Tau‐PET correlates of mild behavioral impairment in preclinical and prodromal Alzheimer's disease: A head‐to‐head comparison of Flortaucipir and MK6240

Abstract INTRODUCTION We compared the association between mild behavioral impairment (MBI) and first‐ versus second‐generation tau‐positron emission tomography (PET) tracers in preclinical and prodromal Alzheimer's disease (AD). METHODS We assessed 110 individuals with head‐to‐head [ 18 F]MK6240 and [ 18 F]Flortaucipir tau‐PET. Voxel‐wise and region‐of‐interest analyses investigated relationships between tau‐PET and MBI Checklist (MBI‐C) scores, which were also compared across tau‐PET positivity and PET‐Braak stages. RESULTS For both tracers, MBI severity was associated with tau‐PET signal in all Braak regions and increased across PET‐Braak stages. [ 18 F]MK6240 showed more extensive voxel‐wise associations with MBI‐C scores and additional correlations with affective symptoms in stratified analyses by diagnostic groups. Tau positivity was associated with a higher frequency of MBI. Individuals positive for [ 18 F]MK6240 but negative for [ 18 F]Flortaucipir exhibited greater MBI burden than individuals negative for both tracers. DISCUSSION MBI in early AD is associated with tau‐PET, with [ 18 F]MK6240 providing greater sensitivity to detect MBI‐related symptoms.