The deterioration of semantic memory in Alzheimer's disease.

Semantic memory impairment is a common feature of dementia of the Alzheimer type (DAT). Recent research has shown that patients with DAT are more impaired (relative to non-demented controls) in generating exemplars from a particular semantic category (e.g., animals) than words beginning with a particular letter, exhibit an altered temporal dynamic during the production of category exemplars, are impaired on confrontation naming tasks and make predominantly superordinate or semantically related errors, consistently misidentify the same objects across a variety of semantic tasks, and have alterations in multi-dimensional scaling models of their semantic network that are indicative of a loss of concepts and associations. These results are consistent with the view that Alzheimer's disease results in a breakdown in the organization and structure of semantic knowledge as neurodegeneration spreads to the association cortices that presumably store semantic representations.     

Automatic semantic priming with various category relations in Alzheimer's disease and normal aging.

The 6 experiments reported here tested the effects of various category relations on automatic semantic priming in 20 Alzheimer's disease (AD), 20 older control, and 22 younger control subjects. The tasks were either word pronunciation or lexical decision; the prime-target stimulus-onset asynchrony (SOA) was always 250 ms. A variety of category relationships between prime and target were examined: highly associated category comembers, subordinate-superordinate or superordinate-subordinate pairs, and pairs selected on the basis of category typically to form typical-typical, atypical-typical, typical-atypical, and atypical-atypical pairings. Both for AD versus older control subjects and for older versus younger control subjects, no significant group differences were found in the magnitude of overall semantic priming or in the effects on priming of factors pertaining to the prime-target relationship.     

The attribute priming effect in patients with Alzheimer's disease

Experiments with semantic priming (SP) paradigms have documented early hypopriming in patients with AD when concepts are used as primes and attribute concept features as targets, suggesting that concept attributes are vulnerable to damage very early in the disease course. The aims of this study were to confirm early priming reduction in the attribute condition in patients with AD and to determine which of several semantic indexes (such as the level of distinctiveness, correlation or feature dominance of concept features) best predicts the priming effect size in AD. We administered an SP attribute condition paradigm to 20 mildly demented patients with AD and to 10 NCs. We used concept–attribute pairs for which normative data of semantic indexes relative to both concept primes (i.e., number, type, mean level of dominance, distinctiveness and correlation of features constituting the concepts) and target features (i.e., level of feature dominance, correlation and distinctiveness) were available. Results showed that compared to NCs, the AD group obtained very reduced priming facilitation. Furthermore, the item regression analyses showed that the priming decrement in the AD group was predicted by the feature dominance of the target in the related pairs; that is, the lower the target feature dominance, the lower the priming effect elicited. These results confirmed hypopriming in the attribute condition from the very early phase of AD and support the view that attributes which are more salient for the identification of a given concept are also those most resistant to semantic memory degradation in AD pathology.     

Use of semantic context by patients with Alzheimer's disease

In this study we used semantic-priming procedures to examine limitations in the use of semantic context by patients with Alzheimer's disease. We also tried to determine whether any such contextual effects were mediated solely through automatic processes or whether attentional processes were also involved. Three tasks were applied to examine the effect of semantic context on the performance of 18 normal elderly and 18 normal young subjects, and on 18 patients with Alzheimer's disease. When normal and demented subjects were asked to decide whether a given item was a member of a certain category, results showed that their response times were equally affected by the item's dominance in the category. The time that demented patients took to recognize a word was actually affected more by the semantic context provided by a priming sentence than was that of normal subjects. When asked to generate the final word of an incomplete sentence, demented subjects performed very poorly unless potential responses were highly constrained by sentence context.     

