Kris Onishi

Progressive nonfluent aphasia: Language, cognitive, and pet measures contrasted with probable alzheimer's disease

The purpose of this study was to compare the language and cognitive profiles of four progressive nonfluent aphasia (PNFA) patients with 25 probable Alzheimers disease (pAD) patients, and to identify the distinct cortical defects associated with cognitive deficits in PNFA using positron emission tomography (PET). Longitudinal observations of PNFA patients revealed progressively telegraphic speech and writing and a gradual deterioration of sentence comprehension, but memory and visual functioning were relatively preserved. Direct contrast with PAD patients revealed that PNFA patients are significantly impaired on grammatical phrase structure aspects of sentence comprehension and expression, phonemic judgments, repetition, and digit span, but not on other cognitive measures. PET studies of PNFA revealed reduced cortical activity throughout the left hemisphere. In addition, there was a prominent defect in left superior and middle temporal and inferior frontal regions of PNFA patients that differed significantly from the distribution of regional cerebral dysfunction in pAD. We conclude that PNFA is associated with a distinct profile of language and cognitive difficulty, and that this pattern of impairment is related to cortical dysfunction in a specific distribution of the left hemisphere.

Language comprehension profiles in Alzheimer's disease, multi-infarct dementia, and frontotemporal degeneration.

We assessed language functioning in 116 age-, education-, and severity-matched patients with the clinical diagnosis of Alzheimers disease (AD), multi-infarct dementia (MID) due to small-vessel ischemic disease, or a frontotemporal form of degeneration (FD). Assessments of comprehension revealed that patients with AD are significantly impaired in their judgments of single word and picture meaning, whereas patients with FD had sentence comprehension difficulty due to impaired processing of grammatical phrase structure. Patients with MID did not differ from control subjects in their comprehension performance. Traditional aphasiologic measures did not distinguish between AD, MID, and FD. Selective patterns of comprehension difficulty in patients with different forms of dementia emphasize that language deficits cannot be explained entirely by the compromised memory associated with a progressive neurodegenerative illness. NEUROLOGY 1996;47: 183-189

Working Memory Impairments in Multiple Sclerosis: Evidence From a Dual-Task Paradigm

The aim of this study was to investigate working memory in multiple sclerosis (MS) patients. To test the hypothesis that the central executive system (CES) of working memory is impaired, 36 MS patients were administered a dual-task paradigm in which a judgment of line orientation measure was performed concurrently with finger tapping, humming a melody, or reciting the alphabet. MS patients exhibited a significantly greater decrement in performance than controls during the more demanding dual-task conditions (concurrent humming or alphabet recitation) as compared with the single-task condition. Dual-task performance in MS patients correlated with performance on the Paced Auditory Serial Addition Test but not with other cognitive or clinical measures. The authors conclude that MS patients have a working memory deficit reflecting an impaired central executive system. Moreover, impairments in speed of information processing in MS patients are associated with this CES deficit. Memory dysfunction is the most common cognitive impairment observed in patients with multiple sclerosis (MS). A long-term memory deficit in these patients is well documented (Grafman, Rao, & Litvan, 1990), but most early studies of MS patients have concluded that short-term memory (STM) is intact. Support for this claim was derived from the observation of a normal digit span, as well as an intact recency effect on supraspan list learning, measures commonly used to assess STM (Caine, Bamford, Schiffer, Shoulson, & Levy, 1986; Rao, Hammeke, McQuillen, Khatri, & Lloyd, 1984). Although most studies continue to focus on the long-term memory impairments in MS patients (Rao, Leo, & Aubin-Faubert, 1989), evidence is accumulating that STM deficits may also exist (Grigsby, Ayarbe, Kravcism, & Busenbark, 1994; Rao et al., 1993). However, the nature of these deficits remain unclear. The purpose of this study was to further investigate STM processing in MS patients. Several experimental tasks have been useful for identifying impairment in various aspects of STM in MS patients. One experimental measure, the Brown-Peterson task (Peterson & Peterson, 1959), measures consolidation of information in STM and the effect of interference on temporarily stored information. With this task, two groups of investigators (Beatty, Goodkin, Monson, Beatty, & Hertsgaard, 1988; Grant,

Language comprehension and regional cerebral defects in frontotemporal degeneration and Alzheimer's disease

We related profiles of language comprehension difficulty to patterns of reduced cerebral functioning obtained with high-resolution single photon emission computed tomography (SPECT) in patients with neurodegenerative conditions. We found different patterns of reduced relative cerebral perfusion in patients with frontotemporal degeneration (FD) and patients with Alzheimers disease (AD). Cognitive assessments also showed different patterns of impaired comprehension in patients with FD and patients with AD. Grammatical comprehension difficulty in FD correlated with relative cerebral perfusion in left frontal and anterior temporal brain regions; impaired semantic processing in AD correlated with relative cerebral perfusion in inferior parietal and superior temporal regions of the left hemisphere. These findings are consistent with the hypothesis that a neural network distributed throughout the left hemisphere subserving different aspects of language comprehension, rather than a single brain region, is responsible for understanding language.

