Both environmental and genetic factors are involved in the development of PD and biotransformation of exogenous and endogenous compounds and may play a role in inter-individual susceptibility. Therefore, we investigated the presence of null genotypes of GSTM1, GSTT1, and two polymorphisms of mEPHX in subjects with Parkinson's disease and in a reference population. The study included 35 male PD patients and a male control group including 283 subjects. Homozygosity of the histidine (H) 113 isoform of mEPHX was significantly increased in PD patients (odds ratio = 3.8 CI 95% 1.2–11.8) and analysis of allele frequencies displayed an increased frequency of the H-allele among PD patients (odds ratio = 1.9 CI 95% 1.1–3.3). However, a significantly elevated median age for the onset of PD was found among GSTM1 gene carriers (median age = 68 years) compared to PD patients being GSTM1 null genotypes (median age = 57 years). Our observations suggest that (H) 113 isoform of mEPHX, which has been suggested as a low activity isoform, is overrepresented in PD patients and that inherited carriers of the GSTM1 gene postpone the onset of PD. These detoxification pathways may represent important protective mechanisms against reactive intermediates modifying the susceptibility and onset of PD.

Caudate nucleus dopamine (DA) D2 receptors were studied in patients with vascular dementia (VaD) and in a control group using [3H]raclopride as a radioligand. There was no significant difference in the number of DA D2 receptors in the VaD group as compared with controls. The binding affinity was significantly lower in the VaD group. When the VaD group was subdivided into subjects with or without neuroleptic treatment, there were no differences in the numbers of receptors as compared with controls, and the significant differences in binding affinity remained for both VaD subgroups. The present results are discussed with reference to the previous finding of a reduced density of caudate nucleus DA uptake sites in the same VaD group and to results from studies on DA D2 receptors in Alzheimer's disease and Parkinson's disease. Copyright ⌐ 2002 S. Karger AG, Basel.

Glutamate is the principal excitatory neurotransmitter in the central nervous system and it is implicated in neural transmission, learning, memory processes and neuronal plasticity. In the glutamatergic synapse two main components are present; the glutamate receptors and the glutamate transporters. The receptors, the NMDA, AMPA, kainite and the metabotroptic receptors, are responsible for conveying neural transmission, including long term potentiation (LTP), synaptic strengthening and modification. The transporters, located to the neuronal membrane and to the membranes of surrounding astrocytes, regulates the extracellular concentration of glutamate and thereby the duration of the synaptic signal.

Alterations in both receptor and transporter systems have been suggested to be important in the pathogenesis of several acute and chronic nervous system diseases, such as psychosis, mood disorders, epilepsy, Parkinson's disease and Alzheimer's disease. The pathophysiology of these disorders is not yet completely understood and the involvement of glutamate is unclear. In this thesis we have sought to investigate the role of the glutamatergic system in the treatment of mood disorders and dementia. The antidepressant drug amitriptyline exerts its main effects on the serotonergic and noradrenergic systems and the antidementia drug rivastigmine acts mainly on the cholinergic system. However, given the close relationship between different neurotransmitter systems we have investigated the influence of amitriptyline and rivastigmine on the mRNA expression of the neuronal transporter, EAAC1, in rats. The results showed for the first time an involvement of EAAC1 in amitriptyline and rivastigmine treatment. Amitriptyline induced an acute increase in EAAC1 mRNA expression, which 24 hour after administration returned to baseline levels. Chronic treatment, on the other hand, induces a significant decrease in cortical areas, which we suggest results in enhanced neuronal transmission. Rivastigmine treatment, acute as well as chronic, induced increases in the mRNA expression in hippocampus. We hypothesize that this counteracts the excitotoxic glutamate levels seen in Alzheimer's disease.

Further, environmental enrichment has been shown to have beneficial effects on capillary supply, the number of glial cells and dendritic spines, the thickness and weight of cortex, the concentration of cholinesterase, LTP and synaptic strength in animals. It has also been reported that humans that lead an active life have a reduced risk of developing Alzheimer's disease. This suggests that an active and stimulated life may have a protective effect against dementia in man, by creating a cognitive reserve which provides a buffer against brain pathology or age-related changes. We investigated the influence of environmental enrichment on the mRNA expression of NMDA and AMPA receptors and on EAACl and showed for the first time that EAAC1 mRNA is decreased after environmental enrichment. This is probably followed by an increase of glutamate in the synapse, which in turn leads to enhanced neuronal transmission including enhanced memory formation and learning. Furthermore, we confirmed in greater detail previous findings on the upregulation of NMDA mRNA and show that the regulation is regionally and hemisphere specific. We also confirm that AMPA mRNA is not per se changed by environmental enrichment in adult animals.

This work provides further evidence about the involvement of the glutamatergic system in affective and cognitive disorders. Improved knowledge of the glutamatergic system will contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions.

