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J R Hodges

Publications and source records attributed to J R Hodges.

At least 127 records · Page 7Linked to original sources

Spatial and non-spatial working memory at different stages of Parkinson's disease.

Groups of patients with Parkinson's disease, either medicated or unmedicated, were compared with a matched group of normal control subjects on a computerized battery of tests designed to assess spatial, verbal and visual working memory. In the spatial working memory task, subjects were required to search systematically through a number of boxes to find 'tokens' whilst avoiding those boxes in which tokens had previously been found. In the visual and verbal conditions, the subjects were required to search in exactly the same manner, but through a number of abstract designs or surnames, respectively, avoiding designs or names in which a token had previously been found. Medicated Parkinson's disease patients with severe clinical symptoms were impaired on all three tests of working memory. In contrast, medicated patients with mild clinical symptoms were impaired on the test of spatial working memory, but not on the verbal or visual working memory tasks. Non-medicated patients with mild clinical symptoms were unimpaired on all three tasks. These data are compared with the results of a previous study comparing groups of neurosurgical patients with frontal, temporal or amygdalo-hippocampectomy excisions on the same three tests of working memory. Taken together, the findings suggest that working memory deficits in Parkinson's disease emerge, and subsequently progress, according to a defined sequence, the evolution of which may be linked to the likely spatiotemporal progression of dopamine depletion within the striatum, in relation to the terminal distribution of its cortical afferents.

Antiparkinson Agents↗

Dysgraphia in mild dementia of Alzheimer's type.

We assessed writing abilities in a cohort of 31 patients with a diagnosis of DAT (in two subgroups, with minimal [MMSE 24-28] and mild [MMSE 16-23] levels of dementia), and 10 matched controls. Central aspects of writing were assessed by both written and oral spelling to dictation of 72 single words varying in frequency (high or low) and predictability of sound-to-spelling correspondences (predictable, unpredictable and irregular). All subjects achieved better scores on high, as compared to low, frequency words. The performance of both patient groups was significantly affected by degree of predictability, and was equivalent in the written and oral spelling conditions. Phonologically acceptable alternative spellings (e.g. 'wade'-->WAID) constituted the majority of errors. More peripheral processes in writing were assessed by copying and cross-case transcription of single letters. Subjects were more successful at copying within case than transcribing across case. Performance was also better--substantially so for the mild DAT group--when the target response in either task was an upper- rather than a lower-case letter. There was considerable heterogeneity in performance on the spelling and the letter tasks. Some patients (even in the more affected DAT group) were unimpaired on both tasks, suggesting that dysgraphia is not a constant feature in early DAT. When writing deficits do become apparent, in the earliest stages of the disease the pattern is most likely to be one of mild surface dysgraphia, a form of central dysgraphia; impairments in more peripheral aspects of writing tend to emerge once the disease has progressed beyond the minimal stage.

Aged↗

The relationship between naming and semantic knowledge for different categories in dementia of Alzheimer's type.

We studied the relationship between naming and semantic memory in a group of 10 patients with dementia of Alzheimer's type. In an extension to a previous cross-sectional study (Hodges, J. R. et al., Brain and Language, 1996, 54, 302-325), this relationship was investigated at two longitudinal points within each patient's cognitive decline. Two types of naming performance were compared: items that each patient named correctly at the first stage but failed to name at the second stage, as contrasted with items named correctly at both stages (thereby providing a control for cognitive decline in general). Semantic knowledge of the concepts represented by the pictures in the naming test was investigated at each stage using definitions to the spoken object name, scored particularly for the number of sensory and associative/functional features provided by the patient. At stage 2, an analysis of the definitions for named-->unnamed items as contrasted with named-->named objects revealed a significant loss of both sensory and associative information. A comparison between natural kinds (animals and birds) and artefacts (household objects, vehicles, etc.), however, demonstrated a striking interaction between category and type of information contained in the definitions. Specifically, stage 2 definitions of artefacts in the named-->unnamed set showed a disproportionate loss of associative/functional information, while definitions of animal names that patients failed to produce in response to the pictures were notably lacking in sensory features. This pattern supports the notion that successful naming relies on a subset of critical semantic features which vary somewhat across different categories of semantic knowledge. We suggest that these findings are best encompassed by a conception of semantic organization, Weighted Overlappingly Organized Features (WOOF), in which (i) knowledge about all objects is represented by a central, distributed network of features activated by both words and pictures, but (ii) natural kinds and artefacts are differentially weighted in favour of those features that are involved in learning about and experiencing different kinds of objects.

