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- Bixo, Marie, 1957-
(författare)
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Ovarian steroids in rat and human brain : effects of different endocrine states
- 1987
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ovarian steroid hormones are known to produce several different effects in the brain. In addition to their role in gonadotropin release, ovulation and sexual behaviour they also seem to affect mood and emotions, as shown in women with the premenstrual tension syndrome. Some steroids have the ability to affect brain excitability. Estradiol decreases the electroshock threshold while progesterone acts as an anti-convulsant and anaesthetic in both animals and humans. Several earlier studies have shown a specific uptake of several steroids in the animal brain but only a few recent studies have established the presence of steroids in the human brain.In the present studies, the dissections of rat and human brains were carried out macroscopically and areas that are considered to be related to steroid effects were chosen. Steroid concentrations were measured by radioimmunoassay after extraction and separation with celite chromatography. The accuracy and specificity of these methods were estimated.In the animal studies, immature female rats were treated with Pregnant Mare's Serum Gonadotropin (PMSG) to induce simultaneous ovulations. Concentrations of estradiol and progesterone were measured in seven brain areas pre- and postovulatory. The highest concentration of estradiol, pre- and postovulatory, was found in the hypothalamus and differences between the two cycle phases were detected in most brain areas. The preovulatory concentrations of progesterone were low and the highest postovulatory concentration was found in the cerebral cortex.In one study, the rats were injected with pharmacological doses of progesterone to induce "anaesthesia". High uptake of progesterone was found and a regional variation in the formation of 5<*-pregnane-3,20-dione in the brain with the highest ratio in the medulla oblongata.Concentrations of progesterone, 5a-pregnane-3*20-dione, estradiol and testosterone were determined in 17 brain areas of fertile compared to postmenopausal women. All steroids displayed regional differences in brain concentrations. Higher concentrations of estradiol and progesterone were found in the fertile compared to the postmenopausal women.In summary, these studies show that the concentrations of ovarian steroids in the brain are different at different endocrine states in both rats and humans and that there are regional differences in brain steroid distribution.
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| 2. |
- Codita, Alina, et al.
(författare)
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Of mice and men : more neurobiology in dementia.
- 2006
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Ingår i: Curr Opin Psychiatry. - : Ovid Technologies (Wolters Kluwer Health). - 0951-7367. ; 19:6, s. 555-63
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
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| 4. |
- Grundberg, Åke
(författare)
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Mental health promotion among community-dwelling seniors with multimorbidity : perspectives of seniors, district nurses and home care assistants
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The prevalence of mental illness is increasing among the older population in Sweden. One of the most vulnerable groups for mental health problems is older persons with multimorbidity, i.e. seniors with multiple chronic conditions. Many of them remain in their own homes with a comprehensive and complex need of support and healthcare, mainly provided by home care assistants (HCAs) and district nurses (DNs). However, the detection of mental health problems for adequate treatment or to promote mental health among community-dwelling seniors with multimorbidity, calls for skills and competences in this area.This thesis aimed to gain a deeper understanding of how mental health may be promoted among community-dwelling seniors with multiple chronic conditions. Four studies have been included in this thesis (I-IV). All studies had a qualitative descriptive design with either a phenomenographic approach or latent and manifest qualitative content analysis technique. The aim of study I was to describe the variations in how community-dwelling seniors with multimorbidity perceived the concept of mental health and what may influence it. The findings showed the participants conceptualised mental health as having both positive and negative facets. The participants further conceived that social contact, physical activity and optimism may improve mental health, while social isolation, ageing, and chronic pain may worsen it. Study II aimed to describe the experience of health-promoting dialogues from the perspective of community-dwelling seniors with multimorbidity, and what these seniors believed to be important for achieving a dialogue that may promote their mental health. The main finding was the necessity of being seen as a unique individual by an accessible and competent person. Further, the participants missed having friends and relatives to talk to and they especially lacked healthcare or social service providers for health-promoting dialogues that may promote mental health. The aim of study