Alzheimer’s disease is a neurodegenerative disorder that affects the cholinergic, glutamatergic and monoaminergic systems in the neocortex and hippocampus. Today, the major pharmacological treatment involves the use of acetylcholinesterase inhibitors (AChEIs). In this study, an in situ hybridisation technique (using digoxigenin-labelled cRNA probes) was used to elucidate changes in mRNA expression of the neuronal glutamate transporter, rat excitatory amino carrier 1 (rEAAC1), after treatment with the AChEI rivastigmine. Compared with saline-treated rats, the rats subchronically (3 days) and chronically (21 days), but not acutely, treated with rivastigmine showed a significant increase in rEAAC1 mRNA expression in the hippocampal areas cornu anterior 1 (CA1), CA2, CA3 and dentate gyrus (p < 0.01), but not in the cortical areas. These results provide the first evidence that the glutamatergic system is modulated following acetylcholinesterase inhibition by rivastigmine, a finding, which is likely to be of importance for the clinical effects.

Interaction with the environment has a key role in refining the neuronal circuitry required for normal brain function throughout life. Profound effects of enriched environment have been shown on neuronal structure and chemistry in experimental animals. Epidemiological studies imply that this is true also in man, thus cognitive stimulation has a protective effect on neurodegeneration, e.g., in Alzheimer's disease. Glutamatergic pathways are imperative for cognitive functions, such as memory, learning and long-term potentiation, and relies on the AMPA and NMDA glutamate receptors and the hippocampus, with its specific subregions, is an important anatomical substrate in this. The glutamate signalling is also dependent on a fine-tuned transport system, in the hippocampus primarily achieved by the glutamate transporter EAAC1. In this study we show how environmental enrichment modulates these parts of the glutamatergic system using quantitative in situ hybridisation. This work demonstrates for the first time that environmental enrichment modulates the mRNA expression of EAAC1 which is significantly and region specifically decreased in the hippocampus. We also provide evidence for regional and hemisphere-specific upregulation of NMDA mRNA in the hippocampus after environmental enrichment. The current work also shows that AMPA mRNA of the hippocampus is not per se changed by environmental enrichment in adult animals. Taken together, our results extend the knowledge of the glutamatergic system of specific regions of the hippocampus and its modulation by environmental enrichment and could contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions. © 2007.

Interaction with the environment has a key role in refining the neuronal circuitry required for normal brain function throughout life. Profound effects of enriched environment has been shown on neuronal strucrure and chemistry in experimental animals. Epidemiological studies imply that this is true also in man, thus cognitive stimulation has a protective effect on neurodegeneration, e.g. Alzheimer's disease. Glutamatergic corticocortical pathways are imperative for cognitive functions, such as memory and learning, and long term porenriation relies on the AMPA and NMDAglutamate rcceptors. The glutamate signalling is also dependent on a fine-runed transport system, in the hippocampus primarily by theglutamate transporter EAACl. In this study we show how environmental enrichment modulates these parts of the glutamarergic system using in siru hybridization. This work demonstrates for the first time that environmental enrichment modulates the mRNA expression of EAAC1 which is significantly decreased in hippocampal and cortical areas. We also provide further evidence about the upregulation of NMDA mRNA after environmental enrichement, and show it to have a regionally and hemisphere specific regulation. The current work also confirms that AMPA mRNA is nor per se changed by environmental enrichment in adult animals. Taken together, our results extend the knowledge of the glutamatergic system and its modulation by environmental enrichment and could contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions.

Glutamate transporters regulate the glutamate concentration in the synaptic cleft within the CNS, a regulation required for normal brain function. In several neurological conditions, the amount of glutamate is altered. One reason for the changes in glutamate concentration might be impaired glutamate transporter function. In this study, an in situ hybridisation technique has been used to elucidate changes in mRNA expression of the glutamate transporter, excitatory amino acid carrier 1 (EAAC1), after treatment with the tricyclic antidepressant (TCA) amitriptyline. The results lead to the suggestion that treatment with tricyclic antidepressants leads to changes in the EAAC1 mRNA expression in rat brain suggesting involvement of the glutamate system in the tricyclic treatment of depression.

This thesis addresses: 1) The involvement of the monoaminergic and neuropeptidergic neurotransmitter systems in the aging process, and 2) The contribution of these systems in the etiology of an age-related mental disorder: the depressive syndrome. Because of the evidence suggesting the efficacy of the SSRI in the treatment of some age-related symptoms, a comparison study of the binding characteristics of two SSRI, i.e. [3H]paroxetine and [3H]citalopram, to the human brain 5-HT uptake site was included.

Neurochemical analysis, involving HPLC, binding assays and RIA methods, was performed in several brain regions from 23 control subjects and 18 suicides pooled according to the method of death and the prior existence of depressive symptoms.

Both [3H]paroxetine and [3H]citalopram were found to label the same number of presynaptic 5-HT binding sites, which is in accordance to their ability to identify the same membrane protein. However, the 15 to 30-fold higher affinity displayed by [3H]paroxetine gives evidence to this SSRI having a more easily accesible binding domain in the 5-HT transport complex than [3H]citalopram, and hence being a better marker of thispresynaptic 5-HT carrier system.

