Lewy bodies and Alzheimer's disease.
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Alzheimer Disease↗
Biomedical subjects
A Fairbairn
Publications and source records attributed to A Fairbairn.
Neuroleptic sensitivity in patients with senile dementia of Lewy body type.
OBJECTIVE: To determine the outcome of administration of neuroleptics to patients with senile dementia of Lewy body type confirmed at necropsy. DESIGN: Retrospective analysis of clinical notes blind to neuropathological diagnosis. SETTING: Specialist psychogeriatric assessment units referring cases for necropsy to a teaching hospital neuropathology service. PATIENTS: 41 elderly patients with diagnosis of either Alzheimer type dementia (n = 21) or Lewy body type dementia (n = 20) confirmed at necropsy. MAIN OUTCOME MEASURES: Clinical state including extrapyramidal features before and after neuroleptic treatment and survival analysis of patients showing severe neuroleptic sensitivity compared with the remainder in the group. RESULTS: 16 (80%) patients with Lewy body type dementia received neuroleptics, 13 (81%) of whom reacted adversely; in seven (54%) the reactions were severe. Survival analysis showed an increased mortality in the year after presentation to psychiatric services compared with patients with mild or no neuroleptic sensitivity (hazard ratio 2.70 (95% confidence interval 2.50-8.99); (chi 2 = 2.68, p = 0.05). By contrast, only one (7%) of 14 patients with Alzheimer type dementia given neuroleptics showed severe neuroleptic sensitivity. CONCLUSIONS: Severe, and often fatal, neuroleptic sensitivity may occur in elderly patients with confusion, dementia, or behavioural disturbance. Its occurrence may indicate senile dementia of Lewy body type and this feature has been included in clinical diagnostic criteria for this type of dementia.
Aged↗
Senile dementia of Lewy body type. A clinically and neuropathologically distinct form of Lewy body dementia in the elderly.
A dementing syndrome has been identified in a group of psychiatric cases aged 71-90 years, presenting initially with a subacute/acute confusional state, often fluctuating and associated with visual hallucinations and behavioural disturbances. Clinically, these cases did not meet criteria for a diagnosis of Alzheimer's disease, and many were assigned to the multiinfarct dementia group, although no significant ischaemic lesions were evident at autopsy. Mild extrapyramidal features were apparent in a number of cases but the characteristic clinical triad of Parkinson's disease, i.e., tremor, rigidity, and akinesia, was absent. Detailed neuropathological examination revealed Lewy body formation and selective neuronal loss in brain stem and other subcortical nuclei, accompanied by Lewy body formation in neo- and limbic cortex, at densities well below those previously reported in diffuse Lewy body disease. A variable degree of senile degenerative change was present; numerous senile plaques and minimal neurofibrillary tangles in most cases. Neither the clinical nor the neuropathological features of this group are typical of Parkinson's or Alzheimer's disease, but suggest a distinct neurodegenerative disorder, part of the Lewy body disease spectrum, in which mental symptoms predominate over motor disabilities and lead to eventual psychogeriatric hospital admission. In a sequential series of autopsies conducted on clinically assessed demented patients, neuropathological analysis has indicated that such cases may comprise up to 20% of a hospitalized population of demented old people over the age of 70 years, an observation clearly relevant to the diagnosis and management of dementia in the elderly.
Aged↗
Plasma N-POMC, ACTH and cortisol concentrations in a psychogeriatric population.
Elderly patients with depression and Alzheimer-type dementia (ATD) were compared with age-matched control subjects using a protocol which measured cortisol, adrenocorticotrophic hormone (ACTH) and N-terminal pro-opiomelanocortin (N-POMC) to determine diurnal variation and the effect of dexamethasone administration. Depressed patients had significantly elevated cortisol concentrations both before and after dexamethasone administration. Basal ACTH and N-POMC concentrations were normal in depressed patients but were both elevated, compared with controls, after dexamethasone. By contrast, in ATD patients, cortisol was elevated only after dexamethasone, as was ACTH, but not N-POMC. This may imply that the pattern of secretion of POMC-derived peptides underlying increased cortisol secretion is different in ATD from that in depression.
