We recently identified a subgroup of patients with a frontal variant of AD who had early and disproportionate impairments on tests of frontal lobe functioning and also a greater than expected degree of neurofibrillary tangle, but not neuritic senile plaque, pathology in the frontal cortex.1 Dr Caselli raises the point that the cognitive profile of cortical dementias is dictated more by the location of the pathological lesions than by the histological features. Dr Caselli also highlights, however, that genetic and neuropathological heterogeneity may also have an increasingly important role in explaining phenotypic differences.
Johnson JK, Head E, Kim R, Starr A, Cotman CW. Topography, Histology, and Seminology in Dementia—Reply. Arch Neurol. 2000;57(6):899-900. doi: