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Biomedical subjects

G Blessed

Publications and source records attributed to G Blessed.

At least 37 records · Page 2Linked to original sources

Confusion ratings and abbreviated mental test performance: a comparison.

Ninety-nine residents, 10% of the total population of elderly in Part III accommodation in Newcastle upon Tyne, were examined for the presence of psychiatric disorder, tested for cognitive impairment, and rated for the presence of confusion. Those allocated a diagnosis of dementia were most impaired and confused, and those living in specialist homes for the mentally infirm were more impaired than other residents. Confusion ratings, which proved very simple and quick to perform, correlated highly with the results of testing for the presence of cognitive impairment--a slightly more laborious and less universally applicable procedure. The Confusion Rating therefore offers a reliable and easy method for identifying the prevalence of dementia among residents of institutions.

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Cognitive functioning in Parkinson's disease: in relation to prevalence of dementia and psychiatric diagnosis.

Forty-three neurologically and psychiatrically assessed patients with idiopathic Parkinson's disease (PD) underwent detailed cognitive assessment. Cognitive deficits typical of senile dementia of Alzheimer's type (SDAT) were found in 7% but the majority showed definite impairments not typical of SDAT. Cognitive impairment was significantly more likely in those with more severe PD symptoms. There was substantial agreement between psychiatric diagnosis and psychological picture of SDAT and some links were found between other diagnostic categories and nature of cognitive functioning. However, cognitive deficits were also found in two-thirds of patients with no psychiatric diagnosis.

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Blood acetyl- and butyrylcholinesterases in senile dementia of Alzheimer type.

The major neurochemical abnormality described to date in senile dementia of the Alzheimer type (SDAT) is a central cholinergic deficit. To determine whether this central deficit is reflected by changes in the levels of blood cholinesterases, plasma and erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE), were measured in SDAT and other psychiatric disorders. Plasma AChE, which has only recently been described in human blood, was significantly elevated (P less than 0.01) in the SDAT group compared with the control and other clinical groups investigated. In contrast there were no significant differences in the activities of either erythrocyte AChE or plasma BChE between any of the clinical groups. Although the source of plasma AChE is unknown the possibility that some portion originates from the central nervous system and that the elevated AChE levels in SDAT reflect increased release from degenerating cholinergic neurons is discussed.

Acetylcholinesterase↗

Cholinergic correlates of cognitive impairment in Parkinson's disease: comparisons with Alzheimer's disease.

Dementia in Parkinson's disease has previously been attributed to the presence in the cerebral cortex of Alzheimer-type neuropathological abnormalities. New evidence suggests, however, that dementia in this disease usually occurs in the absence of substantial Alzheimer-type changes in the cortex and may be related to abnormalities in the cortical cholinergic system. Thus, in Parkinsonian patients with dementia there were extensive reductions of choline acetyltransferase and less extensive reductions of acetylcholinesterase in all four cortical lobes. Choline acetyltransferase reductions in temporal neocortex correlated with the degree of mental impairment assessed by a test of memory and information but not with the extent of plaque or tangle formation. In Parkinson's but not Alzheimer's disease the decrease in neocortical (particularly temporal) choline acetyltransferase correlated with the number of neurons in the nucleus of Meynert suggesting that primary degeneration of these cholinergic neurons may be related, directly or indirectly, to declining cognitive function in Parkinson's disease.

Acetylcholinesterase↗

Cortical serotonin-S2 receptor binding abnormalities in patients with Alzheimer's disease: comparisons with Parkinson's disease.

Reductions in the numbers of binding sites for the serotonergic S2-receptor antagonist, ketanserin, are, as previously reported, evident in Alzheimer's disease. New findings indicate that these sites are not affected in the cortex of patients with Parkinson's disease despite the presence of cognitive impairment. In contrast S1-receptor binding sites were reduced to a small but significant extent in both Alzheimer's and Parkinson's disease with cognitive deficit. The S2-receptor binding loss was not related to the cholinergic deficit (decreased choline acetyltransferase) common to both disorders nor to the presence of cortical senile plaques but did relate to the extent of cortical neurofibrillary tangle formation, evident in Alzheimer's but not generally in Parkinson's disease. These observations suggest that S2- but not S1-receptor binding abnormalities may reflect an important intrinsic cortical involvement specifically associated with the Alzheimer disease process.

