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

Objective: 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. Background: 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. 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,
tau-PET, 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. 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. 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.