Timing of Alzheimer's disease biomarker progressions: A two‐decade observational study from the Alzheimer's Disease Neuroimaging Initiative (ADNI)

Abstract

INTRODUCTION: Alzheimer's Disease Neuroimaging Initiative (ADNI) has been pivotal in identifying and refining Alzheimer's disease (AD) biomarkers for clinical trials. This study leverages longitudinal data from participants who have progressed to amyloid-positivity during their study participation to track evolution of biomarkers and cognitive function. METHODS: We modeled AD biomarker (positron emission tomography [PET], structural, cerebrospinal fluid [CSF], cognition) trajectories before and after observed amyloid-positivity onset time to detect time at which each biomarker had detectable trajectory changes. RESULTS: Analysis of a sub-cohort of the 20-year ADNI study (N = 90) recapitulated Alzheimer's progression beginning with amyloid alterations -4.8 to -5.3 years relative to amyloid-positivity, succeeded by neurodegeneration (t = -4.0 to -4.1 years), and CSF tau (t = -0.4 to -0.5 years). Cognitive decline was observed to significantly correspond with emergence of amyloid-positivity (t = 0.2 to 2.4 years). DISCUSSION: Our results corroborate temporal progression curves of AD biomarkers, providing insights on earliest detectable changes in objective and subjective cognitive function assessments.