Clinical and demographic factors modify the association between plasma phosphorylated tau-181 and cognition

INTRODUCTIONPlasma phosphorylated tau181 (p-tau181) associations with global cognition and memory are clear, but the link between p-tau181 with other cognitive domains and subjective cognitive decline (SCD) across the clinical spectrum of Alzheimers disease (AD) and how this association changes based on genetic and demographic factors is poorly understood. METHODSParticipants were drawn from the Alzheimers Disease Neuroimaging Initiative and included 1185 adults aged >55 years with plasma p-tau181 and neuropsychological test data. Linear regression models related plasma p-tau181 to neuropsychological composite and SCD scores with follow-up models examining plasma p-tau181 interactions with cognitive diagnosis, APOE {varepsilon}4 carrier status, age, and sex on cognitive outcomes. RESULTSHigher plasma p-tau181 was associated with worse memory, executive functioning, and language abilities, and greater informant-reported SCD. Visuospatial abilities and self-report SCD were not associated with plasma p-tau181. Associations were generally stronger in MCI or dementia, APOE {varepsilon}4 carriers, women, and younger participants. DISCUSSIONHigher levels of plasma p-tau181 are associated with worse neuropsychological test performance across multiple cognitive domains; however, these associations vary based on disease stage, genetic risk status, age, and sex.