Peter Garrard

Structure and Deterioration of Semantic Memory: A Neuropsychological and Computational Investigation.

Wernicke (1900, as cited in G. H. Eggert, 1977) suggested that semantic knowledge arises from the interaction of perceptual representations of objects and words. The authors present a parallel distributed processing implementation of this theory, in which semantic representations emerge from mechanisms that acquire the mappings between visual representations of objects and their verbal descriptions. To test the theory, they trained the model to associate names, verbal descriptions, and visual representations of objects. When its inputs and outputs are constructed to capture aspects of structure apparent in attribute-norming experiments, the model provides an intuitive account of semantic task performance. The authors then used the model to understand the structure of impaired performance in patients with selective and progressive impairments of conceptual knowledge. Data from 4 well-known semantic tasks revealed consistent patterns that find a ready explanation in the model. The relationship between the model and related theories of semantic representation is discussed.

Experimental models of vascular dementia and vascular cognitive impairment: a systematic review

J. Neurochem. (2010) 115, 814–828.

Semantic feature knowledge and picture naming in dementia of Alzheimer's type: a new approach

This study addresses continuing controversies concerning the nature of semantic impairment in early dementia of the Alzheimer type (DAT), and the relationship between conceptual knowledge and picture naming. A series of analyses of fine-grained feature knowledge data show that: (1) distinctive features of concepts were more vulnerable than shared; (2) the amount of attribute knowledge about a concept was associated reliably, and in a graded fashion, with the ability to name a picture of that item; (3) sensory features were differentially important in naming; and (4) the degree of disruption to different types of attribute knowledge did not vary between items from living and nonliving domains. These findings are discussed in the context of contemporary cognitive and computational models of semantic memory organisation.

Innovative diagnostic tools for early detection of Alzheimer's disease

Current state‐of‐the‐art diagnostic measures of Alzheimers disease (AD) are invasive (cerebrospinal fluid analysis), expensive (neuroimaging) and time‐consuming (neuropsychological assessment) and thus have limited accessibility as frontline screening and diagnostic tools for AD. Thus, there is an increasing need for additional noninvasive and/or cost‐effective tools, allowing identification of subjects in the preclinical or early clinical stages of AD who could be suitable for further cognitive evaluation and dementia diagnostics. Implementation of such tests may facilitate early and potentially more effective therapeutic and preventative strategies for AD. Before applying them in clinical practice, these tools should be examined in ongoing large clinical trials. This review will summarize and highlight the most promising screening tools including neuropsychometric, clinical, blood, and neurophysiological tests.

Longitudinal Profiles of Semantic Impairment for Living and Nonliving Concepts in Dementia of Alzheimer's Type

Two types of theoretical account have been proposed to explain the phenomenon of category-specific impairment in tests of semantic memory: One stresses the importance of different cortical regions to the representation of living and nonliving categories, while the other emphasize the importance of statistical relationships among features of concepts belonging to these two broad semantic domains. Theories of the latter kind predict that the direction of a domain advantage will be determined in large part by the overall damage to the semantic system, and that the profiles of patients with progressive impairments of semantic memory are likely to include a point at which an advantage for one domain changes to an advantage for the other. The present series of three studies employed semantic test data from two separate cohorts of patients with probable dementia of Alzheimers type (DAT) to look for evidence of such a crossover. In the first study, longitudinal test scores from a cohort of 58 patients were examined to confirm the presence of progressive semantic deterioration in this group. In the second study, Kaplan-Meier survival curves based on serial naming responses and plotted separately for items belonging to living and nonliving domains indicated that the representations of living concepts (as measured by naming) deteriorated at a consistently and significantly faster rate than those of nonliving concepts. A third study, carried out to look in detail at the performance of mildly affected patients, employed an additional cross-sectional cohort of 20 patients with mild DAT and utilized a graded naming assessment. This study also revealed no evidence for a crossover in the advantage of one domain over the other as a function of disease severity. Taken together with the model of anatomical progression in DAT based on the work of Braak and Braak (1991), these findings are interpreted as evidence for the importance of regional cerebral anatomy to the genesis of semantic domain effects in DAT.

Semantic dementia with category specificity: a comparative case-series study.

Patients with semantic dementia, the temporal variant of frontotemporal dementia, are relevant to both the neuroanatomical and neuropsychological debates in the category-specific literature. These patients present with a selective and progressive semantic deficit consequent on circumscribed atrophy of the inferolateral polar temporal lobes bilaterally, including the inferotemporal gyrus. In this study, a patient KH with a significant advantage for artefacts over living things was compared to five other semantic dementia patients with commensurate levels of semantic impairment. KH demonstrated a consistent category difference in favour of artefacts across all the expressive and receptive semantic tests. This difference was reliable even when familiarity, frequency, and other potential confounding factors were controlled. While KH demonstrated an association between poor knowledge of sensory attributes and a consistently greater impairment on living things than artefacts, the other patients did not. As observed in a number of previous studies, all five of the patients, contrasted to KH, exhibited an advantage for functional/associative over sensory attributes but without demonstrating the category-specific deficit that the sensory-functional theory (and the locus of their atrophy) might predict. The results of this and other studies are discussed in relation to four accounts of category specificity: the sensory-functional theory, domain-specific knowledge systems, intercorrelated features, and individual differences.

