INTRODUCTION: The utility of blood-based biomarkers for discriminating Alzheimer's disease (AD)-related versus non-AD-related cognitive deficits in preclinical populations remains poorly understood. Here, we tested the capability of blood markers to detect and discriminate variation in performance across multiple cognitive domains in a cognitively unimpaired sample. METHODS: Participants (n = 648, aged 69.9 ± 3.8, 71% female) underwent a comprehensive cognitive assessment and assays for plasma-based biomarkers amyloid beta (Aβ)1-42/1-40 by mass spectrometry, phosphorylated tau (p-tau) 181 and 217, p-tau217/Aβ1-42, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). RESULTS: Greater p-tau217 was exclusively associated with poorer episodic memory performance (β = -0.11, SE = 0.04, p = .003), and remained so after covarying for NfL. Higher NfL was non-specifically associated with poorer performance across a range of cognitive domains and remained so after covarying for p-tau217. DISCUSSION: Blood-based biomarkers may differentiate non-AD-related versus AD-related cognitive deficits. This characterization will be important for early intervention and disease monitoring for AD. HIGHLIGHTS: There is heterogeneity in the causes of cognitive decline in aging. AD-related blood biomarkers may help characterize these causes. Elevated p-tau217 was exclusively associated with poorer episodic memory. Elevated NfL was associated with poorer cognition in a broad range of domains. Blood biomarkers may help differentiate AD- and non-AD-related cognitive deficits.