Frontal tau pathology underlies behavioural/dysexecutive presentations of Alzheimer's disease

<p><b>Objective: </b>To determine the associations between amyloid-PET, tau-PET and atrophy with the behavioural/dysexecutive presentation of Alzheimer's disease (AD) and how these differ from amnestic AD.</p> <p><b>Background:</b> The behavioural/dysexecutive variant of AD is a rare clinical syndrome presenting with behavioural changes, apathy and/or executive dysfunction, similar to frontotemporal dementia. Small autopsy studies provide conflicting reports of frontal pathology and recent studies challenge the notion of frontal involvement in this condition. We tested the hypothesis that patterns of cortical tau pathology differentiate behavioural/dysexecutive AD from amnestic AD and correlate to clinical symptoms.</p> <p><b>Methods:</b> 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, tau-PET, MRI and neuropsychological testing.</p> <p><b>Results:</b> Voxelwise contrasts identified patterns of frontal cortical tau aggregation in behavioural/dysexecutive AD, with peaks in medial prefrontal, anterior cingulate and frontal insular cortices. No differences were observed in the distribution of amyloid-PET. 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.</p> <p><b>Conclusions:</b> 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.</p>