Hemispheric differences in strong versus weak semantic priming: evidence from event-related brain potentials

GOALS: Research with lateralized word presentation has suggested that strong ("close") and weak ("remote") semantic associates are processed differently in the left and right cerebral hemispheres [e.g., Beeman, M. j., & Chiarello, C. (1998). Complementary right- and left-hemisphere language comprehension. Current Directions in Psychological Science, 7(1), 2-8]. Recently, this hypothesis has been challenged [Coney, J. (2002). The effect of associative strength on priming in the cerebral hemispheres. Brain and Cognition, 50(2), 234-241]. We predicted that foveal presentation of strong and weak associates would elicit different patterns of hemispheric activity, as indexed by high-density event-related brain potentials (ERPs), and that source localization of the scalp potentials would help clarify the nature of hemispheric contributions to semantic organization. METHODS: 128-channel ERPs were recorded in two experiments as subjects performed a lexical decision task. Word trials were equally divided into strongly related, weakly related, and unrelated word pairs. All words were foveally presented. SOA was 800 ms in Experiment 1, and 200 ms in Experiment 2. RESULTS: Topographic analyses revealed medial frontal (MFN) and parietal (N400/LPC) effects for both strong and weak associates. Between approximately 450 and 550 ms, the magnitude of the N400/LPC effect indicated priming for both strong and weak associates over left parietal sites, while priming over right parietal sites was restricted to strongly related word pairs. During this interval, spatiotemporal source modeling showed that these scalp effects were best accounted for by ipsilateral sources in the medial temporal lobe. The observed pattern of asymmetries for strong versus weak associates is not consistent with certain proposals regarding the complementarity of right- and left-hemisphere contributions to semantics. It is, however, consistent with findings from visual half-field studies (Hasbrooke and Chiarello, 1998). We discuss the relevance of these results for theories of hemispheric asymmetry and meta-control in lexical semantic access.     

Physiological evidence that a masked unrelated intervening item disrupts semantic priming: implications for theories of semantic representation and retrieval models of semantic priming

Event-related potentials were recorded in a paradigm where an unrelated word was interposed between two related words. In one condition, the intervening item was masked and in another condition it was not. The N400 component indicated that priming of the related word was disrupted by the intervening item whether it was masked or not. The data are interpreted to be inconsistent with retrieval models of priming.     

Episodic and semantic memory in early versus late onset Alzheimer's disease.

The aim of this study was to replicate and extend previous work demonstrating selective impairment of semantic, but not episodic, memory in late versus early onset Alzheimer's disease (AD). Measures of episodic and semantic memory were administered to 12 pairs of patients; early (less than or equal to 62) and late (greater than or equal to 68) onset pairs were matched on dementia severity and education. As hypothesized, the groups did not differ on the three episodic memory measures but did on two of three semantic memory measures. In conjunction with prior research, these findings indicate that late onset AD is characterized by more profound impairment on measures of semantic processing.     

Pictorial and lexical priming: Patterns of implicit memory in Alzheimer's and Parkinson's disease patients

Lexical and pictorial priming were examined in patients with Alzheimer's disease and in demented and nondemented patients with Parkinson's disease. Control subjects were divided into young and elderly. Lexical priming used a word‐stem completion task. Pictorial priming task was based on Rey's superimposed pictures test. Elderly normal subjects demonstrated lower lexical priming scores than those of young subjects. Analysis of covariance with age and educational level as covariates showed that normal controls, demented and nondemented Parkinsonian patients, and Alzheimer patients did not differ significantly on the lexical priming task. Pictorial priming scores did not differ significantly between elderly and younger controls. In contrast there was a striking impairment of pictorial priming in Parkinsonian patients, both demented and nondemented. Performance of subjects with mild Alzheimer's disease was superior to that of nondemented Parkinsonian patients. Our results suggest that performance in lexical priming task diminishes with physiological ageing but is unaffected by mild or moderate Alzheimer's disease. Our study also observes the existence of a selective pictorial priming deficit in Parkinson's disease; however, this deficit is not specific, as it is also observed to a lesser degree in Alzheimer's disease. It may therefore be concluded that the systems serving pictorial priming are both cortical and subcortical.     

