C. G. Gottfries

Increased activity of brain and platelet monoamine oxidase in dementia of Alzheimer type

Abstract Two groups of patients with dementia of Alzheimer type were studied with respect to monoamine oxidase (MAO) activity. In one group of 11 patients MAO activity was determined in platelets and in the other group of 14 patients in the brain (hypothalamus, caudate nucleus, hippocampus and cortex gyrus cinguli) post mortem. The results were compared to controls matched for age and sex. Platelet MAO activity was significantly higher in patients with dementia of Alzheimer type compared to controls. Brain MAO-B activity but not MAO-A activity was significantly higher in the dementia group in hyppocampus and cortex gyrus cinguli. In the controls there were positive correlations for MAO-B activity with age in the four brain regions, but these correlations were absent in the dementia group. This could be explained by differences in age of onset of dementia and that the disease process does not develop homogeneously in different brains.

Post-mortem distribution of dopamine and homo-vanillic acid in human brain, variations related to age, and a review of the literature

The post-mortem brain concentrations of dopamine (DA) and homo-vanillic acid (HVA) were determined in 16 parts of the brain from patients with no history of neurologic or psychiatric illness. Fifteen men and nine women, with a mean age of 61.0±18.7 years (range 23–92 years) were included. They had died from either ischaemic heart disease or cancer. In the post-mortem investigation several factors were controlled: age, time between death and autopsy, time between autopsy and chemical analysis and storage time (−20 °C). The DA concentrations in the different brain areas were found to be positively intercorrelated, especially those in the basal ganglia, hippocampus and the mesencephalon. The HVA concentrations measured in various cortical structures were also positively intercorrelated. In several regions of the brain there was a significant inverse correlation between the DA and HVA concentrations. The DA and HVA concentrations did not differ according to sex, but age had a marked influence on the DA concentration. Significant decrease with age was observed in the nucleus caudatus, globus pallidus, mesencephalon, hippocampus and in the cortex gyrus hippocampus. These findings are discussed in relation to the effect of aging neurons. A review of human post-mortem investigations on DA and HVA concentrations is also presented.

Prevalence of dementia disorders in institutionalized Swedish old people THE WORK LOAD IMPOSED BY CARING FOR THESE PATIENTS

The prevalence of dementia disorders was determined among 3,523 institutionalized patients aged 65 years or more in the county of Vasterbotten. Approximately one‐third of the clientele were considered demented. The prevalence was calculated to be 3.7 % of the population in the county. The frequency of dementia disorders among the patients in the somatic long‐stay wards, the nursing homes, and the mental hospital was rather similar (55–65 %). A surprisingly high percentage of demented (17.1 %) was found in the homes for the aged. The work load was nighest in the somatic long‐stay wards and in the nursing homes. Patients in the mental hospital, however, differed markedly from those in other institutions with higher scores for aggressive and disturbing behaviour, which accounted for the large number of patients in the mental hospital with maximal work load. The findings are discussed with regard to future institutional care of demented patients and point out the need for better education in psychiatric care for the staff.

Distribution of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in human brain in relation to age, drug influence, agonal status and circadian variation

The post-mortem brain concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in 16 parts of the brain from patients with no history of neurologic, psychiatric or metabolic illness. The causes of death were either ischemic heart disease, infections disease, cancer or accidents. Forty-two men with a mean age of 57 years (range 18–95 years) and 19 women with a mean age of 62 years (range 23–79 years) were included. The influence of several factors were studied: brain weight, time between death and autopsy, storage time before chemical analysis, age, sex, agonal status, cerebral arteriosclerosis, cancer, opiate treatment and time of death during the day. Most correlations between the 5-HT concentrations in different brain parts were positive, the strongest correlations in the basal ganglia and the limbic system. No consistent pattern of age-related 5-HT changes were found. The females had significantly higher 5-HIAA concentrations in the cortex of the gyrus hippocampus. Final hypoxia seemed to decrease 5-HT concentrations. Opiate treatment reduced 5-HT and increased 5-HIAA concentrations. A marked circadian variation of 5-HT was found, most pronounced in the hypothalamus, the limbic system and some neocortical areas.