No statistical differences in either the monoamines 5-HT, NA and DA, their metabolites or the 5-HT binding sites were found between controls and overall suicides. However, a diminished number of 5-HTl D binding sites with advancing age, together with a significant decrease in the number of 5-HTl D binding sites and binding affinity was noticed in the nondepressed and depressed suicides, respectively. These results might indicate the involvement of this novel 5-HT receptor in both some of the physical disturbances present in the elderly population and in the mechanisms underlying the depressive syndrome. Advancing age was also found to be negatively correlated with brain NA, DA and HV A concentrations, thus supporting the increased likelihood of changes in feeding habits and in the hypothalamic-mediated endocrine dysfunctionscommonly observed in senescence.

With regard to the neuropeptidergic neurotransmitter systems, age-related decreases in gyrus cinguli NPY and CRF concentrations were noted. In addition, although unchanged NPY, SOM and CRF concentrations were observed in the overall suicide group, the HPLC analysis revealed that the depressed suicides showed a different pattern of NPY-LI fragments, which is in agreement with depression being associated with an altered processing or metabolism of the intact NPY molecule.

There is a latency period of several weeks before the onset of clinical effect of antidepressant drugs. The detailed mechanisms underlying drug-induced adaptive neuronal changes are not known. To elucidate the involvement of changes in gene expression of candidate transcription factors, we treated rats for 21 days with buspirone, fluoxetine, 8-OH-DPAT and moclobemide. In situ hybridization was used to study mRNAs encoding NGFI-A, NGFI-B and the glucocorticoid receptors, MR and GR. NGFI-A mRNA expression increased profoundly in the hippocampal formation and the cerebral cortex after all drug treatments, especially after moclobemide treatment (77-122% increase), with the exception of buspirone. MR mRNA expression was induced in hippocampal CA1/CA2 subregions (27-37%) by all antidepressants, while moclobemide and 8-OH-DPAT significantly increased GR gene expression mainly in the CA1 region (31-44%). NGFI-B mRNA was significantly decreased in the hippocampal CA3 subfield (23%) and restrosplenial granular cortex (38%) by moclobemide treatment. There are selective effects of antidepressant drugs on specific transcription factors. These may be important for adaptive neuronal and neuroendocrine changes after antidepressant treatment including HPA axis negative feedback regulation.

Person-centred care for people with dementia is an aspiration of both family and professional carers, but what constitutes person-centred care and how it can be achieved is less clear. This article describes a Swedish study in which in-depth interviews were completed with both family and professional carers of people with dementia with the purpose of exploring what they considered to be "best care". Important areas of similarity and difference were identified and the results suggest that both groups of carers need to work closely together if person-centred care is to become a reality.

The binding of [H-3]tiagabine ((RS-1-(4,4-(3-methyl-2-thienyl)-3-butenyl)-3 carboxylic acid) to homogenates of frozen post-mortem human brain has been characterized. Inhibition experiments with gamma-aminobutyric acid (GAB,4), GABA uptake inhibitors, ligands active at postsynaptic GABA receptors and receptors for other neurotransmitters, suggest that [H-3]tiagabine binds with high affinity to GABA uptake sites. Inhibition and kinetic experiments suggests that 70%-80% of the binding is to a high affinity site. Saturation experiments showed that the binding was saturable. B-max was 3.4 pmol/mg protein and K-d 16 nM in frontal cortex. The dissociation constants (K-d) measured in kinetic and equilibrium experiments were in the same range (16-56 nM). The regional distribution was studied in nine brain regions and the binding was heterogenous, with the highest binding in frontal cortex and parietal cortex and the lowest binding in nucleus caudatus and putamen. This is, to our knowledge, the first study on [H-3]tiagabine binding in human tissue. It is concluded that [H-3]tiagabine binding can be used as a specific marker for the GABA transporter GAT-1 in homogenates of human brain.

This community-based study of Parkinson's disease (PD) investigated age at death and cause of death in a cohort of 170 previously studied patients. The current study is a 9-year follow-up, and the results are compared to 510 sex- and age-matched controls from the same area. A total of 170 patients were diagnosed with PD on August 31, 1989, within a defined area of Sweden. A control group of 510 persons from the same area and with the same age and sex distribution was also examined regarding age at death and cause of death. After 9.4 years, 121 cases (71.1%) and 229 controls (44.9%) were no longer alive. Thus, the mortality rate ratio was 1.6 (95% confidence interval [CI], 1.3-1.8) when comparing PD patients with controls. The all-cause hazard ratio for cases compared to controls was 2.4 (95% CI, 1.9-3.0). The mean age at death for the cases was 81.9 (95% CI, 80.3-83.0) years and for the controls 82.9 (95% CI, 82.0-83.7) years. Survival analysis also showed a shorter survival time (P < 0.001) for PD patients. Only 53% of the death certificates for the deceased patients recorded PD as an underlying or contributory cause of death. Many PD patients reached a high age but had a shorter survival than the controls. There was a significant increase in deaths from pneumonia.