Unpicking the semantic impairment in Alzheimer's disease: qualitative changes with disease severity

Despite a vast literature examining semantic impairment in Alzheimer's disease (AD), consensus regarding the nature of the deficit remains elusive. We re-considered this issue in the context of a framework that assumes semantic cognition can break down in two ways: (1) core semantic representations can degrade or (2) cognitive control mechanisms can become impaired. We hypothesised and confirmed that the nature of semantic impairment in AD changes with disease severity. Patients at mild or severe stages of the disorder exhibited impairment across various semantic tasks but the nature of those deficits differed qualitatively for the two groups. Commensurate with early dysfunction of the cognitive control, temporoparietal-frontal-cingulate network, characteristics of deregulated semantic cognition were exhibited by the mild AD cases. In contrast, the severe AD group reproduced features of additional degradation of core semantic representations. These results suggest that spread of pathology into lateral anterior temporal lobes in later stage AD produces degradation of semantic representations, exacerbating the already deregulated system. Moreover, the dual nature of severe patients' impairment was highlighted by disproportionately poor performance on tasks placing high demand on both conceptual knowledge and control processes--e.g., category fluency.     

Repetition, semantic priming, and stimulus quality: implications for the interactive-compensatory reading model

Recognition latencies of single words were manipulated by repetition, degradation, or both, and the effects of context were observed. In both lexical decision and pronunciation tasks, repeated words were recognized faster than nonrepeated words yet were not any less affected by semantic context. Both inserting asterisks between a word's letters and masking slowed word recognition in comparison with a clear presentation, but only the masking manipulation showed contextual inhibition. In short, the magnitude of context effects did not always vary monotonically with the word recognition latencies in the neutral condition. Also, presentation of a word in an unrelated rather than related context did not produce larger repetition effects. The implications of these findings for Stanovich and West's (1983) and Jacoby's (1983) models are discussed.     

Word recognition in Alzheimer's disease: Effects of semantic degeneration

Impairments of word recognition in Alzheimer's disease (AD) have been less widely investigated than impairments affecting word retrieval and production. In particular, we know little about what makes individual words easier or harder for patients with AD to recognize. We used a lexical selection task in which participants were shown sets of four items, each set consisting of one word and three non‐words. The task was simply to point to the word on each trial. Forty patients with mild‐to‐moderate AD were significantly impaired on this task relative to matched controls who made very few errors. The number of patients with AD able to recognize each word correctly was predicted by the frequency, age of acquisition, and imageability of the words, but not by their length or number of orthographic neighbours. Patient Mini‐Mental State Examination and phonological fluency scores also predicted the number of words recognized. We propose that progressive degradation of central semantic representations in AD differentially affects the ability to recognize low‐imageability, low‐frequency, late‐acquired words, with the same factors affecting word recognition as affecting word retrieval.     

Naming and categorical knowledge in Alzheimer''s disease: The process of semantic memory deterioration

Semantic memory deterioration in Alzheimer's disease (AD) has been theorized to proceed from a loss of object attribute knowledge to a loss of category knowledge. The theory is based on the belief that naming is a computational process requiring object attribute knowledge. It is strengthened by reports that AD patients misname by giving category information and perform poorer on tests of attribute than category knowledge. The purpose of this study was to test the theory's validity by administering naming and category knowledge tasks to AD and normal elderly control subjects. Results revealed a theoretically unexpected outcome, that is, naming became easier relative to the recall and recognition of category information.     

Implications of measures of reliability for theories of priming: Activity in semantic memory is inherently noisy and uncoordinated

In experiments on semantic priming, participants vary substantially in the absolute magnitude of priming they produce. Are these individual differences systematic or do they arise from random processes, and does the answer carry theoretical implications? To find out, we examined split‐half and test–retest reliability of semantic priming in a series of two‐session experiments that crossed relatedness proportion (RP, at .25, .50, and .75) with stimulus–onset asynchrony (SOA, at 200, 350, and 800 ms). Low reliability would indicate little coherence of activity within semantic memory, so that the degree to which any given association influences performance is uncorrelated from one association and time of testing to the next. High reliability would indicate that each person tends to harness his or her semantic knowledge consistently, applying semantic relations among words in much the same way from one word to the next and one time of testing to the next to help task performance, resulting in systematic individual differences. What we observed was low reliability—often zero. When conditions highlighted “automatic activation” (low RP, short SOA), priming was completely uncorrelated from item to item and session to session. Both split‐half and test–retest reliability increased to significant levels under conditions that raised the probability that an activated or retrieved episode of prime experience would help with target recognition, and the probability of intentionally generating the target from the prime. Thus, task‐relevant" utility imposes a modicum of order on semantic associations that are otherwise noisy and uncoordinated. Harnessing semantic memory is like herding cats—without considerable constraint, associations tend to come and go their own ways in independent fashion.     

