Biomedical subjects

J R Hodges

Publications and source records attributed to J R Hodges.

At least 19 recordsLinked to original sources

PubMed2001

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 Alzheimer's 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.

Aged↗

PubMed2001

Episodic memory: insights from semantic dementia.

Semantic dementia, also known as the temporal lobe variant of fronto-temporal dementia, results in a progressive yet relatively pure loss of semantic knowledge about words, objects and people, and is associated with asymmetric, focal atrophy of the antero-lateral temporal lobes. Semantic dementia provides a unique opportunity to study the organization of long-term memory particularly since initial observations suggested sparing of episodic memory. Recent studies reveal, however, a more complex but theoretically revealing pattern. On tests of autobiographical memory, patients with semantic dementia show a 'reverse step function' with sparing of recall of events from the most recent 2 to 5 years but impairment on more distant life periods. Anterograde recognition memory for visual materials is extremely well preserved, except in the most deteriorated cases, although performance is heavily reliant upon perceptual information about the studied stimuli, particularly for items that are no longer known by the subjects. On tests of verbal anterograde memory such as word learning, performance is typically poor even for words which are 'known' to the patients. A source discrimination experiment, designed to evaluate familiarity and recollection-based anterograde memory processes, found that patients with semantic dementia showed good item detection, although recollection of source was sometimes impaired. Semantic knowledge about studied items and measures of item detection and source discrimination were largely independent. The implications of these findings for models of long-term memory are discussed. The results support the concept that episodic memory, or at least the recall of temporally specific autobiographical experiences, draws upon a number of separable memory processes, some of which can function independently of semantic knowledge.

Dementia↗

PubMed2001

Psychiatric symptoms and CAG repeats in neurologically asymptomatic Huntington's disease gene carriers.

The putative relationship between the psychiatric profile of a sample of neurologically asymptomatic Huntington's disease gene carriers and CAG repeats was investigated. The psychiatric assessments (by consultant psychiatrist and computerised battery) were undertaken before the genetic testing was carried out. In this way, the informational distortions caused by neurological and cognitive deficits were avoided. The hypothesis that there is a relationship between psychiatric and CAG repeats was tested by seeking direct correlations between psychiatric systems and CAG repeats, and also by correcting the correlation by the number of years above or below the estimated age of onset in Huntington's disease. Scores for irritability and cognitive failures were high in the sample. There was no correlation between any psychiatric variable and CAG repeats. Possible explanations for this lack of correlations are discussed.

Adenine↗

PubMed2001

Differing patterns of temporal atrophy in Alzheimer's disease and semantic dementia.

OBJECTIVE: To characterize and quantify the patterns of temporal lobe atrophy in AD vs semantic dementia and to relate the findings to the cognitive profiles. Medial temporal lobe atrophy is well described in AD. In temporal variant frontotemporal dementia (semantic dementia), clinical studies suggest polar and inferolateral temporal atrophy with hippocampal sparing, but quantification is largely lacking. METHODS: A volumetric method for quantifying multiple temporal structures was applied to 26 patients with probable AD, 18 patients with semantic dementia, and 21 matched control subjects. RESULTS: The authors confirmed the expected bilateral hippocampal atrophy in AD relative to controls, with involvement of the amygdala bilaterally and the right parahippocampal gyrus. Contrary to expectations, patients with semantic dementia had asymmetric hippocampal atrophy, more extensive than AD on the left. As predicted, the semantic dementia group showed more severe involvement of the temporal pole bilaterally and the left amygdala, parahippocampal gyrus (including the entorhinal cortex), fusiform gyrus, and the inferior and middle temporal gyri. Performance on semantic association tasks correlated with the size of the left fusiform gyrus, whereas naming appeared to depend upon a wider left temporal network. Episodic memory measures, with the exception of recognition memory for faces, did not correlate with temporal measures. CONCLUSIONS: Hippocampal atrophy is not specific for AD but is also seen in semantic dementia. Distinguishing the patients with semantic dementia was the severe global but asymmetric (left > right) atrophy of the amygdala, temporal pole, and fusiform and inferolateral temporal gyri. These findings have implications for diagnosis and understanding of the cognitive deficits in AD and semantic dementia.

Aged↗

PubMed2001

Perceptual and semantic components of memory for objects and faces: a pet study.

