Quantitative and qualitative analyses of clock drawings in Alzheimer's and Huntington's disease.

Although visuoconstructive impairment has been reported in both Alzheimer's (DAT) and Huntington's (HD) disease, there is little knowledge concerning how this cognitive deficit differs quantitatively and qualitatively in these two progressive dementias. To address this issue, the present study compared performances on the Clock Drawing Test (CDT: command and copy) of 25 DAT patients, 25 equally demented HD patients, and 25 elderly normal controls (NC). In the command condition, both patients groups were significantly impaired compared to the NC group. Although there was no significant difference between DAT and HD patients' total quantitative scores, a qualitative error analysis revealed a number of dissociations between the two patient groups. Graphic difficulties, very common in HD patients, were virtually absent in DAT patients; in contrast, conceptual errors were almost exclusively seen in DAT patients and were related to the severity of their dementia. Perseveration and "stimulus-bound" responses were also more frequent in DAT patients, and both groups made visuospatial errors. In the copy condition, the DAT, but not the HD, patients evidenced a marked improvement in performance. These results indicate that while both DAT and HD patients have significant visuoconstructive difficulties even in the early stages of their disorders, the specific cognitive processes underlying their quantitative impairments are quite different. It is possible that the DAT patients' conceptual errors are yet another indicator of the deterioration of their semantic knowledge.     

Category size effects in semantic and letter fluency in Alzheimer's patients

Many studies have found that patients with Alzheimer's disease (AD) perform significantly worse than normal controls on verbal fluency tasks. Moreover, some studies have found that AD patients' deficits compared to controls are more severe for semantic fluency (e.g., vegetables) than for letter fluency (e.g. words that begin with F). These studies, however, have not taken category size into account. A comparison of AD patients and age-matched controls on three semantic and three letter categories revealed that both the size and type of a category significantly predicted AD patients' deficits on verbal fluency tasks. These results suggest that the verbal fluency of AD patients will be most attenuated on large semantic categories.     

Semantic Fluency Performance of Patients with Cortical and Subcortical Neurodegenerative Diseases

Previous studies using the Animals Fluency Test have shown that dementia patients with Alzheimer's disease (AD), Huntington's disease (HD), or Parkinson's disease (PD) produce fewer correct words and have smaller semantic cluster sizes than controls or PD patients without dementia (PDND). Although the number of correct words generated by the patients with AD was positively correlated with mental status, cluster size, surprisingly, was not. To increase word output and increase the reliability of estimates of cluster size, semantic fluency was reexamined using the Supermarket Fluency Task. Overall, patients with HD or PD with dementia (PDD) exhibited reduced cluster sizes compared to older controls or PDND patients, but cluster sizes were only marginally reduced for patients with AD. These effects were evident only for female participants, because the cluster sizes for elderly control men were substantially smaller than those of elderly women. For the female patients with AD, cluster size was correlated with mental status, but the relationship was nonlinear. Cluster size was normal for mildly demented patients with AD, but much reduced for moderately or severely demented participants. In contrast to a previous report, in the present study the proportion of category labels generated was increased for patients with HD with dementia but not for patients with AD. This finding questions one line of evidence that semantic memory stores undergo “bottom-up” degradation in AD. Together with previous results, these findings indicate that semantic cluster size reflects efficiency of access to semantic knowledge which is similarly compromised in subcortical and cortical diseases.     

Declines in switching underlie verbal fluency changes after unilateral pallidal surgery in Parkinson's disease

Declines in verbal fluency are consistently reported in patients with Parkinson's disease (PD) after pallidal surgery. In the present study, the clustering and switching components of semantic or category fluency (oral naming of items obtainable in supermarkets) were examined at baseline and four months after unilateral deep brain stimulation or pallidotomy in 45 patients with PD (30 left, 15 right pallidal surgery). Post-operative declines were observed for supermarket fluency total score and switching, but not for average cluster size. These findings support the proposal that semantic fluency decrements after pallidal surgery reflect a disruption of frontal-basal ganglia circuits mediating efficient shifting between semantic categories, or perhaps efficient access to categories, rather than a degradation of semantic stores.     