Deregulated semantic cognition contributes to object‐use deficits in Alzheimer's disease: A comparison with semantic aphasia and semantic dementia

Executive control is impaired from the early stages of Alzheimer's Disease (AD) and this produces deregulated semantic cognition (Corbett, Jefferies, Burns, & Lambon Ralph, 2012 ; Perry, Watson, & Hodges, 2000 ). While control deficits should affect semantic retrieval across all modalities, previous studies have typically focused on verbal semantic tasks. Even when non‐verbal semantic tasks have been used, these have typically employed simple picture‐matching tasks, which may be influenced by abnormalities in covert naming. Therefore, in the present study, we examined 10 patients with AD on a battery of object‐use tasks, in order to advance our understanding of the origins of non‐verbal semantic deficits in this population. The AD patients’ deficits were contrasted with previously published performance on the same tasks within two additional groups of patients, displaying either semantic degradation (semantic dementia) or deregulation of semantic retrieval (semantic aphasia; Corbett, Jefferies, Ehsan, & Lambon Ralph, 2009 ). While overall accuracy was comparable to the scores in both other groups, the AD patients’ object‐use impairment most closely resembled that observed in SA; they exhibited poorer performance on comprehension tasks that placed strong demands on executive control. A similar pattern was observed in the expressive domain: the AD and SA groups were relatively good at straightforward object use compared to executively demanding, mechanical puzzles. Error types also differed: while all patients omitted essential actions, the SA and AD groups’ demonstrations also featured unrelated intrusions. An association between AD patients’ object use and their scores on standard executive measures suggested that control deficits contributed to their non‐verbal semantic deficits. Moreover, in a task specifically designed to manipulate executive demand, patients with AD (and SA) exhibited difficulty in thinking flexibly about the non‐canonical uses of everyday objects, especially when distracted by semantically related objects. This study provides converging evidence for the notion that a failure of regulatory control contributes to multimodal semantic impairment in AD and uniquely demonstrates this pattern for the highly non‐verbal domain of object use.     

Joint effects of semantic priming and repetition in a lexical decision task: Implications for a model of lexical access

An experiment is reported which showed that in a lexical decision task semantic priming by a related preceding word and repetition of target words produce additive effects on decision latency. Previous models of lexical access and modifications of them are discussed, and it is argued that some such models predict an interaction of priming and repetition, while others are insufficiently precise to make a prediction. It is suggested that the generality of effects across tasks requiring lexical access must be established and the components of complex effects must be separated before an adequate model can be devised to account for the data.     

Patterns of memory failure after scopolamine treatment: implications for cholinergic hypotheses of dementia

To test the idea that scopolamine provides a suitable pharmacological model of the memory defects associated with cortical or subcortical dementias, we assessed memory on a battery of tasks in healthy young normal subjects who received 0.5 mg scopolamine, 0.1-0.2 mg glycopyrrolate or physiological saline, once each on three separate occasions, and compared the pattern of memory failure induced by scopolamine to that observed on the same tasks in patients with Alzheimer's disease (AD) or Huntington's disease (HD). In agreement with previous reports, scopolamine impaired acquisition and delayed recall of a 14-word list and disrupted retention on the Brown-Peterson distractor task, whereas the peripherally active anticholinergic glycopyrrolate was without effect. However, under scopolamine the pattern of errors made on these memory tasks was quite different from that seen in patients with AD. Scopolamine did not increase the number of false positive errors on delayed recognition of the word list and also failed to increase the number of prior-item intrusions on the Brown-Peterson task. Also, scopolamine did not impair learning of a symbol-digit paired-associate task, and did not reduce the number of words retrieved or increase the number of words repeated on a standardized verbal fluency test. When the effects of scopolamine on memory were compared to the pattern of impairments observed in demented patients with HD, several differences were found. Although scopolamine clearly produces deficits on some measures of anterograde memory, the present findings question whether anticholinergic drugs adequately mimic the full range of memory impairments observed in cortical or subcortical dementias.     

