Von Economo Neuron Loss in Frontotemporal Dementia: A Meta‐Analysis of Neuropathological Studies

ABSTRACT Von Economo neurons (VENs) have been reported to be vulnerable to neurodegeneration in frontotemporal dementia (FTD), particularly the behavioral variant (bvFTD), but these findings have not been systematically assessed across independent brain banks. We conducted a meta‐analysis of neuropathological studies measuring VEN density in the anterior cingulate cortex or frontoinsular cortex in FTD using random‐effects models with cluster‐robust variance estimation. Seven studies (135 FTD, 68 controls) from four international brain banks showed significantly reduced VEN density in FTD with a large effect size (g = −1.45, 95% CI [−1.69, −1.21], p < 0.001) and remarkable consistency (I 2 = 0%). VEN loss was greater in FTD than Alzheimer's disease and occurred across TDP‐43 and tau pathological subtypes.