RESUMO
Background: Discourse analyses yield quantitative measures of functional communication in aphasia. However, they are historically underutilized in clinical settings. Confrontation naming assessments are used widely clinically and have been used to estimate discourse-level production. Such work shows that naming accuracy explains moderately high proportions of variance in measures of discourse, but proportions of variance remain unexplained. We propose that the inclusion of circumlocution productions into predictive models will account for a significant amount more of the variance. Circumlocution productions at the naming-level, while they may not contain the target word, are similar to the content that contributes to discourse informativeness and efficiency. Thus, additionally measuring circumlocution may improve our ability to estimate discourse performance and functional communication. Aim: This study aimed to test whether, after controlling for naming accuracy, the addition of a measure of circumlocution into predictive models of discourse-level informativeness and efficiency would account for a significant amount more of the variance in these discourse-level outcomes. Methods & Procedures: Naming and discourse data from 43 people with poststroke aphasia were analyzed. Naming data were collected using 120 pictured items and discourse data were collected using two picture description prompts. Data scoring and coding yielded measures of naming accuracy, incorrect response type, communicative informativeness, and efficiency. We used robust hierarchical regression to evaluate study predictions. Outcomes & Results: After controlling for naming accuracy, the inclusion of circumlocution into predictive models accounted for a significant amount more of the variance in both informativeness and efficiency. The subsequent inclusion of other response types, such as real word and nonword errors, did not account for a significant amount more of the variance in either outcome. Conclusions: In addition to naming accuracy, the production of circumlocution during naming assessments may correspond with measures of informativeness and efficiency at the discourse-level. Reducing the burden of estimating patients' functional communication will increase our ability to estimate functional communication using tools that are easy to administer and interpret.
RESUMO
Synaptopathy underlying memory deficits in Alzheimer's disease (AD) is increasingly thought to be instigated by toxic oligomers of the amyloid beta peptide (AßOs). Given the long latency and incomplete penetrance of AD dementia with respect to Aß pathology, we hypothesized that factors present in the CNS may physiologically protect neurons from the deleterious impact of AßOs. Here we employed physically separated neuron-astrocyte cocultures to investigate potential non-cell autonomous neuroprotective factors influencing AßO toxicity. Neurons cultivated in the absence of an astrocyte feeder layer showed abundant AßO binding to dendritic processes and associated synapse deterioration. In contrast, neurons in the presence of astrocytes showed markedly reduced AßO binding and synaptopathy. Results identified the protective factors released by astrocytes as insulin and insulin-like growth factor-1 (IGF1). The protective mechanism involved release of newly bound AßOs into the extracellular medium dependent upon trafficking that was sensitive to exosome pathway inhibitors. Delaying insulin treatment led to AßO binding that was no longer releasable. The neuroprotective potential of astrocytes was itself sensitive to chronic AßO exposure, which reduced insulin/IGF1 expression. Our findings support the idea that physiological protection against synaptotoxic AßOs can be mediated by astrocyte-derived insulin/IGF1, but that this protection itself is vulnerable to AßO buildup.