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Studies on neurotransmitter receptor systems in neocortex and hippocampus in senile dementia of the Alzheimer-type.

Ligand binding to alpha 1-, alpha 2- and beta-adrenergic, serotonin, benzodiazepine and GABA receptors was studied in neocortex and hippocampus of controls and patients with senile dementia of the Alzheimer-type. A selective loss of serotonergic binding sites characterised as a loss of both S1 and S2 sites was observed. The reduction in serotonin receptors did not correlate with a clinical assessment of the degree of dementia, or with the extent of Alzheimer-type neuropathological change.

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The place of the specialist home for the elderly mentally infirm in the care of mentally disturbed old people.

In a city where specialist homes for the elderly mentally infirm (EMI) have been extensively developed, a study was carried out to determine if residents in such homes were mentally impaired to a degree intermediate between that of residents in ordinary homes, and those in psychogeriatric beds. The study, using valid measures of cognitive impairment and functional disability, showed that while the proportion of cases of senile dementia was similar in all three settings, the severity of disability was graded in the expected direction. Furthermore, cases of mental illness other than senile dementia were almost exclusively found in the EMI homes and psychogeriatric hospitals. However, one in ten of ordinary home residents suffered from senile dementia of a severity which presented problems to the care attendants and the implication of this finding for the level of provision of psychogeriatric beds is discussed.

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Intralaminar neurochemical distributions in human midtemporal cortex: comparison between Alzheimer's disease and the normal.

The intralaminar distributions of transmitter and nontransmitter enzyme activities and amino acid levels were determined in the midtemporal cortices from normal individuals and established cases of Alzheimer's disease. In the normal, choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activities were relatively high in the outer cortical layers, particularly, for CAT, in the two granular layers (II and IV). Both activities were reduced in Alzheimer's disease at all, although generally most extensively in the outer and middle layers of the grey matter whereas activities were near normal in the white matter. Further, the enzyme distribution patterns of these cholinergic activities were also disrupted in Alzheimer's disease and the activity of CAT throughout the cortex was generally reduced to that found in the white matter. No such differences in distribution were found for two other enzymes, pseudocholinesterase and lactate dehydrogenase. Assessment of the gamma-aminobutyric acid (GABA) system in the normal revealed a much more extensive intralaminar variation in the enzyme, glutamate decarboxylase, compared with the level of GABA itself. In contrast with the cholinergic enzymes, neither the levels nor intralaminar patterns of GABA were altered in Alzheimer's disease. From an analysis of free amino acids at the different cortical levels, the cortical pattern of glutamic acid in the normal was different from that for GABA, aspartic acid, or nontransmitter amino acids such as alanine. Neither of the putative amino acids, glutamate or aspartate, was altered in Alzheimer's disease. These findings demonstrate the relatively selective nature of microchemical changes occurring in the cortex in Alzheimer's disease and suggest that a functional abnormality in cholinergic input to the outer neocortical layers (I-IV) with predominantly receptive and associative functions may be an important feature of the disease.

Acetylcholinesterase↗

Molecular forms of acetylcholinesterase in senile dementia of Alzheimer type: selective loss of the intermediate (10S) form.

Using density gradient centrifugation, three molecular forms of acetylcholinesterase have been distinguished in both normal and senile dementia of Alzheimer-type (SDAT) postmortem neocortex. Whilst the levels of the light and heavy forms were unaltered in SDAT there was a selective and extensive loss of the intermediate form. This form is predominantly hydrophobic and its loss from the cerebral cortex in SDAT may reflect degeneration of cholinergic axonal processes. This is the first report of an altered distribution of acetylcholinesterase molecular forms in a disease of the central nervous system.

Acetylcholinesterase↗

Pathological changes in the nucleus of Meynert in Alzheimer's and Parkinson's diseases.

