Comparing criteria for objective cognitive staging in preclinical Alzheimer's disease

INTRODUCTION: Individuals with preclinical Alzheimer's disease may develop objective subtle cognitive decline (OSCD) as they transition between the cognitively unimpaired and mild cognitive impairment stages. Selection of individuals with OSCD into clinical trials may provide enrichment for participants likely to benefit from treatment. We examined how choice of operational criteria for OSCD impacted clinical staging. METHODS: We analyzed data from 6154 older adults in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease clinical trial to evaluate differences in clinical categorization rates by operational approach, as well as interactions with sex, race, and ethnicity. RESULTS: Multinomial generalized estimating equation models yielded significant differences in clinical categorization rates: Interview-based methods led to the lowest proportion of individuals categorized with OSCD, cognitive screeners yielded the highest proportion, and multi-test neuropsychological methods provided a balance. These main effects were moderated by significant interactions with sex and race/ethnicity. DISCUSSION: Choice of OSCD criteria will have significant impacts on trial sample makeup.