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J S Snowden

Publications and source records attributed to J S Snowden.

At least 55 records · Page 3Linked to original sources
PubMed1994

Choice of reference region in the quantification of single-photon emission tomography in primary degenerative dementia.

This study evaluated the effect of using two different reference regions in the quantification of single-photon emission tomography (SPET). SPET scans of 30 patients with Alzheimer's disease (AD) and 30 patients with frontotemporal dementia were compared with the scans of ten age-matched controls. Regions of interest (ROIs) were defined on transaxial slices by a semi-automatic method. Regional cerebral blood flow indices (rCBFi) in each ROI were determined by normalizing the count densities to both cerebellar and occipital cortex reference regions. Mean rCBFi for each ROI were calculated for the patient and control groups and significant group differences determined. The number and topographical distribution of ROIs with significant group differences varied depending upon the choice of reference region. The magnitude of these differences was greatest when the cerebellum was used as the reference region. The disparity between results obtained with the two reference regions was most apparent in the AD group. The reasons for these differences are discussed and we conclude that the cerebellum is the more appropriate choice of reference region in the quantification of SPET in primary degenerative dementia.

Alzheimer Disease↗
PubMed1993

The topographic distribution of brain atrophy in Huntington's disease and progressive supranuclear palsy.

The topographic distribution of brain atrophy was quantified by image analysis of fixed coronal brain slices from 12 patients dying with Huntington's disease (HD) and from 4 other patients dying with progressive supranuclear palsy (PSP). In HD, atrophy was maximal within the caudate nucleus, putamen and globus pallidus. However, the cerebral cortex was also atrophied with reductions in cross-sectional area within frontal, temporal and parietal lobes. In general, more white matter than grey matter was lost leading to an elevation in the grey/white matter ratio. The amygdala and thalamus were reduced in area. In PSP, lesser reductions in cortical area than those of HD were seen, these again being mostly due to a loss of white matter, resulting in an elevation of the grey/white ratio. The globus pallidus and thalamus were decreased in area, but no changes in the caudate nucleus and putamen were measured.

Adult↗
PubMed1993

Familial progressive aphasia: its relationship to other forms of lobar atrophy.

Two brothers presented with slowly progressive aphasia. One brother, who became behaviourally disturbed only at the end of his illness, was found at necropsy to have predominant left frontotemporal atrophy. The other brother developed severe behavioural disturbances shortly after the onset of language impairment. His brain revealed bilateral frontotemporal atrophy. In both there was non-Alzheimer's disease pathology with the histological features of loss of large cortical nerve cells, spongiform change and mild gliosis. The differential anatomical atrophy supports the view that clinical manifestations of lobar atrophy are dictated by the topographical distribution of a common underlying pathology, linking the syndromes of progressive aphasia to dementia of frontal lobe type (DFT) and DFT with motor neuron disease.

Aphasia↗
PubMed1993

Dementia of frontal lobe type: neuropathology and immunohistochemistry.

Brains from 12 patients dying with a clinical diagnosis of frontal lobe dementia have been examined at post mortem. In pathological terms four groups were encountered. Groups A and B showed severe frontal and temporal lobe atrophy characterised histologically in group A by severe neuronal loss, spongiform change of the superficial laminae, and mild astrocytosis; in group B severe neuronal loss was accompanied by intense gliosis but with little or no spongiform change. Two patients in this latter group also showed inclusions in frontal cortex and hippocampus typical of "Pick bodies"; such patients were considered as having classic "Pick's disease". Group C patients showed severe striatal atrophy with variable cortical (frontal or temporal) involvement, with histological changes similar to patients in groups A and B. The single patient in group D showed mild frontotemporal atrophy with spongiform degeneration of the superficial laminae of the cortex and nigral damage, and was considered to have motor neuron disease with dementia. This study is consistent with previous reports showing that the clinical syndrome of frontal lobe dementia is pathologically heterogeneous. However, the nosological relationships within these pathological variants, and between them and conditions such as progressive aphasia were similar histopathological changes are present, remain uncertain.

