INTRODUCTION: Timely detection and tracking of Alzheimer's disease (AD) -related cognitive decline has become a public health priority. We investigated whether the NIH Toolbox for Assessment of Neurological and Behavioral Function-Cognition Battery (NIHTB-CB) detects AD-related cognitive decline. RESULTS: Compared to Aβ-negative healthy controls, Aβ-positive individuals with amnestic MCI or mild AD performed worse on all NIHTB-CB measures and showed an accelerated decline in processing speed, working memory, and auditory word comprehension tests. DISCUSSION: These findings support the use of the NIHTB-CB in early AD, but also imply that the optimal NIHTB-CB composite score to detect change over time may differ across clinical stages of AD. Future directions include replication of these findings in larger and more demographically diverse samples. HIGHLIGHTS: We examined NIH Toolbox-Cognition Battery scores across the clinical AD spectrum.All NIH Toolbox tests detected cross-sectional cognitive impairment in MCI-to-mild AD.Three NIH Toolbox tests captured further decline over time in MCI-to-mild AD.The NIH Toolbox can facilitate timely detection of AD-related cognitive decline.