Aged↗

On the relationship between knowledge and memory for pictures: evidence from the study of patients with semantic dementia and Alzheimer's disease.

Current views of long-term memory presume that both the hippocampal complex and the neocortex play interactive, but separate, roles in the storage of memories. While the neocortex is considered the eventual and permanent store for our memories, the encoding of recently experienced events is thought to be initially dependent upon the hippocampus and closely related structures. Neuropsychological studies have demonstrated that damage to the medial temporal lobe results in a retrograde amnesia extending back in time, with better preservation of older memories. The converse pattern has been shown in patients with semantic dementia, who have focal atrophy of the inferolateral temporal neocortex, but relative sparing of the hippocampal complex (Graham & Hodges, 1997). Here we demonstrate that such patients can show relatively preserved new learning on a forced-choice recognition memory test (based on real and chimeric animals), while patients in the early amnestic phase of Alzheimer's disease show severely impaired learning on the same test. This result provides support for the view that new learning is primarily dependent upon the hippocampus and related structures.

Alzheimer Disease↗

Generating 'tiger' as an animal name or a word beginning with T: differences in brain activation.

Positron emission tomography was used to investigate differences in regional cerebral activity during word retrieval in response to different prompts. The contrast of semantic category fluency and initial letter fluency resulted in selective activation of left temporal regions; the reverse contrast yielded activation in left frontal regions (BA44/6). A further comparison between types of category fluency demonstrated a more anterior temporal response for natural kinds and more posterior activation for manipulable manmade objects. These results support behavioural data suggesting that category fluency is relatively more dependent on temporal-lobe regions, and initial letter fluency on frontal structures; and that categorical word retrieval is not a uniformly distributed function within the brain. This is compatible with the category-specific deficits observed after some focal lesions.

Adult↗

Semantic memory is impaired in schizophrenia.

Memory is emerging as a key area of neuropsychological deficit in schizophrenia, with evidence suggesting that the impairment is restricted to long-term memory. Semantic memory, the component of long-term memory containing stored representations of the meanings of words and knowledge about the world, was examined in 46 schizophrenic patients and 40 normal controls using a recently devised battery of tests. Evidence of semantic memory impairment was found which was wide ranging and substantial; in some cases it approached the levels seen in a group of 22 patients with mild-to-moderate Alzheimer's disease. Both group analysis and a more detailed examination of two single cases suggested that semantic memory impairment represents a disproportionate and possibly specific neuropsychological deficit in schizophrenia.

Adolescent↗

Alzheimer disease and nonfluent progressive aphasia.

OBJECTIVE: To describe a patient with pathologically proven Alzheimer disease (AD) who presented with a non-fluent progressive aphasic syndrome. DESIGN: Longitudinal neuropsychological assessment, structural (magnetic resonance imaging) and functional (single photon emission computed tomography) imaging, and postmortem brain examination. SETTING: Memory and cognitive disorders clinic in a tertiary referral hospital. PATIENT: A 66-year-old man presented with a 5-year history of progressive nonfluent aphasia characterized by marked deficits in phonology and syntax with preservation of everyday abilities. His condition deteriorated rapidly and he died suddenly of a myocardial infarction 12 months later. RESULTS: Neuropsychological testing revealed mild global intellectual impairment with marked impairment of auditory verbal short-term memory, syntactic, and phonological abilities. His naming errors were predominantly phonological paraphasias. Magnetic resonance imaging scans showed left perisylvian atrophy and results of a Tc 99m hexamethyl-propyleneamine-oxime single photon emission computed tomographic scan were normal. Postmortem pathological examination revealed typical AD pathological features with atypical distribution, involving predominantly perisylvian language areas, but sparing the medial temporal lobe. CONCLUSIONS: The language deficits in AD, which have received considerable attention, are thought to involve predominantly lexicosemantic processes. When AD presents as a relatively isolated language disturbance, the aphasia is usually of the fluent anomic type. To our knowledge, our patient represents the first fully documented case of progressive nonfluent aphasia with pathologically verified AD.

