Profiling and predicting distinct tau progression patterns: An unsupervised data-driven approach to flortaucipir positron emission tomography

Introduction: How to detect patterns of greater tau burden and accumulation is still an open question.

Methods: An unsupervised data-driven whole-brain pattern analysis of longitudinal tau positron emission tomography (PET) was used first to identify distinct tau accumulation profiles and then to build baseline models predictive of tau-accumulation type.

Results: The data-driven analysis of longitudinal flortaucipir PET from studies done by the Alzheimer's Disease Neuroimaging Initiative, Avid Pharmaceuticals, and Harvard Aging Brain Study (N = 348 cognitively unimpaired, N = 188 mild cognitive impairment, N = 77 dementia), yielded three distinct flortaucipir-progression profiles: stable, moderate accumulator, and fast accumulator. Baseline flortaucipir levels, amyloid beta (Aβ) positivity, and clinical variables, identified moderate and fast accumulators with 81% and 95% positive predictive values, respectively. Screening for fast tau accumulation and Aβ positivity in early Alzheimer's disease, compared to Aβ positivity with variable tau progression profiles, required 46% to 77% lower sample size to achieve 80% power for 30% slowing of clinical decline.

Discussion: Predicting tau progression with baseline imaging and clinical markers could allow screening of high-risk individuals most likely to benefit from a specific treatment regimen.