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Biomedical subjects

J S Snowden

Publications and source records attributed to J S Snowden.

71 records · Page 4Linked to original sources
PubMed1986

Alzheimer's disease: a correlative study.

In a study of 17 patients with histologically proven Alzheimer's disease the relationship between psychological, pathological and chemical measures of disorder was examined. Severity of dementia, determined by mental test performance, correlated highly with pathological change in large cortical neurons (cell loss and reduction in nuclear and nucleolar volume and cytoplasmic RNA content), to a lesser extent with cortical senile plaque and neurofibrillary tangle frequency and reduction in acetylcholine (ACh) synthesis, and not with reduction in choline acetyltransferase (CAT) activity. A strongly significant relationship was demonstrated between cell loss and reductions in nuclear and nucleolar volume and cytoplasmic RNA content. Reduction in CAT activity and senile plaque frequency were significantly correlated, thereby linking changes in the sub-cortical projection system of the nucleus basalis with the cortical pathology. The pattern of correlations suggests that the dementia of Alzheimer's disease is largely a reflection of the state of large cortical neurons, and it is argued that abnormalities in the latter may not be directly related to primary loss of cholinergic neurons in the subcortex.

Acetylcholine↗
PubMed1985

Neurochemical studies of early-onset Alzheimer's disease. Possible influence on treatment.

Multiple neurotransmitter deficits found in recent autopsy studies of patients with Alzheimer's disease may militate against the success of "simple cholinergic replacement" as treatment. To study acetylcholine synthesis, we measured the incorporation of radiolabeled glucose into the transmitter in temporal-cortex specimens obtained at diagnostic craniotomy in 17 young patients with Alzheimer's disease. Synthesis of acetylcholine was significantly correlated with cognitive impairment. These results are consistent with the view that the deficit in the presynaptic cholinergic system is a relatively early change in the development of the clinical features of the disease. Other alterations in noradrenergic cells, some cortical neurons, postsynaptic cortical receptors, and possibly serotoninergic cells may not be closely associated with Alzheimer's disease.

Acetylcholine↗
PubMed1985

Putative amino acid transmitters in lumbar cerebrospinal fluid of patients with histologically verified Alzheimer's dementia.

Concentrations of individual free amino acids were determined in lumbar cerebrospinal fluid (CSF) from patients with various complaints including histologically verified Alzheimer's dementia. Glycine and glutamine in the CSF of Alzheimer's dementia samples were lower than that of control samples. Only the concentration of glutamic acid in Alzheimer's dementia patients correlated with psychological measures. The reduction in glycine concentration was not specific for Alzheimer's dementia.

Adult↗
PubMed1981

Alterations in protein synthetic capability of nerve cells in Alzheimer's disease.

Cytoplasmic RNA content, nuclear and nucleolar volume are all significantly reduced in nerve cells of the temporal cortex in cases of Alzheimer's disease, examined both at diagnostic craniotomy and post mortem, when compared with non=demented control cases of similar age. On average, at necropsy, all three parameters are equally reduced by about 40-50%, but in biopsy cases, nuclear volume is decreased by the greatest amount (43%), followed by nucleolar volume is decreased by the greatest amount (43%), followed by nucleolar volume (36%), and cytoplasmic RNA (26%). These findings indicate that a change in protein synthesis occurs daily in the course of Alzheimer's disease which may result from a primary alteration within the nuclear apparatus.

Adult↗
PubMed1980

Glucose metabolism and acetylcholine synthesis in relation to neuronal activity in Alzheimer's disease.

The metabolism of (U--14C) glucose and its incorporation into acetylcholine were determined in vitro in fresh cortical biopsy samples from patients with Alzheimer's disease and controls. Synthesis of 14C acetylcholine was significantly reduced (60% and 67% reduction under stimulated and resting conditions, respectively) without significant changes in the overall metabolism of glucose (as measured by 14CO2 production). Acetylcholine synthesis was directly related to the activity of choline acetyltransferase. The changes in cholinergic markers reflected the severity of psychological defects. Acetylcholine synthesis was not reduced in biopsy samples from patients suffering from presenile dementia with no histological evidence of Alzheimer's disease.