III was to describe DNs’ perspectives on detecting mental health problems and promoting mental health among community-dwelling seniors with multimorbidity. Findings revealed that the DNs’ focus was on assessment, collaboration and social support as a way of detecting mental health problems and promoting mental health. Study IV described HCAs’ perspectives on detecting mental health problems and promoting mental health among the seniors in focus. The findings revealed that continuity of care and the seniors’ own thoughts and perceptions were regarded as essential for the detection of mental health problems. Further, observation, collaboration, and social support emerged as important means of detecting mental health problems and promoting mental health.Conclusions: The results of this thesis are based on interviews and show that: 1) Seniors with multimorbidity should have an opportunity to describe how multiple chronic conditions may affect their life situation; 2) An optimal level of care can be achieved through continuity, involvement, and by providing a health-promoting dialogue based on the person’s wishes and needs; 3) Even if DNs seemed engaged in primary mental healthcare, there were no expressed goals set in the improvement of mental health, and it seemed that these DNs could not bear the primary responsibility for early detection of mental health problems and early interventions to improve mental health; 4) HCAs had knowledge about risk factors for mental health problems and it appears that they were dependent on care managers’ decision-making in granted support, as well as supervision from DNs in the detection of mental health problems and to promote mental health.In summary, the finding in the present thesis demonstrates that managing mental health problems is still an ongoing challenge for those organisations providing continuity in home care and home healthcare for homebound elderly persons with complex chronic conditions. The finding in the thesis also shows that DNs and HCAs seem to be dependent on each other in this area. Mental health promotion was expressed as an important assignment among DNs and HCAs, even though they describe different prerequisites and factors which could be seen as barriers in the detection of common mental health problems such as depression, anxiety and sleep problems. These personnel further described difficulties in collaboration and transmission of information between care- and healthcare providers from the community and primary care context. Social and physical interventions - as well as social contacts and social support to break social isolation - seemed important according to all the informants, with their different perspectives of how mental health may be promoted.
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| 5. |
- Gustafson, Yngve, 1949-
(författare)
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Acute confusional state (delirium) : clinical studies in hip-fracture and stroke patients
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Acute confusional state (ACS) or delirium according to DSM-III-R holds a central position in the medicine of old age. ACS is a common and sometimes the only symptom of diseases and medical complications in the elderly patient.The aim of this study was to elucidate ACS in patients with femoral neck fractures and patients with acute stroke with regard to frequency, predictors, possible pathogenetic mechanisms, associated complications, assessment and documentary routines and the clinical outcome for the patients. An intervention program to prevent postoperative ACS based on our results was developed and evaluated.The main findings of the study were high frequencies of ACS in elderly patients with femoral neck fractures (61 %) and in patients with acute stroke (48 %). The main risk factors for ACS in patients with femoral neck fractures were old age, diseases and drug treatment interfering with cerebral cholinergic metabolism. There was no link between anaesthetic technique and ACS but the connection between peroperative hypotension, early postoperative hypoxia and ACS was close.In stroke patients the degree of extremity paresis and old age were independent ACS risk factors. ACS was commonly associated with post stroke complications such as myocardial infarction, pneumonia, urinary infection and urinary retention. In stroke patients there was a close connection between high hypothalamic-pituitary-adrenal axis (HPA-axis) activity and ACS. High HPA-axis activity and disturbances in the cerebral cholinergic system may be two important ACS mechanisms.A correct diagnosis is a prerequisite for proper treatment of ACS and its underlying causes. In the orthopaedic wards both physicians and nurses diagnosed and documented ACS poorly and therefore associated complications were insufficiently treated.The intervention program for postoperative ACS, aimed mainly at protecting the cerebral oxidative metabolism and thereby the cerebral cholinergic metabolism which is especially sensitive to hypoxia. Postoperative complications associated with ACS were also treated. The intervention resulted in reduced frequency, duration and severity of postoperative ACS and in shorter orthopedic ward stay for patients with femoral neck fractures.Key words: Acute confusional state, delirium, elderly
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| 6. |
- Håkansson, Krister, 1952-, et al.
