HAI Book 2025 - Flipbook - Page 195
Background: We recently demonstrated the sensitivity of PET spatial extent (EXT) measures of amyloid-beta (A´)
when targeting the earliest stage of preclinical Alzheimer9s disease (AD). In cognitively-unimpaired older adults
from the Harvard Aging Brain Study (HABS), [11C]PiB spatial extent (% neocortex with elevated uptake) was a
better predictor of subsequent tau proliferation and cognitive decline than traditional measures of neocortical
uptake. We sought to validate the PET EXT approach through replication in an independent sample with a
different A´ radioligand.
Methods: 1,117 cognitively-unimpaired older adults (Table1) were included from A4 Study (n=537, placebo) and
LEARN (n=576) with baseline A´-PET ([18F]florbetapir) and longitudinal cognitive assessments using Preclinical
Alzheimer9s Cognitive Composite (PACC, median=4.9 years). A subsample of 245 participants (nA4=189, nLEARN=55)
also had longitudinal [18F]flortaucipir (FTP) Tau-PET. We quantified A´ using SUVR and EXT within a neocortical
aggregate. Linear mixed-effects models assessed how well SUVR and EXT predicted three outcomes over time:
cognition and tau SUVR in the medial temporal lobe (MTL) and temporal neocortex (NEO). Further analysis within
subsamples assessed the relative performance of EXT and SUVR at different stages of amyloidosis.
HAI2025 - 195
