign and magnitude by exposure and sex.