Assessment of competence to complete advance directives. Standardised instruments are needed to guide the measurement of competence.
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Advance Directives↗
Biomedical subjects
S Eagger
Publications and source records attributed to S Eagger.
Neocortical cholinergic activities differentiate Lewy body dementia from classical Alzheimer's disease.
Activity of the enzyme which synthesizes acetylcholine, choline acetyltransferase, was estimated in the neocortex of three series of control and demented cases. Clinically demented cases were divided into those with the classical neuropathological features of Alzheimer's disease (numerous neocortical plaques and tangles) and those with Lewy bodies in the brain stem and cortex (together with plaques and variable neurofibrillary pathology). In the Lewy body cases neocortical choline acetyltransferase was consistently lower than in the classical Alzheimer-type cases. Two of the Lewy body cases with extremely low cholinergic activity were responders in therapeutic trials of the cholinesterase inhibitor, tacrine, and the combined data suggest that cholinergic therapy may be particularly relevant to patients with Lewy body type dementia.
Alzheimer Disease↗
Lewy bodies and response to tacrine in Alzheimer's disease.
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Alzheimer Disease↗
Morphologic (CT) and functional (rCBF-SPECT) correlates in Alzheimer's disease.
Thirty-five patients with a clinical diagnosis of probable Alzheimer's disease underwent computed tomography (CT) and regional cerebral blood flow (rCBF) studies using single photon emission computed tomography (SPECT). Two sets of images in each subject were scored for the extent of structure and function changes. Thirty-four of 35 patients had various degrees of atrophy on CT, 33 of whom also had perfusion deficits of varying severity. One patient with normal CT had perfusion deficits, and another patient with a normal perfusion pattern had changes on CT. Regional perfusion deficits on SPECT were seen with and without associated changes on CT. Correlations were studied between CT and SPECT scores using Spearman's rank correlation coefficients. While regional scores on CT and SPECT did not significantly correlate, the total and left hemisphere scores on two sets of images showed fair correlations (r = 0.425 and r = 0.535, respectively, P less than 0.01). The correlations between cognitive performance in patients as assessed on Mini-Mental State Examination (MMSE) and CAM-COG and perfusion scores were highly significant while CT scores showed lower correlations. These findings suggest that the relationship between structural and functional changes in Alzheimer's disease is not straightforward and that the extent of changes in function as assessed by regional cerebral blood flow studies is a reliable measure of deficits in cognitive function.
Aged↗
Patterns of regional cerebral blood flow in Alzheimer's disease.
Regional cerebral blood flow was assessed in 35 patients with Alzheimer's disease and the same number of matched normal volunteers. Images were scored for regional perfusion deficits. Mildly demented patients had parietal and temporal perfusion deficits, often unilateral. Moderate to severely demented patients had bilateral temporal and parietal perfusion deficits. All severely demented patients also had involvement of both occipital regions. Frontal lobe deficits were seen in 14 patients. Left cortical perfusion deficits were more severe than the right cortical perfusion deficits in general. Patients with early onset of the disease showed left frontal deficits, more often, however, the total perfusion deficit scores in early and late onset groups were not statistically significant. Also, the cognitive performance scores were not statistically significant in these two groups. These results suggest a stage-dependent reduction in regional cerebral blood flow in patients with Alzheimer's disease.
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Quantification of regional cerebral blood flow (rCBF) using 99Tcm-HMPAO and SPECT: choice of the reference region.
The effects of the choice of the reference region in determining the relative regional cerebral blood flow (rCBF) using 99Tcm-hexamethylpropylene amine oxime (HMPAO) single photon emission tomography (SPECT) have been studied in order to establish or exclude it as a cause of inconsistencies in these studies. Relative rCBF was estimated by normalizing the regional count densities to two reference regions, the cerebellum and the whole slice, in 35 patients with Alzheimer's disease (AD), 25 patients with chronic schizophrenia (SCH) and the same number of matched normal volunteers. The statistical significance of the differences in rCBF between patients and their matched normals varied in the two sets of rCBF data. Smaller differences were highly significant while some larger differences were of less significance with whole slice normalization. The results suggest that the choice of reference region is one of the causes resulting in discrepancies in the results from various centres. The need to use a standard reference region is indicated.
Alzheimer Disease↗
A study of regional cerebral blood flow and cognitive performance in Alzheimer's disease.
Thirty five patients with dementia of the Alzheimer type (DAT) and 35 controls matched for age, sex and handedness were investigated using single photon emission computer tomography (SPECT) with 99m technetium HMPAO. Regional cerebral blood flow (rCBF) was assessed semi-quantitatively in 18 cortical and 4 subcortical areas by normalising mean information density in each region to cerebellar mean information density. Analysis revealed significantly reduced rCBF to temporal, parietal, frontal and left occipital cortex in the patients whilst blood flow to subcortical areas showed no differences between the 2 groups. In addition, significant left-sided cortical hypoperfusion was seen in the DAT group but not in controls. When patients were sub-divided on the basis of disease severity, those with mild disease showed temporal, parietal and left frontal changes with more severely affected patients also showing right frontal and left occipital involvement. rCBF patterns did not distinguish between presenile and senile onset cases once duration and severity of illness were controlled. Eight cortical areas were also rated visually for perfusion deficits on a simple 4 point scale. Perfusion deficits were detected in 34 of 35 patients but in only 4 of 35 controls. In the DAT group significant correlations were found between many of the neuropsychological tests used and rCBF. Memory correlated with left temporal activity, praxis, perception, object assembly and block design with right parietal activity and language with activity throughout the left hemisphere. Significant correlations were also seen between subcortical and cortical blood flow, possibly explaining the correlations observed between many of the neuropsychological tests and thalamic blood flow.
