Discrete serum protein signatures discriminate between human retrovirus-associated hematologic and neurologic disease.

The human T-cell leukemia virus type I (HTLV-I) is the causative agent for adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Approximately 5% of infected individuals will develop either disease and currently there are no diagnostic tools for early detection or accurate assessment of disease state. We have employed high-throughput expression profiling of serum proteins using mass spectrometry to identify protein expression patterns that can discern between disease states of HTLV-I-infected individuals. Our study group consisted of 42 ATL, 50 HAM/TSP, and 38 normal controls. Spectral peaks corresponding to peptide ions were generated from MS-TOF data. We applied Classification and Regression Tree analysis to build a decision algorithm, which achieved 77% correct classification rate across the three groups. A second cohort of 10 ATL, 10 HAM and 10 control samples was used to validate this result. Linear discriminate analysis was performed to verify and visualize class separation. Affinity and sizing chromatography coupled with tandem mass spectrometry was used to identify three peaks specifically overexpressed in ATL: an 11.7 kDa fragment of alpha trypsin inhibitor, and two contiguous fragments (19.9 and 11.9 kDa) of haproglobin-2. To the best of our knowledge, this is the first application of protein profiling to distinguish between two disease states resulting from a single infectious agent.

Confrontation naming in Alzheimer's patients: relation to disease severity.

Reports of Alzheimer's disease patients in whom naming performance is disproportionate to other cognitive performances raise questions about the stage model, or dementia-severity level, for predicting naming performance. Thus, dementia severity as defined by Global Deterioration Scale ratings, Mini-Mental State Examination scores, and combinations of them was evaluated as a predictor of naming performance in 102 Alzheimer's patients and was found to account for approximately 1/3 of performance variability. Additional contributions from age at onset, duration, family history, and gender were negligible. Therefore, naming ability can be argued to have a subcomponent that is not subsumed by overall cognitive ability.

Relation of linguistic communication abilities of Alzheimer's patients to stage of disease.

A battery of linguistic communication (L-C) tasks was administered to 152 Alzheimer's disease patients in different stages of the disease and 60 normal elders. Subject performance data are used to construct a profile of L-C deficits by disease stage, as determined by ratings on the Global Deterioration Scale. Specification also is made of the L-C tasks on which mild Alzheimer's patients perform like normal elders, the relative difficulty of various L-C processes, the disease stage in which the greatest change occurs in L-C functions, and the degree of variation in L-C for individuals at a particular level of dementia severity.

Category and attribute knowledge deterioration in Alzheimer's disease.

A prevalent theory regarding the deterioration of semantic memory in Alzheimer's disease is that it is a bottom-up process. If this is true, performance on tests of attribute knowledge should decline more rapidly than performance on tests of categorical knowledge as dementia severity increases. In the present study, a convincing pattern of findings to either support or reject the theory failed to emerge. This raised questions regarding the ability to separate attribute and categorical knowledge, and whether one can be tested without influence of the other. Questions also were raised regarding the additional cognitive processes needed to complete tasks of semantic memory.

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.

Measures of deficit unawareness for predicted performance experiments.

Predicted performance experiments attempt to quantify an impaired individual's awareness of his or her deficit. These experiments measure perceived ability by the individual's prediction of his or her performance on a specific cognitive task and actual ability by his or her subsequent performance on that task. To date, the most comprehensive predicted performance experiment is the one proposed and implemented by McGlynn and Kaszniak (1991b). This experiment is potentially capable of removing a number of influences that may be confounded with deficit unawareness; however, it is not obvious what method of quantitative analysis best exploits this capability. In the present report, several possibilities are discussed. The limitations of McGlynn and Kaszniak's method are identified, and a more satisfying measure of deficit unawareness is proposed.

Semantic memory deterioration in Alzheimer's subjects: evidence from word association, definition, and associate ranking tasks.

The nature of semantic memory impairment in 23 persons with dementia of the Alzheimer type (DAT) was studied using three semantic tasks: word association, definition, and associate rank ordering. Using hierarchical log-linear analysis of the responses to the word association task, DAT subjects were more likely than normal control subjects to give multiword, repetitious, or unrelated responses. Additionally, the ratio of paradigmatic to syntagmatic responses was significantly decreased in DAT subjects. Surprisingly, DAT subjects were able to provide definitions for many stimulus words for which they were unable to provide meaningful associates. This finding suggests the need for caution in interpreting a decrease in the number of paradigmatic responses as indicative of a loss of conceptual knowledge. Results of other analyses demonstrated that DAT subjects had significant impairment in identifying highly related and unrelated semantic associates of words. Taken together, results of this study indicate that one feature of DAT is deterioration in the associative relations between concepts.

