Topographical distribution of amyloid-β, tau and atrophy in behavioral / dysexecutive AD patients.

Objective To determine the associations between amyloid-PET, tau-PET and atrophy with the behavioural/dysexecutive presentation of Alzheimer9s disease (AD), how these differ from amnestic AD, and how they correlate to clinical symptoms. Methods We assessed 15 cases of behavioural/dysexecutive AD recruited from a tertiary care memory clinic, all of whom had biologically defined AD. They were compared with 25 disease severity- and age-matched amnestic AD patients and a group of 131 cognitively unimpaired (CU) elderly individuals. All subjects were evaluated with amyloid-PET with [18F]AZD4694, tau-PET with [18F]MK6240, MRI and neuropsychological testing. Results Voxelwise contrasts identified patterns of frontal cortical tau aggregation in behavioural/dysexecutive AD, with peaks in medial prefrontal, anterior cingulate and frontal insular cortices in contrast to amnestic AD. No differences were observed in the distribution of amyloid-PET or atrophy as determined by voxel-based morphometry. Voxelwise area under the ROC curve analyses revealed that tau-PET uptake in the medial prefrontal, anterior cingulate and frontal insular cortices were best able to differentiate between behavioural/dysexecutive and amnestic AD (AUC = 0.87). Voxelwise regressions demonstrated relationships between frontal cortical tau load and degree of executive dysfunction. Conclusions Our results provide evidence of frontal cortical involvement of tau pathology in behavioural/dysexecutive AD and highlight the need for consensus clinical criteria in this syndrome.