The aim of this thesis was to investigate possible factors concerning weight loss in elderly patients with untreated, as well as treated Parkinson's disease (PD) and to compare PD patients with age and sex matched controls. Twenty-eight PD patients (15 newly diagnosed and 13 previously treated) and 28 sex and age matched controls were included in the study.

Data on body weight, body fat mass, lean body mass, PD symptoms, cognitive function, dysphasia, oral and dental state, resting energy expenditure, food habits, olfactory ability and physical activities were collected prospectively, and all variables were assessed repeatedly three times with one year between investigations: Baseline, year 1 and year 2. The previously treated PD patients and their controls were assessed twice, at year 1 and year 2. After one year, when the de novo PD patients had been optimally treated with L-dopa, the two groups of PD patients were combined into one group for the purpose of analysis.

Twenty-six of the PD patients were able to participate to the end of the study, and the results were compared with those of their 26 controls. The PD patients had lower housework activity, a longer period of daily rest, fewer could do their own food shopping and cooking and more patients had impaired olfaction and presence of dysphagia, both at year 1 and at year 2. At year two, the PD patients also had lower body weight, body fat mass, lean body mass, physical activity and mobility. The PD patients had a higher number of eating events, compared with the controls at year one, but at year two the patients consumed fewer high quality snacks than their controls. There were no significant differences between PD patients and their controls with regard to daily intakes of energy, protein, fat and carbohydrates.

Nineteen of the PD patients lost body weight between year one and year two. In the weight losing patients, the PD symptoms, L-dopa dosage, and energy intake (kcal/kg body weight) increased as did their daily recumbent rest, while their cognitive function decreased. Multiple regression analysis showed that women with low cognitive function were predisposed to weight loss. The consumption of solid food decreased.

Conclusion: Weight loss was common in PD patients, in spite of increased energy intake. Food habits changed toward a lower number of adequate foods and their intake of solid food decreased. It has to be discussed whether weight loss in PD patients is part of this neurodegenerative process and L-dopa treatment could contribute to the weight loss.

Objective –  Weight loss is reported frequently in patients with Parkinson's disease (PD). The objective of this study was to find the underlying factors of this phenomenon.

Participants and methods –  Twenty-six l-dopa-treated patients with PD and 26 age- and sex-matched healthy controls were assessed twice within a 1-year interval. Body weight, body fat mass, resting energy expenditure, physical activity, energy intake, thyroid hormones and cognitive function were investigated.

Results –  Nineteen (73%) of the PD patients lost body weight, although energy intake and the time for rest increased. Weight loss was most marked in patients with more severe PD symptoms and in whom cognitive function had decreased. Multiple regression analyses showed that determinants for weight loss were female gender, age and low physical activity.

Conclusion –  Weight loss was common in PD patients, in spite of the increased energy intake and was most obvious in patients with increased PD symptoms and decreased cognitive function.

Background: Weight loss is reported frequently in patients with Parkinson´s disease also early during the disease.

Objective: To investigate food habits and nutrient intake in elderly Parkinson´s disease patients compared with matched controls, as well as to compare PD patients with and without weight loss.

Methods: Twenty-six elderly free-living patients with PD, and 26 sex- and age-matched healthy controls, were assessed twice with one year interval between. All food consumed was recorded over 3 consecutive days. Food habits were assessed with the Food Based Concept for Classification of Eating Episodes and intakes of energy and nutrients were calculated. PD symptoms, olfaction, swallowing function, daily activities and serum concentration of different nutri ents were investigated.

Results: After 1 year, the PD patients decreased their intakes of daily high quality snacks from 0.5 ± 0.7 to 0.3 ± 0.3 (p < 0.05) and their prepared complete meals from 0.8 ± 0.3 to 0.6 ± 0.3 (p < 0.05), while their daily number of prepared incomplete meals increased from 0.2 ± 0.2 to 0.3 ± 0.3 (p < 0.01). PD patients with weight loss increased their daily intakes of fat by 12 ± 34 g and their energy intake per kg body weight increased by 21 ± 31 kJ (p < 0.05), respectively, and this was higher than in those without weight loss (p < 0.01). PD patients required more help with buying and cooking food compared with the controls.

Conclusions: PD patients’ food habits changed so that they consumed a lower number of prepared complete meals. PD patients with weight loss had a higher intake of fat and energy than those without weight loss, although this was obviously not sufficient to prevent weight loss. Impaired absorption of fat in PD should be discussed.

