Michael Fisman

A study of language functioning in Alzheimer patients

Abstract Language functioning in Alzheimers disease is reviewed and the performance of 25 Alzheimer patients on a standard battery is reported. All these hospitalized patients were aphasic to some degree. As a group, they differed from normals on all language variables, and from stroke patients in terms of higher fluency and lower comprehension. Spontaneous speech showed high incidence of circumlocutions and semantic jargon, but no phonemic paraphasias or target approximations. Syllabic perseverations, shouting, inappropriate laughter, and mutism were late-appearing features. Transcortical Sensory, and Wernickes aphasias were frequent, but Brocas and Transcortical Motor aphasias notably absent. Extent of language impairment correlated with current length of hospitalization but not age. Reading, writing, and performance scores except praxis, were lower than oral language scores. Findings were discussed in relation to previous results, methodology, and language organization in the brain.

A questionnaire investigation of anxiety and depression in early dementia.

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.

The Dissolution of Language in Alzheimer's Disease

Language impairment in Alzheimers 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 Alzheimers 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. Wernickes and global aphasias. Accurate assessment of language may turn out to be one of the most reliable predictors of the stages of Alzheimers 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.

Metals and the liver in Alzheimer's disease. An investigation of hepatic zinc, copper, cadmium, and metallothionein.

Significant alterations of tissue metal levels have been reported in Alzheimers 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°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 < .001) and zinc (P < .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.

Metabolic Changes in Alzheimer's Disease

Patients with Alzheimers disease (AD) and matched controls fasted for 24 hours, and serial glucose, pyruvate, lactate, β‐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.

Correlative studies in Alzheimer's disease

An approach is described for establishing and maintaining a correlative study of Alzheimers Disease. A sample of the findings by the University of Western Ontario (U.W.O.) Dementia Study Group is provided.

Apolipoprotein E Polymorphism and Response to Electroconvulsive Therapy

The aim of this study was to determine whether the apolipoprotein E genotype differs in patients who respond or do not respond to electroconvulsive therapy (ECT). Inpatients, outpatients, and day-treatment patients who had received ECT comprised the study group. The 34 patients included met DSM-III-R criteria for affective or schizoaffective disorder. Responder or nonresponder status was assessed using the Clinical Global Inventory and Montgomery Asberg Depression Rating Scale. Blood samples were taken and coded when the patients entered the study. DNA extraction and apolipoprotein E genotyping were performed with no knowledge of the clinical classification of the patients. A significant difference in E4 genotype distribution was found between ECT responders and nonresponders (p < 0.02); psychosis was significantly less frequent in this group (p = 0.046), and there was a trend toward older onset of depression among these persons (p = 0.10). Only the E3/3 genotype was found in the patients with early-onset depression. The E4 genotype appears to define a subgroup of patients with late-onset depression who respond to ECT. If confirmed in prospective studies, this may provide a useful marker in the treatment decision-making process for late-onset depression.

Dementia in the elderly male alcoholic— a retrospective clinicopathological study

Although intellectual decline associated with alcohol use has been extensively documented, the neuropathological basis for this cognitive change remains controversial. We have therefore undertaken a naturalistic survey of a population of patients identified as having an excessive alcohol intake. Records of all autopsies on patients resident in a chronic hospital between 1983 and 1993 were reviewed for evidence of alcohol abuse. Multiple brain pathology was found in the demented alcoholic patients. The most unexpected finding in this series was that seven of 12 cases of dementia with history of alcohol abuse presented with significant cerebrovascular disease, meeting NINDS– AIREN criteria for vascular dementia, suggesting that cerebrovascular disease may be a significant component of dementia in older alcoholics. Our finding that in four of six cases mamillary pathology may be secondary to vascular lesions suggests that unless these lesions are sought, the presence of mamillary pathology may lead to overdiagnosis of nutritional factors as the basis for alcoholic dementia.

The EEG in Alzheimer type dementia: lack of progression with sequential studies.

Our findings dispel the commonly held belief that the EEG always worsens progressively in dementia of the Alzheimers type. In a continuing cohort analytical study of dementia, 139 patients with Alzheimers 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 Alzheimers disease showed improvement of EEG findings.