Tau PET visual reads find sources of tau not explained by typical Alzheimer disease pathophysiology

18 F-flortaucipir-PET received FDA approval to visualize tauopathy in the brains of adult patients with cognitive impairment being evaluated for Alzheimer disease (AD). However, manufacturer’s guidelines for the visual interpretation of 18 F-flortaucipir-PET differs greatly from how 18 F-flortaucipir-PET has been measured in research settings using standardized uptake value ratios (SUVRs). How visual interpretation relates to 18 F-flortaucipir-PET SUVR, CSF biomarkers, or longitudinal clinical assessment is not well understood. Here we compare these various diagnostic methods in participants enrolled in studies of aging and memory (n=189, of whom 23 were cognitively impaired). Visual interpretation had high agreement with SUVR (98.4%); discordant participants had hemorrhagic infarcts or atypical AD tauopathies. Visual interpretation had moderate agreement with CSF p-tau181 (86.1%). Two participants demonstrated 18 F-flortaucipir uptake from meningiomas. Visual interpretation could not predict follow-up clinical assessment in 9.52% of cases. We conclude that close association between AD tauopathy and clinical onset in group-level studies does not always hold at the individual level, with discrepancies arising from atypical AD, vascular dementia, or frontotemporal dementia. A better understanding of relationships across imaging, CSF biomarkers, and clinical assessment is needed to provide appropriate diagnoses for these individuals.