Objective subtle cognitive decline and plasma phosphorylated tau181: Early markers of Alzheimer's disease‐related declines

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.