Clinicopathological features of sporadic frontotemporal lobar degeneration with TDP-43-positive inclusions

Abstract

Frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP) and Pick's disease are common pathological substrates in FTLD patients. Because most Japanese FTLD-TDP patients lack a family history, characterizing clinical features in sporadic FTLD-TDP is important to infer the underlying pathologies in FTLD patients. Our recent study suggested that these two diseases tended to show different clinical pictures. Early impairment of semantic memory was frequent in sporadic FTLD-TDP, but very rare in Pick's disease. In contrast, early impairment of speech output, including non-fluent aphasia and speech apraxia, was more frequent in Pick's disease. Asymmetric motor disturbances (e.g., pyramidal signs, parkinsonism, and contracture) were frequent in sporadic FTLD-TDP, but rare in Pick's disease. The most common first syndrome in FTLD-TDP was semantic dementia (39%), but that in Pick's disease was frontotemporal dementia (64%). Pathologically, consistent with clinical features, the temporal cortex, striatum, globus pallidus, substantia nigra, and pyramidal tract were more severely degenerated in sporadic FTLD-TDP. These findings suggest that the early impairment of semantic memory and asymmetric motor disturbances in sporadic FTLD patients predict FTLD-TDP rather than Pick's disease, while initial behavioral symptoms or non-fluent aphasia without subsequent asymmetric motor disturbances predict Pick's disease rather than FTLD-TDP.