Combined neuropathological and neurochemical assessment of the nucleus of Meynert in senile dementia of Alzheimer type (SDAT) have demonstrated that the cholinergic biochemical activity, choline acetyltransferase, is more extensively reduced in the nucleus (over 90%) than the loss of putative cholinergic perikarya (35%). Acetylcholinesterase histochemical activity was however substantially retained in individual neurones in the nucleus although virtually absent from the neocortex in SDAT. These abnormalities are consistent with a primary degeneration of cholinergic axons projecting to the cortex and secondary loss of perikarya from the subcortical nucleus. In contrast, preliminary observations on cases of Parkinson's disease suggest that the neuronal loss from the nucleus of Meynert may be greater in this disease than in SDAT, and previous studies have not consistently demonstrated a reduction in cortical choline acetyltransferase activities in Parkinson's disease. These observations, together with major differences in the neuropathology of the nucleus in SDAT and Parkinson's disease (neurofibrillary tangle and Lewy body formation, respectively) suggest that the involvement of the cholinergic system may differ in the two disease processes.

Acetylcholinesterase↗

Decreased imipramine binding in the brains of patients with depressive illness.

The binding of tritiated imipramine was significantly reduced in the hippocampus and occipital cortex from a series of patients with depressive illness compared with age-matched patients with no psychiatric disorder. In contrast there was no change in imipramine binding in established cases of senile dementia of Alzheimer-type. Scatchard analysis indicated normal binding affinity but a reduction in the number of imipramine binding sites in depression. These observations parallel previous findings of decreased binding sites in platelets from depressed patients and suggest there may be an abnormality in the uptake mechanism for serotonin in depression.

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Extensive loss of choline acetyltransferase activity is not reflected by neuronal loss in the nucleus of Meynert in Alzheimer's disease.

Choline acetyltransferase activity in discrete tissue punches from the nucleus of Meynert and in tissue from the temporal cortex was reduced by at least 90% and 75%, respectively, in 5 out of 6 elderly cases of Alzheimer's disease compared with 5 normal cases. In contrast, estimates of neurone density in these same cases revealed that there was only, on average, a 33% neurone loss in the nucleus of Meynert in Alzheimer's disease. These observations suggest that a key pathological change in Alzheimer's disease may be the 'down regulation' of transmitter-specific enzyme production in cholinergic neurones, and that neurone loss itself may be a secondary feature of the disease.

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The contemporary natural history of mental disorder in old age.

A classificatory system for mental disorders in the elderly proposed by Roth in 1955 was examined in a contemporary population. Ninety per cent of patients could be allocated to the five psychosyndromes originally defined. Examination of outcome in the present sample, at six month and two years, showed important differences. The outlook for patients with paranoid psychoses showed an improvement though for those with affective illness (at 2 years) there was little change. Of special importance was the increased long-term survival of very elderly female patients with senile dementia. This, in conjunction with the general rise in admissions for mental disorders in the aged over the past 25 years, has considerable implications for the future development of psychiatric services for the elderly mentally ill.

Affective Disorders, Psychotic↗

Reduced dopamine-beta-hydroxylase activity in Alzheimer's disease.

The activity of the noradrenergic marker enzyme dopamine-beta-hydroxylase was measured in brains removed postmortem from control patients and patients with Alzheimer's disease. Enzyme activity was decreased in the frontal and temporal cortices and hippocampus in patients with Alzheimer's disease, but was within the normal range in patients with depression, multiinfarct dementia, and terminal coma.The decrease in enzyme activity in Alzheimer's disease may reflect an abnormality of cortical noradrenergic fibres in some patients with the disease.

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Cell loss in the locus coeruleus in senile dementia of Alzheimer type.

Sample counts of the pigmented cells of the locus coeruleus (LC) were performed in 10 middle-aged and 15 old people considered to be intellectually well preserved and in 15 cases of senile dementia of Alzheimer type (SDAT). Evidence of a gradual loss of neurons from early middle to old age was found in the control group. In the cases of SDAT 7 counts were within the lower range for the controls but 8 had fewer neurons than any control recorded and the mean count for all the SDAT cases was significantly less than that of the older controls. Some evidence exists that the more severe cases of SDAT in terms of neocortical plaque formation have the greatest loss of LC neurons.

Adult↗