Abbreviations FTD: frontotemporal dementia GRN: progranulin MAPT: microtubule-associated protein tau C9orf72 : chromosome 9 open reading frame 72 bvFTD: behavioural variant of frontotemporal dementia MRI: magnetic resonance imaging CNCs: cognitively normal controls DBM: deformation-based morphometry FTLDNI: frontotemporal lobar degeneration neuroimaging initiative T1-w: T1 weighted GENFI: Genetic frontotemporal dementia initiative MMSE: Mini mental state examination MOCA: Montreal cognitive assessment FTLD-CDR: Frontotemporal lobar degeneration Clinical Dementia Rating score CGI: Clinical global impression FRS: Frontotemporal dementia rating scale FDR: False Discovery Rate PCA: Principal component analysis PCs: Principal components SF: Semantic fluency ROC: Receiver operating characteristic curves AUC: Area under the curve LR+: positive likelihood ratio LR-: negative likelihood ratio Abstract INTRODUCTION: Brain structural imaging is paramount for the diagnosis of behavioral variant of frontotemporal dementia (bvFTD), but it has low sensitivity leading to erroneous or late diagnosis.
METHODS:A total of 515 subjects from two different bvFTD databases (training and validation cohorts) were included to perform voxel-wise deformation-based morphometry analysis to identify regions with significant differences between bvFTD and controls. A random forest classifier was used to individually predict bvFTD from morphometric differences in isolation and together with bedside cognitive scores.
RESULTS:Average ten-fold cross-validation accuracy was 89% (82% sensitivity, 93% specificity) using only MRI and 94% (89% sensitivity, 98% specificity) with the addition of semantic fluency. In a separate validation cohort of genetically confirmed bvFTD, accuracy was 88% (81% sensitivity, 92% specificity) with MRI and 91% (79% sensitivity, 96% specificity) with added cognitive scores.
DISCUSSION:The random forest classifier developed can accurately predict bvFTD at the individual subject level.