Factors associated with age at tau pathology onset and time from tau onset to dementia in Alzheimer's disease

Abstract INTRODUCTION Elevated tau (T+) is temporally proximal to dementia onset but less is known about factors influencing T+ onset age and time to dementia after T+ in Alzheimer's disease (AD). We used sampled iterative local approximation (SILA) estimated T+ onset age (ETOA) to investigate factors associated with T+ age and time from T+ to dementia onset in the Alzheimer's Disease Neuroimaging Initiative. METHODS Using SILA‐estimated amyloid positivity and T+ onset ages derived from 18 F‐Flortaucipir, 18 F‐Florbetapir, and 18 F‐Florbetaben positron emission tomography and Cox proportional hazards and accelerated failure time models, we analyzed apolipoprotein E ( APOE ), sex, amyloid burden, age, educational attainment, and literacy associations with ETOA and time from T+ to dementia. RESULTS 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. DISCUSSION This work highlights the prognostic value of ETOA and the need to better characterize factors contributing to ETOA and dementia onset in AD. Highlights We applied sampled iterative local approximation (SILA) to Alzheimer's Disease Neuroimaging Initiative 18 F‐Flortaucipir data, to estimate individuals’ age of tau pathology onset (T+) and time from T+ onset to dementia. Higher amyloid, apolipoprotein E ε4, lower education, and lower literacy associated with younger estimated T+ onset age. Older T+ onset age and higher amyloid associated with shorter time from T+ to dementia. Only one individual was observed to remain dementia free 14 years after T+ onset. This work highlights the prognostic value of T+ onset age and the need to better characterize factors contributing to T+ onset age and dementia onset in Alzheimer's disease.