Acetylcholine↗
PubMedDate not supplied

Autobiographical experience and word meaning.

The role of current personal experience in understanding of word meaning was investigated in a patient, WM, who suffers from semantic dementia. The study was prompted by the observation that WM, despite being severely impaired on formal tests of word comprehension and naming, retained a range of vocabulary pertaining to her daily life. If autobiographical experience has a general facilitatory effect, then this should affect which concepts are retained and which lost, but not influence the quality of that conceptual knowledge. Conversely, if personal autobiography has a direct role in investing concepts with meaning, then WM's understanding of nominal terms that she uses spontaneously in conversation ought not to be normal, but should be constrained by the autobiographical context in which she uses those terms. WM could define nouns and noun phrases drawn from her conversational vocabulary, but her definitions had a markedly autobiographical quality. Moreover, WM was extremely impaired in her ability to define new noun phrases, constructed by combining words from her conversational vocabulary (e.g. "dog licence", constructed from "driving licence" and "dog"; "oil field" constructed from "oil" and "field"). It was concluded that WM does not have normal conceptual understanding of nouns and noun phrases that she uses appropriately in conversation. Her understanding is narrow and autobiographically constrained. The findings, which suggest an interactive relationship between autobiographical and semantic memory, have implications for understanding of the progressive breakdown of semantic knowledge.

Amnesia↗
PubMedDate not supplied

Neurofibrillary pathology and protein synthetic capability in nerve cells in Alzheimer's disease.

Nucleolar volume was measured in nerve cells of the temporal cortex in cases of Alzheimer's disease, obtained at both biopsy and autopsy. Measurements were made on those nerve cells containing neurofibrillary tangles and also on ones free of such changes. Results showed that nucleolar volume is significantly reduced, by at least 40%, in both tangle and non-tangle bearing cells, in both biopsy and autopsy cases, when compared with corresponding values from appropriate control cases. Furthermore, in the autopsy cases, nerve cell nucleolar volume was reduced by a further 30% in tangle bearing cells compared to non-tangle bearing neighbours. No such difference was noted in these cells in the biopsy cases. These findings imply that alterations in protein synthetic capability occur in nerve cells early in the course of Alzheimer's disease, and that this change is not, at least in these initial stages, related to accumulation of neurofibrillary material within the cell body, although later on such accumulation may result in added disruption of cell metabolism.

Adult↗
PubMedDate not supplied

An ultrastructural analysis of the effects of accumulation of neurofibrillary tangle in pyramidal neurons of the cerebral cortex in Alzheimer's disease.

Quantitative morphometric (stereological) methods have been used to assess the effects of accumulation of neurofibrillary material on the fine structure of pyramidal cells in biopsy specimens of temporal cortex from nine patients with Alzheimer's disease. When compared with non-tangled cells from the same patients, tangled cells show an increase in total area of cytoplasm due to the accumulation of tangle and a reduction in the area of the nucleus; the area proportion of the cell body occupied by total cytoplasm, therefore, increases whereas that of the nucleus decreases. Within the total cytoplasm, nucleolar and mitochondrial areas are maintained, but that of lipofuscin is increased, though all are increased when expressed as a proportion of the useful cytoplasm alone (i.e. total cytoplasmic area minus area occupied by tangle). Measures of the amount of rough endoplasmic reticulum and ribosomes are decreased overall in tangled cells, though when related to useful cytoplasm alone such measures approach non-tangled cell values. Measures of smooth endoplasmic reticulum are unaltered throughout. When related to the amount of tangle within cells it was found that the most heavily tangled cells retain 28% of useful cytoplasm, 72% of the nuclear area, 50% of the rough endoplasmic reticulum and 27% of ribosomes present within least tangled and non-tangled cells. By contrast, mitochondrial area is maintained and that of lipofuscin increased. The capacity for protein synthesis in tangled cells appears, therefore, to be progressively decreased with accumulation of tangle, whereas that for oxidative metabolism is maintained and lysosomal activity, perhaps, increased. Neurofibrillary tangle formation and accumulation may, therefore, lead to the eventual death of neurons and be the major cause of nerve cell loss in Alzheimer's disease.

