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.     

Pattern of language impairment is different in Alzheimer's disease and multi-infarct dementia.

Language impairment was assessed in 33 patients with Alzheimer's disease (AD), in 52 patients with multi-infarct dementia (MID), and in 86 elderly community residents. The investigation included the D-Test Battery based on the Luria's Neuropsychological Investigation for all subjects. An extended battery of Luria's language items was used for 30 demented patients (11 AD and 19 MID patients) and 86 controls. The changes in language functions in normal subjects could be clearly differentiated from those seen in patients with mild dementia. The patients with different degrees of dementia differed also significantly from each other in regard to language impairment. Moreover, patients with AD and MID appeared to have different patterns of language impairment although the severity of dementia and the levels of orientation, mnestic, and conceptual functions were equal. AD was associated especially with a defect in understanding of grammatical structures and MID with disorders in recognition of words, naming, and repetition. The differential diagnostic capacity of 23 selected language items proved to be 97% between AD, MID, and control subjects. The results indicate that the examination of language functions is valuable in the differential diagnosis of dementia.     

Cue utilization following different forms of encoding in mildly, moderately, and severely demented patients with Alzheimer's disease

The ability of patients with Alzheimer's disease (AD) to utilize semantic category cues in order to improve memory performance was examined. Categorizable lists of words or objects were presented under five different encoding conditions: (a) nouns, (b) objects, (c) objects with a semantic orienting question, (d) objects with self-generated motoric acts, and (e) objects with experimenter-instructed motoric acts. Subjects were asked to memorize the items for a free recall test, and were subsequently provided with the category names in a cued recall test. Mildly, moderately, and severely demented AD patients, and a group of normal older adults participated in the study. Results showed that normal older adults and mildly demented AD subjects were able to utilize cues to improve memory performance in all conditions. Moderately demented patients utilized cues in all conditions except in the verbal condition (condition [a]), whereas severely demented patients utilized cues only in the motoric condition (condition [e]). These results suggest that the ability to utilize category cues following a motoric encoding is preserved later in AD than the ability to utilize cues after a semantic encoding.     

Inhibitory control and affective valence processing in dementia of the alzheimer type

Emotional and traditional Stroop effects were contrasted in individuals with Alzheimer's disease (AD) and age‐equated, non‐demented individuals to examine (a) differences in the speed of processing emotional versus neutral words; and (b) the extent to which the emotional valence influences interference effects. Individuals with moderate AD experienced larger traditional Stroop interference effects than did healthy elderly or individuals with mild AD. Emotional Stroop effects were evident among individuals with moderate AD and significantly greater than elderly and individuals with mild AD who exhibited minimal effects. For negative words, significant differences were only observed between individuals with moderate AD and healthy elderly. Emotional Stroop effects among individuals with AD were not statistically different for positive and negative words. The impact of stimulus intensity level and AD‐associated changes to the prefrontal cortex and amygdala on emotional Stroop effects requires further investigation.     

Performance on a measure of category fluency in cognitively impaired elderly

ABSTRACT

Measures of verbal fluency are widely used in the assessment of cognitive functioning of the elderly. However, limited research has evaluated patterns (across specific timed intervals) of performance on tasks of language fluency in different forms of dementia. The current study investigated semantic fluency in 488 elderly individuals (249 with Alzheimer's dementia, 97 Vascular dementia, 97 Mild Cognitive Impairment and 45 cognitively intact) across 15-second intervals in an animal naming task using retrospective chart review. Normal controls produced significantly more exemplars and AD patients produced fewer animal names than the other groups. After the first 15- second time interval, the demented groups produced significantly fewer exemplars than the non-demented. At the end of 30 seconds it was possible to differentiate normal aging from MCI who no longer differed from the VaD group. Overall, it appears that the greatest and most clinically meaningful differences between the diagnostic groups were detected in the first three 15-second intervals. The present findings support the use of time intervals and total scores on tasks of verbal fluency in clinical settings and for research purposes.     

Impairments of speech fluency in Lewy body spectrum disorder

Few studies have examined connected speech in demented and non-demented patients with Parkinson’s disease (PD). We assessed the speech production of 35 patients with Lewy body spectrum disorder (LBSD), including non-demented PD patients, patients with PD dementia (PDD), and patients with dementia with Lewy bodies (DLB), in a semi-structured narrative speech sample in order to characterize impairments of speech fluency and to determine the factors contributing to reduced speech fluency in these patients. Both demented and non-demented PD patients exhibited reduced speech fluency, characterized by reduced overall speech rate and long pauses between sentences. Reduced speech rate in LBSD correlated with measures of between-utterance pauses, executive functioning, and grammatical comprehension. Regression analyses related non-fluent speech, grammatical difficulty, and executive difficulty to atrophy in frontal brain regions. These findings indicate that multiple factors contribute to slowed speech in LBSD, and this is mediated in part by disease in frontal brain regions.     

