Biomedical subjects
Publications and source records attributed to M Fisman.
Two elderly patients with musical hallucinations are described. In the first case, the musical hallucinations were precipitated by the administration of benzodiazepines. The symptoms in the second case resembled those described in cases of visual hallucinosis (Charles Bonnet syndrome) in the elderly. Issues related to the presentation and course of musical hallucinations are discussed.
Alzheimer's disease is a frequent cause of dementia in the elderly. The prevalence and incidence increase with aging. It is hypothesised that the age related decline in liver size and lysosomal function results in decreased clearance as well as decreased or altered proteolysis of the Alzheimer precursor protein, and results in the deposition of A4 protein in cerebral blood vessels and brain with congophilic angiopathy and senile/amyloid plaque formation.
Significant alterations of tissue metal levels have been reported in Alzheimer's disease (AD). Because the liver is intimately involved in metabolism and storage of metals, it may provide a useful site for study of these metals in AD. This study compares livers in AD and controls in their concentrations of zinc, copper, cadmium, and metallothionein, a metal-binding protein important in regulation of metal metabolism. Liver tissue was obtained from 17 patients with AD and 17 age- and sex-matched controls within 12 hours of death and stored at -70 degrees C. Neuropathologic confirmation of diagnosis was available in all cases. Liver homogenates (20%) were used for metal analysis by atomic absorption spectroscopy after wet digestion. Cytosolic metallothionein levels were quantitated by the cadmium or silver saturation method. A significant decline in body and liver weight was found in patients with AD, with no significant change in liver protein or DNA concentration. Total hepatic cadmium (P less than .001) and zinc (P less than .030) concentrations were significantly elevated in AD. The Sephadex G75 chromatographic profile was altered in AD with reduction in zinc bound to metallothionein fractions and increased binding to high molecular weight fractions. These data suggest that the metabolism of cadmium and zinc is altered in AD.
We report findings on a study of anxiety and depression by questionnaire in 50 patients with mild dementia and 134 control subjects using the Hospital Anxiety and Depression Scale. Thirty-eight percent of patients and 9% of controls had a possible or probable diagnosis of an anxiety disorder. Possible or probable depression was found in 28% of the patients and 3% of the controls. These rates for the patients were above those in normal populations. All patients and control subjects were tested with the Extended Scale for Dementia (ESD). Neither group showed a significant relationship between depression and ESD scores. In the control subjects there was a negative correlation (P less than .006) between anxiety and cognitive scores, one that was not found in the patients.
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1. Hepatic metabolism of oxazepam in Alzheimer's disease (AD) was assessed by measurement of urinary metabolites in a group of hospitalized patients with AD, a hospitalized schizophrenic control group and a normal community based group. 2. A subgroup of six AD patients showed marked elevations of the hydroxylated metabolite. The median excretion of conjugated oxazepam in the AD and schizophrenic patients was almost one third that in normal controls (p less than .005). 3. A relationship between decline in level of conjugated metabolite and increase in the mental confusion score on the London Psychiatric Rating Scale (r = -.5253, p less than .05) was found in the AD patients. 4. Changes in hepatic metabolism in AD may be relevant not only for drug metabolism and the development of side effects, but also for the pathogenesis of AD.
Patients with Alzheimer's disease (AD) and matched controls fasted for 24 hours, and serial glucose, pyruvate, lactate, beta-hydroxybutyrate, acetoacetate, insulin, and glucagon levels were measured. Patients with AD showed a glucose insulin correlation pattern over the 24 hours that differed from the control group. These differences may be secondary to weight loss or to other metabolic or nutritional factors affecting the AD patients.
Two cases are presented to illustrate some of the issues that arise in the management of patients diagnosed as suffering from the dementia syndrome of depression (Pseudodementia). Case 1 illustrates the dilemma of relatively normal autopsy findings in the brain in a patient presenting with a history of depression and dementia. Case 2 deals with a patient successfully treated for depression 14 years after the diagnosis of presenile dementia. Issues raised include the problem of labelling and the Rip Van Winkle situation of unanticipated recovery 14 years after this diagnosis was made. A planned approach to the treatment of pseudodementia systematically exploring available treatment options is recommended.
Clinical findings in a group of 11 patients who failed to respond to at least one course of antidepressant (usually tricylic) treatment and at least seven bilateral electroconvulsive treatments (ECTs) were compared with the findings in a group of 19 patients with similar sociodemographic characteristics who were responsive to ECT. The major correlates of ECT nonresponse were onset of physical illness during the index episode, fewer life events preceding the onset of the index episode, and a higher frequency of preceding depressive episodes of longer duration in the nonresponder group.
