Which MCI Patients Should be Included in Prodromal Alzheimer Disease Clinical Trials?

ABSTRACT

BACKGROUND: Prodromal Alzheimer disease (AD) clinical trials enroll patients with mild cognitive impairment (MCI) meeting biomarker criteria, but specific enrollment criteria vary among trials. METHODS: We used data from AD Neuroimaging Initiative (ADNI) MCI participants to assess AD biomarker eligibility, variation in trial outcome measures, and statistical power. RESULTS: Most (65%) participants meet eligibility criteria based on low cerebrospinal fluid amyloid beta (Aß). Relative to trials enrolling exclusively based on low cerebrospinal fluid Aß, trials including participants with a high ratio of phosphorylated tau to Aß would include an additional 15% of participants. Fewer (34% to 62%) participants met criteria for Aß and tau. Differences in clinical and demographic characteristics of modeled trial samples were minimal. Those with low Aß and high tau showed the greatest change over time on outcome measures. CONCLUSIONS: Eligibility rates for prodromal trials vary depending on the specific biomarker criteria, though differences in demographics and the variation associated with outcome measures are minimal. Broadening inclusion criteria beyond amyloid alone may facilitate recruitment but include patients showing slower progression over time. Biomarker criteria selection should be informed by the goal of enrolling individuals most likely to utilize and benefit from the intervention under investigation in a particular setting.