Strong evidence supports the role of low-grade systemic inflammation in neurodegeneration, including cognitive decline. Given the literature documenting chronic persistent inflammation in older Black adults, we investigated the association between circulating inflammatory proteins and cognitive decline in this high-risk population. We used data (n = 642) from the Minority Aging Research Study (MARS) and the Rush Clinical Core, including plasma samples to assess circulating inflammatory proteins (Olink® Target-96 Inflammation) and cognition (global cognition and five cognitive domains) assessed annually following proteomics measurement using previously stored blood samples. Linear mixed-effect and latent class mixed models (age at blood draw for proteomics measurement, sex, and education-adjusted), and elastic-net regression were used. Statistical significance was determined using an FDR threshold of 10%. Participants (62.3 to 99.4 years) were mostly women (80.68%) with 15.1 years of education. In multivariable linear mixed-effect models, we found that higher levels of osteoprotegerin (OPG) and chemokine (C-C motif) ligand 23 (CCL23) were cross-sectionally associated with poorer global cognition (beta=-0.205 and beta=-0.148), and higher CCL23 was associated with poorer semantic memory (beta=-0.206). Furthermore, protein × time interaction analyses indicated that higher OPG, Stem cell factor (SCF), and chemokine (C-X-C motif) ligand 9 (CXCL9) levels were associated with faster decline in global cognition (OPG × time term: beta=-0.042), semantic memory (SCF × time term: beta=-0.059, OPG × time term: beta=-0.043), episodic memory (SCF × time term: beta=-0.064; OPG × time term: beta=-0.044), and visuospatial ability (CXCL9×time term: beta=-0.012). In latent class mixed models, several significant protein × time interactions were observed for episodic memory in the subgroup with initial below-average performance and gradual decline. Using elastic net regression, we identified signatures of global cognitive level (26 proteins), but the prediction of cognitive decline was poor. In older Black adults, circulating inflammatory proteins were linked to cognition, reinforcing the role of systemic inflammation as a potential driver of neurodegeneration in this population.
Anat Yaskolka Meir, H. Adeola, S. Tasaki et al.· Brain : a journal of neurolo...· 0 citations
BACKGROUND
Inflammation is a key driver of age-related disease and has been associated with social conditions. We examined how cumulative community-level social and structural disadvantage is associated with inflammatory proteomic profiles in older Black adults.
METHODS
We employed data from the Minority Aging Research Study and the Rush Clinical Core, including the Social Vulnerability Index (SVI; global score and four domains) and 92 plasma inflammatory proteins (Olink® Target-96 Inflammation). Cross-sectional associations between each SVI metric and inflammatory proteins (principal component (PC)-derived global proteomic profile and protein-specific) were assessed using multivariable linear models (demographic, behavioral, and individual-level socioeconomic factors adjusted), with additional sex-by-SVI interaction terms. In a secondary analysis, we replaced SVI with the Index of Concentration at the Extremes (ICE) for household income (ICEincome).
RESULTS
A total of 580 participants (mean (SD) age of 74.9 (6.50) years; 79.7% women) had global SVI and proteomics assessed. Lower household composition (SVIHHC) was associated with the primary global proteomic profile, represented by the 1st proteomic PC (beta = -0.429, p-value = 0.019). A secondary exploratory analysis using the first five proteomic PCs showed that higher minority status/language (SVIMSL) and socioeconomic status (SVISES) were associated with an inflammatory proteomic profile (SVIMSL-PC3: beta=0.160, p-value = 0.048; SVISES-PC2: beta = 0.286, p-value = 0.012). In protein-specific analyses, no SVI-protein associations were found. We found an SVIHHC-by-sex interaction for interleukin-10 receptor alpha (IL-10RA; beta = -0.258, p-value = 5.01×10-4), and among men, SVIMSL was associated with Sirtuin 2 (beta = -0.397, p-value = 8.51×10-04) and STAM binding protein (beta = -0.304, p-value = 9.87×10-04). ICEincome was inversely associated with the global proteomic profile (beta = -0.233, p-value = 0.051), and an ICEincome-by-sex interaction was found for IL-10RA (beta=0.279, p-value = 4.66×10-04).
CONCLUSIONS
By analyzing associations between community-level factors and inflammation-related proteins, our study provides new molecular insights into how social context may relate to biological risk, identifies proteomic patterns that could inform the development of community-level interventions, and underscores the utility of integrating multi-omics approaches to investigate biological pathways relevant to health disparities research.
Anat Yaskolka Meir, H. Adeola, S. Tasaki et al.· BMC Medicine· 0 citations
It is suggested that routinely measured clinical characteristics may help identify populations with greater expected blood pressure response to sodium reduction, and salt sensitivity varied across age, SBP, and body mass index strata.