Knowledge of natural kinds in semantic dementia and Alzheimer's disease

We examined the semantic impairment for natural kinds in patients with probable Alzheimer's disease (AD) and semantic dementia (SD) using an inductive reasoning paradigm. To learn about the relationships between natural kind exemplars and how these are distinguished from manufactured artifacts, subjects judged the strength of arguments such as "Humans have a chemical called sebum. Therefore, frogs have a chemical called sebum." These judgments depend on subjects' perception of the similarity between the familiar objects named in the premise and the conclusion. Controls rated arguments generalizing from a natural kind to an artifact as significantly weaker than arguments generalizing from one natural kind to another natural kind. SD patients demonstrated a graded profile of generalization without evidence of a categorical distinction between natural kinds and artifacts. AD patients' judgments also suggested more difficulty than controls at distinguishing between natural kinds and artifacts. Both SD patients and AD patients resembled controls in their judgments of arguments where both objects are from the natural kinds category. Semantic knowledge thus appears to be sufficiently preserved in both AD and SD to support within-category similarity judgments. We suggest that SD patients may be impaired in part at identifying the features critical to diagnosing membership in a semantic category, while AD patients' performance is consistent with their semantic categorization deficit.     

Strategic and automatic priming of semantic memory in alcoholic Korsakoff patients

To examine whether the organization of semantic memory is intact in alcoholic Korsakoff patients, three semantic memory tasks which do not require active search for stored information were administered to a group of Korsakoff patients and alcoholic controls. The first two tasks used a perceptual identification paradigm in which patients had to identify briefly presented targets preceded by associatively (experiment 1) or categorically (experiment 2) related primes. On both tasks, Korsakoff patients demonstrated intact priming effects. Because priming in these tasks was thought to reflect the operation of strategic processes, experiment 3 was designed to assess automatic spreading activation using a lexical decision task. Here as well, Korsakoff patients demonstrated intact priming. Taken together, these results support the view that the organization of semantic memory in Korsakoff patients has not been disrupted by their brain injury. The implications of these findings for understanding Korsakoff patients' impaired performance on semantic search tasks are discussed.     

Verb deficits in Alzheimer's disease and agrammatism: implications for lexical organization

This study examined the nature of verb deficits in 14 individuals with probable Alzheimer's Disease (PrAD) and nine with agrammatic aphasia. Production was tested, controlling both semantic and syntactic features of verbs, using noun and verb naming, sentence completion, and narrative tasks. Noun and verb comprehension and a grammaticality judgment task also were administered. Results showed that while both PrAD and agrammatic subjects showed impaired verb naming, the syntactic features of verbs (i.e., argument structure) influenced agrammatic, but not Alzheimer's disease patients' verb production ability. That is, agrammatic patients showed progressively greater difficulty with verbs associated with more arguments, as has been shown in previous studies (e.g., Kim & Thompson, 2000; Thompson, 2003; Thompson, Lange, Schneider, & Shapiro, 1997), and suggest a syntactic basis for verb production deficits in agrammatism. Conversely, the semantic complexity of verbs affected PrAD, but not agrammatic, patients' performance, suggesting "bottom-up" breakdown in their verb lexicon, paralleling that of nouns, resulting from the degradation or loss of semantic features of verbs.     

Summation priming in aphasia: evidence for alterations in semantic integration and activation

The present study used a lexical decision paradigm to study the summation of priming effects in normal and aphasic participants. The amount of priming produced by pairs of definitionally converging associative words was compared to the amount of priming produced by pairs of single associative words and non-words in two experiments in which the ISI between primes and targets varied from 200 ms (Experiment 1) to 600 ms (Experiment 2). Control subjects showed a pattern of additive summation priming at the short ISI and overadditive summation priming at the longer ISI. Broca's aphasics showed overadditive priming at the short ISI and no significant priming at the longer ISI; Wernicke's aphasics showed no significant priming at the short ISI and additive priming at the longer ISI. These results suggest that aphasics differ from normals in their ability to integrate the activation derived from multiple linguistic associations and may provide an account of some of the clinical phenomenology of these patients.