Category and letter fluency in semantic dementia, primary progressive aphasia, and Alzheimer's disease

This study examined the impact of various degenerative dementias on access to semantic knowledge and the status of semantic representations. Patients with semantic dementia, primary progressive aphasia, and Alzheimer's disease were compared with elderly controls on tasks of category and letter fluency, with number of words generated, mean lexical frequency and errors recorded. The findings are consistent with the view that category and letter fluency rely on both common and unique cognitive processes. Fluency tasks, with the richness of data obtained, are valuable in distinguishing different dementia syndromes from one another.     

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.     

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.     

Verbal fluency output in children aged 7-16 as a function of the production criterion: qualitative analysis of clustering, switching processes, and semantic network exploitation

Developmental changes in children's verbal fluency were explored in this study. One hundred and forty children aged from 7 to 16 completed four verbal fluency tasks, each with a different the production criterion (letter, sound, semantic, and free). The age differences were analyzed both in terms of number of words produced, and clustering, switching, and semantic network exploration. Analysis of the number of words produced showed a larger difference between the 7-8- and the 9-10-year-olds in semantic than in letter fluency, but this difference gradually disappeared with increasing age for semantic fluency while remaining constant for letter fluency. In letter fluency production, age modified both the number of switches and clusters formed whereas in semantic fluency tasks, only cluster size changed with age. Concerning the semantic network exploration indicators derived from the supermarket fluency task, the number of categories sampled increased from 11 to 12 years, but efficient semantic exploitation occurred only after the age of 13-14 years. These results are discussed in terms of the development of strategic retrieval components and categorical knowledge.     

Monitoring the Changing Status of Semantic Memory in Alzheimer's Disease: An Evaluation of Several Process Measures

The deficits in generating correct words on verbal fluency tasks exhibited by patients with Alzheimer's disease (AD) are accompanied by fewer switching responses, smaller phonemic and semantic cluster sizes, and greater than normal percentages of errors and category labels. On category fluency tasks, patients generate a greater proportion of words that are prototypical of their semantic class. To determine whether any of these supplementary measures of verbal fluency performance might be useful in revealing processes involved in the decline of semantic memory in AD, we studied 219 patients with AD and 115 elderly control participants longitudinally. Previously reported group differences between patients and controls were replicated, but changes in average cluster size, error rates, and prototypicality were not related to changes in overall severity of dementia and test-retest stability was only modest. The change in the percentage of labels generated on the Supermarket task was related to changes in dementia severity, but test-retest stability on this measure was quite low. All of these process measures appear to reflect only the current status of the patient's attention to the task and access to semantic knowledge, but they do not forecast future performance. The numbers of switching responses on the fluency tasks were sensitive to differences between clinically deteriorated and clinically stable patients and showed fairly high test-retest stability. However, the number of switching responses is so highly correlated with the number of correct words that it contributes little to the understanding of the processes involved in the progressive decline in performance on fluency tasks by patients with AD.     

Contribution of perceptual and lexical-semantic errors to the naming impairments in Alzheimer's disease

The contribution of perceptual and semantic processing deficits to naming-test performance by Alzheimer's Disease subjects was examined. Groups of 34 Alzheimer subjects and 25 elderly controls completed tests of naming standard line drawings and naming perceptually degraded figures, and a test of verbal fluency for a specific semantic category. Alzheimer subjects were impaired on all measures and, when their naming-test errors were analyzed, they showed higher proportions of perceptual errors and failures to respond. Further, considerable variability in the proportions of different types of error was found both among subjects and among test items. These findings indicate that poor naming-test performance cannot necessarily be attributed to a specific deficit in semantic processing. Also, the discrepancies between previous reports of the naming deficits in Alzheimer's Disease may reflect differences in task difficulty and item selection that were apparent in this study.     

