Quantitative Brain Amyloid Measures Predict Time-to-Progression from Amnestic Mild Cognitive Impairment to Alzheimer's Disease.

Abstract

This study was designed to investigate factors that predict progression from amnestic mild cognitive impairment (aMCI) to probable Alzheimer's disease (AD). We studied the usefulness of quantitative assessment of amyloid burden measured by Florbetapir PET scan. The study cohort consisted of aMCI participants older than 65 and those with available Florbetapir PET scan at diagnosis from the ADNI database (http://adni.loni.usc.edu). To assess the prognostic impact of amyloid burden, a staging system based on the global SUVr of the PET scan was applied. We defined the stages as: stage I, negative amyloid scan; stage II, positive amyloid in 1st tertile; stage III, positive amyloid in 2nd tertile; and stage IV, positive amyloid in 3rd tertile. Of 250 eligible aMCI subjects (age 74.1±5.4, female n = 105), 71 (28.4%) were diagnosed with probable AD within 3 years. Higher amyloid stages showed faster cognitive decline by Kaplan-Meier analysis. In multivariate Cox analysis, with stage I as a reference, the hazard ratio (HR) increased as the stage increased: stage II (HR, 4.509; p = 0.015), stage III (HR, 7.616; p = 0.001), and stage IV (HR, 9.421; p < 0.001). Along with amyloid stage, ApoE ɛ4 (HR, 1.943; p = 0.031), score of CDR-SB (HR, 1.845; p < 0.001) and ADAS 11 (HR, 1.144; p < 0.001), and hippocampal volume (HR, 0.002; p = 0.005) were also identified as predictors of dementia progression in aMCI subjects. Large amyloid burden measured from amyloid PET scan could be a predictor of faster cognitive decline in aMCI patients.