Aged↗
PubMedDate not supplied

A quantitative study of the ultrastructure of pyramidal neurons of the cerebral cortex in Alzheimer's disease in relationship to the degree of dementia.

Quantitative morphometric (stereological) methods have been used to measure the number or amount of organelles in pyramidal nerve cells, unaffected by neurofibrillary degeneration, in biopsy specimens of temporal cortex from 11 patients with Alzheimer's disease, and to relate these to the degree of dementia, as measured by psychometric testing. Only areal proportion (AA) and surface area (SA) of rough endoplasmic reticulum were significantly reduced in line with the severity of the degree of dementia. It is suggested that these changes reflect a progressively diminishing requirement for packaging and transport of replacement proteins, particularly in relation to neurotransmitter metabolism in nerve terminals following the loss of synapses which we have shown to occur in these patients.

Aged↗
PubMedDate not supplied

The progression of the pathological changes of Alzheimer's disease in frontal and temporal neocortex examined both at biopsy and at autopsy.

Brains were obtained at autopsy from five patients with Alzheimer's disease, each of whom had undergone diagnostic craniotomy 3-7 years previously. It was possible, therefore, to examine the number (density) and nucleolar volume of pyramidal nerve cells, and the density of senile plaques and neurofibrillary tangles within the cerebral cortex on two occasions during the progression of their illness, and to assess how these measures might have changed during the period between biopsy and death. In all five patients, at biopsy, the density and the nucleolar volume of pyramidal nerve cells was significantly less than controls and, in general, values for both these measures fell significantly further from biopsy to death. By contrast, in none of the five patients did senile plaque density consistently change from biopsy to death; neurofibrillary tangle density either did not change, or indeed sometimes decreased from biopsy to death. These data show that both the clinical and the pathological progression of Alzheimer's disease is marked by a continuing loss of pyramidal cells from frontal and temporal cortex, although the densities of plaques and tangles within the cortex do not, per se, correlate with the stage of the illness. The usefulness of measurement of plaque and tangle densities as pathological criteria by which the clinical and neurochemical deficits of Alzheimer's disease can be compared in different patients is clearly questionable.

Alzheimer Disease↗
PubMedDate not supplied

The clinical pathological correlates of lobar atrophy.

Three clinical syndromes associated with fronto-temporal cerebral atrophy, studied in one centre are discussed: dementia of frontal type (DFT), DFT and motor neurone disease (MND) and progressive aphasia (PA). The pathological findings in DFT (13 brains), DFT and MND (5 brains) and PA (5 brains) permit a number of clinical pathological groupings. The nosological status of fronto-temporal atrophy is discussed with reference to the literature and it is suggested that a common underlying pathology, including Picks disease as strictly defined by the presence of inclusion bodies, underlies the clinical syndromes, each being determined by the anatomical distribution of the pathology.

Aphasia↗
PubMedDate not supplied

Progressive language dysfunction and lobar atrophy.

The patterns of language disorder associated with 'progressive aphasia' due to lobar atrophy were compared with the language dysfunction of patients with dementia of frontal lobe type (DFT). The progressive aphasias were characterised primarily by impairment at the structural levels of language: phonology, grammar and semantics, whereas DFT was associated primarily with spontaneity and loss of generative capability. However, there was overlap in language symptomatology, particularly with progression of disease. The findings lend support to the argument that progressive aphasia and DFT represent different clinical manifestations of a common pathology, and form part of the spectrum of lobar atrophies.

Adult↗
PubMedDate not supplied

Memory dysfunction in multiple sclerosis corresponds to juxtacortical lesion load on fast fluid-attenuated inversion-recovery MR images.