The activity of monoamine oxidase -A and -B in brains from chronic alcoholics

The activity of monoamine oxidase-A was found to be lower in homogenates of hypothalamus and caudate nucleus, but not in cortex of the gyrus cinguli and hippocampus, from chronic alcoholics with respect to homogenates from autopsy cases without histories of alcohol abuse. The activity of monoamine oxidase -B was also lower in the alcoholics, but this could be due to the selective effect of age upon this enzyme form, since the alcoholics were younger than controls. No difference was found for either monoamine oxidase -A or -B activities in brain homogenates from an alcohol preferring (AA) strain of rats, with respect to those from a water preferring (ANA) strain.

Visual averaged evoked responses (aer) and monoamine metabolites in cerebrospinal fluid (csf).

Observations by Goodwin et al. (1963) seem to lend support to the hypothesis that a positive relationship may exist between the level of homovanillic acid (HVA) in CSF and the amplitude of visual AER. Results from our own laboratory (Muttsson 6’ Perris (1974)) in a psychotic patient suffering from Addison’s disease, who has been studied longitudinally, point in the same direction. Moreover a shortening of latencies, especially as concerns the first three peaks, has also been observed. No investigations have been published so far concerning the relationship between AER and 5 -hydroxyindoleacetic acid (5-HIAA).

GRAVE LITHIUM INTOXICATION WITH FATAL OUTCOME

Despite considerably increased use of lithium in psychiatry and its being regarded as a very toxic preparation, reports of serious complications following treatment are surprisingly few. The literature only describes a few cases with fatal outcome (Schou et al. 1967, Hawkins et al. 1969). One lithiumtreated patient who suffered myocarditis leading to death is reported (Len Tseng 1971) where the lithium was judged the cause. Disturbances in cardiac rhythm and T-wave changes during lithium treatment have been described (Tangendahl et al. 1972). Hypothyreosis and goiter have also been reported in several cases (Schou et al. 1968, Sedvall et al. 1969). The following case of lithium intoxication with fatal outcome is interesting in view of the investigations and section findings. 4

HUNTINGTON'S CHOREA: PATHOLOGY AND BRAIN AMINES

The most striking findings in the brains of patients with Huntington’s chorea (HC) is a marked atrophy in the basal ganglia, especially in the neostriatum. There is also an evident atrophy in the cerebral cortex. In an early phase of the disease the changes in the neostriatum are most pronounced in the small neurons, later the larger neurons are involved and the proliferation of the glial cells is evident. In the more unusual hypokinetic rigid typc mostly seen in young paticnts, no uniform pathological findings have been described in contrast to the common adult-hyperkinetic type. Surprisingly, little has actually been added to the knowledge of the pathological picture in HC from about the beginning of the 20th century when the first pathological studies were reported (Alzheimer (191 l), Stone & Falstein (1938)).

Monoamines and their metabolites and monoamine oxidase activity related to age and to some dementia disorders

Most psychotropic drugs exert their effects by influencing the activity in monoaminergic systems in the human brain. It is therefore of importance, when discussing drugs and the elderly, to know whether and, in what way, age and dementia disorders influence the metabolism of monoamines in the CNS. In animal exp-eriments, it has been shown that there is a reduced turnover of the catecholamines in the old rat brain (Finch, 1973, 1976; Algeri et al 1976). The activities of tyro-sine hydroxylase (TH) as well as dopamine decarboxylase (DOD) have been ex-amined post mortem in humans and highly significant age declines have been reported (Lloyd and Hornykiewicz, 1970; McGeer, McGeer and Wada, 1971; McGeer and McGeer, 1973; Cote and Kremzner, 1974). Post-mortem studies in man have also shown reduced levels of dopamine (DA) and noradrenaline (NA) related to age (Carlsson and Winblad, 1976; Adolfsson, Gottfries and Winblad, 1976; Robinson et al 1977). In senile dementia and Alzheimer’s disease reduced levels of homo-vanillic acid (HVA) have been found (Gottfries, Gottfries and Roos, 1968, 1969) as well as reduced levels of DA and NA (Gottfries, Roos and Winblad, 1976) when compared with age-matched controls.

A pilot trial of sectorized and decentralized psychiatric care in northern Sweden

SummaryAn attempt to decentralize and sectorize the psychiatric out-patient service in a rural area in northern Sweden is described and the theoretical background is discussed. A psychiatrist and a specially trained nurse visit the district health centers in the area once every other week to see some patients and to have a conference with the district doctors, district nurses and social workers. The experiences are so far encouraging and the experiment will continue.