Thrombopoietin is associated with δ's intercept, and only in Non-Hispanic Whites

Donald R Royall, Raymond F Palmer, Donald R Royall, Raymond F Palmer

Abstract

Introduction: Serum thrombopoietin (THPO) is a biomarker of Alzheimer's disease (AD) and the latent dementia phenotype, "δ". Both associations may be specific to non-Hispanic whites (NHW), not Mexican-Americans (MA). In this analysis, we examine ethnicity's effect on THPO's association with change in δ scores, in the Texas Alzheimer's Research and Care Consortium (TARCC).

Methods: We constructed an ethnicity equivalent δ homolog ("dEQ") among n = 1113 MA and n = 1958 NHW. dEQ was output as a composite "dEQ-score" for each of five annual TARCC waves. Those composites were used as indicators of a latent growth curve (LGC). The mean dEQ intercept (idEQ) and slope (ΔdEQ) were estimated in a random subset of N = 1528 participants and replicated in the remainder (n = 1544). THPO was regressed onto idEQ and ΔdEQ. Those associations were tested separately in MA and NHW.

Results: dEQ correlated strongly with CDR-SB (r = 0.99, P < .001) and achieved high AUCs for AD diagnosis at each wave (range = 0.95-0.99). THPO was significantly associated with idEQ but not ΔdEQ. That effect was observed in NHW only. In MA, THPO had no associations with either idEQ or ΔdEQ.

Discussion: We confirm THPO's ethnicity-specific association with δ in NHW. It is further clarified that this association is specific to δ's intercept and not its slope. This analysis provides a model for how dementia's specific serum biomarkers can be characterized.

Keywords: Aging; Cognition; Dementia; Functional status; Intelligence; THPO.

Figures

Supplementary Figure 1
Supplementary Figure 1
The latent variable dEQ's construction. Abbreviations: CFI, comparative fit index; COWA, Controlled Oral Word Association Test; DF, degrees of freedom; DST, Digit Span Test; IADL, instrumental activities of daily living; RMSEA, root mean square error of association; SE, standard error; WMS LM II, Weschler Memory Scale: delayed logical memory; WMS VR I, Weschler Memory Scale: immediate visual reproduction.
Supplementary Figure 2
Supplementary Figure 2
Observed serum THPO by diagnosis and ethnicity
Fig. 1
Fig. 1
dEQ histograms for selected waves (dEQ scores are referenced to the entire cohort's standardized mean [i.e., dEQ = 0.0]). NOTE. Rightward increase in dEQ scores.
Fig. 2
Fig. 2
THPO predicts dEQ's intercept but not its slope (group 1 loadings. Standardized parameter estimates. dEQ indicators are adjusted for age, gender, and education [but not ethnicity]).

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