Visually Identified Tau F-18-MK6240 PET Patterns in Symptomatic Alzheimer's Disease

Background: In Alzheimer's disease, heterogeneity has been observed in the postmortem distribution of tau neurofibrillary tangles. Visualizing the topography of tau in vivo may facilitate clinical trials and clinical practice. Objective: This study aimed to investigate whether tau distribution patterns that are limited to mesial temporal lobe (MTL)/limbic regions, and those that spare MTL regions, can be visually identified using F-18-MK6240, and whether these patterns are associated with different demographic and cognitive profiles. Methods: Tau F-18-MK6240 PET images of 151 amyloid-beta positive participants with mild cognitive impairment (MCI) and dementia were visually rated as: tau negative, limbic predominant (LP), MTL-sparing, and Typical by two readers. Groups were evaluated for differences in age, APOE epsilon 4 carriage, hippocampal volumes, and cognition (MMSE, composite memory and non-memory scores). Voxel-wise contrasts were also performed. Results: Visual rating resulted in 59.6% classified as Typical, 17.9% as MTL-sparing, 9.9% LP, and 12.6% as tau negative. Intra-rater and inter-rater reliability was strong (Cohen's kappa values of 0.89 and 0.86 respectively). Tracer retention in a "hook"-like distribution on sagittal sequences was observed in the LP and Typical groups. The visually classified MTL-sparing group had lower APOE epsilon 4 carriage and relatively preserved hippocampal volumes. Higher MTL tau was associated with greater amnestic cognitive impairment. High cortical tau was associated with greater impairments on non-memory domains of cognition, and individuals with high cortical tau were more likely to have dementia than MCI. Conclusion: Tau distribution patterns can be visually identified using F-18-MK6240 PET and are associated with differences in APOE epsilon 4 carriage, hippocampal volumes, and cognition.