Previous studies have suggested differences in the neural substrates of recognition memory when the contributions of perceptual and semantic information are manipulated. In a within-subjects design PET study, we investigated the neural correlates of the following factors: material type (objects or faces), semantic knowledge (familiar or unfamiliar items), and perceptual similarity at study and test (identical or different pictures). There was consistent material-specific lateralization in frontal and temporal lobe regions when the retrieval of different types of nonverbal stimuli was compared, with objects activating bilateral areas and faces preferentially activating the right hemisphere. Retrieval of memories for nameable, familiar items was associated with increased activation in the left ventrolateral prefrontal cortex, while memory for unfamiliar items involved occipital regions. Recognition memory for different pictures of the same item at study and test produced blood flow increase in left inferior temporal cortex. These results have implications for our understanding of the neural correlates of perceptual and semantic contributions to recognition memory.

Adult↗

PubMed2001

Cortical degeneration associated with phonologic and semantic language impairments in AD.

OBJECTIVE: To compare the pattern of cortical degeneration associated with different language deficits in cases of AD. METHODS: Cases for detailed neuropathologic analysis (Patients 1 and 2) were selected because of their detailed clinical and neuropsychological assessments of language dysfunction in AD. Patient 1 had severe phonologic impairment with relatively preserved semantic aspects of language. Patient 2 had severe semantic language impairment with relatively preserved phonologic skills. The tissue volume of cortical regions associated with speech and language function was measured using standardized three-dimensional techniques. Neuronal areal fraction was also measured from histologic tissue samples. The degree of volume atrophy and neuronal loss was calculated in comparison to control measures (n = 10 men and 11 women). Measurements more than 2 SD from controls were considered abnormal. RESULTS: Both AD cases had significant degeneration of the superior temporal gyrus and area 37. Cortical language regions affected only in Patient 1 included the anterior and posterior insula and part of Broca's area. In contrast, Patient 2 had a greater degree of degeneration in the temporal gyri and their white matter connections with the hippocampal/entorhinal complex. CONCLUSIONS: Variable patterns of neurodegeneration underlie the clinical differences observed in patients with AD. Disconnection within the temporal lobe appears associated with semantic language difficulties, whereas disconnection of the anterior and posterior language areas appears associated with phonologic and grammatical impairment.

Aged↗

PubMed2001

No right to speak? The relationship between object naming and semantic impairment: neuropsychological evidence and a computational model.

The processes required for object naming were addressed in a study of patients with semantic dementia (a selective decline of semantic memory resulting from progressive temporal lobe atrophy) and in a computational model of single-word production. Although all patients with semantic dementia are impaired in both single-word production and comprehension, previous reports had indicated two different patterns: (a) a parallel decline in accuracy of naming and comprehension, with frequent semantic naming errors, suggesting a purely semantic basis for the anomia and (b) a dramatic progressive anomia without commensurate decline in comprehension, which might suggest a mainly postsemantic source of the anomia. Longitudinal data for 16 patients with semantic dementia reflected these two profiles, but with the following additional important specifications: (1) despite a few relatively extreme versions of one or other profile, the full set of cases formed a continuum in the extent of anomia for a given degree of degraded comprehension; (2) the degree of disparity between these two abilities was associated with relative asymmetry in laterality of atrophy: a parallel decline in the two measures characterized patients with greater right- than left-temporal atrophy, while disproportionate anomia occurred with a predominance of atrophy in the left-temporal lobe. In an implemented computational model of naming, semantic representations were distributed across simulated left- and right-temporal regions, but the semantic units on the left were more strongly connected to left-lateralized phonological representations. Asymmetric damage to semantic units reproduced the longitudinal patient profiles of naming relative to comprehension, plus additional characteristics of the patients' naming performance. On the basis of both the neuropsychological and computational evidence, we propose that semantic impairment alone can account for the full range of word production deficits described here.

Anomia↗

PubMed2001

Motor neurone disease, dementia and aphasia: coincidence, co-occurrence or continuum?

Cognitive, and particularly aphasic, symptoms associated with motor neurone disease (MND) are still frequently described as rare and "recently discovered". This review demonstrates that the association between MND and dementia was described and recognised as an entity as early as 1929, and its close relationship to Pick's disease was postulated in 1932. Changes in language production and comprehension were also observed by early authors, although they were rarely described as aphasia. The striking similarity to the contemporary descriptions is, however, sometimes obscured by diverging terminology. The syndromes of MND/dementia and MND/aphasia are well established but represent a comparatively small subgroup of MND. In addition, subtle cognitive alterations have also been reported in non-demented MND patients; most studies have found evidence of frontal-executive dysfunction, similar in pattern, but much milder than in patients with frank MND/dementia. These findings are strengthened further by post-mortem studies demonstrating pathological changes in the frontal lobes, and functional neuroimaging studies, showing reduced frontal activation. The issue of whether memory, visuospatial skills and language are affected in non-demented subjects remains, however, controversial. Further studies are required to establish whether MND/dementia and MND/aphasia form separate disease entities or can be viewed as extreme forms of a cognitive deficit characteristic of MND in general.