Aged↗

Naming and knowing in dementia of Alzheimer's type.

We studied the relationship between naming and the integrity of physical and associative knowledge in a group of patients with dementia of the Alzheimer type (DAT) and matched normal controls. All subjects named 48 line drawings and later generated verbal definitions in response to the names of a subset of the 48 items, which included a minimum of six definitions for correctly named objects and six definitions for items that the subject failed to name. A comprehensive scoring system was designed for the definitions, including physical and associative features of a general and a specific type, a superordinate label, the core concept, and various categories of errors. The definitions generated by the DAT patients, even those in the minimal group, contained significantly less correct information than those of normal subjects, and definitions corresponding to unnamed items were more impoverished than those for named items. Particularly striking was the loss of core concept for unnamed items. There was also a disproportionate reduction in physical information on unnamed compared to named items. We conclude that quantitative assessment of verbal definitions is a sensitive index of semantic memory breakdown. Our findings offer some support for the hypothesis that successful naming depends upon integrity of the subset of semantic knowledge comprising physical features.

Aged↗

Clinical features of frontal lobe dementia in comparison to Alzheimer's disease.

Over the past decade it has become evident that a substantial minority of patients with primary dementing diseases, particularly those presenting in the presenium, have dementia of frontal lobe type (DFT) due to non-Alzheimer's pathology. Although post-mortem remains the only method of definitive diagnosis, DFT and Alzheimer's disease (AD) can, we would claim, be separated with a high degree of certainty based on a combination of informant history, neuropsychology and neuroimaging. In DFT, changes in personality, motivation, social interaction and organisational abilities, in the presence of well preserved memory and visuospatial abilities, are characteristic. The lack of insight emphasises the need for independent information particularly as patients may perform normally on bedside (and more sophisticated) tests of cognition. Psychiatric features especially mood disturbance appear to be common, but their prevalence remains to be established. In contrast, AD is a progressive amnestic disorder with episodic and semantic memory deficits, followed by breakdown in other attentional, perceptual and visuo-spatial abilities, which reflects the major locus of pathology in AD, namely the medial temporal lobe. These features are illustrated by reference to a longitudinal study of 52 patients with minimal to moderate AD. In addition, we shall describe the results of retrospective and prospective neuropsychiatric studies of a group of DFT patients.

Aged↗

Neuroradiological findings in primary progressive aphasia: CT MRI and cerebral perfusion SPECT.

Primary progressive aphasia (PPA) is defined as progressive decline in language for 2 or more years with preservation of activities of daily living and general cognitive functions. Whereas the clinical features of this syndrome have been well documented, the neuroradiological findings have not been studied systematically. We studied 13 patients with PPA retrospectively: 10 underwent CT, 12 MRI and 12 cerebral perfusion studies using 99mTc-HMPAO SPECT.CT and MR images were scored for focal atrophy by two independent assessors. Initial qualitative assessment of SPECT images was confirmed by quantitative analysis. CT was normal in 5 patients. Focal atrophy, affecting predominantly the left temporal lobe, was seen in 4 of 10 patients on CT, and 10 of 12 on MRI. Atrophy was localised primarily to the superior and middle temporal gyri on MRI. All 12 patients who underwent SPECT had unilateral temporal lobe perfusion defects, in 2 patients of whom MRI was normal. CT is relatively insensitive to focal abnormalities in PPA; MRI and SPECT are the imaging modalities of choice. MRI allows accurate, specific localisation of atrophy within the temporal neocortex. SPECT may reveal a functional decrease in cerebral perfusion prior to establishment of structural change.