Connected speech as a marker of disease progression in autopsy-proven Alzheimer’s disease

Although an insidious history of episodic memory difficulty is a typical presenting symptom of Alzheimer’s disease, detailed neuropsychological profiling frequently demonstrates deficits in other cognitive domains, including language. Previous studies from our group have shown that language changes may be reflected in connected speech production in the earliest stages of typical Alzheimer’s disease. The aim of the present study was to identify features of connected speech that could be used to examine longitudinal profiles of impairment in Alzheimer’s disease. Samples of connected speech were obtained from 15 former participants in a longitudinal cohort study of ageing and dementia, in whom Alzheimer’s disease was diagnosed during life and confirmed at post-mortem. All patients met clinical and neuropsychological criteria for mild cognitive impairment between 6 and 18 months before converting to a status of probable Alzheimer’s disease. In a subset of these patients neuropsychological data were available, both at the point of conversion to Alzheimer’s disease, and after disease severity had progressed from the mild to moderate stage. Connected speech samples from these patients were examined at later disease stages. Spoken language samples were obtained using the Cookie Theft picture description task. Samples were analysed using measures of syntactic complexity, lexical content, speech production, fluency and semantic content. Individual case analysis revealed that subtle changes in language were evident during the prodromal stages of Alzheimer’s disease, with two-thirds of patients with mild cognitive impairment showing significant but heterogeneous changes in connected speech. However, impairments at the mild cognitive impairment stage did not necessarily entail deficits at mild or moderate stages of disease, suggesting non-language influences on some aspects of performance. Subsequent examination of these measures revealed significant linear trends over the three stages of disease in syntactic complexity, semantic and lexical content. The findings suggest, first, that there is a progressive disruption in language integrity, detectable from the prodromal stage in a subset of patients with Alzheimer’s disease, and secondly that measures of semantic and lexical content and syntactic complexity best capture the global progression of linguistic impairment through the successive clinical stages of disease. The identification of disease-specific language impairment in prodromal Alzheimer’s disease could enhance clinicians’ ability to distinguish probable Alzheimer’s disease from changes attributable to ageing, while longitudinal assessment could provide a simple approach to disease monitoring in therapeutic trials.

Logopenic aphasia in Alzheimer's disease: clinical variant or clinical feature?

Background Primary progressive aphasia (PPA) is a clinical syndrome characterised by progressive decline in components of the language system. Recent evidence suggests that the logopenic/phonological (LPA) variant is a reliable in vivo marker of Alzheimer related pathology. The aim of this study was to determine if patients with clinically typical early stage Alzheimers disease (AD) display a characteristic language disorder that resembles LPA, or if LPA is a clinical manifestation of an atypical form of AD. Methods Spoken language samples were obtained using the Cookie Theft picture description task from 18 post mortem confirmed cases of AD, where speech samples were taken at the first point of clinical diagnosis, and 18 post mortem confirmed healthy controls. Spoken samples were transcribed from tape recordings and analysed using the scoring system described by Wilson et al. Results Group comparisons between normal controls and AD patients showed no significant overall differences. Individual review of the linguistic variables compared with the PPA variants showed that a third of patients had normal language (n=6). The remainder showed varied patterns of linguistic impairment. In the majority of the affected group, the most salient feature was a reduction in one or more measures of syntactic complexity. One patients deficit was comparable to that found in LPA. Conclusions The impairment found in clinically typical early stage AD did not correspond consistently to the linguistic profiles described in any of the sub-syndromes of PPA. The only reliably distinguishing feature was a reduction across a range of syntactic complexity measures. The findings suggest that LPA represents an atypical clinical presentation of AD rather than a common clinical feature of typical AD.

The treatment of object naming, definition, and object use in semantic dementia: The effectiveness of errorless learning

Background: Patients with semantic dementia are impaired in both object naming and, to a lesser extent, in object use (Bozeat, Lambon Ralph, Patterson, & Hodges, 2002a; Hodges, Graham, & Patterson, 1995). To date there have been relatively few studies examining the relearning of object names, and only one examining the relearning of object use. No study has examined relearning object naming, definition, and use simultaneously. Aims: To explore the relatedness of object naming, definition, and object use in semantic dementia; to explore whether or not therapy is effective; and to explore the effectiveness of errorless learning. Methods & Procedures: Two patients with mild to moderate semantic dementia and two matched control participants were tested in naming, defining, and demonstrating the use of 33 household objects. The quality of the definitions was rated as poor, adequate, or good by three independent raters. Three components of object use were examined: hold, orientation, and movement. The assessment was repeated with the patients following 3 weeks of therapy, and 1 month after completion of therapy. For the therapy objects were divided into individual trained and untrained sets based on familiarity and performance at initial assessment. Patients received therapy sessions twice weekly, and engaged in independent practice. During the therapy sessions, the researcher modelled the name, definition, and use of each item, which the patient then repeated. In the independent practice each patient watched a DVD in which she named and defined the object and used it correctly. Outcomes & Results: Patients were severely impaired on object naming and definition, but less so on object use. Both patients showed some improvement as a result of therapy, which was maintained at follow‐up in one case. Conclusions: The results show that relearning in semantic dementia is possible. Factors affecting the results and the interaction between lexical and conceptual impairments are discussed. An unexpected finding of the study was that patients performed better in verb production both in the preliminary tests and in object definition.

Semantic dementia: implications for the neural basis of language and meaning

The clinical differentiation of progressive disorders of language is described in the context of the evolution of current terminology. The syndromes of semantic dementia and progressive non-fluent aphasia can be distinguished on clinical and neuropsychological grounds; the former is characterized by a progressive and selective disintegration of the semantic component of longterm memory. Semantic dementia is also associated with characteristic structural and functional neuroimaging findings, and may represent a form of Picks disease (focal lobar atrophy without Alzheimer histology). Selective impairment of this fundamental component of human cognition has allowed the empirical investigation of a range of theoretical questions. We discuss ideas about the organization and representation of knowledge, the interaction of semantic and episodic memory, and the contribution of semantic memory to reading ability. Many of these ideas can be informatively modelled in the framework of connectionist theory.