Differential impacts of age of acquisition on letter and semantic fluency in Alzheimer's disease patients and healthy older adults

The degree to which the typical age of acquisition (AoA) of words and word frequency have separable influences on verbal production tasks has been strongly debated. To examine the overlap between these factors in verbal fluency tasks, the performance of Alzheimer's disease (AD) patients (N?=?34) and normal elderly controls (N?=?36) was compared on semantic (e.g., vegetables) and letter (e.g., words that begin with F) fluency tasks. These comparisons revealed that words generated for the semantic fluency task had an earlier AoA while words generated for the letter fluency task had a higher word frequency. Differences in AoA between AD patients and controls were larger for semantic than letter fluency. These results suggest that AoA has an effect on verbal production that is independent of word frequency and that AoA has a semantic locus.     

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.     

Increased Proportion of Farm Animal Names Generated by Patients with Alzheimer's Disease: What Does it Mean?

Binetti et al. (1995) reported that patients with Alzheimer's disease (AD) produced fewer semantic clusters than controls on the Animals Fluency task; of the clusters produced, 80% involved farm animals for the patients with AD compared to 40% for controls. In the present study we replicated the finding of Binetti et al.; however, the differential distribution of animal names by subcategory for the patients and controls could be accounted for by differences in the overall output and by assuming that word generation was strictly determined by prototypicality of the animal names. Thus, the increased proportion of farm animal names produced by patients with AD can be accounted for simply by postulating impaired access to semantic memory rather than degraded representations, the idea favored by Binetti et al.     

Parkinsonian Patients Reduce Their Stroke Size with Increased Processing Demands

Parkinson's disease (PD) patients often show reductions in writing size (micrographia) as the length of the text they produce increases. The cause for these reductions in stroke size are not well understood. Reductions in stroke size could be associated with either concurrent processing demands that result from the coordination and control of fingers, wrist, and arm during writing and the processing of future words or increased extension of the wrist joint as the execution of the writing progresses to the right across the page, resulting in increased stiffness in the pen-limb system. Parkinson's patients and elderly controls wrote phrases of different lengths with target patterns in various serial positions. When the number of words to be written increased, PD patients reduced their stroke size of the initial target pattern, while the elderly controls did not reduce their stroke size. There was no systematic change in stroke size of the second pattern as function of serial position. This result suggests that PD patients reduce the size of their handwriting strokes when concurrent processing load increases.     

The effect of semantic and syntactic structure on verbal memory in Alzheimer's disease

This study examined the ability of 17 patients with Alzheimer's disease and 17 normal-old subjects to recall short sentences that were normal, or had a disruption in either their semantic structure, their syntactic structure, or both their semantic and syntactic structure. Results showed that sentence recall performance was affected similarly in the demented and normal-old subjects by both the syntactic and semantic structure of the sentences. The presence of either type of language structure appeared to allow both normal and demented subjects to organize strings of words into multiword chunks for more efficient memory encoding.     

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.     

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.     

Gait variability in people with neurological disorders: A systematic review and meta-analysis

There has been growing evidence showing gait variability provides unique information about gait characteristics in neurological disorders. This study systemically reviewed and quantitatively synthesized (via meta-analysis) existing evidence on gait variability in various neurological diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), cerebellar ataxia (CA), Huntington’s disease (HD), multiple sclerosis (MS), and Parkinson’s disease (PD). Keyword search were conducted in PubMed, Web of science, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library. Meta-analysis was performed to estimate the pooled effect size for gait variability for each neurological group. Meta-regression was performed to compare gait variability across multiple groups with neurological diseases. Gait variability of 777 patients with AD, ALS, CA, HD, MS, or PD participating in 25 studies was included in meta-analysis. All pathological groups had increased amount of gait variability and loss of fractal structure of gait dynamics compared to healthy controls, and gait variability differentiated distinctive neurological conditions. The HD groups had the highest alterations in gait variability among all pathological groups, whereas the PD, AD and MS groups had the lowest. Interventions that aim to improve gait function in patients with neurological disorders should consider the heterogeneous relationship between gait variability and neurological conditions.     

Lexical but not semantic priming in Alzheimer's disease.

The hypothesis that patients with Alzheimer's disease (AD) have a disturbance in semantic processing was tested using a new lexical-priming task, threshold oral reading. Healthy elderly controls showed significant effects of priming for word pairs that are associatively related (words that reliably co-occur in word association tests) and for word pairs that are semantically related (high-frequency exemplars that belong to the same superordinate category but are not high-frequency associates). AD patients showed effects of priming for associatively related words but not for word pairs that are related only by shared semantic features. These results are consistent with the hypothesis that semantic processing is impaired in AD and suggest that independent networks of relationships among words and among concepts in semantic memory may be differentially disrupted with various forms of brain damage.     

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.     

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.     

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.