Word production and comprehension in Alzheimer's diseáse: The breakdown of semantic knowledge

Relatively mildly impaired patients with suspected Alzheimer's disease (N = 14; Verbal IQ = 96) and normal controls of similar age and education (N = 11) were administered tests requiring production (naming and fluency) and comprehension of single words. Word comprehension was assessed on a superordinate level (rating words for degree of “pleasantness”) and on a more specific level (matching abstract pictorial representations with printed words denoting objects, actions, emotions, and modifiers). Performance on standardized measures of semantic knowledge (Vocabulary and Similarities subtests of the WAIS) was also evaluated. The naming and fluency abilities of the Alzheimer's patients were found to be highly correlated (r = .80) and impaired. Naming errors often consisted of semantic field errors which were either hierarchically or linearly related to the target name. In comparison with normals, verbal fluency was characterized by a tendency to generate proportionally more category names concurrent with reduced production of items within a category. Single-word comprehension was also impaired, except when judgments of affective meaning were required. It was argued that these results suggest that Alzheimer's disease may lead to a specific disruption in semantic knowledge characterized by a difficulty in differentiating between items within the same semantic category concurrent with the relative preservation of broader categorical information.     

Divergent thinking in Alzheimer's and frontotemporal dementia

Twenty-three patients with mild dementia of the Alzheimer's type (DAT) or frontotemporal type (DFT) and age- and education-matched control subjects were administered tests of complex fluency involving divergent thinking and tests of letter, category, and figural fluency. The tests of complex fluency discriminated the dementia patients from control subjects more strongly than did the other fluency tests. The results suggest that divergent thinking as assessed by complex fluency tests is a cognitive domain that is impaired early in the course of dementia. The sensitivity of complex fluency tests compared to that of letter, category, and figural fluency tests may be related to greater demands for conceptualization in relating stimulus attributes to function and greater demands for flexible thinking during self-directed search processes.     

Associative encoding and retrieval in Alzheimer's and Huntington's disease

The associative encoding and retrieval abilities of patients with dementia of the Alzheimer type (DAT) and patients with Huntington's disease (HD) were investigated using an encoding specificity paradigm. When compared to age- and education-matched intact control subjects, both patient groups were severely (and equally) impaired on overall memory for word lists. However, the HD and DAT patients showed differential improvement in recall performance with the introduction of associated cues during stimulus presentation and recall. Although the HD patients, like intact subjects, were able to benefit from semantic retrieval cues (strong and weak) which were present during input, the performance of the patients with DAT improved only with the introduction of strong cues at output, regardless of whether the cues were present or absent during initial presentation. These findings suggest that patients with DAT failed to encode the semantic relationship between the to-be-recalled and cue words and simply generated free associations to the cue words during retrieval. Similarities between the performances of the patients with DAT and alcoholic Korsakoff patients are noted and discussed with regard to the neuropathological basis of the disorders.     

Semantic memory in Alzheimer's disease

Patients with Alzheimer's disease have been suggested to have a semantic memory impairment not present in the normal old. This article reviews the performance of Alzheimer patients on tests of various aspects of semantic memory, including word finding, knowledge of the semantic attributes, and associates of concepts, as well as their category membership. The effect that semantic context has on cognitive processes such as lexical and semantic priming and memory encoding is also reviewed. Finally, the ability of theoretical constructs such as implicit memory and automaticity to explain intertask variability in Alzheimer patients' semantic performance is discussed.     

Behavioral and electrical brain measures of semantic priming in patients with Alzheimer's disease: implications for access failure versus deterioration hypotheses

This study investigated the nature of anomia and semantic memory deficits in patients with Alzheimer's disease (DAT). We measured reaction time (RT) and the N400 event-related brain potential (ERP) in a word-picture semantic priming paradigm for DAT patients and elderly controls. For patients, pictures were classified as a function of the individual's naming ability to determine whether naming deficits reflected a failure to access a picture's name or reflected a deterioration of its semantic representation. As expected, DAT patients had significantly poorer naming performance than controls. For successfully named pictures, robust RT and ERP priming effects were obtained in both groups. In DAT patients, priming for unnamed pictures was heterogeneous. The results are discussed in terms of current hypotheses of semantic memory deficits in DAT.     

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.     