Adult↗

Neuropsychological performance, disease severity, and depression in progressive supranuclear palsy.

To investigate the relationship between disease severity, cognitive impairment and depression in progressive supranuclear palsy (PSP) we studied a group of 25 patients who fulfilled strict research criteria and 25 matched controls. Disease severity was judged from the duration of symptoms, level of physical disability using the Columbia Rating Scale (CRS), and the degree of eye movement abnormality. The neuropsychological battery was designed to assess attention and executive function, visual and auditory perception, semantic memory and language production. Although the PSP group were significantly impaired on almost all of these measures, the most profound deficits were on tests of sustained and divided attention. There was no correlation between cognitive impairment and either disease duration or scores on the CRS, but performance on tests of attention correlated significantly with the degree of ocular motor impairment. Depression was found to be common in PSP but did not correlate with any other parameters. It is concluded that the cognitive deficit in PSP is widespread and independent of depression. The association between the severity of eye movement disorder and deficits in sustained and divided attention leads us to postulate that pathology involving the midbrain periaqueductal region may be critical for breakdown in these fundamental processes.

Aged↗

The alpha(2) antagonist idazoxan remediates certain attentional and executive dysfunction in patients with dementia of frontal type.

Abstract The mixed alpha(1)/alpha(2) adrenoceptor agonist clonidine has been shown by us previously to impair certain attentional and executive functions in healthy volunteers. The present investigation examines the effects of the alpha(2) adrenoceptor antagonist idazoxan (IDZ) on cognitive function in patients with dementia of frontal type (DFT). Using a placebo-controlled ABBA design, three DFT patients were given two doses of IDZ and tested on a range of computerised tests of attention, memory and executive function. Idazoxan was found to produce dose-dependent improvements in performance, particularly on tests of planning, sustained attention, verbal fluency and episodic memory. In contrast, IDZ produced deficits in performance on a test of spatial working memory. These results suggest that IDZ may be useful as a putative cognitive enhancer, particularly in patients showing a specific pattern of frontal lobe dysfunction.

Adrenergic alpha-Antagonists↗

Neuropsychology of memory and SPECT in the diagnosis and staging of dementia of Alzheimer type.

We studied the role of neuropsychology and SPECT imaging in the diagnosis and staging of dementia of Alzheimer type (DAT) in 33 patients with mild disease and 30 matched controls. Working, episodic, semantic and remote memory were assessed. For diagnosis, it was determined by logistic regression analysis that one of the memory tests (delayed verbal recall of the Doors and People Test) could correctly classify subjects as DAT or controls in 97% of cases. For staging, stepwise regression analysis using five of the memory tests could predict 70% of the variance in Mini Mental State Examination (MMSE) scores. The measures most useful for staging were tests of immediate recall, and tests of working, semantic and autobiographical memory. In a separate experiment, SPECT imaging on 31 of the above 33 patients and 24 different controls was used to address the issue of diagnosis and staging. 99Tc-HMPAO SPECT scans were analysed quantitatively to obtain measures of regional cerebral blood flow (rCBF). Logistic regression analysis showed that three of the SPECT regions of interest (left posterior temporal, right high frontal and right posterior temporal) could correctly classify subjects in 75% of cases. Of note was the fact that 39% of the DAT patients had normal SPECT scans. SPECT data were of limited use in modelling disease severity; only 38% of the variance in MMSE scores could be predicted from SPECT data. In addition, we found that the pattern of rCBF in DAT was much more heterogeneous than previously described.

Aged↗

Analysis of the episodic memory deficit in early Alzheimer's disease: evidence from the doors and people test.