Adrenocorticotropic Hormone↗
Preventing psychogeriatric referrals.
Physical illness and drug effects contribute significantly to the morbidity of old people with psychiatric problems. Since many of these patients are seen regularly by their doctors, appropriate preventive action should be possible.
Aged↗
Muscarinic cholinergic receptor subtypes in hippocampus in human cognitive disorders.
Total muscarinic receptor levels, the levels of the subtypes exhibiting high and low affinity for pirenzepine, and the high- and low-affinity agonist states of the receptor were investigated in hippocampal tissue obtained at autopsy from mentally normal individuals and the following pathological groups: Alzheimer's disease, Parkinson's disease, Down's syndrome, alcoholic dementia, Huntington's chorea, and motor-neurone disease. A moderate decrease in the density of both high-affinity pirenzepine and high-affinity agonist subtypes was found in Alzheimer's disease, whereas a trend towards an increase in the overall muscarinic receptor density was apparent in the parkinsonian patients without dementia, mainly due to an increase in the low-affinity agonist state; the differences between the Alzheimer's disease and nondemented parkinsonian cases were highly significant. As previously reported, the levels of both choline acetyltransferase and acetylcholinesterase were markedly reduced in both Alzheimer's disease and Parkinson's disease--with a greater loss of both enzymes in the demented subgroup of parkinsonian patients. Activities of the cholinergic enzymes were also extensively reduced in Down's syndrome, accompanied by a loss of high-affinity pirenzepine binding. There were no significant receptor or enzyme alterations in the other groups studied. These observations suggest that in the human brain, extensive degeneration of cholinergic axons to the hippocampus, as indicated by a loss of cholinergic enzymes, is not necessarily accompanied by extensive muscarinic receptor abnormalities (as might be expected if a major subpopulation were presynaptic). Moreover, the opposite changes in muscarinic binding in Parkinson's and Alzheimer's diseases may be related to the greater severity of dementia in the latter disease.
Acetylcholinesterase↗
Serum creatine kinase-BB levels and cerebral cortical creatine kinase activity in senile dementia of the Alzheimer type.
A rise in serum creatine kinase-BB (CK-BB) levels has been reported previously in cases of dementia. In the present study the levels of serum CK-BB have been measured in patients clinically assessed to have senile dementia of the Alzheimer's type (SDAT) and in cognitively intact individuals, matched for age, by a specific two-site monoclonal immunoradiometric assay. No significant difference was found between the 2 groups. Total creatine kinase activity in temporal cortex (Brodmann area 21 and 22) was also found to be similar in brains from SDAT or control cases, obtained at autopsy. These results suggest no major change in the permeability of the blood-brain barrier to this enzyme in SDAT patients.
Alzheimer Disease↗
Amnesic sensitivity to proactive interference: its relationship to priming and the causes of amnesia.
A group of alcoholic amnesics was compared with a group of controls on an A-B, A-C word pairs interference paradigm. With memory instructions the amnesics needed 5 presentation trials to their controls' single trials to match the groups on A-B cued recall. Under these conditions they still showed more proactive interference on the A-C list. When both groups were given five presentation trials for each list and 'free association' instructions, then they both showed this level of interference. This suggested that the amnesic interference effect only occurs because priming is not modulated by conscious memory, i.e. it is an effect of poor conscious memory. This interpretation was further supported by the finding that amnesics forgot the A-B list faster over 2 hr than their controls, when memory instructions were given.
Aged↗
The evaluation of an ultrasound detector (UD) in the measurement of oro-facial dyskinesia.
An ultrasound detector (UD) was compared with a clinical rating (CR) scale in the assessment of oro-facial movements in 23 chronic schizophrenic patients and 23 normal subjects over a period of 4 weeks. The apparatus distinguished well between normal volunteers and dyskinetic patients. There were also highly significant correlations between UD scores and clinical ratings. The results thus confirm both the construct and concurrent validity of the technique. Nevertheless, there was significant variation in the UD scores for some patients between assessments. A technical problem was the inability of some patients to cooperate for more than 30 seconds. The scores of the normal subjects were consistent. With further development and repeated 30-second assessments the technique might be of value in the ascertainment of early dyskinesia in patients at risk and also in measuring drug effects.