Objective - The objective of the present study was to find risk factors for low bone mineral density (BMD) in patients with Parkinson's disease (PD). Material and methods - Twenty-six PD patients and 26 age-and sex-matched healthy controls were assessed twice within a 1-year period. PD symptoms, body weight, body fat mass, BMD, physical activity, smoking and serum concentrations of several laboratory analyses were investigated. Results - BMD in different locations was lower in PD patients compared with their controls and decreased during the investigated year. BMD was lower in PD patients with low body weight. BMD Z-score of trochanter in the PD group was directly correlated to the degree of physical activity and indirectly to the length of recumbent rest. Total body BMD Z-score in the PD group was directly correlated to the degree of rigidity. Serum 25-hydroxy-vitamin D was slightly lower in PD patients. Conclusion - Low body weight and low physical activity were risk factors for low BMD in PD, while rigidity seemed to be protective. © 2007 The Authors.

The main aim of this paper is to consider the experiences of Swedish spouses who have placed a partner in a care home for older people. Data were gathered from semi-structural interviews with 14 spouses (11 wives and 3 husbands) who had been involved in a care home placement within the previous 6 months. The results reported here are from the first component of a larger grounded theory study, the aim of which is to explore, describe and understand the experience of care home placement from a variety of perspectives and to identify the implications for policy and practice in Sweden. The focus here is on the experience of spouses, relating to the decision-making process, the move into care and subsequent contact with the care home. Four themes emerged from the data – making the decision, making the move, adjusting to the move and reorientation. The results show a lack of planning for the elder person’s entry to a care home, and professional dominance of this stage of the process. The largely ambivalent emotional responses to the move that spouses experience and the difficulties in initiating and sustaining relationships with staff in the home are discussed in the light of previous research.

[No abstract available]

Alzheimer disease (AD) treatment guidelines state that cholinergic agents are not cost-effective in patients with more severe disease. Because many physicians may deem an older patient unlikely to respond to treatment, older AD patients may remain untreated. Galantamine (Reminyl), a novel cholinergic agent, is effective in mild to moderate AD. This post hoc analysis of pooled phase III galantamine clinical trials was designed to assess whether older (=80 years) and younger (=79 years) AD patients experience similar benefits with galantamine based on changes in the ADAS-cog and CIBIC-plus. Mean ADAS-cog scores for older patients treated with galantamine 24 mg/day significantly improved versus baseline and versus placebo at month 3. Cognitive improvement was maintained versus placebo at month 6, the ADAS-cog score for placebo patients dropped below baseline at month 6. Change in CIBIC-plus for galantamine was significantly different from placebo at months 5 to 6. Mean ADAS-cog score in older patients taking galantamine for 12 months remained above baseline. The score for patients taking placebo for 6 months before switching to galantamine did not differ significantly from baseline at 12 months but was lower than in patients receiving galantamine for 12 months. Incidence of adverse events in patients > 80 years was similar to that in the overall study population. Galantamine maintained cognitive and global function in patients > 80 years with mild to moderate AD for at least 5 to 6 months and cognitive efficacy for 12 months. Prescribing approved therapies such as galantamine for older patients with AD is recommended.

A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the a2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE e4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE e4 allele. No change in A2M exon 17-18mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.

The presence of a family member is often a prerequisite for successful palliative home care. The overall aim of this thesis was to contribute to a deeper understanding of family members' experiences of having a dying relative or friend cared for by advanced palliative home care. Two methodological approaches were used. Semi-structured tape-recorded interviews were analysed with a hermeneutic approach (19 family members; 30 interviews). Two postal questionnaires with open-ended questions were distributed and the responses (217 and 233, respectively) were analysed with qualitative and quantitative content analyses.

All studies had a salutogenic orientation, i.e. with the origin of health in focus, and therefore facilitating as well as burdensome aspects were studied. In the interview studies, Antonovsky's salutogenic theory of Sense of coherence was applied as a framework, and the concepts of comprehensibility, manageability and meaningfulness were used.

The studies showed that when the family members evaluated the palliative home care, they mentioned both positive and negative aspects with regard to the service, e.g. accessibility and staff competence, and comfort factors, e.g. feeling secure and being at the centre of attention.

Comprehensibility concerned more than traditional information-giving and included symbols, basic life assumptions and previous knowledge, which were important for creating an inner congruent reality, as opposed to an inner chaos.

Staff - family member interactions contributed to manageability by facilitating the family member's feeling of sharing the responsibility and contributing to the care together with the staff.

Having a dying relative of friend could include also feelings of meaningfulness in an otherwise burdensome situation. Participating in the care, feeling hope, knowing that the patient did not suffer and doing the best possible had contributed to a feeling of meaningfulness.

Of the family members, 36% had experienced powerlessness and/or helplessness, whereas 33% stated that they had never had such feelings during the palliative home care period. The feelings were characterised by perception of the patient's suffering, his/her fading away, and a feeling of own insufficiency. Moreover, the meaning of powerlessness and helplessness involved a deeper level including feelings of guilt, anger and loneliness.

