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Factors associated with age at tau pathology onset and time from tau onset to dementia

Heston, M. B.; Teague, J. P.; Cody, K. A.; Deming, Y.; Ruiz de Chavez, E.; Morse, J.; Chin, N. A.; Engelman, C. D.; Chappell, R. J.; Langhough, R. E.; Gleason, C. E.; Clark, L. R.; Zuelsdorff, M. L.; Betthauser, T. J.; Alzheimer's Disease Neuroimaging Initiative,

2025-03-13 neurology
10.1101/2025.03.11.25323773 medRxiv
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INTRODUCTIONElevated tau is temporally proximal to dementia onset but less is known about factors influencing T+ onset age and time to dementia following T+ in Alzheimers disease. We used sampled iterative localized approximation (SILA) estimated T+ onset age (ETOA) to investigate factors associated with T+ age and time from T+ to dementia onset in ADNI. METHODSUsing SILA-estimated A+ and T+ onset ages derived from 18F-Flortaucipir, 18F-Florbetapir, and 18F-Florbetaben PET and Cox proportional hazards and accelerated failure time models, we analyzed APOE, sex, amyloid burden, age, educational attainment, and literacy associations with ETOA and time from T+ to dementia. RESULTSHigher amyloid, APOE-{varepsilon}4, lower education, and lower literacy associated with younger ETOA. Older ETOA and higher amyloid associated with shorter time from T+ to dementia. DISCUSSIONThis work highlights the prognostic value of ETOA and the need to better characterize factors contributing to ETOA and dementia onset in AD.

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