Aged↗
PubMed1992

Pathological changes in the brain of a patient with familial Alzheimer's disease having a missense mutation at codon 717 in the amyloid precursor protein gene.

The brain of a 61-year-old patient with familial Alzheimer's disease, showing a missense (valine----glycine) mutation at codon 717 of the amyloid precursor gene, has been examined at postmortem. Sections of brain showed pathological features entirely typical of Alzheimer's disease with no unusual characteristics. It seems therefore that this particular mutation is indeed pathogenic and that the altered amyloid precursor protein resulting from expression of this mutation is processed in a way that triggers or promotes the pathological cascade of Alzheimer's disease.

Adult↗
PubMed1992

Progressive language disorder due to lobar atrophy.

Sixteen patients with progressive language disorder have been studied longitudinally. Anomia was a prominent presenting characteristic and mutism ultimately occurred. Patients, however, were clinically heterogeneous. Some exhibited nonfluent, agrammatic features, whereas others demonstrated a fluent aphasia, with profound loss of word meaning. Although language disorder remained the sole symptom in a minority of patients, in others an associative agnosia or personality and behavioral changes, or both, emerged. Findings on computed tomography and single photon emission tomography mirrored the areas of dysfunction suggested by the neuropsychological profiles and demonstrated abnormalities restricted to the left hemisphere or involving bilateral frontotemporal cortices. Brains of 3 patients, with distinctive clinical pictures, have been examined at autopsy. Each revealed a focal distribution of atrophy, gliosis and spongiform change, and an absence of senile plaques and neurofibrillary tangles. There was clinical and pathological overlap with frontal lobe dementia. We argue that progressive language disorder is clinically heterogeneous and forms part of a spectrum of clinical presentations of non-Alzheimer lobar atrophy.

Aged↗
PubMed1992

Deposition of amyloid beta protein in non-Alzheimer dementias: evidence for a neuronal origin of parenchymal deposits of beta protein in neurodegenerative disease.

In two elderly patients with frontal lobe dementia and in two others with progressive aphasia an inverse relationship between the severity of beta protein deposition and the principal pathology of these disorders was noted. Deposition of beta protein occurred only in areas of cortex where functional (viable) neurones were still present and was absent where neuronal decimation had taken place. Such findings suggest that the presence of functional neurones is necessary for beta protein deposition to occur and, therefore, that neurones may be the source of the amyloid protein that is deposited within brain parenchyma not only in these disorders but also in other conditions, particularly Alzheimer's disease.

Aged↗
PubMed1990

Frontal lobe dementia and motor neuron disease.

Four patients are described, in whom a profound and rapidly progressive dementia occurred in association with clinical features of motor neuron disease. The pattern of dementia indicated impaired frontal lobe function, confirmed by reduced tracer uptake in the frontal lobes on single photon emission computed tomography (SPECT). Pathological examination of the brains of two patients revealed frontal-lobe atrophy, with mild gliosis and spongiform change. The spinal cord changes were consistent with motor neuron disease. The clinical picture and pathological findings resembled those of dementia of frontal-lobe type and were distinct from those of Alzheimer's disease. The findings have implications for the understanding of the spectrum of non-Alzheimer forms of primary degenerative dementia.

Adult↗
PubMed1990

Assessment of outcome in clinical trials in Alzheimer's disease.

Assessment instruments used to measure psychological outcome in clinical trials in dementia include rating scales of activities of daily living and scales of cognitive function. Each has specific advantages and limitations. The popularity of certain dementia scales results from their demonstrated correlation with measures of pathological change, implying that they accurately reflect dementia severity. It is argued that the inference of test validity on the basis of such clinicopathological correlation may be unfounded. Alzheimer's disease is a heterogeneous disorder, encompassing varying profiles of cognitive disability. Dementia scales, which are weighted in favour of specific areas of dysfunction, may be differentially sensitive to the deficits of certain patients relative to others, thus yielding a spurious measure of dementia severity.

