[Dementia--research results give hope for treatment].
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Aged↗
Biomedical subjects
B Winblad
Publications and source records attributed to B Winblad.
[Alzheimer's disease--an amyloid disease of the brain].
During recent years, Alzheimer's disease (AD) has attracted increasing interest among clinicians and neuropathologists throughout the world. The amyloid core of the neuritic plaques found in the brains of individuals with the disease has been shown to be composed of a distinct peptide formed through proteolytic degradation of a large precursor protein, the Alzheimer amyloid precursor protein (APP), which exists in at least three isoforms differing from each other in the splicing of the primary transcript from which they derive. Although the physiological function of APP remains unknown, it has been suggested to function as a protease inhibitor and to be important to the blood coagulation system. The gene encoding APP is located on the long arm of chromosome 21. Individuals with Down's syndrome (trisomy 21) often develop AD in early middle age, suggesting that the 50 percent increase in APP, gene expression may promote the development of the disease. Mutations in the APP gene have also been shown to be associated, probably pathogenetically with familial forms of AD. The conclusions drawn from these studies include (i) that the amyloidosis associated with AD is probably a central pathogenetic factor and (ii) that the development of drugs capable of inhibiting amyloidosis might be an appropriate strategy for the treatment of AD.
Alzheimer Disease↗
Preservation of Gi-protein inhibited adenylyl cyclase activity in the brains of patients with Alzheimer's disease.
The coupling of inhibitory guanine nucleotide binding (Gi) proteins to the adenylyl cyclase signal transduction complex was compared in 4 brain regions from a series of Alzheimer's disease and matched control subjects by measuring the inhibition of membrane enzyme activities in response to guanosine 5'-[beta gamma-imido]diphosphate (Gpp[NH]p) and aluminium fluoride (AlF4-). Basal adenylyl cyclase activities were significantly lower in preparations of angular gyrus and frontal and temporal cortices, but not cerebellum, from the Alzheimer's disease cases compared to controls. Gpp[NH]p and AlF4- gave significant inhibitions of adenylyl cyclase activity in all brain regions. The magnitude of these inhibitions, when corrected for altered basal activities, were similar for the Alzheimer's disease and control cases. These results indicate that there is no impairment of Gi-protein mediated inhibition of adenylyl cyclase activity in Alzheimer's disease brain.
Adenylyl Cyclases↗
Hippocampal nerve growth factor levels are related to spatial learning ability in aged rats.
Brain nerve growth factor (NGF) was determined in two groups of aged rats: 'good' and 'poor' performers. The animals were selected out of a population of 40 aged rats (26-28 months old) trained in a spatial learning task. Animals performing well in the test had significantly higher NGF in the hippocampus when compared to 'poor' performers. No differences in the levels of NGF were found in the cortex, septum and cerebellum. The results implicate hippocampal NGF in cognitive functioning of aged rats, and suggests that the forebrain cholinergic neuronal atrophy which has been observed in cognitively impaired aged rats may be due to reduced availability of target-derived NGF.
Aging↗
Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment.
Enriched environment has been shown to enhance learning and memory and to induce morphological changes in the hippocampus. We report that rats housed in an enriched environment showed improved performance in the Morris water maze and decreased spontaneous motor activity. Exposure to behavioural tests increased expression of the mRNA that encodes brain-derived neurotrophic factor in the hippocampus. This was not seen when rats subjected to impoverished housing were tested suggesting that environmental history of the animal is of importance to induce expression of brain-derived neurotrophic factor in the hippocampus that may promote neuronal changes related to learning and memory.
Analysis of Variance↗
Clinical diagnosis of Alzheimer's disease and other dementias in a population survey. Agreement and causes of disagreement in applying Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, Criteria.