Aphasia↗

PubMed2001

Deficits in irregular past-tense verb morphology associated with degraded semantic knowledge.

Two distinct mechanisms are often considered necessary to account for generation of the past-tense of English verbs: a lexical associative process for irregular forms like speak-->spoke, and a rule-governed process ("add -ed") for regular and novel forms like talk-->talked and wug-->wugged. An alternative account based on a parallel-distributed processing approach proposes that one complex procedure processes all past-tense types. In this alternative view, neuropsychological dissociations are explained by reduced input from word meaning that plays a greater role in successful generation of the past-tense for lower frequency irregular verbs, and by phonological deficits that disproportionately affect regular and novel forms. Only limited evidence has been available concerning the relationship between knowledge of word meaning and verb-tense processing. The study reported here evaluated the past-tense verb abilities of 11 patients with semantic dementia, a neurodegenerative condition characterised by degraded semantic knowledge. We predicted and confirmed that the patients would have essentially normal ability to generate and recognise regular (and novel) past-tense forms, but a marked and frequency-modulated deficit on irregular verbs. Across the set of 11 patients, the degree of impairment for the irregular past-tense was significantly correlated with the degree of comprehension impairment as measured by verb synonym judgements. These results, plus other features of the data such as the nature of the errors to irregular verbs, are discussed in relation to currently developing theories of the language system.

Aged↗

PubMed2001

Selective impairment of verb processing associated with pathological changes in Brodmann areas 44 and 45 in the motor neurone disease-dementia-aphasia syndrome.

We report six patients with clinically diagnosed and electrophysiologically confirmed motor neurone disease (MND), in whom communication problems were an early and dominant feature. All patients developed a progressive non-fluent aphasia culminating in some cases in complete mutism. In five cases, formal testing revealed deficits in syntactic comprehension. Comprehension and production of verbs were consistently more affected those that of nouns and this effect remained stable upon subsequent testing, despite overall deterioration. The classical signs of MND, including wasting, fasciculations and severe bulbar symptoms, occurred over the following 6-12 months. The behavioural symptoms ranged from mild anosognosia to personality change implicating frontal-lobe dementia. In three cases, post-mortem examination has confirmed the clinical diagnosis of MND-dementia. In addition to the typical involvement of motor and premotor cortex, particularly pronounced pathological changes were observed in the Brodmann areas 44 (Broca's area) and 45. The finding of a selective impairment of verb/action processing in association with the dementia/aphasia syndrome of MND suggests that the neural substrate underlying verb representation is strongly connected to anterior cortical motor systems.

Aged↗

PubMed2001

Focal autobiographical amnesia in association with transient epileptic amnesia.

Although problems with remembering significant events from the past (e.g. holidays, weddings, etc.) have been reported previously in patients with transient epileptic amnesia (TEA), to date there have been no detailed studies of autobiographical memory in patients with this disorder. To investigate this issue, a 68-year-old right-handed man (R.G.) who suffered from TEA and reported significant autobiographical memory problems was tested on a battery of neuropsychological tests of anterograde and remote memory. Tests of autobiographical memory revealed that R.G. was unable to evoke detailed autobiographical recollections from a substantial part of his life. By contrast, he performed well on tests of new learning and general knowledge and possessed good personal semantic information about his past. In summary, a distinct form of autobiographical amnesia, which is characterized by loss of experiential remembering of significant events, may be associated with TEA. It is proposed that the autobiographical memory deficit seen in the disorder may result from the progressive erasure of cortically based memory representations. This case adds to growing evidence for a dissociation between mechanisms subserving anterograde memory and those required to evoke remote episodic memories.

Aged↗

PubMed2001

Semantic dementia: relevance to connectionist models of long-term memory.