Activities of Daily Living↗
PubMed1988

The use of [99mTc]-HM-PAO in the diagnosis of primary degenerative dementia.

The clinical value of single photon emission computed tomography (SPECT) in the differential diagnosis of dementia due to cerebral atrophy was evaluated by comparing the pattern of distribution [99mTc]-HM-PAO in three dementing conditions. Imaging was carried out in 26 patients with suspected Alzheimer's disease, 14 with dementia of the frontal-lobe type, and 13 with progressive supranuclear palsy. Images were evaluated and reported without knowledge of clinical diagnosis with respect to regions of reduced uptake of tracer. Reduced uptake in the posterior cerebral hemispheres was characteristic of Alzheimer's disease, while selective anterior hemisphere abnormalities characterized both dementia of the frontal-lobe type and progressive supranuclear palsy. The latter conditions could be distinguished on the basis of the appearance of integrity of the rim of the frontal cortex. The technique has an important role in the differentiation of degenerative dementias.

Aged↗
PubMed1988

Dementia of frontal lobe type.

A significant proportion of patients with presenile dementia due to primary cerebral atrophy do not have Alzheimer's disease. One form of non-Alzheimer dementia may be designated as dementia of frontal lobe type (DFT), on the basis of a characteristic neuropsychological picture suggestive of frontal lobe disorder, confirmed by findings on single photon emission tomography. The case histories of seven patients exemplify the disorder: a presentation of social misconduct and personality change, unconcern and disinhibition, in the presence of physical well-being and few neurological signs. Assessment revealed economic and concrete speech with verbal stereotypes, variable memory impairment, and marked abnormalities on tasks sensitive to frontal lobe function. Visuo-spatial disorder was invariably absent. Comparisons of DFT and Alzheimer patients revealed qualitative differences in clinical presentation, neurological signs, profile of psychological disability, electroencephalography, single photon emission tomography and demography. DFT, which may represent forms of Pick's disease, may be more common than is often recognised.

Alzheimer Disease↗
PubMed1987

Catecholaminergic neurones assessed ante-mortem in Alzheimer's disease.

Indices of dopaminergic and noradrenergic varicosities were assayed in neocortical tissue obtained at diagnostic craniotomy from patients with Alzheimer's disease in the presenium. Dopaminergic markers (concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid) were not significantly different from controls in either frontal or temporal cortex. In the frontal cortex, the release of endogenous dopamine and noradrenaline (in the presence of both resting and stimulating concentrations of potassium) was also unaffected whereas release of endogenous serotonin was significantly reduced. In the temporal cortex, noradrenergic markers (concentration of noradrenaline and uptake of radiolabelled noradrenaline) were significantly reduced, to at least 47% of mean control values. These deficits are interpreted as reflecting denervation and were present in patients examined only some two years after developing symptoms of dementia. The ratio of 3-methoxy-4-hydroxyphenylglycol to noradrenaline (a putative index of noradrenaline turnover) was elevated in the temporal cortex, suggesting increased activity of the remaining noradrenergic varicosities. Noradrenergic markers did not correlate with either clinical or histological indices of the severity of the disease which contrasts with presynaptic cholinergic and serotonergic markers.

Adult↗
PubMed1987

Somatostatin content and release measured in cerebral biopsies from demented patients.