It is concluded that a salutogenic perspective is relevant in palliative home care. When staff interacts with family members in palliative care, there is a potential for facilitating the family members' perception of manageability, comprehensibility and meaningfulness. Understanding of home as a place of palliative care seems important and includes the contribution of a familiar environment, retained everyday life and of a basis for self-transcendence. Staff needs also to be aware of the risk of negative aspects, such as lost privacy and changed meaning of the home. Higher abstraction levels, including existential dimensions, such as security and powerlessness were essential parts of the family members' experiences. If such experiences are not considered in goal-setting and in service evaluation, important parts of palliative care will not be reflected by the chosen/measured parameters.

The presence of an informal carer is often a prerequisite for successful palliative home care, and the staff's ability to support informal carers' coping in such situations is important. Recent research has revealed that it is possible to achieve positive psychological states in palliative care despite the burdening situation. As there is a lack of theory-based coping studies, the aim of this study was to describe, within the context of palliative home care, two concepts in Antonovsky's theory of Sense of Coherence: comprehensibility (a perception that the challenge is understood) and manageability (a perception that the resources to cope are available). Tape-recorded semi-structured interviews with 19 informal carers during ongoing palliative home care were transcribed and analysed with a qualitative hermeneutic approach. Elements that facilitated comprehensibility included open information, symbolic information, basic life assumptions and previous knowledge. These were important for creating a congruent inner reality (as opposed to chaos). Resources contributing to manageability dealt with power, support, competence and accessibility, which on a more abstract level resulted in a feeling of togetherness (as opposed to isolation). The findings are discussed in relation to the complexity of communication between staff and carers within palliative care.

Objective: An increasing number of patients are cared for at home and the presence of next of kin is often a prerequisite for successful home care. The aim of this study was to describe and interpret the construct of meaningfulness in next of kin of cancer patients who are in advanced palliative home care.

Methods: The perspective of Antonovsky's salutogenic framework of sense of coherence was applied in the analysis. Using a hermeneutic approach, 19 next of kin were interviewed (n = 30 interviews) during ongoing palliative home care.

Results: Elements that facilitated meaningfulness included comfort, retaining everyday life, action, commitment, and hope, which were of great importance for creating a perception of self-transcendence and that the best possible was done.

Significance of results: The findings are discussed in relation to the concepts of meaning-based coping, tragic optimism, and existentialism. Clinical implications are suggested.

Goals: (1) To describe what aspects are important when next-of-kin evaluate advanced palliative home care (APHC) and (2) to compare the expressed aspects and describe eventual differences among the three settings, which differed in terms of length of services, geographic location, and population size.

Subjects and methods: Four to 7 months after the patient's death (87% from cancer), 217 consecutive next-of-kin from three different settings in Sweden responded (response rate 86%) to three open-ended questions via a postal questionnaire. Qualitative content analysis was performed.

Main results: Service aspects and comfort emerged as main categories. The staff's competence, attitude and communication, accessibility, and spectrum of services were valued service aspects. Comfort, such as feeling secure, was another important aspect and it concerned the next-of-kin themselves, the patients, and the families. Additionally, comfort was related to interactional issues such as being in the center and sharing caring with the staff. The actual place of care (i.e., being at home) added to the perceived comfort. Of the respondents, 87% described positive aspects of APHC and 28% negative aspects. No major differences were found among the different settings.

Conclusions: Next-of-kin incorporate service aspects and aspects relating to the patient's and family's comfort when evaluating APHC. The importance of these aspects is discussed in relation to the content of palliative care and potential goals.

Goals of work  Powerlessness and helplessness have been very little studied. The aims of this study were (1) to describe what characterise such experiences and the meaning of them to next of kin of cancer patients in advanced palliative home care and (2) to make quantifications.

Patients and methods  The study design was cross-sectional and targeted next of kin during ongoing palliative home care and next of kin of patients who had died 3–9 months earlier; 233 next of kin responded (response rate 72%) to a postal questionnaire with both Likert-type and open-ended questions. The text responses were analysed with a combined qualitative and quantitative content analysis.

Main results  Thirty-six percent of respondents stated that they had experienced powerlessness and/or helplessness every day or several times per week, whereas 33% had never had this experience during the palliative home care period. Powerlessness and helplessness concerned next of kins perception of the patients suffering, of the patients fading away and the next of kins own feelings of insufficiency and resulted in both physical and psychological symptoms, such as muscle tension, headache, loss of appetite, anxiety and depression. In addition, powerlessness and helplessness concerned also a deeper meaning with existential and social aspects, such as feelings of guilt, anger and loneliness.

Conclusions  The main findings provide tools for the practitioner to identify situations contributing to next of kins sense of powerlessness and helplessness. The findings are discussed in relation to the concepts of symptom control, communication of awareness and humans search for action.

The clinical dementia diagnosis has become more complex with increasing knowledge of the heterogeneity of the disorder and its different aetiological aspects. A clinical dementia population and a control group were investigated with the following aims: I. To study the CSF levels of tau phosphorylated at threonine 181 (P-tau), total tau (T-tau) and ß-amyloid_1-42 (Aß42) in the different diagnoses. II. To study associations between dementia disorder, cobalamin and/or folate deficiency, and gastritis. III. To study the presence and severity of CT brain changes in different dementia diagnoses. IV. To investigate to what extent different biomarkers and disease history contribute to the diagnostics of clinical dementia.

