HAI Book 2025 - Flipbook - Page 113
Fu, Jessie Fang-Lu
6
Baseline tau burden and performance on a digital clock drawing test
uniquely contributes to predicting future tau accumulation in preclinical AD
Jessie Fang-Lu Fu1,2, Talia Robinson2, Michelle Farrell2, Roos Jutten2, Emma Thibault2, Marina
Rodriguez Alonso2, Jackson Thompson2, Cristina Lois2, Amal Tiss2, Kuang Gong2,3, Charles
Chen1,2, Dana Penney4, Randall Davis5, Reisa Sperling2, Keith Johnson2, Dorene Rentz2, Julie
Price1,2
1
Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, US
Massachusetts General Hospital, Harvard Medical School, Boston, MA, US
3
University of Florida, Gainesville, FL, US
4
Lahey Hospital and Medical Center, Burlington, MA, US
5
Massachusetts Institute of Technology, Cambridge, MA, US
2
Background: Longitudinal [18F]MK-6240 PET tracks tau accumulation across the AD continuum and evaluates
anti-tau therapeutics. Identifying individuals likely to exhibit greater tau accumulation could improve screening
efficiency. Current screening relies on Ab and tau PET and cognitive assessments (e.g., Preclinical Alzheimer9s
Cognitive Composite, PACC-5). We previously demonstrated association between higher baseline Ab and tau
burden and worse baseline performance and accelerated decline on a 2-minute digital clock-drawing test
(DCTclockTM) in cognitively normal (CN) individuals. This study evaluates the extent to which baseline Ab and tau
burden and DCTclock performance impact rates of subsequent tau accumulation.
Methods: Seventy-four CN individuals underwent DCTclock and PACC-5 cognitive assessments, baseline [11C]PiB
PET, and longitudinal [18F]MK-6240 PET up to three years (Table.1). Global Ab and tau burden were estimated in
neocortical aggregate and early-tau regions (rhinal, entorhinal, amygdala, inferior temporal cortex), respectively.
Kernel-based within-reconstruction partial-volume-correction was applied to tau PET data. Linear mixed-effect
models examined the impact of baseline Ab and DCTclock performance on subsequent tau accumulation,
corrected for age, sex and education, with and without controlling for baseline tau burden.
Results: Higher baseline entorhinal and rhinal tau was significantly associated with higher Ab burden (ยด: 0.900.94, p
