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 18F-Flortaucipir, 18F-Florbetapir, and 18F-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 18F-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.