I. CSF Levels of P-tau, T-tau and Aß42 were analysed with ELISA methods. Elevated CSF levels of P-tau were found in probable Alzheimer's disease (AD) patients compared with cognitively non-disturbed controls. Increased CSF T-tau, and decreased levels of Aß42 were found in both AD, mixed type of dementia, and vascular dementia (VaD) patients compared with the controls. Increased P-tau levels were more specific for AD pathology, but there was still an overlap with the controls, mixed dementia and VaD patients.

II. Serological markers for cobalamin and folate deficiencies, and for gastritis were assessed in patients with different dementia diagnoses. Hyperhomocysteinaemia were commonly found in dementia without predominance in any of the investigated categories. Low levels of serum cobalamin or blood folate rarely reflected the elevated Hey levels. A lack of association between serological markers for cobalamin and folate deficiencies and for gastritis was demonstrated.

III. A protocol for evaluation of the CT scans was used. Atrophy on the CT scans, although common in dementia, is an unspecific fmding in dementia of different backgrounds. White-matter changes and lacunes, indicating small-vessel disease, were common in dementia of different aetiologies. Dementia of mixed-type pathology was underestimated. More distinct criteria for this diagnostic category are warranted.

IV. Partial Least Squares Discriminant Analysis (PLS-DA) was used on a large number of variables covering cognitive and biological markers and disease history. There were good discriminations of subgroups of dementia from the controls. However, the included variables were not able to distinguish between the investigated groups, indicating that several clinical parameters used in diagnosing dementia are in fact observed across different subtypes of dementia.

It is concluded that there are no known biomarkers available that can provide a precise differential diagnosis of dementia. The clinical dementia diagnosis must still be based on a combination of a careful disease history, evaluation of risk factors, symptomatology, clinical findings, neurocognitive tests, blood analysis and other available methods such as CT and CSF markers.

The presynaptically located gamma-aminobutyric acid (GABA) transporter (GAT-1) was studied in a group of patients with Alzheimer's disease (AD) and in a control group using the GAT-1 selective radioligand [H-3]tiagabine. Post mortem brain tissue from frontal cortex, temporal cortex, and caudate nucleus from 18 AD patients and 23 age-matched controls were studied. The binding was saturable (Kd 26 nM) and region specific. There were no significant differences between the groups with respect to the binding capacity (Bmax) and binding affinity (Kd). The unaltered [H-3]tiagabine binding to GAT-1 protein indicates that intrinsic GABA neurons are spared in Alzheimer's disease.

Diagnosing clinical dementia is based on an assessment of different variables, such as the patient’s medical history, known risk factors, and biochemical features. Partial least squares discriminant analysis was used to evaluate variables of importance for diagnosing dementia in a clinical dementia population. Polymorphism for genotypes of glutathione S-transferase (GST) and sulfotransferase 1A1, hypothetically of importance in dementia disorders, was also included in the analysis. The study population consisted of 73 patients with Alzheimer’s disease (AD), 14 with mixed dementia, 75 patients with vascular dementia, and 28 control cases. We found that several of the variables, such as the presence of ApoE4 allele, high cerebrospinal fluid levels of total tau protein, low levels of β-amyloid_(1–42), and a low score on the Mini-Mental State Examination, facilitated a discrimination between the diagnoses compared with the controls. The different diagnoses overlapped. There were indications that genotypes of GSTs contributed to a subgrouping within AD.

The two most frequently examined biomarkers in the diagnosis of dementia are cerebrospinal fluid (CSF) tau and β-amyloid_1-42 (Aβ_1-42). An assay for tau phosphorylated at threonine 181 (phospho-tau) has recently been developed. We studied these three markers in patients with possible Alzheimer's disease (AD; n = 23), probable AD (n = 50), AD with relevant cerebrovascular disease (AD with CVD; n = 14), possible vascular dementia (VaD; n = 39), probable VaD (n = 36), cognitively impaired (n = 13) and 27 neurologically healthy controls. Compared with the controls, tau levels were significantly increased in possible AD, probable AD, AD with CVD and probable VaD. Aβ_1-42 was decreased in all dementia groups compared with the controls. In contrast, phospho-tau levels were increased only in probable AD compared with the controls. From the results of the present study, it is concluded that neither measurement of phospho-tau, tau nor Aβ_1-42 in CSF can discriminate entirely between dementia and cognitively non-disturbed controls or between dementia of different aetiologies in the clinical diagnostic procedure.

