Background Social determinants of health (SDOH) are increasingly recognized as important drivers of cognitive outcomes. However, most existing evidence focuses on individual SDOH components and older populations. Objectives To develop a comprehensive SDOH index and examine its association with subsequent changes in cognitive function and structural brain measures in midlife. Design Prospective cohort study with repeated measures of cognition and brain imaging. Setting Community-based cohort from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants A total of 3488 participants with SDOH data in early midlife (mean age 40.0 ± 3.6 years); 645 participants had repeated brain magnetic resonance imaging (MRI) data. Measurements A weighted aggregate SDOH index was constructed from 12 items across 5 domains: economic stability, community and social context, education, neighborhood and built environment, and health care access. Cognitive function was assessed using the Digit Symbol Substitution Test (DSST), Stroop Test, and Rey Auditory Verbal Learning Test (RAVLT). Brain MRI outcomes included white matter hyperintensities (WMHs) and total gray matter (GM) volume. Mixed linear regression models examined associations between SDOH quartiles and longitudinal cognitive and MRI outcomes, adjusting for demographics, vascular risk factors, depression, and intracranial volume (for MRI). Results At baseline, participants in the most disadvantaged SDOH quartile performed worse across all cognitive tests compared with the least disadvantaged quartile (p < 0.001). Over time, the most disadvantaged quartile showed steeper decline in DSST performance (adj. mean change: −0.72, 95% CI: −0.93 to −0.52 vs. −0.55, 95% CI: −0.76 to −0.34, p = 0.013), greater WMH accumulation (ratio: 1.07, 95% CI: 1.05 to 1.09 vs. 1.04, 95% CI: 1.03 to 1.05, p = 0.007), and steeper decline in total GM volume (−2.02 cm³, 95% CI: −2.39 to −1.65 vs. −1.46 cm³, 95% CI: −1.71 to −1.20, p = 0.011) per 5-year interval compared to the least disadvantaged quartile. Conclusions Greater social disadvantage in midlife is associated with worse baseline cognition and accelerated decline in cognitive function and brain integrity. These findings highlight the importance of SDOH as key determinants of brain health in midlife and suggest that strategies to mitigate social disadvantage may help preserve cognitive and brain health.
C. Dintica, Julia Cheunkarndee, R. Bryan et al.· The journal of prevention of...· 0 citations
Abstract OBJECTIVE To examine associations of inherited chromosomally integrated human herpesvirus 6 (iciHHV‐6) with incident dementia and mortality, characterize proteomic and metabolomic correlates of carrier status, and evaluate whether these biomarkers relate to dementia and mortality risk. METHODS We analyzed UK Biobank participants ≥50 years of age with plasma metabolomics (N = 138,676) and proteomics (N ≤ 15,416) data and ≈15 years of follow‐up. Cox proportional hazards models adjusted for key confounding factors evaluated associations of iciHHV‐6 with dementia and mortality. Multivariable linear models assessed iciHHV‐6 associations with metabolomic and proteomic profiles. Mediation and interaction were evaluated using structural equation models and Cox models with biomarker interactions. Least absolute shrinkage and selection operator regression identified independent proteomic and metabolomic predictors using imputed biomarker data. RESULTS iciHHV‐6 was associated with higher dementia risk (hazard ratio [HR] = 1.32), particularly among women (HR = 1.66) and individuals with elevated Alzheimer's disease polygenic risk (HR = 1.49). Branched‐chain amino acids (leucine and isoleucine) were elevated among carriers without mediating dementia risk. Proteomic analyses identified 126 nominally associated iciHHV‐6–related proteins, many of which (Neurofilament Light Chain (NEFL), Glial Fibrillary Acidic Protein (GFAP), Yes‐Associated Protein 1 (YAP1), Sialic Acid‐binding Immunoglobulin‐like Lectin 5 (SIGLEC5), Interleukin 19 (IL19), A Disintegrin And Metalloproteinase with Thrombospondin Motifs 16 (ADAMTS16), Sphingomyelin Phosphodiesterase 1 (SMPD1)) were also associated with dementia and/or mortality. Exploratory pathway analyses suggested enrichment of proteins related to immune regulation and post‐translational modification. Predictive models identified NEFL, GFAP, Vascular Endothelial Growth Factor A (VEGF), Brevican (BCAN), remnant cholesterol, and polyunsaturated fatty acids as dementia predictors (area under the curve [AUC] = 0.83), whereas NEFL, Growth Differentiation Factor 15 (GDF15) Latent Transforming Growth Factor Beta Binding Protein 2 (LTBP2), Ectodysplasin A2 Receptor (EDA2R) and Advanced Glycosylation End‐product Specific Receptor (AGER) predicted mortality (AUC = 0.70). DISCUSSION iciHHV‐6 was associated with increased dementia risk, particularly among women and genetically susceptible individuals, with neuroimmune and metabolic biomarker profiles potentially relevant to brain aging and mortality risk.
M. Beydoun, Minkyo Song, Choa Yun et al.· Alzheimer's & Dementia· 0 citations
Findings highlight complex relationships linking air pollution, metabolic dysregulation, and neurodegeneration, and support integrative multi-omics approaches to identify pathways relevant to prevention of neurodegenerative diseases and premature mortality.
M. Beydoun, Tianyi Huang, Yi-Han Hu et al.· Ecotoxicology and Environmen...· 0 citations
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