P4‐308: [18f]flutemetamol Amyloid Pet Imaging: Outcome of a Phase Iii Study in Subjects With Amnestic Mild Cognitive Impairment After a 3‐year Follow‐up

Mild cognitive impairment (MCI) is characterized by cognitive deficits not severe enough to impact daily functioning and thus not meeting the definition of dementia. Identifying MCI subjects at high risk of progressing to AD could allow more focused allocation of healthcare resources. This Phase 3 study tested the ability of [18 F]flutemetamol images to stratify amnestic MCI (aMCI) patients by risk of progression to probable Alzheimer's Disease (pAD). Consenting subjects with aMCI (n=232), diagnosed by the Petersen criteria at 28 centres in the EU and USA were administered 185 MBq Flutemetamol F18 Injection and underwent a 30-minute brain scan. Images were read visually by 5 independent blinded readers and classified as [18 F]Flutemetamol negative or positive for the presence of brain amyloid. Subjects were assessed clinically on-site every 6 months until progression to pAD (determined by an independent Clinical Adjudication Committee) or for 3 years, whichever occurred first. A Cox proportional hazards model was used to estimate hazard ratios (HR) for progression to pAD between negative and positive [18 F]Flutemetamol image evaluation groups. Risk factors (age, ApoE genotype, aMCI stage) were assessed as part of the model or in separate subgroup analyses. A positive [18 F]Flutemetamol PET scan interpretation was a highly significant predictor of progression to pAD. The median HR was 2.58 (p=0.0001) among the 5 readers ranging from 1.962 to 3.418 and was >2.5 for each of 4 readers; the HR was highly significant for each reader. Using the median HR, the odds were about 2.6 to 1 that subjects with positive [18 F]Flutemetamol scans would convert to pAD earlier than those with negative scans. Patient age was highly significant in predicting conversion to pAD for each reader (median HR 1.051; p = 0.0009) whereas ApoE status was not. Subjects with late-stage aMCI (ADNI definition, based on Logical Memory II scores) were more likely to progress to pAD than those with early-stage aMCI (median HR 2.199; p = 0.0016). Both a [18 F]Flutemetamol PET scan and patient age were highly significant indicators of the risk of earlier progression from aMCI to pAD.