Anterograde episodic memory was assessed in a cohort of 33 patients with early dementia of Alzheimer type (DAT) and 30 matched controls using immediate and delayed prose recall, the CERAD word learning test and the recently developed doors and people test of visual and verbal recall and recognition. DAT patients showed markedly impaired learning on all three measures, with little evidence of cumulation of information across trials. Patients showed more forgetting than controls on prose recall and the CERAD word list, but more detailed analysis suggested that this differential loss was attributable to the contribution of primary memory to immediate but not delayed recall. No differences in forgetting rate were observed on the doors and people test. Scaled scores were used to derive a recall-recognition index, together with a measure of material-specific memory based on the ratio of verbal to visual memory deficits. There was no evidence for differential sensitivity of recall over recognition, implying that the episodic memory deficit is one of learning, rather than of the retrieval of learned material. Although individuals varied in the relative degree of impairment of verbal and visual memory, there was no general tendency for material-specificity. It was concluded that the episodic memory deficit in DAT is general in nature and primarily reflects impaired learning rather than accelerated forgetting or disrupted retrieval.

Aged↗

Nonfluent progressive aphasia and semantic dementia: a comparative neuropsychological study.

Two patients with nonfluent progressive aphasia, who have been studied longitudinally, are contrasted with a group of 5 patients with fluent progressive aphasia or semantic dementia. The most prominent feature of the nonfluent syndrome is the severe distortion of speech output with phonological errors and agrammatic sentence structure. This contrasts with the fluent, well articulated and syntactically correct, but empty, anomic speech found in semantic dementia. Performance on tests of comprehension separates the patient groups: The nonfluent patients show normal single-word comprehension, but marked impairment on tests of syntactic comprehension, while those with semantic dementia demonstrate the opposite pattern. Category fluency is severely defective in semantic dementia, but initial letter-based fluency is more impaired in the nonfluent syndrome. Performance on nonverbally mediated tests of semantic knowledge is impaired in semantic dementia only. The 2 forms of progressive aphasia have in common the sparing of perceptual and visuospatial skills, nonverbal problem solving abilities, and day-to-day (episodic) memory. Neuroradiological investigations have shown marked selective and striking inferolateral left temporal lobe atrophy in all 5 patients with semantic dementia. The changes in nonfluent progressive aphasia appear to be less focal and involve left perisylvian structures more diffusely. These 2 forms of progressive aphasia are, we argue, distinct in their manifestations.

Aged↗

Identification of famous faces and famous names in early Alzheimer's disease. Relationship to anterograde episodic and general semantic memory.

We assessed remote memory in 33 patients with dementia of Alzheimer's type (DAT) with Mini-Mental State Examination (MMSE) scores between 17 and 30, and 30 matched controls using a Famous Faces Test and Famous Names Test designed to assess face recognition, identification and naming, and name recognition and identification, respectively, together with a range of anterograde episodic and semantic memory tests. Patients with DAT were impaired on all components of the remote memory tests, i.e. famous face recognition, identification and naming, and famous name recognition and identification. There was also evidence of a modest temporal gradient, with relatively greater impairment of more recent memory, which may be artefactual resulting from the very insidious onset of their anterograde amnesia. In contrast to the uniform impairment of anterograde memory, there was considerable heterogeneity in performance on remote memory. Although the DAT patient group's performance on remote memory measures was impaired with respect to controls, some patients had significant impairment on all measures, whereas others had intact remote memory. Overall, there was only a weak correlation between dementia severity and remote memory, and no correlation between performance on the Faces and Names tests and measures of anterograde memory. At a cognitive level, the deficit in face and name processing in DAT involved recognition, identification and naming. This would suggest that so called 'face and name recognition units', semantic knowledge of famous persons and post-semantic processing are all affected by the disease. There was also supporting evidence for the concept that recognition of famous faces and names both draw on common sources. Similar results were found for face and name identification. This suggests that face and name recognition units are closely linked, and that identification of a face or name accesses the same central pool of semantic knowledge regarding the famous person. Performance on famous names tests correlated, to a limited degree, with that on general semantic tests, suggesting that knowledge of famous people, at least as accessed by names, is associated with general semantic memory. By contrast, no correlation was found between performance on the famous faces and on other general semantic tasks.

Aged↗