Assess neuropathological correlates of amnestic dysfunction in Fronto-Temporal Lobar Degeneration (FTLD).

A critical review of literature has found amnesia to be more common than generally thought in FTLD but very few studies have systematically studied amnestic dysfunction in FTLD. In this study we have reviewed clinical, neuropsychological, and neuropathological correlates of amnestic dysfunction in a cohort of autopsy confirmed FTLD cases to expand on our knowledge on amnestic dysfunction in FTLD.

The charts of 60 autopsy-confirmed FTLD cases were retrospectively reviewed for data including initial presentation, initial neuropsychological assessment, consensus diagnosis at an interdisciplinary adjudication meeting, and autopsy reports.  These were participants in the Alzheimer’s Disease Research Center (ADRC) at the University of Pittsburgh.

Of the total 60 autopsy-confirmed FTLD cases, 13 had predominantly memory complaints, thus presenting with amnestic clinical syndrome, 8 of which were given diagnosis of probable Alzheimer’s dementia, and the rest diagnosed with frontotemporal dementia or unspecified dementia, based on consensus criteria.  Among the remaining 47 cases who had no or minimal memory complaints but with predominant behavioral or language complaints, only 9 had non-impaired memory scores on neuropsychological evaluation. The neuropathological subtypes did not differ between two groups and were distributed similarly for Pick’s disease, progressive supranuclear palsy, cortico-basal degeneration, argyrophilic grain disease, atypical tauopathy including primary age related tauopathy, and hippocampal sclerosis. Almost half of 13 amnestic cases did not have significant hippocampal neuronal loss.

FTLD can present as amnestic predominant dementia (21.6% in this series) and may be misdiagnosed by presentation alone as Alzheimer’s dementia. The amnestic dysfunction could not be accounted by any distinct FTLD pathological subtype, significant hippocampal pathology (TDP-43 or tau), or hippocampal neuronal loss. Involvement of other elements of Papez circuit beyond hippocampus may explain the amnestic dysfunction and could be further explored in future studies.