Blood biomarkers for dementia in Hispanic and non-Hispanic White adults.

Introduction: The study evaluated if blood markers reflecting diverse biological pathways differentiate clinical diagnostic groups among Hispanic and non-Hispanic White adults.

Methods: Within Hispanic (n = 1193) and non-Hispanic White (n = 650) participants, serum total tau (t-tau), neurofilament light (NfL), ubiquitin carboxyl-terminal hydrolase LI, glial fibrillary acidic protein (GFAP), soluble cluster of differentiation-14, and chitinase-3-like protein 1 (YKL-40) were quantified. Mixed-effects partial proportional odds ordinal logistic regression and linear mixed-effects models were used to evaluate the association of biomarkers with diagnostic group and cognition, adjusting for age, sex, ethnicity, apolipoprotein E ε4, education, and site.

Results: T-tau, NfL, GFAP, and YKL-40 discriminated between diagnostic groups (receiver operating curve: 0.647-0.873). Higher t-tau (odds ratio [OR] = 1.671, 95% confidence interval [CI] = 1.457-1.917,  < .001), NfL (OR = 2.150, 95% CI = 1.819-2.542,  < .001), GFAP (OR = 2.283, 95% CI = 1.915-2.722,  < .001), and YKL-40 (OR = 1.288, 95% CI = 1.125-1.475,  < .001) were associated with increased likelihood of dementia relative to cognitively unimpaired and mild cognitive impairment groups. Higher NfL was associated with poorer global cognition (β = -0.455, standard error [SE] = 0.083,  < .001), semantic fluency (β = -0.410, SE = 0.133,  = .002), attention/processing speed (β = 2.880, SE = 0.801,  < .001), and executive function (β = 5.965, SE = 2.037,  = .003). Higher GFAP was associated with poorer global cognition (β = -0.345, SE = 0.092,  = .001), learning (β = -1.426, SE = 0.359,  < .001), and memory (β = -0.890, SE = 0.266,  < .001). Higher YKL-40 (β = -0.537, SE = 0.186,  = .004) was associated with lower memory scores. Interactions with ethnicity were observed for learning (NfL, GFAP, YKL-40), memory (NfL, GFAP), and semantic fluency (NfL; interaction terms < .008), which were generally no longer significant in a demographically matched subset of Hispanic and non-Hispanic White participants.

Discussion: Blood biomarkers of neuronal/axonal and glial injury differentiated between clinical diagnostic groups in a bi-ethnic cohort of Hispanic and non-Hispanic Whites. Our results add to the growing literature indicating that blood biomarkers may be viable tools for detecting neurodegenerative conditions and highlight the importance of validation in diverse cohorts.