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      Pauses During Autobiographical Discourse Reflect Episodic Memory Processes in Early Alzheimer’s Disease

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          Abstract

          There is a large body of research on discourse production in Alzheimer’s disease (AD). Some studies have focused on pause production, revealing that patients make extensive use of pauses during speech. This has been attributed to lexical retrieval difficulties, but pausing may also reflect other forms of cognitive impairment as it increases with cognitive load. The aim of the present study was to analyze autobiographical discourse impairment in AD from a broad perspective, looking at pausing behavior (frequency, duration, and location). Our first objective was to characterize discourse changes in mild cognitive impairment (MCI) due to AD. Our second objective was to determine the cognitive and neuroanatomical correlates of these changes. Fifteen patients with MCI due to AD and 15 matched cognitively normal controls underwent an ecological episodic memory task, a full neuropsychological assessment, and a 3D T1-weighted MRI scans. Autobiographical discourse collected from the ecological episodic memory task was recorded, transcribed, and analyzed, focusing on pausing. Intergroup comparisons showed that although patients did not produce more pauses than controls overall, they did make more between-utterance pauses. The number of these specific pauses was positively correlated with patients’ episodic memory performance. Furthermore, neuroimaging analysis showed that, in the patient group, their use was negatively correlated with frontopolar area (BA 10) grey matter density. This region may therefore play an important role in the planning of autobiographical discourse production. These findings demonstrate that pauses in early AD may reflect a compensatory mechanism for improving mental time travel and memory retrieval.

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          Most cited references23

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          The gateway hypothesis of rostral prefrontal cortex (area 10) function.

          Rostral prefrontal cortex (PFC) is a large brain region, and is unusually large in humans. Therefore, it seems likely that it might support functions that are central to cognition. However, until recently, almost nothing was known about what these functions might be. The 'gateway hypothesis' places these abilities at the centre of human mental processing. It maintains that rostral PFC supports mechanisms that enable us to attend, to a novel degree, either to environmental stimuli, or by contrast, to self-generated or maintained representations (i.e. the 'thoughts in our head'). In this way, investigations into the functions of rostral PFC will reveal key new insights into how human and non-human mental abilities differ.
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            Amnestic syndrome of the medial temporal type identifies prodromal AD: a longitudinal study.

            To compare the power of tests assessing different cognitive domains for the identification of prodromal Alzheimer disease (AD) among patients with mild cognitive impairment (MCI). Given the early involvement of the medial temporal lobe, a precocious and specific pattern of memory disorders might be expected for the identification of prodromal AD. A total of 251 patients with MCI were tested at baseline by a standardized neuropsychological battery, which included the Free and Cued Selective Recall Reminding Test (FCSRT) for verbal episodic memory; the Benton Visual Retention Test for visual memory; the Deno 100 and verbal fluency for language; a serial digit learning test and the double task of Baddeley for working memory; Wechsler Adult Intelligence Scale (WAIS) similarities for conceptual elaboration; and the Stroop test, the Trail Making test, and the WAIS digit symbol test for executive functions. The patients were followed at 6-month intervals for up to 3 years in order to identify those who converted to AD vs those who remained stable over time. Statistical analyses were based on receiver operating characteristic curve and Cox proportional hazards models. A total of 59 subjects converted to AD dementia. The most sensitive and specific test for diagnosis of prodromal AD was the FCSRT. Significant cutoff for the diagnosis was 17/48 for free recall, 40/48 for total recall, and below 71% for index of sensitivity of cueing (% of efficacy of semantic cues for retrieval). The amnestic syndrome of the medial temporal type, defined by the Free and Cued Selective Recall Reminding Test, is able to distinguish patients at an early stage of Alzheimer disease from mild cognitive impairment non-converters.
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              [Formal and semantic lexical evocation in normal subjects. Performance and dynamics of production as a function of sex, age and educational level].

              A protocol of formal lexical evocation (words beginning with a letter) and semantic evocation was applied to 168 normal subjects evenly distributed on the basis of three factors (sex, three age classes and two levels of education). Correct answers, their distribution within the allotted time (proportions of correct answers in four thirty-second periods) and errors were analysed globally and in relation to the said factors. Level of education had a decisive influence in all tests; age had no influence on performance in formal evocation, whereas the subjects in the middle age class presented the best performance in semantic evocation. Distribution of the answers over time was unrelated to any of the factors considered. Errors were related to age in half the test.
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                Author and article information

                Journal
                J Alzheimers Dis
                J. Alzheimers Dis
                JAD
                Journal of Alzheimer's Disease
                IOS Press (Nieuwe Hemweg 6B, 1013 BG Amsterdam, The Netherlands )
                1387-2877
                1875-8908
                12 January 2015
                2 February 2016
                2016
                : 50
                : 3
                : 687-698
                Affiliations
                [a ]“Brain Imaging and Neurological Disabilities” joint research unit (UMR 825), INSERM, Toulouse University Hospital , Toulouse, France
                [b ]“Brain Imaging and Neurological Disabilities” joint research unit (UMR 825), University of Toulouse III – Paul Sabatier, Toulouse University Hospital , Toulouse, France
                [c ]Octogone-Lordat interdisciplinary research unit (EA 4156), University of Toulouse II - Jean Jaurès , Toulouse, France
                [d ]Centre for Brain Research and Cognition (CerCo), CNRS - University of Toulouse III - Paul Sabatier , Toulouse, France
                [e ]Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet , Novum, Stockholm, Sweden
                [f ]Neurology Department, Neuroscience Centre, Toulouse University Hospital , Toulouse, France
                [g ]Adult and elder psychiatry Department, Limoges Hospital , Limoges, France
                Author notes
                [* ]Correspondence to: Aurélie Pistono, INSERM U825, Pavillon Baudot CHU Purpan, Place du Dr Baylac, 31059 Toulouse Cedex, France. Tel.: +33 5 62 74 61 88; E-mail: aurelie.pistono@ 123456inserm.fr .
                Article
                JAD150408
                10.3233/JAD-150408
                4927846
                26757034
                7dfcd771-b2d9-4ee6-b2bc-3f0eed8b7083
                IOS Press and the authors. All rights reserved

                This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 October 2015
                Categories
                Research Article

                episodic memory,language,mild cognitive impairment,natural language processing,neuroimaging

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