Comparative analyses of Alzheimer's disease blood biomarkers and cognitive domains.

INTRODUCTION

Whether Alzheimer's disease (AD) blood biomarker-cognition associations differ across cognitive domains, analytic context, and biomarker modeling strategy in population-based cohorts is unclear.

METHODS

In 1,170 older adults from the Health and Retirement Study Harmonized Cognitive Assessment Protocol, we examined cross-sectional (2016) and prospective (2016-2022) associations of blood p-tau181, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and amyloid-β42/40 with memory, executive function, language, visuospatial ability, and global cognition using individual biomarker, principal components analysis-derived composite, and multibiomarker panel models.

RESULTS

Cross-sectionally, NfL and GFAP showed the broadest associations. Prospectively, p-tau181 was independently associated with memory and global cognition, whereas GFAP was associated with executive function, memory, and global cognition. P-tau181 also showed relative memory-versus-executive selectivity. The comparatively best-fitting modeling approach differed by cognitive domain and analytic context.

DISCUSSION: AD blood biomarker-cognition associations in community-dwelling older adults are domain-differentiated and context-dependent, supporting domain-specific outcomes and flexible biomarker modeling strategies.