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

Elevated tau is temporally proximal to dementia onset but less is known about factors influencing T+ onset age and time to dementia following T+ in Alzheimer's 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.

Using 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.

Higher amyloid, APOE-ε4, lower education, and lower literacy associated with younger ETOA. Older ETOA and higher amyloid associated with shorter time from T+ to dementia.

This work highlights the prognostic value of ETOA and the need to better characterize factors contributing to ETOA and dementia onset in AD.