In a population survey aimed to detect cases of Alzheimer's disease and other dementias, two preliminary diagnoses were made independently with the purpose of using the concordant diagnoses as final diagnoses. Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, diagnostic criteria were followed. The 668 subjects examined were selected from the population of an area in Stockholm, Sweden, aged 75 years or more, with the Mini-Mental State Examination used as a screening test. The agreement on dementia diagnosis was moderate (kappa = .54) and could be clearly improved (kappa = .70) with modifications to the diagnostic criteria, such as adding a category of questionable dementia and giving more guidelines in the definition of impairment of a function. The agreement on the diagnosis of Alzheimer's disease vs vascular dementia vs secondary dementia was substantial (kappa = .67) when the cases with concordant dementia diagnoses were examined.
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Nicotinic and muscarinic subtypes in the human brain: changes with aging and dementia.
Different effects of normal aging on muscarinic and nicotinic receptor subtypes were observed in postmortem brain tissue from different regions of the human brain. A significant decrease in M1 and M2 receptors was found in cerebral cortex, while the M1 and especially the M2 receptors increased with age in the thalamus. A similar pattern of changes was also observed when using (-)3H-nicotine as ligand for nicotinic receptors in the cortex and thalamus. No significant changes in nicotinic receptor binding were observed with age in the cortex or thalamus when using 3H-acetylcholine as ligand. Nicotinic and muscarinic receptors in the brain are not equally affected in dementia disorders. A marked loss of high affinity nicotinic receptors was observed in cortical tissue from patients with Alzheimer's disease and with multi-infarct dementia (MID). The muscarinic receptors were (both M1 and M2) increased in Alzheimer cortical tissue while they were decreased in MID.
Adolescent↗
Neurotransmitter-mediated inhibition of post-mortem human brain adenylyl cyclase.
The effects of a range of neurotransmitter agonists showing selectivity for receptor types inhibitorily coupled to adenylyl cyclase were compared in membrane preparations of hippocampus, frontal cortex and caudate nucleus/striatum from previously frozen post-mortem human and rat brain. Agonists were tested against basal and forskolin stimulated activities, forskolin being a potent activator of the catalytic sub-unit of the enzyme. Of those agonists tested, only somatostatin (100 microM) and neuropeptide Y (10 microM) gave consistent inhibitions of basal and forskolin stimulated enzyme activities in all three regions of both human and rat brain. Somatostatin-mediated inhibition of human brain adenylyl cyclase was reduced in the absence of GTP and in the presence of the guanine nucleotide partial agonist, guanosine 5'-O-thiodiposphate, consistent with a G-protein-linked receptor. No such GTP-dependence was found for the neuropeptide Y-mediated adenylyl cyclase inhibition. GTP-dependent somatostatin mediated inhibitions of human brain adenylyl cyclase activity were of highest magnitude in the thalamus, intermediate magnitude in the hippocampus and caudate nucleus and lowest magnitude in the frontal cortex. It is concluded that of a range of neurotransmitter receptor agonists tested, only somatostatin gives robust, GTP-dependent responses that are reproducible enough to be used with post-mortem tissue for the comparison of receptor function in human brain disorders.
Adenylyl Cyclase Inhibitors↗
Health and social consequences for relatives of demented and non-demented elderly. A population-based study.
A population-based study was performed to investigate the subjective and objective burden due to caring for a demented relative. All the relatives of the subjects with cognitive impairment, detected in a district of Stockholm, living at home, were included in the study. When compared with relatives of elderly, mentally healthy persons living at home in the same district, they had high ORs for subjective burden and for use of psychotropic drugs. Spouses were the most stressed. However, the ORs for use of medical facilities and somatic drugs were close to unity, showing that caring for a demented person did not affect the physical health of the relative. A second comparison between relatives of demented persons living at home and in institutions, showed that the relatives of institutionalized subjects were less frequently spouses and had more problems with their physical health, but both groups had similar subjective feeling of stress.
Adolescent↗
A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid.