Adult↗
Nicotinic receptor abnormalities in Alzheimer's and Parkinson's diseases.
The status of cholinergic receptors in dementia is related to the question of potential cholinergic therapy. Whilst muscarinic receptor binding is generally reported to be normal or near normal, findings are reported which indicate substantial reductions of hippocampal nicotinic (high affinity nicotine) binding (occurring in conjunction with decreased choline acetyltransferase) in both Alzheimer's and Parkinson's but not Huntington's disease. A further indication that nicotinic receptor function may be abnormal in Alzheimer's disease is the extensive loss of an endogenous compound, detected for the first time in human brain, which inhibits normal nicotinic binding. Both receptor binding and the inhibitor are also substantially decreased with increasing age in the normal hippocampus.
Adult↗
Aluminosilicates and senile plaque formation in Alzheimer's disease.
Aluminium and silicon were found to be colocalised in the central region of senile plaque cores in studies with energy dispersive X-ray microanalysis. The distribution of these elements was similar in cores isolated from the cerebral cortex of patients with senile dementia of the Alzheimer type and in cores studied in situ from tissue sections from the cerebral cortex of presenile and senile patients with Alzheimer's disease, and elderly, mentally normal patients. High-resolution solid-state nuclear magnetic resonance techniques showed aluminium and silicon to be present as aluminosilicates. The presence of aluminosilicates at the centre of senile plaque cores contrasts with the distribution of other inorganic constituents and suggests that they may be involved in the initiation or early stages of senile plaque formation.
Aged↗
Broken necks of the femur in a psychogeriatric hospital.
We report a prospective study of the results of treatment of fractures of the neck of the femur in 102 patients in a psychogeriatric hospital. The results show that early operation may reduce complications but the aftercare should be in the familiar surroundings of the mental hospital. The costs of this policy are also considered.
Adult↗
Cholinergic receptors in cognitive disorders.
Cholinergic receptors (muscarinic subtypes M1 and M2, and putative nicotinic binding) have been examined in the hippocampus obtained at autopsy from a variety of patients with cognitive disorders (Alzheimer's, Parkinson's, and Huntington's diseases, Down's Syndrome and alcoholic dementia) and compared with neurologically normal controls and cases of Motor Neuron disease. In all of the disorders associated with a pre-synaptic cortical cholinergic deficit reflected by an extensive loss of choline acetyltransferase (Alzheimer's disease, Parkinson's disease and Down's Syndrome) there was a substantial reduction in the binding of (3H) nicotine to the nicotinic receptor. By contrast reductions in both muscarinic subtypes (M1 and M2) were apparent to only a moderate extent in Alzheimer's disease, whereas in Parkinson's disease binding was significantly increased (apparently not in relation to anti-cholinergic drug treatment) in the non-demented but not demented cases. A further abnormality detected in Alzheimer's disease but not the other disorders investigated was a decrease in an endogenous inhibitor of nicotinic binding, the identity of which is as yet unknown but which may be a candidate for a possible endogenous modulator of the nicotinic receptor. These observations suggest that in Alzheimer's disease not only muscarinic but also nicotinic receptor function should be considered in relation both to future therapeutic strategies and, in the search for a clinical marker which might be of diagnostic value, to potential probes of the cortical cholinergic system.
Cognition Disorders↗
Alzheimer's disease and the hippocampus.
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Alzheimer Disease↗
Cognitive performance of medicated schizophrenics with tardive dyskinesia.
Twenty schizophrenic patients with tardive dyskinesia and an equal number of matched controls were tested on a novel cognitive task. The task had two components: cued response and spatial memory. Relative to controls, the dyskinetic subjects showed a superior cued response performance but an equal spatial memory ability. We speculate that this selective facilitation may reflect dopaminergic hyperactivity in the dyskinetic group.
Antipsychotic Agents↗
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↗
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↗