Constraints on the cerebral basis for semantic processing from neuroimaging studies of Alzheimer’s disease

OBJECTIVE Functional activation studies of semantic processing in healthy adults have yielded conflicting results. The purpose was to evaluate the relative role of the brain regions implicated in semantic processing with converging evidence from imaging studies of patients with impaired semantic processing. METHODS Semantic memory was assessed in patients with Alzheimer’s disease using two measures, and these performance patterns were related to profiles of reduced cerebral functioning obtained with high resolution single photon emission computed tomography (SPECT). Patients with frontotemporal degeneration were similarly evaluated as a control group. RESULTS Reduced relative cerebral perfusion was seen in parietal and posterior temporal brain regions of patients with Alzheimer’s disease but not patients with frontotemporal degeneration. Impairments on semantically guided category membership decision tasks were also seen in patients with Alzheimer’s disease but not those with frontotemporal degeneration. Performance on the semantic measures correlated with relative cerebral perfusion in inferior parietal and superior temporal regions of the left hemisphere only in Alzheimer’s disease. Relative perfusion was significantly lower in these regions in patients with Alzheimer’s disease with semantic difficulty compared with patients with Alzheimer’s disease with relatively preserved semantic processing. CONCLUSION These findings provide converging evidence to support the contribution of superior temporal and inferior parietal regions of the left hemisphere to semantic processing.

Serial position and temporal cue effects in multiple sclerosis: Two subtypes of defective memory mechanisms

Neurocognitive studies of multiple sclerosis (MS) have identified a robust long-term memory deficit. We hypothesized that this is due in part to the limited representation and use of serial order information. MS patients and controls were studied with a supraspan list learning procedure with post-encoding retrieval and recognition trials. MS patients demonstrated post-encoding negative recency with normal recognition, and word order recall was impaired. These findings appear to be in part to difficulty using temporal order cues in long-term memory. Two dissociable memory deficits were identified, suggesting that there are at least two neurocognitive mechanisms underlying memory impairment in MS.

Verb comprehension deficits in probable Alzheimer's disease.

Studies of lexical comprehension in probable Alzheimers disease (pAD) have focused almost exclusively on nouns. In the following preliminary study, we examined whether lexical comprehension for verbs is also impaired in 25 pAD patients. The semantic meaning of motion verbs, cognition verbs, and perception verbs was assessed with a triadic comparison task. Structural meaning associated with these verbs was evaluated by asking the patients to judge the coherence of sentence frames that accept these verbs naturally or awkwardly. We found that pAD patients are significantly impaired at identifying semantic relations among verbs. pAD patients also encountered significantly more difficulty judging the coherence of sentences than control subjects. Correlation and regression analyses demonstrated that semantic characteristics of verbs are projected from the verbs sentence frames in control subjects, but there was minimal evidence for such a structural-semantic relationship in pAD. We consider several possible explanations for our preliminary observations of an impairment that has consequences for processing both semantic and structural aspects of verb meaning.

Sentence comprehension in multiple sclerosis

Introduction ‐ Explanations of sentence processing difficulty in aphasia have implicated slowed information processing speed. We tested this hypothesis by evaluating sentence comprehension in multiple sclerosis (MS), and relating comprehension performance to measures of information processing speed. Material & methods ‐ Twenty right‐handed, high school‐educated, non‐demented, native English speakers with clinically definite MS and 16 age‐ and education‐matched control subjects were examined on 3 different sentence comprehension measures that stress grammatical appreciation. Performance was related to quantitative assessments of mental information processing speed. Results ‐ Group‐wide analyses demonstrated a trend toward sentence comprehension difficulty in MS. Analyses of individual patient profiles identified a subgroup of MS patients who were consistently impaired to a significant extent across all sentence comprehension tasks. Their sentence comprehension difficulty was associated with selectively compromised mental information processing speed. Conclusion ‐ Sentence comprehension difficulty in MS is associated with slowed information processing speed. This finding supports the claim that information processing speed contributes to sentence processing.

Lexical Acquisition in Probable Alzheimer's Disease

Patients with probable Alzheimers disease (pAD) were exposed to a new verb in a naturalistic fashion. We probed their knowledge of the words semantic and grammatical characteristics for several minutes following this exposure, and compared this with their performance on parallel measures assessing known words. Significant differences were seen between pAD patients and controls in the acquisition of the new verbs semantic meaning and its argument structure, but pAD patients did not differ from controls in the acquisition of the new words grammatical form class. Individual patient analyses demonstrated parallel deficits restricted to the semantic meaning and argument structure of the new word and known words in several pAD patients, suggesting that a selective language impairment contributed to their word learning deficit. This pattern is consistent with an intimate relationship between semantic meaning and argument structure in semantic memory. Other pAD patients had difficulty learning about all aspects of the new word, despite good performance with known words, suggesting that compromised memory may have limited their lexical acquisition.

An aspect of sentence processing in Alzheimer's disease: quantifier-noun agreement.

Article abstract-We assessed sentence processing in Alzheimers disease (AD) with measures of sentence-picture matching, grammaticality judgments of sentences, and sentence completion. The results demonstrated significant and consistent difficulty with a grammatical feature of sentences on all three experiments. This impairment could not be explained by factors such as sentence length, dementia severity, or a short-term memory deficit and was independent of difficulty interpreting the meanings of words. We hypothesize that AD patients are impaired at appreciating the conceptual relations that underlie certain grammatical features of sentences. NEUROLOGY 1995;45: 85-91