On the basis of a theory about the role of semantic knowledge in the recognition and production of familiar words and objects, we predicted that patients with semantic dementia would reveal a specific pattern of impairment on six different tasks typically considered “pre-” or “non-” semantic: reading aloud, writing to dictation, inflecting verbs, lexical decision, object decision, and delayed copy drawing. The prediction was that all tasks would reveal a frequency-by-typicality interaction, with patients performing especially poorly on lower-frequency items with atypical structure (e.g., words with an atypical spelling-to-sound relationship; objects with an atypical feature for their class, such as the hump on a camel, etc). Of 84 critical observations (14 patients performing 6 tasks), this prediction was correct in 84/84 cases; and a single component in a factor analysis accounted for 87% of the variance across seven measures: each patient's degree of impairment on atypical items in the six experimental tasks and a separate composite score reflecting his or her degree of semantic impairment. Errors also consistently conformed to the predicted pattern for both expressive and receptive tasks, with responses reflecting residual knowledge about the typical surface structure of each domain. We argue that these results cannot be explained as associated but unrelated deficits but instead are a principled consequence of a primary semantic impairment.

Two types of theoretical account have been proposed to explain the phenomenon of category-specific impairment in tests of semantic memory: One stresses the importance of different cortical regions to the representation of living and nonliving categories, while the other emphasize the importance of statistical relationships among features of concepts belonging to these two broad semantic domains. Theories of the latter kind predict that the direction of a domain advantage will be determined in large part by the overall damage to the semantic system, and that the profiles of patients with progressive impairments of semantic memory are likely to include a point at which an advantage for one domain changes to an advantage for the other. The present series of three studies employed semantic test data from two separate cohorts of patients with probable dementia of Alzheimer's type (DAT) to look for evidence of such a crossover. In the first study, longitudinal test scores from a cohort of 58 patients were examined to confirm the presence of progressive semantic deterioration in this group. In the second study, Kaplan-Meier survival curves based on serial naming responses and plotted separately for items belonging to living and nonliving domains indicated that the representations of living concepts (as measured by naming) deteriorated at a consistently and significantly faster rate than those of nonliving concepts. A third study, carried out to look in detail at the performance of mildly affected patients, employed an additional cross-sectional cohort of 20 patients with mild DAT and utilized a graded naming assessment. This study also revealed no evidence for a crossover in the advantage of one domain over the other as a function of disease severity. Taken together with the model of anatomical progression in DAT based on the work of Braak and Braak (1991), these findings are interpreted as evidence for the importance of regional cerebral anatomy to the genesis of semantic domain effects in DAT.

Previous studies have suggested differences in the neural substrates of recognition memory when the contributions of perceptual and semantic information are manipulated. In a within-subjects design PET study, we investigated the neural correlates of the following factors: material type (objects or faces), semantic knowledge (familiar or unfamiliar items), and perceptual similarity at study and test (identical or different pictures). There was consistent material-specific lateralization in frontal and temporal lobe regions when the retrieval of different types of nonverbal stimuli was compared, with objects activating bilateral areas and faces preferentially activating the right hemisphere. Retrieval of memories for nameable, familiar items was associated with increased activation in the left ventrolateral prefrontal cortex, while memory for unfamiliar items involved occipital regions. Recognition memory for different pictures of the same item at study and test produced blood flow increase in left inferior temporal cortex. These results have implications for our understanding of the neural correlates of perceptual and semantic contributions to recognition memory.

Three patients with semantic dementia, involving progressive deterioration of semantic memory, performed immediate serial recall of short sequences of familiar words. On the basis of their performance in other tasks of word comprehension and production, the stimuli were selected individually for each patient as either known or unknown words. All patients showed a marked advantage in recall of known as compared to familiar but now unknown words. Errors consisted primarily of incorrect combinations of correct phoneme sequences in the stimulus string, with a large number of errors preserving onsethime syllable structure (e.g., mint, rug reproduced as “rint, mug”). Discussion focuses on the implication of these errors for the structure of phonological representations, and in particular on a hypothesis that meaning plays a crucial role in binding the elements of phonological word forms.