Semantic dementia is a recently documented syndrome associated with non-Alzheimer degenerative pathology of the polar and inferolateral temporal neocortex, with relative sparing (at least in the early stages) of the hippocampal complex. Patients typically show a progressive deterioration in their semantic knowledge about people, objects, facts and the meanings of words. Yet, at least clinically, they seem to possess relatively preserved day-to-day (episodic) memory. Neuropsychological investigations of semantic dementia provide, therefore, a unique opportunity to investigate the organization of human long-term memory and, more specifically, to determine the relationship between semantic memory and other cognitive systems, such as episodic memory. In this review, we summarize recent empirical findings from patients with semantic dementia and discuss whether the neuropsychological phenomena of the disease are consistent with current cognitive and computational models of human long-term memory and amnesia. Six specific issues are addressed: (i) the relative preservation of category-level (superordinate) compared with fine-graded (subordinate) semantic knowledge as the disease progresses; (ii) the better recall of recent autobiographical and semantic memories compared with those in the distant past; (iii) the preservation of new learning, as measured by recognition memory, early in the disease; (iv) the interaction between autobiographical experience and semantic knowledge in the current, but not the distant, time-period; (v) increased long-term forgetting of newly learned material; and (vi) impaired implicit memory. It is concluded that recent findings from semantic dementia offer strong support for the view that memory consolidation in humans is dependent upon interactions between the hippocampal complex and neocortex. Furthermore, these investigations have provided computational modellers of human memory with a novel set of neuropsychological data to be simulated and tested.

Amnesia↗

PubMed2001

The classification, genetics and neuropathology of frontotemporal dementia. Introduction to the special topic papers: Part I.

Interest in the neuropsychology and neuropsychiatry of frontotemporal dementia (FTD) has escalated in the past decade, as evidenced by the accompanying 10 special topic papers from research groups in the UK, France, North America and Australia addressing a wide range of theoretical and clinical issues. The first part of this review deals with the confusing terminologies that have been used in the area and argues for the retention of the term FTD as the general clinical label, with further subcategorization into the three principal clinical syndromes seen at presentation: frontal variant FTD (often called dementia of frontal type), semantic dementia and progressive non-fluent aphasia. Each of these syndromes has a characteristic profile of presenting clinical features, but may be accompanied by any one of five types of non-Alzheimer pathological change. There have also been significant advances in the genetics of FTD with the identification of tau gene mutations on chromosome 17 in some familial cases. The remarkable story of the discovery of these, the tau gene mutations, is briefly described. Part II of this review (Hodges and Miller, 2001) sets the special issue papers within the context of advances in the neuropsychology of frontal variant FTD and semantic dementia.

Dementia↗

PubMed2001

Severe anterograde amnesia with extensive hippocampal degeneration in a case of rapidly progressive frontotemporal dementia.

Frontotemporal dementia (FTD) is usually characterized as a spectrum of relatively slowly progressive disorders with largely focal frontal or temporal presentations. The development of clinical and research criteria for discriminating FTD from Alzheimer's disease has relied, in part, on the relative preservation of episodic memory in FTD. We present a patient with FTD who, in addition to the more typical behavioural and language deficits, had a profound anterograde amnesia at the time of diagnosis. Neuroimaging confirmed atrophy of frontal and temporal lobes bilaterally, most marked in the anterior left temporal region. At post-mortem, non-Alzheimer pathology resulting in devastating cell loss was revealed in the hippocampi, as well as in the frontal and temporal cortex, thus providing neuroanatomical corroboration of the episodic memory deficit. Progression of the disease was extraordinarily rapid, with just 2 years between reported onset and time of death. This case demonstrates that the pattern of FTD may include severe anterograde amnesia as a prominent and early consequence of the disease.

Amnesia, Anterograde↗

PubMed2001

The neuropsychology of frontal variant frontotemporal dementia and semantic dementia. Introduction to the special topic papers: Part II.

The second part of this review, which accompanies 10 special topic articles dedicated to frontotemporal dementia (FTD), describes some of the advances in understanding frontal variant FTD (fvFTD) and semantic dementia, and the theoretical insights gained into normal cognitive processes from the study of these syndromes. Recent work has clarified the neuropsychiatric features that distinguish fvFTD from Alzheimer's and has begun to spread light on the underlying deficits in social judgement, theory of mind, processing of emotional stimuli and decision making. With regard to central aspects of cognitive processing, such as memory, patients with fvFTD may have a distinctive profile of performance on tests of explicit and implicit memory, and contrary to current views some patients may even have a severe amnesic syndrome. There is also growing evidence that despite relatively well preserved general language skills, patients with fvFTD have particular problems with verb processing. Although there is agreement regarding the key features of semantic dementia, much controversy has surrounded the issue of whether the cognitive findings favour an explanation in terms of progressive breakdown of a central amodal semantic store or differential involvement of verbal and non-verbal systems. Other topics discussed include the impact of semantic breakdown on phonological processes and episodic memory. We also review recent structural and functional neuroimaging findings in semantic dementia.

