Is semantic memory consistently impaired early in the course of Alzheimer's disease? Neuroanatomical and diagnostic implications.

To establish whether semantic memory is consistently impaired in patients with very mild dementia of Alzheimer's type (DAT), we assessed episodic and semantic memory in 52 patients with DAT who were divided into three sub-groups according to dementia severity on the Mini-Mental State Examination (minimal > 23, mild 17-23 and moderate < 17) and 24 matched controls. The minimal group showed impairment on the following semantic memory measures: category fluency, naming of line drawings, naming to verbal description, answering semantic feature questions and a non-verbal picture-picture matching task (the Pyramids and Palm Trees Test). The mild and moderate groups showed additional deficits on picture sorting and word-picture matching tests. Within the minimal and mild groups there was, however, considerable heterogeneity. While some patients showed a consistent impairment across all of the semantic memory tests, others were impaired on only on a subset of these tests and a few even performed flawlessly. In contrast, all patients showed a profound deficit in episodic memory: delayed recall of new verbal and non-verbal material appears to be a particularly sensitive marker of early DAT. These data are in keeping with recent neuropathological studies demonstrating that the transentorhinal region is consistently involved at a very early stage. Lesions in this site cause a functional disconnection of the hippocampus, and hence a profound episodic memory disorder. The fact that many, but not all, patients with early disease also show impairment of semantic memory suggests that damage to the transentorhinal region is not sufficient to produce significant disruption of semantic memory. Such disruption reliably occurs, we hypothesize, only when the pathology extends to the temporal neocortex proper.