Aged↗
Psychiatric morbidity in patients with peripheral vestibular disorder: a clinical and neuro-otological study.
This study reports the psychiatric morbidity in 54 patients with objective evidence of peripheral vestibular disorder seen three to five years after their original referral. A third of the patients were free from vestibular symptoms at follow up and a further third had experienced some improvement. Two thirds of the patients had experienced psychiatric symptoms during this period, although only 50% were rated above the cut off point for significant psychiatric disturbance when interviewed. Panic disorder with or without agoraphobia and major depression were the commonest psychiatric diagnoses. Patients with classical "labyrinthine" symptoms had a more severe canal paresis than the rest, but the degree of the abnormalities in the neuro-otological tests was unrelated to outcome or to psychiatric morbidity. On the other hand, there was a significant correlation between the presence of vestibular symptoms and psychiatric morbidity, which in turn correlated with measures of anxiety, perceived stress and previous psychiatric illness.
Adolescent↗
Tacrine in Alzheimer's disease. Time course of changes in cognitive function and practice effects.
This paper concerns certain questions which arose during the analysis of a trial showing positive effects of tacrine in Alzheimer's disease. Cognitive improvement occurred during the first two weeks, reached a maximum at one month and was maintained during the rest of the three-month treatment period. Rebound effects were not detected in any of the key outcome variables, but were suggested by one of the supporting cognitive tests and other measures. Practice effects occurred on tests which were repeated at short intervals or too frequently. The paper discusses the significance of these findings for the interpretation of other trials and for practical management.
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Effects of tetrahydroaminoacridine on liver function in patients with Alzheimer's disease.
Detailed liver function test analysis is reported for 30 patients with Alzheimer's disease who were treated with tetrahydroaminoacridine. Results show that a benign elevation of aspartate transaminase occurs in up to 50% cases, that the reaction can be a symptomatic one and that clinical hepatitis can occasionally result. Liver function test changes appear dose-dependent and normalize within 2-4 weeks of stopping the drug or of reducing the dose. Women appear more likely to develop hepatotoxicity than men. Rechallenge with THA in patients previously showing abnormalities in liver function shows that some patients are able to tolerate the drug a second time.
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Platelet and erythrocyte membrane changes in Alzheimer's disease.
Previous reports have suggested that the physical properties of cell membranes and calcium homeostasis in both the central and peripheral nervous system are changed in Alzheimer's disease (AD). This study has examined the biophysical properties of erythrocyte and platelet membranes by measuring the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and possible related changes in lipid peroxidation. In addition, we have studied calcium homeostasis by measuring thrombin-stimulated changes in intraplatelet free calcium and Ca2(+)-ATPase activity in AD and healthy age and sex-matched controls. Our results show that there was no significant difference in the fluorescence anisotropy of DPH in erythrocyte membranes isolated from the three groups. There was also no significant difference in lipid peroxidation levels in erythrocytes and plasma of AD patients compared to controls. However, there was a significant reduction in the fluorescence anisotropy of DPH in platelet membranes from AD patients, compared with healthy controls. Recent evident suggests that the increase in platelet membrane fluidity results from alterations in internal membranes. We measured the specific activities of enzyme markers associated with intracellular and plasma membranes in platelets from AD patients and healthy controls. There was a significant reduction in the specific activity of antimycin A-insensitive NADH-cytochrome-c reductase (a specific marker for smooth endoplasmic reticulum (SER)), in AD patients compared to controls, but no change in the specific activity of bis(p-nitrophenyl)phosphate phosphodiesterase (a specific marker for plasma membrane). We have also shown that SER mediated [Ca2+] homeostasis is possibly impaired in AD platelets, i.e., the percentage of thrombin-stimulated increase in intraplatelet [Ca2+] above basal levels was significantly higher in AD compared to matched controls and there were significant reductions in the specific activities of Ca2+/Mg2(+)-ATPase and Ca2(+)-ATPase (but not Mg2(+)-ATPase) in AD platelets. Finally electron microscopic analysis of platelets showed that there was a significant increase in the incidence of abnormal membranes in AD patients compared to controls. The ultrastructural abnormalities seem to consist of proliferation of a system of trabeculated cisternae bounded by SER. These results suggest that both SER structure and function might be defected in AD platelets, which could explain the fluidity changes observed here.
Alzheimer Disease↗
Sparing of attentional relative to mnemonic function in a subgroup of patients with dementia of the Alzheimer type.
Patients with dementia of the Alzheimer type (DAT) received two tests of visual selective attention, together with tests of spatial and visual recognition memory and visuospatial conditional learning previously used to show deficits early in the course of DAT. One set of attentional tests compared visual discrimination learning along intra- and extra-dimensional shifts, using a "total change" design. In the 12 DAT patients capable of attempting the extra-dimensional shift (subgroup 1), performance was equivalent to that of controls. This subgroup was also unimpaired at simple and compound discrimination learning and reversal and an intra-dimensional shift. They were as accurate as controls on a visual search task requiring matching of stimuli on two dimensions with variable numbers of alternatives, but were significantly impaired in the tests of recognition memory and learning. By contrast, the other 13 patients showed marked impairments in the attentional tasks. This subgroup was also significantly worse than subgroup 1 in performance on the visual recognition and conditional learning tasks, and showed greater severity on most of the clinical ratings of dementia. The sparing of attentional shifting in patients early in the course of DAT is contrasted with the impairments previously described in patients with Parkinson's disease with only mild or absent memory loss. The implications of this double dissociation of deficits for understanding the neural bases of the cognitive deficits in these two neurodegenerative diseases are discussed and their significance for the staging of DAT is considered.
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