HAI Book 2025 - Flipbook - Page 674
Thibault, Emma
164
Neocortical amyloid spatial extent predicts cognitive decline over
time in memory and executive function domains
Emma Thibault1, Jessie Fanglu Fu1, Jackson C. Thompson1, Elliott D. Slade1, Heidi I.L.
Jacobs1, Julie C. Price1, Dorene M. Rentz1,2, Reisa A. Sperling1,2, Keith A. Johnson1, Michelle E.
Farrell1
1
Massachusetts General Hospital, Boston, MA, US
Brigham and Women’s Hospital, Boston, MA, US
2
Background: Use of PET spatial extent (EXT) is a novel, sensitive metric for quantification of amyloid spread (A´)
that reveals a stronger association to cognitive decline than traditional measures of global A´ level. We sought to
use EXT to delve deeper into the association between cognitive measures of executive function and memory and
A´ spread.
Methods: 352 cognitively unimpaired individuals (Table 1) from the Harvard Aging Brain Study (HABS) underwent
baseline [11C]-Pittsburgh Compound-B (PiB)-PET and annual longitudinal cognitive evaluation. Baseline EXT (%
neocortex PiB+) was further classified into three A´-EXT stages: EXT0 (A´-, EXT
95.6%). A series of linear mixed models assessed differences in cognitive decline
on Digit Symbol Substitution (DSST, executive domain) and Free and Cued Selective Reminding free recall (fcSRT,
memory domain) by baseline EXT stage. Further analysis within the EXT1 subsample evaluated the continuous
association between spreading A´ and cognitive decline in these domains. Models covaried for age, sex, years of
education, and included random intercepts and slopes.
Results: The rate of cognitive decline on DSST and fcSRT tracked with baseline EXT (Table 2, Fig.1A,B), with faster
decline detected for EXT1 vs. EXT0 after 2 years for DSST and 5 years for fcSRT. Within the EXT1 subsample, there
was a significant association between continuous baseline EXT and the rate of DSST decline (p=0.022, h2=0.10;
Table 2, Fig.1E) and a trend level association with fcSRT (p=0.055, h2=0.07; Table 2, Fig.1F).
Conclusions: The spread of A´ throughout the neocortex, as quantified with EXT, is associated with early
changes in executive function and memory. Consistent with prior evidence using longitudinal changes in A´ level,
executive function changes were observed earlier than memory.
HAI2025 - 674
