UC San Diego

INTRODUCTION: Objectively-defined subtle cognitive decline (Obj-SCD) and plasma phosphorylated-tau181 (p-tau181) are promising early Alzheimer's disease (AD) markers. However, associations between Obj-SCD and p-tau181, and their combined prognostic potential, are unknown. METHODS: Baseline and 4-year longitudinal p-tau181 changes were compared across cognitively unimpaired (CU; n = 402), Obj-SCD (n = 199), and mild cognitive impairment (MCI; n = 346) groups. CU and Obj-SCD participants were further classified as p-tau181-positive or negative. RESULTS: CU and Obj-SCD has lower baseline p-tau181 than MCI and did not differ from one another. Longitudinally, Obj-SCD had the steepest p-tau181 increase. Obj-SCD/p-tau181-positive participants had the fastest rates of amyloid accumulation, cognitive decline, and functional decline. CONCLUSIONS: Despite assumptions that cognitive changes invariably follow biomarker changes, early neuropsychological difficulties may emerge before/concurrently with plasma p-tau181 changes. Combining Obj-SCD and p-tau181, two potentially accessible early markers, was associated with the faster declines in AD-related outcomes.