BACKGROUND AND PURPOSE: MR imaging is a sensitive diagnostic tool and paraclinical marker of disease activity and prognosis in multiple sclerosis (MS), yet the role of MR imaging of MS is controversial. The aim of this study was to describe the relationship between cognitive function and MS lesion size and position, as shown on comparative images from conventional spin-echo (CSE) and fast fluid-attenuated inversion-recovery (fast FLAIR) MR studies. METHODS: CSE and fast FLAIR sequences consisted of 40 noncontiguous, 3-mm-thick axial sections matched for geometric position in 18 patients with relapsing-remitting MS. Lesions were scored for size, anatomic position, and their comparative appearance on CSE and fast FLAIR images. The neuropsychological assessment tested general psychological performance, memory, and frontal lobe executive function. RESULTS: Fast FLAIR images showed significantly more small (146 versus six) and medium-sized (18 versus four) juxtacortical lesions than did CSE sequences. Small juxtacortical lesions displayed only on fast FLAIR images had a distinctive appearance, suggestive of small areas of perivascular inflammation. The number of these lesions corresponded to reduced performance on the fifth and delayed trials of the Rey Auditory Verbal Learning memory function test. CONCLUSION: Fast FLAIR images show small lesions at the juxtacortical boundary that are not seen on CSE studies. The presence of such lesions correlates with impaired retention of information in memory tasks, which is characteristic of cognitive problems in patients with MS.

Adult↗
PubMedDate not supplied

[Diagnostic criteria for fronto-temporal lobe degeneration].

Circumscribed atrophy of the frontal and temporal lobes (frontotemporal lobar degeneration) accounts for about one fifth of cases of primary degenerative dementia occurring before the age of 65. It produces three prototypical clinical syndromes. The most common is frontotemporal dementia, characterized by personality change and profound alteration in social conduct and associated with bilateral atrophy of the frontal and anterior temporal lobes. Progressive non-fluent aphasia is characterized by difficulty in verbal expression, anomia and phonemic errors in the presence of relative preservation of comprehension and associated with atrophy predominantly of the left hemisphere. In semantic dementia there is fluent speech with semantic errors and severely impaired comprehension and naming, together with a visual associative agnosia, resulting from bilateral atrophy of the inferior and middle temporal gyri. The clinical syndromes occur with either of two main histological types: prominent microvacuolar change, without specific histological features (frontal lobe degeneration-type), severe astrocytic gliosis with or without ballooned cells and inclusion bodies (Pick-type). To improve clinical recognition and advance understanding of this relatively common form of cerebral degeneration, members of an international workshop on Frontotemporal Lobar Degeneration developed consensus criteria, building upon earlier published clinical diagnostic guidelines for frontotemporal dementia. The consensus criteria reported here specify core and supportive features for each of the prototypical clinical syndromes: frontotemporal dementia, progressive aphasia and semantic dementia, as well as providing broad inclusion and exclusion criteria for the generic entity of frontotemporal lobar degeneration.

Aged↗
PubMedDate not supplied

Behavioral changes in Huntington Disease.

OBJECTIVES: This study aimed to gain a better understanding of behavioral abnormalities in Huntington disease (HD) and to develop a method for reliably assessing these changes. BACKGROUND: Behavioral changes are a central feature of HD and often cause considerable distress and difficulty to patients and their relatives. However, they have received little attention from research despite their prevalence and clinical significance. METHODS: One hundred thirty-four patients with HD were assessed using the Problem Behaviors Assessment for Huntington Disease (PBA-HD), an instrument for rating the presence, severity and frequency of behavioral abnormalities in HD. RESULTS: The findings confirm that behavioral problems are common among patients with HD. The most common symptoms were loss of energy and initiative, poor perseverance and quality of work, impaired judgment, poor self-care and emotional blunting. Affective symptoms such as depression, anxiety and irritability occurred in around half the patients studied. Psychotic symptoms (hallucinations and delusions) were rarely reported. Factor analysis distinguished three clusters of behavioral symptoms, which were interpreted respectively as reflecting Apathy, Depression and Irritability. The 'Apathy' factor was highly correlated with duration of illness, whereas no such relationship was observed for the 'Depression' and 'Irritability' factors. CONCLUSIONS: The results suggest that certain behavioral changes are fundamental to the progression of HD, whereas others have a more complex relationship to the disease process. The findings have implications for the choice of behavioral measures used to evaluate efficacy of therapeutic interventions.

Adult↗