Alzheimer's disease effects on semantic memory: loss of structure or impaired processing?

Results of several prior studies, in which Alzheimer's disease (AD) patients missed the same concepts on multiple tasks, have been used to substantiate the theory that AD causes concept-specific loss of information from semantic memory However, sample sizes in these studies are modest, test-retest intervals small, and typically only a few tasks were used. In the present study 69 An subjects were annually administered 11 tasks, each using the same 13 concepts. Only a few instances were observed in which a concept was missed across all 11 tasks. When performances on the Oral Reading and Dictation tasks were removed from analysis, because of their questionable reliance on semantic memory, the number of missed concepts rose only modestly. A substantial rise in the number of missed concepts occurred, however, when performances on the four multiple- choice tasks were removed. Interpreting the larger number of missed concepts on the five remaining generative semantic tasks as evidence of item-specific loss is problematic, nonetheless, because the generative semantic tasks were among the hardest in the battery and the frequency with which an individual subject missed a concept across all tasks accorded with the subject's dementia severity level. Results also indicate that task difficulty, more than concept specificity, determine whether a concept is missed. Overall, results suggest that a concept will "disappear" when all of the tasks in which it is a stimulus become too difficult for the patient to perform. Study results call into question the appropriateness of using batteries of effortful, attention demanding tasks for ascertaining whether AD causes item-specific loss of conceptual knowledge.

Generative naming in Parkinson disease patients.

The generative naming ability (verbal fluency) of 88 idiopathic Parkinson disease (PD) patients was evaluated and compared to that of 21 Alzheimer disease (AD) patients and 43 normal age- and education-matched normal control subjects. The PD patients were classified according to whether they scored within the normal range on the Mini-Mental State Examination (MMSE), a score of 27 or higher, or in the abnormal range, a score of 26 or lower. Semantic and letter generative naming tasks were administered to assess verbal fluency. Results of the study provide evidence that letter category naming is inherently more difficult than semantic category naming; that age significantly affects generative naming; that PD patients with normal MMSE scores were significantly inferior to normal control subjects in generative naming even after the effects of age and mental status are controlled; that PD patients with non-normal MMSE scores performed like AD patients after controlling for the effects of age and mental status; and, that ideational perseveration is the most common type of error response for all subject groups.

Cross-sectional analysis of Alzheimer disease effects on oral discourse in a picture description task.

To examine the relation of dementia severity to the quality and quantity of oral discourse of individuals with Alzheimer disease (AD), a picture description task was administered to elicit oral discourse samples from 63 AD subjects, five individuals with very mild cognitive impairment, and 52 normal controls. Eight measures of discourse were used: total words, information units, conciseness, circumlocutions, frustrations, aborted phrases, revisions, and ideational repetitions. Information units, which decreased with increased dementia severity, proved to be the best measure for evaluating the effects of AD on oral descriptive discourse. The conciseness index also decreased with increased dementia severity, and a significantly greater proportion of AD discourse samples contained ideational repetitions. Circumlocutions and frustrations rarely occurred, and although the discourse of AD subjects was more likely to contain an aborted phrase, the frequency of aborted phrases did not vary by stage of dementia. Revisions were commonly observed in the discourse of both normal controls and AD subjects and did not differentiate the two groups.

Laryngeal configuration and constriction during two types of whispering.

Laryngeal functioning during the production of whispered speech is not well understood. The efficacy of whispering as a means of voice rest is a common clinical concern that is unresolved. This investigation examined vocal-fold configuration, glottal size, and airway constriction by supraglottal structures during whispering. Ten normally speaking adults produced consonant-vowel syllables with three different vowels while whispering in low-effort and high-effort manners. The larynx was visualized through fiberoptic endonasolaryngoscopy, and the views were recorded on videotape. Analysis and descriptions of the data revealed that low-effort and high-effort whispering were differentiated to a small extent by vocal-fold adjustments and to a somewhat larger degree by supraglottal constriction. However, for each dependent variable, individual subject differences tended to be considerably larger than any systematic effects due to whisper type or vowel.