Pervasive influence of semantics in letter and category fluency: a multidimensional approach

We used multidimensional statistical procedures to study semantic and lexical processes underlying word retrieval in verbal-fluency performance. Forty healthy participants were given a two-choice letter task (i.e., generate items beginning with the letter 'A' or 'F', in any order) and a two-choice category task (i.e., generate animal or fruit names, in any order). Using correspondence analysis (CoA) and hierarchical clustering (HC), we found evidence of prominent semantic organization in both letter and category fluency. For example, a striking categorical segregation between animate and inanimate entities emerged during the letter task. Analysis of inter-item times revealed strong sequential priming effects in both tasks. Taken together, these results indicate that semantic facilitation is pervasive in word retrieval processes, even in the letter-fluency task, and therefore suggest that the traditional view of letter fluency as a purely phonemically based task should be revised. Finally, our findings may help explain patterns of verbal-fluency measures obtained in focal brain lesion patients.     

Pictorial priming and cued recall in Alzheimer's and Huntington's disease

A picture fragment test was used to compare the priming and cued recall performances of patients with Huntington's disease (HD), patients with dementia of the Alzheimer type (DAT), and neurologically intact normal control (NC) subjects. On the pictorial priming test, subjects were asked to say "the first thing you think of" when shown incompletely drawn pictures, half of which were previously exposed to the subject during an unrelated naming task. Normal controls and HD patients, but not DAT patients, demonstrated similar increases in their ability to identify fragmented versions of previously seen pictures relative to novel pictures. These results are consistent with the previously observed pattern of preserved and impaired verbal priming ability in HD and DAT patients, respectively. The NC subjects, as expected, also demonstrated better performance on the cued recall than on the priming version of the picture fragment test, whereas the HD patients evidenced the opposite relationship on these two tasks and DAT patients were found to be equally impaired on both tests. This finding provides further support for the notion that HD patients' memory impairment is characterized primarily by an inability to initiate systematic retrieval strategies.     

Increased regional cerebral glucose metabolism and semantic memory performance in Alzheimer's disease: A pilot double blind transdermal nicotine positron emission tomography study

Nicotinic receptor dysfunction and impaired semantic memory occur early in Alzheimer's disease patients (AD). Previous research implied that nicotine's ability to enhance alertness, arousal, and cognition in a number of nonclinical populations was a function of its ability to stimulate CNS nicotinic cholinergic receptors. In this study it was hypothesized that transdermal administration of nicotine would increase both regional cerebral glucose metabolism (rCMRglc) and semantic memory (as assessed by verbal fluency). Two mild AD and two elderly controls underwent positron emission tomography scanning during a double blind nicotinic agonist verbal fluency challenge procedure. rCMRglc increases occurred in both AD patients, but not controls. In the two AD patients, verbal fluency scores increased by an average of 17%. One elderly control's verbal fluency increased, and the other decreased. These findings suggest that nicotine's effect on metabolism and verbal fluency is due to its ability to stimulate the cholinergic system.     

Inductive Reasoning in Alzheimer''s Disease

We evaluated knowledge of basic level and superordinate semantic relations and the role of cognitive resources during inductive reasoning in probable Alzheimer's disease (AD). Nineteen mildly demented AD patients and 17 healthy control subjects judged the truthfulness of arguments with a premise and a conclusion that contain familiar concepts coupled with "blank" predicates, such as "Spiders contain phosphatidylcholine; therefore all insects contain phosphatidylcholine." Like healthy control subjects, AD patients were relatively insensitive to the typicality of the premise category when judging the strength of arguments with a conclusion containing a basic-level concept, but were relatively sensitive to typicality during judgments of arguments containing a superordinate in the conclusion. Moreover, AD patients resembled control subjects in judging arguments with an immediate superordinate in the conclusion compared to arguments with a distant superordinate. AD patients differed from control subjects because they could not take advantage of two premises in an argument containing basic-level concepts. We conclude that semantic knowledge is sufficiently preserved in AD to support inductive reasoning, but that limited cognitive resources may interfere with AD patients' ability to consider the entire spectrum of information available during semantic challenges.