INTRODUCTION: New Alzheimer's disease (AD) treatments have created an urgent need for accurate early diagnosis of high-risk adults with Down syndrome (DS), distinguishing prodromal DS-AD symptoms from lifelong cognitive impairments. Often, clinicians will need to evaluate dementia status during a single assessment, and here we describe empirically supported methods effective under such circumstances. METHODS: Archived data collected between 1987 and 2017 included longitudinal findings for 144 individuals maintaining cognitive stability and 126 developing prodromal DS-AD. Response operating characteristic analyses compared groups, defined by the presence/absence of prodromal DS-AD, for a single assessment. RESULTS: Groups differed on all measures without adjusting for developmental history, 0.717 <
areas under the curve <
0.859, DISCUSSION: The present study demonstrated that one-time assessments can inform clinical judgments when diagnosing adults at risk for DS-AD. Knowledge of developmental history is valuable but non-essential. HIGHLIGHTS: Non-overlapping distributions were observed for preclinical and prodromal Alzheimer's disease (AD) groups.Receiver operating characteristic area under the curve analyses were in the acceptable to excellent range for all measures.Performance was sensitive to both the severity of intellectual disability and the stage of Down syndrome-AD progression.Episodic memory tests were sensitive to the transition from preclinical to prodromal AD.Performance results at a single time point can inform dementia status decisions.