Somatostatin-like immunoreactivity (SLIR) has been assayed in frontal and temporal cortex obtained at diagnostic craniotomy and post-mortem from patients with histologically verified Alzheimer's disease. SLIR content was not significantly different from controls in the frontal and temporal lobes, except in the temporal cortex post-mortem. The K+-stimulated release of endogenous SLIR from tissue prisms ('mini-slices') prepared from neocortex obtained at diagnostic craniotomy from Alzheimer patients was not below the control values. Indices of cholinergic varicosities in similar samples from the frontal and temporal lobes are reduced; accordingly, somatostatin does not seem to be as prominently involved in these regions. Patients with Alzheimer's disease underwent neuropsychological assessment shortly before sampling the temporal lobe. Scores for WAIS full scale and the verbal subscale and the Token Test (measure of language comprehension) significantly correlated with the SLIR content; mean values (fmole/mg protein) were 817, 1468 and 1363 for aphasic and non-aphasic Alzheimer patients and controls, respectively. Ventricular fluid obtained from Alzheimer patients during surgery, did not have a significantly different SLIR content compared to controls. SLIR contents of ventricular fluid and neocortex from demented patients, without any specific histological changes in the sample obtained at diagnostic craniotomy, were also not significantly different from controls. Previously, we have shown that these demented patients, as well as those with histologically verified Alzheimer's disease, have a reduced SLIR content of lumbar fluid so it seems that somatostatin neurones located outside the frontal and temporal lobes are affected relatively early in the disease process.

Aged↗
PubMed1987

Presynaptic serotonergic dysfunction in patients with Alzheimer's disease.

Indices of presynaptic serotonergic nerve endings were assayed in neocortical biopsy samples from patients with histologically verified Alzheimer's disease. The concentrations of 5-hydroxytryptamine (serotonin) and 5-hydroxyindoleacetic acid, serotonin uptake, and K+-stimulated release of endogenous serotonin were all found to be reduced below control values. Changes occurred in samples from both the frontal and temporal lobes, but they were most severe (at least a 55% reduction) in the temporal lobe. This is indicative of substantial serotonergic denervation. Values for serotonergic markers in Alzheimer's disease samples did not show correlations with rating of the severity of dementia, indices of cholinergic innervation, or senile plaque and cortical pyramidal neurone loss. However, neurofibrillary tangle count and an index of glucose oxidation (both probably reflecting pyramidal cells) correlated with the concentration of 5-hydroxyindoleacetic acid.

Alzheimer Disease↗
PubMed1987

Single photon emission tomography using 99mTc-HM-PAO in the investigation of dementia.

Single photon emission tomographic imaging of the brain using 99mTc HM-PAO was carried out in patients with a clinical diagnosis of Alzheimer's disease, non-Alzheimer frontal-lobe dementia, and progressive supranuclear palsy. Independent assessment of reductions in uptake revealed posterior hemisphere abnormalities in the majority of the Alzheimer group, and selective anterior hemisphere abnormalities in both other groups. The findings were consistent with observed patterns of mental impairment. The imaging technique has potential value in the differential diagnosis of primary cerebral atrophy.

Aged↗
PubMed1986

Cerebral biopsy in the investigation of presenile dementia due to cerebral atrophy.

Investigation by cerebral biopsy of patients with dementia associated with cerebral atrophy permits the examination of clinico-pathochemical relationships, and provides a means of distinguishing and classifying forms of cerebral atrophy. Benefits of the procedure must however be weighed against possible adverse effects of surgical intervention. The study examines the outcome following biopsy of 24 patients with presenile dementia. No major operative complications were encountered, and recovery was uneventful in all but a single patient. The relevance of the findings to the study of dementia by cerebral biopsy is discussed.

Aged↗
PubMed1986

Neuropsychological syndromes in presenile dementia due to cerebral atrophy.

In a prospective study of 24 patients with presenile dementia associated with cerebral atrophy, clinical and psychological characteristics of patients' disorder were examined in relation to pathological and chemical findings obtained from tissue analysis following cerebral biopsy. The histological features of Alzheimer's disease were found in 75% of cases, but not in 25%. Distinctive patterns of neuropsychological breakdown emerged allowing clinical grouping of patients. While clinical patterns were helpful in differentiating Alzheimer's disease from non-Alzheimer's disease, there was not an absolute concordance between clinical and patho-chemical groupings. The findings, which support the notion that the "cerebral atrophies" represent a heterogeneous group of conditions, have relevance for the clinical diagnosis of presenile dementia.

Aged↗