Dementia↗

PubMed2001

Dissociation of social cognition and executive function in frontal variant frontotemporal dementia.

In this paper, we adopt a neurodevelopmental stance to examining frontal variant frontotemporal dementia (fv-FTD) by using experimental procedures from the literature on the growth of social behaviour in children to examine the deficits in social reasoning which may underpin behavioural disturbance in fv-FTD. We present the case of a 47-year-old man with a diagnosis of fv-FTD and severe antisocial behaviour. Tests of general neuropsychology and of executive function were performed. In addition, the patient, JM, was assessed on tasks which test theory of mind. Theory of mind develops in distinct stages through childhood and is a core ability to represent the thoughts and feelings of others, independent of the level of intellectual ability. The results indicate relatively intact general neuropsychological and executive function, but extremely poor performance on tasks of theory of mind. This indicates a dissociation of social cognition and executive function suggesting that in psychiatric presentations of fv-FTD there may be a fundamental deficit in theory of mind independent of the level of executive function. The implications of this finding for diagnostic procedures and possible behavioural management are discussed.

Antisocial Personality Disorder↗

PubMed2001

Semantic memory is impaired in both dementia with Lewy bodies and dementia of Alzheimer's type: a comparative neuropsychological study and literature review.

OBJECTIVE: To test the hypothesis that semantic impairment is present in both patients with dementia with Lewy bodies (DLB) and those with dementia of Alzheimer's type (DAT). METHODS: A comprehensive battery of neuropsychological tasks designed to assess semantic memory, visuoperceptual function, verbal fluency, and recognition memory was given to groups of patients with DLB (n=10), DAT (n=10) matched pairwise for age and mini mental state examination (MMSE), and age matched normal controls (n=15). RESULTS: Both DLB and DAT groups exhibited impaired performance across the range of tasks designed to assess semantic memory. Whereas patients with DAT showed equivalent comprehension of written words and picture stimuli, patients with DLB demonstrated more severe semantic deficits for pictures than words. As in previous studies, patients with DLB but not those with DAT were found to have impaired visuoperceptual functioning. Letter and category fluency were equally reduced for the patients with DLB whereas performance on letter fluency was significantly better in the DAT group. Recognition memory for faces and words was impaired in both groups. CONCLUSIONS: Semantic impairment is not limited to patients with DAT. Patients with DLB exhibit particular problems when required to access meaning from pictures that is most likely to arise from a combination of semantic and visuoperceptual impairments.

Aged↗

PubMed2001

Perception, attention, and working memory are disproportionately impaired in dementia with Lewy bodies compared with Alzheimer's disease.

OBJECTIVE: To test the hypotheses that visuoperceptual and attentional ability are disproportionately impaired in patients having dementia with Lewy Bodies (DLB) compared with Alzheimer's disease (AD). METHODS: A comprehensive battery of neuropsychological tasks designed to assess working, episodic, and semantic memory, and visuoperceptual and attentional functions was given to groups of patients with DLB (n=10) and AD (n=9), matched for age, education, and mini mental state examination (MMSE), and to normal controls (n=17). RESULTS: Both patient groups performed equally poorly on tests of episodic and semantic memory with the exception of immediate and delayed story recall, which was worse in the AD group. Digit span was by contrast spared in AD. The most striking differences were on tests of visuoperceptual/spatial ability and attention. Whereas patients with AD performed normally on several subtests of the visual object and space perception battery, the DLB group showed substantial impairments. In keeping with previous studies, the AD group showed deficits in selective attention and set shifting, but patients with DLB were more impaired on virtually every test of attention with deficits in sustained, selective, and divided attention. CONCLUSIONS: Patients with DLB have substantially greater impairment of attention, working memory, and visuoperceptual ability than patients with AD matched for overall dementia severity. Semantic memory seems to be equally affected in DLB and AD, unlike episodic memory, which is worse in AD. These findings may have relevance for our understanding of the genesis of visual hallucinations, and the differential diagnosis of AD and DLB.

Aged↗