Clinical and pathologic diagnoses are compared in 65 patients who had dementia and who had been studied longitudinally during life. The sensitivity of diagnosis for dementia of the Alzheimer type (DAT) without any other diagnosis was 87%, and the specificity was 78%. The ischemic scale score did not discriminate well between patients with pure multi-infarct dementia and those with both DAT and multi-infarct dementia. However, 35 of 38 cases of pure DAT had a score of 4 or less on the ischemic scale.
As part of a longitudinal cohort study of dementia, 139 patients with Alzheimer's disease (dementia of the Alzheimer type, senile dementia of the Alzheimer type, and mixed type [ischemic score, 4 to 7]) and 148 age-matched control subjects were evaluated for electroencephalographic (EEG) abnormalities and their evolution. Electroencephalograms were significantly different in the two groups; EEGs worsened overall in the two groups during a period of one to four years, but most subjects showed no alteration in their EEGs. Some patients showed improvement in their EEG findings during the follow-up period. A strong correlation between EEG grade and psychometric scores was consistently found over sequential studies. In a subgroup of patients on whom autopsies were performed, morphometric neuron loss correlated significantly with EEG severity.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
As part of a prospective clinicopathological study a cohort of "normal" elderly volunteers (n = 110) has been investigated with CT scans, psychometric testing (Extended Scale for Dementia) and neurological examination. CT scans were evaluated by a neuroradiologist for the presence or absence of white matter lucencies (WML). WML were defined as patchy or diffuse areas of decreased attenuation involving only white matter and with no change in adjacent ventricles or sulci. The 12 subjects with WML had lower scores on the ESD than the 98 subjects without WML (mean ESD with WML 229.5 +/- 14; without WML 236.7 +/- 8.6, t-test p less than .01) and the difference remains significant even after adjusting for the possible confounding effects of age (ANCOVA, P less than .043).
Our findings dispel the commonly held belief that the EEG always worsens progressively in dementia of the Alzheimer's type. In a continuing cohort analytical study of dementia, 139 patients with Alzheimer's disease and 148 controls were studied for EEG abnormalities and progression. EEGs were read without knowledge of the previous EEGs or clinical condition, and classified according to the presence of diffuse delta or theta, bisynchronous spikes, projected activity, and focal activity. EEGs were significantly different in the two groups. EEG scores generally worsened over 1-4 years, but most of the subjects showed no alteration in their EEG scores. A few patients with Alzheimer's disease showed improvement of EEG findings.
Language impairment in Alzheimer's disease has become an important clinical issue. It has been recognized for some time that the disease may begin with aphasia and even before frank aphasia develops, some of the earliest changes in a large number of individuals consist of impairment of word fluency and semantic access manifesting itself in word finding difficulty. The second major issue concerning language in Alzheimer's disease is that the cases which have early severe language impairment may represent a more progressive familial variety of disease as it has been suggested in the literature. This is still subject to controversy. Finally, it will be documented that the later stage of the disease shows language invariably impaired and goes through stages of dissolution that resemble anomic, transcortical sensory. Wernicke's and global aphasias. Accurate assessment of language may turn out to be one of the most reliable predictors of the stages of Alzheimer's disease and provides important insights into the cerebral organization of language, semantic access, relationship of semantic and episodic memory and the pathophysiology of the disease.
We examined the degree of neuronal loss from the nucleus basalis of Meynert (nbM) in two groups of Alzheimer patients differing in the degree of intellectual impairment. Significant cell loss from the nbM was found only in the more severely demented group of patients. Mean cell counts (per 10 mu paraffin section) were compiled separately for the anterior, intermediate and posterior subdivisions of the human nbM in three groups of subjects: Group 1 (N = 4) was severely demented and was untestable on the Extended Scale for Dementia (ESD) for at least the last two years of life; Group 2 (N = 4) was less demented and had completed at least one ESD test within 12 months of death; Group 3 (five controls) had died of non-neurological causes. In Group 2 there was a small (but insignificant) trend toward cell loss in the anterior subdivision, and a normal complement of neurons in both the intermediate and posterior subdivisions. There was, however, significant cell loss from all subdivisions of Group 1. How these cell counts may relate to the severity of the dementia is discussed.