INTRODUCTIONThis study proposes objective, standardized criteria for defining amnestic transitional cognitive decline (aTCD) in aging and preclinical Alzheimers disease (AD), supported by a comprehensive multimodal biomarker characterization.
METHODSThis prospective observational study analyzed 3-year longitudinal data from the Alzheimers and Families+ cohort, including 350 cognitively unimpaired participants. The presence of aTCD was defined using robust longitudinal neuropsychological references with a multivariate base rate threshold of significant cognitive decline; its association with fluid (plasma and CSF) and neuroimaging biomarkers (PET and MRI) was evaluated using mixed-effects and voxel-wise regression models, respectively.
RESULTSApplying the defined criteria, aTCD was identified in 35 individuals (10%), demonstrating significant associations with Core AD biomarkers (A{beta} and tau) and biomarkers of non-specific processes involved in AD pathophysiology (neurodegeneration and inflammation).
DISCUSSIONThese findings underscore the need for standardized clinical staging criteria to improve early detection and risk stratification in aging and preclinical AD.