Mutations at codon 717 in exon 17 of the beta-amyloid precursor protein (APP) gene have previously been shown to segregate with early onset Alzheimer's disease in some families. We have identified a double mutation at codons 670 and 671 (APP 770 transcript) in exon 16 which co-segregates with the disease in two large (probably related) early-onset Alzheimer's disease families from Sweden. Two base pair transversions (G to T, A to C) from the normal sequence predict Lys to Asn and Met to Leu amino acid substitutions at codons 670 and 671 of the APP transcript. This mutation occurs at the amino terminal of beta-amyloid and may be pathogenic because it occurs at or close to the endosomal/lysosomal cleavage site of the molecule. Thus, pathogenic mutations in APP frame the beta-amyloid sequence.
Alzheimer Disease↗
Loneliness among elderly people living in stockholm: a population study.
The purpose was to investigate experienced loneliness among the elderly. The material included 1725 people, aged 75 and over. The study describes relationships between loneliness, social network, cognitive function and health. Thirty-five per cent experienced loneliness, and a higher percentage was found among women. A gradual increase in loneliness was found up to the age of 90, after which a levelling was found. Elderly persons living together with a partner experienced less loneliness. There were no significant differences between those with and without children. Ten per cent reported not having any friends and, of these, one out of two experienced loneliness. A high frequency of experienced loneliness was found among elderly people with reduced cognitive function. Subjectively experienced bad health and loneliness were strongly related to each other, i.e. a person who experienced loneliness did usually not feel completely healthy.
Aged↗
Adenylyl cyclase activity in postmortem human brain: evidence of altered G protein mediation in Alzheimer's disease.
The effects of agonal status, postmortem delay, and age on human brain adenylyl cyclase activity were determined in membrane preparations of frontal cortex from a series of 18 nondemented subjects who had died with no history of neurological or psychiatric disease. Basal and guanosine 5'-O-(3-thiotriphosphate)-, aluminum fluoride-, and forskolin-stimulated enzyme activities were not significantly reduced over an interval from death to postmortem of between 3 and 37 h and were also not significantly different between individuals dying with a long terminal phase of an illness and those dying suddenly. Basal and aluminum fluoride-stimulated enzyme activities showed a negative correlation with increasing age of the individual. In subsequent experiments, basal and guanosine 5'-O-(3-thiotriphosphate)-, aluminum fluoride-, and forskolin-stimulated enzyme activities were compared in five brain regions from a series of eight Alzheimer's disease and seven matched nondemented control subjects. No significant differences were observed between the groups for either basal activity or activities in response to forskolin stimulation of the catalytic subunit of the enzyme. In contrast, enzyme activities in response to stimulation with guanosine 5'-O-(3-thiotriphosphate) and aluminum fluoride were significantly reduced in preparations of neocortex and cerebellum from the Alzheimer's disease cases compared with the nondemented controls. Lower guanosine 5'-O-(3-thiotriphosphate)-, but not aluminum fluoride-, stimulated activity was also observed in preparations of frontal cortex from a group of four disease controls compared with nondemented control values. The disease control group, which contained Parkinson's disease and progressive supranuclear palsy patients, showed increased forskolin-stimulated activity compared with both the nondemented control and the Alzheimer's disease groups. These findings indicate a widespread impairment of G protein-stimulated adenylyl cyclase activity in Alzheimer's disease brain, which occurs in the absence of altered enzyme catalytic activity and which is unlikely to be the result of non-disease-related factors associated with the nature of terminal illness of individuals.
Adenylyl Cyclases↗
A comparative study of the social conditions of spouses of long term patients cared for either in nursing homes or home care.
In order to study the social conditions of spouses of patients suffering from long term illnesses structured interviews were performed. The interviewees were divided into two groups: spouses of persons with chronic conditions cared for at home and spouses of patients cared for in nursing homes. Each group consisted of 27 spouses and there were no differences in physical health score, Mini mental score or ability to manage primary Activities of Daily Living functions between the groups. Home care spouses paid fewer visits to children, had fewer friends and paid fewer visits to friends and they also had time for hobbies or interests significantly more seldom (reading, visits to church) than nursing home spouses. There were no significant differences between the groups concerning sex, socio-economic class, housing conditions and amount of home health services. Their contact with children and their feelings of loneliness were reported to be the same.