Clinical experience indicates that physical diseases are probably underdiagnosed in patients suffering from dementia. We investigated the prevalence of physical diseases in patients with different types of dementia by means of a retrospective patient record survey including 236 inpatients and outpatients referred for dementia evaluation to the Dementia Investigation Unit, University Hospital in Linköping during 1994. Forty-four patients had dementia of the Alzheimer type, 78 had vascular dementia, 28 had dementia due to multiple etiologies, 42 were not demented, and 44 patients could not be classified by the DSM IV criteria. The physical diseases were registered as separate diagnoses comprising all newly-diagnosed physical diseases and previously known diseases that had exacerbated and contributed to the medical contact. Sixty-four percent of the patients had previously unknown physical diseases and/or exacerbation of previously known diseases. The most common physical conditions were cobalamin deficiency and infectious diseases, which occurred in 27% and 24% of the patients, respectively. There was no difference in the number or kinds of diagnoses between the diagnostic groups. Associated physical diseases were underdiagnosed in patients referred for dementia evaluation. We suggest that thorough medical investigation and adequate treatment are of importance in the management of dementia.

The prevalence of dementia disorders, cobalamin and/or folate deficiency as well as gastritis increases with age. To investigate whether there is an association between these conditions, plasma homocysteine (Hcy), serum methylmalonic acid, serum cobalamin and blood folate concentrations were measured. Gastritis was indirectly diagnosed by measuring serum antibodies against H,K-ATPase, Helicobacter pylori and intrinsic factor, using enzyme-linked immunosorbent assays. The studied groups consisted of 47 patients with Alzheimer’s disease (AD), 9 with AD pathology in combination with additive vascular lesions, 59 with vascular dementia, 8 who were cognitively impaired, and 101 control cases. Plasma Hcy concentrations were significantly elevated in the dementia groups, with the highest levels in patients with vascular pathology. We conclude that hyperhomocysteinemia is a common finding in patients with dementia disorders of different etiologies. The markers for gastritis did not contribute to an elucidation of a possible connection between this condition, dementia disorders, or cobalamin/folate deficiency.

Dementia has been found to display a more heterogeneous clinical picture than previously recognized. We investigated brain changes on computed tomography (CT) in a clinical dementia population consisting of 67 cases with Alzheimer's disease (AD), 13 with mixed dementia (AD and vascular dementia, VaD), 71 with VaD, and 12 cases that were not demented. Temporal cortical atrophy and atrophy around the temporal horns were more common in patients with mixed dementia compared to patients with VaD and the non-demented, respectively. Frontal white matter changes were present in 64% of AD, in 85% of mixed dementia and in 79% of VaD cases, but there were no differences between the dementia groups. Lacunes were present in almost 40% of AD cases and in 80 and 85% of VaD and mixed dementia cases, respectively. Only 14% of the VaD cases had large infarcts on the CT. We conclude that large infarcts were rare, even in VaD cases. The increased incidence of white matter changes and lacunes in AD patients strongly indicates an underestimation of the mixed dementia diagnosis. More distinct criteria for this diagnostic category are warranted.

Objective –  Many patients with Parkinson's disease (PD) lose weight also early during the disease. The objective of the study was to investigate possible causative factors for this loss.

Materials and methods –  In this report, 28 PD patients and 28 age- and sex-matched controls were repeatedly assessed with the focus on body weight, body fat mass, dysphagia, olfaction, physical activity, PD symptomatology and drug treatment.

Results –  Weight loss was seen in PD patients both before and during l-dopa treatment.

Conclusion –  The underlying disease could play a role, but our results also suggest that l-dopa per se could contribute to the weight loss.

Background Homocysteine levels in circulation are determined by several factors and hyperhomocysteinemia is reportedly associated with cardiovascular diseases and dementia. The aim of this study is to determine the relation of chronic gastritis and other conditions to homocysteine levels and their relation to incident cardiovascular diseases and dementia. Methods An adult population-based cohort (N = 488) was screened for H. pylori infection, gastro-duodenitis ( endoscopic biopsies), disease history, and lifestyle factors. Blood samples were analyzed for pepsinogen I and II ( gastric function), vitamin B12, folate, homocysteine, and cystatin C ( renal function). The methylenetetrahydrofolate reductase C677T polymorphism reportedly associated with hyperhomocysteinemia was analyzed by pyrosequencing. Incident cardiovascular diseases and dementia were monitored during a median follow-up interval of 10 years. Results At baseline, there was a positive relation of S-homocysteine to male gender, age, S-cystatin C, methylenetetrahydrofolate reductase 677TT genotype and atrophic gastritis. During follow-up, cardiovascular diseases occurred in 101/438 and dementia in 25/488 participants, respectively. Logistic regression analysis ( adjusting for gender, age at baseline, follow-up interval, BMI, smoking, alcohol consumption, NSAID use, P-cholesterol, and P-triglycerides) showed an association of S-homocysteine higher than 14.5 mu mol/l to cardiovascular diseases (OR 2.05 [95% c.i. 1.14-3.70]), but not to dementia overall. Conclusions Gender, age, vitamin B12, folate, renal function, atrophic gastritis and the methylenetetrahydrofolate 677TT genotype were significant determinants of homocysteine levels, which were positively related to incident cardiovascular diseases.