Temporally graded semantic memory loss in Alzheimer's disease: cross-sectional and longitudinal studies.

Semantic knowledge of famous names and words that entered popular North American culture at different times in the 20th century was examined in 16 patients with mild-to-moderate Alzheimer's disease (AD), 12 of whom were re-tested 1 year later. All patients showed evidence of temporally graded memory loss, with names and words from the remote past being relatively better preserved than recent names and words. There was considerable between-patient variability with respect to severity of semantic impairment. Most patients exhibited losses extending back 30-40 years; however, two mildly impaired (MMSE >28) patients showed deficits restricted to the last 10-15 years. At the 1-year follow-up, patients not only exhibited more severe deficits overall, but the temporally graded period of loss extended further back in time, suggesting that this deficit reflects a loss of previously intact knowledge and not merely faulty encoding or lack of exposure to the material. The extensive period of graded semantic loss exhibited by most patients contrasts with the temporally limited retrograde semantic loss typical of medial temporal lobe amnesia. We propose that short periods of temporally graded semantic memory loss can be explained by damage to medial temporal structures, but that extensive periods of graded loss occur only with additional damage to neocortical tissue. This pattern contrasts with that of autobiographical memory loss, which is often ungraded and extends for the person's entire lifetime, even when damage is restricted to the medial temporal lobes.