Aged↗
Neurotransmitter, receptor and signal transduction disturbances in Alzheimer's disease.
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Alzheimer Disease↗
Clinical staging of dementia in a population survey: comparison of DSM-III-R and the Washington University Clinical Dementia Rating Scale.
In a population survey in Stockholm, 224 dementia cases were staged using two scales: the Washington University Clinical Dementia Rating Scale and DSM III-R. Both scales had to be modified by adding additional specifications and, in the case of DSM III-R, a new category of questionable dementia. After modification, the comparison of the two scales showed good agreement when all stages were analyzed (kappa = 0.60), but moderate agreement on the questionable and mild stages (kappa = 0.47). These results confirm the staging of mild dementia as the most problematic issue. Finally, the scales both showed moderate agreement with the categorized Mini-Mental State Examination (MMSE) (0-17 for severe and moderate forms; 18-23 for mild cases). Our data suggest new cut-off points for the MMSE when used as a staging scale.
Aged↗
Characterisation of dopamine and serotonin uptake inhibitory effects of tetrahydroaminoacridine in rat brain.
The effects of 1,2,3,4-tetrahydro-9-aminoacridine (THA) on uptake rates of radioactive 5-hydroxytryptamine (5-HT) and dopamine were investigated in rat diencephalon and striatal homogenates, respectively. Six and eight microM of THA were needed to inhibit 50% of dopamine and 5-HT uptake rates. Kinetic parameters, Km and Vmax, using six different concentrations of dopamine and 5-HT were estimated in the presence or absence of THA. A significant decrease in Vmax without any change in Km values was observed for both dopamine and 5-HT in the presence of THA. The results show that THA is a non-competitive uptake inhibitor of dopamine and 5-HT in the nerve terminals. The re-uptake blocking effect of THA on dopaminergic and serotonergic neurones, following THA treatment, might lead to increased levels of these monoamines in brains of Alzheimer patients and contribute in the therapeutic effects of the drug.
Analysis of Variance↗
Occurrence of dementia in advanced age: the study design of the Kungsholmen Project.
The Kungsholmen Project is a study on elderly people living in a parish of Stockholm, Sweden. The study uses a longitudinal approach with the principal purpose of determining the natural history of Alzheimer's disease and other dementias. The study population consists of all 2,368 inhabitants of the Kungsholmen area in Stockholm, aged 75 years and above in October, 1987. The study design consists of three phases. Phase I consists of a screening test used in order to identify the 'possible' dementia cases; phase II is a complete clinical examination carried out in order to reach a final diagnosis of dementia; in phase III the whole population is reexamined in order to ascertain new cases of dementia. DSM-IIIR criteria for dementia and different types of dementia are used. The final diagnosis is based on a consensus using two preliminary diagnoses, made separately by different physicians.
Aged↗
Subjective loneliness--a comparison between elderly and relatives.
The survey was aimed at examining the differences between the elderly's subjectively experienced loneliness and relatives' appraisal of the situation. The interviews contained structured questions about relatives' knowledge of the elderly's loneliness and their social contacts with the elderly. In total, 178 relatives took part in the interviews. The Cognitive-impaired group included 66 pairs elderly/relatives, where the elderly persons were cognitively impaired, and the Cognitive-intact group 112 pairs, where the elderly persons had normal cognitive function. There were differences between relatives' appraisal of loneliness and the elderly's own experience. The elderly with cognitive deficits seemed to feel loneliness more often than persons with intact cognitive ability. Relatives tended to overestimate the elderly's loneliness, especially among persons with cognitive difficulties. These elderly more often had short frequent visits, while persons in the Cognitive-intact group had longer, but not so frequent visits.
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