Biomarkers

BACKGROUND: The relationship between plasma biomarkers for Alzheimer's disease and longitudinal cognitive decline in diverse and underserved communities remains poorly understood. We investigated the associations between baseline plasma biomarkers and changes in cognitive performance over 13.5 years in a diverse cohort of Hispanic/Latino individuals. METHOD: We used data from the Hispanic Community Health Study/Study of Latinos (Visit 1; 2008-2011) and the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA; Visit 2; 2016-2018) and SOL-INCA2 (Visit 3; 2022-2024) ancillary studies. We included 2,343 participants (aged 45-74 years at Visit 1; 54.4 years on average) that completed their third visit of cognitive testing and had plasma samples analyzed (Quanterix Simoa HD-X) for amyloid-beta (Aβ42/40), phosphorylated tau-181 (pTau-181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) at Visit 1. Global cognitive performance was a standardized average composite of four z-scored cognitive tests relative to the baseline mean and standard deviation. The plasma biomarker measures were dichotomized to focus on high-risk groups (bottom 10th percentile for Aβ42/40; top 10th percentile for pTau-181, pTau-181/Aβ42, NfL, and GFAP). Additionally, we used a risk-index score based on the count of plasma biomarker (excluding pTau-181/Aβ42) measures that are high-risk (0,1, and ≥2). We used multilevel linear models to examine cognitive aging trajectories with models covarying for sex, Hispanic/Latino background, and APOE e4 genotype. RESULT: In each model, age was associated with decrements in global cognitive change (Table 1). Individuals in the top 10th percentile for pTau-181, pTau-181/Aβ42, NfL, and GFAP had more pronounced age-related declines in global cognitive performance (Figures 1 and 2). We observed no differences in age-related global cognitive change for individuals in the bottom 10th percentile for Aβ42/40. Individuals with higher risk (≥2 biomarkers in the high-risk groups) had more pronounced age-related cognitive decline. CONCLUSION: Preliminary findings suggest plasma biomarkers for pTau-181, pTau-181/Aβ42, NfL, and GFAP predict cognitive decline before symptoms manifest. Individuals with high levels of these biomarkers are at elevated risk for age-related cognitive decline. The threshold for differences in the trajectories varies by biomarker and differences in trajectories are more apparent in older age suggesting the likelihood for nonlinear change.