(författare)
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Feelings of hopelessness in midlife are associated with dementia risk in later life
- 2012
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Ingår i: 12th International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy. ; , s. 165-165
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Although an association between depressive feelings and dementia has been estab- lished previously, the nature of this relation remains unclear. Establishing causality has been com- plicated by the typical use of a short follow-up and aged participants already at baseline. The aim with this study was to investigate the association between feelings of hopelessness in midlife and cognitive impairment in later life.Methods: From a representative population in Eastern Finland, originally investigated between 1972-1987, a random sample of 2000 survivors was invited for re-examination in 1998, averagely 21 years later. The mean age of the 1449 persons who accepted the invitation was 50.4 (range 39-64) at baseline and 71.3 years (range 65-80) at follow-up. Baseline scores of hopelessness were related to cognitive status at follow-up, mainly through logistic regression. Adjustments were made for age, years of education, gender, APOE4 and a number of health and life style factors at baseline. In addition we analyzed differences in hopelessness scores between baseline and follow-up within the different outcome groups.Results: Participants with high levels of hopelessness at midlife had more than a doubled risk of cognitive impairment in later life as expressed by an odds ratio of 2.24 (1.4-3.6), even higher spe- cifically for Alzheimers disease. Persons with high levels of hopelessness at midlife and who in addition carried the apolipoprotein allele 4 (ApoE ε4) had a highly elevated risk of Alzheimers dis- ease. There were no significant differences in levels of hopelessness between baseline and follow-up within any of the outcome groups.Conclusions: The results confirm previous studies showing elevated scores of depressive feelings in persons diagnosed with dementia, compared to cognitively healthy persons. On the other hand, the results also suggest that the major portion of this difference could have existed already decades before the dementia diagnosis; Carrying feelings of hopelessness in midlife may have long-term implications for cognitive health in later life. Background: Although an association between depressive feelings and dementia has been estab- lished previously, the nature of this relation remains unclear. Establishing causality has been com- plicated by the typical use of a short follow-up and aged participants already at baseline. The aim with this study was to investigate the association between feelings of hopelessness in midlife and cognitive impairment in later life.Methods: From a representative population in Eastern Finland, originally investigated between 1972-1987, a random sample of 2000 survivors was invited for re-examination in 1998, averagely 21 years later. The mean age of the 1449 persons who accepted the invitation was 50.4 (range 39-64) at baseline and 71.3 years (range 65-80) at follow-up. Baseline scores of hopelessness were related to cognitive status at follow-up, mainly through logistic regression. Adjustments were made for age, years of education, gender, APOE4 and a number of health and life style factors at baseline. In addition we analyzed differences in hopelessness scores between baseline and follow-up within the different outcome groups.Results: Participants with high levels of hopelessness at midlife had more than a doubled risk of cognitive impairment in later life as expressed by an odds ratio of 2.24 (1.4-3.6), even higher spe- cifically for Alzheimers disease. Persons with high levels of hopelessness at midlife and who in addition carried the apolipoprotein allele 4 (ApoE ε4) had a highly elevated risk of Alzheimers dis- ease. There were no significant differences in levels of hopelessness between baseline and follow-up within any of the outcome groups.Conclusions: The results confirm previous studies showing elevated scores of depressive feelings in persons diagnosed with dementia, compared to cognitively healthy persons. On the other hand, the results also suggest that the major portion of this difference could have existed already decades before the dementia diagnosis; Carrying feelings of hopelessness in midlife may have long-term implications for cognitive health in later life.
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| 7. |
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| 8. |
- Håkansson, Krister, 1952-
(författare)
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The role of socio-emotional factors for cognitive health in later life
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With increasing life expectancies in most parts of the world, the prevalence of dementia and other age-related chronic diseases is growing. Several factors affect future projections and are discussed in this thesis, including possible limits to a continued growth of life expectancy. A related question is to what extent healthy ageing per se affects cognitive functions in old persons. Previous studies have generally exaggerated ageing effects on cognition, by applying study designs that did not account for common confounders, such as birth cohort differences, and the effects of terminal decline and subclinical dementia. In contrast to healthy ageing, dementia neuropathologies dramatically reduce cognitive performance, and proposed mechanisms behind dementia are briefly discussed with focus on Alzheimer’s disease (AD), on the role of genetic factors and on life course exposures. Three studies (study 1-3) investigated how cohabitant status and feelings of loneliness and hopelessness in midlife were associated with cognitive health in later life. Neurotrophic factors could potentially be involved in the biological mechanisms behind these and other associations between life-style factors and cognitive health. The fourth study aimed to explore how levels of brain-derived neurotrophic factor (BDNF), measured in serum, were affected by performing different activities; physical exercise, cognitive training, and mindfulness.THE FOUR STUDIESStudy 1-3 were epidemiological association studies based on the Cardiovascular Risk Factor, Ageing and Dementia (CAIDE) Study, a population based cohort study on 1511 persons in eastern Finland, who at baseline were 50.4 years. Two re-examinations have been performed in the CAIDE Study, in 1998 when the participants were between 65 and 80 years, and between 2005-2008, averagely 25.3 years after the baseline examinations. The first two studies were based on the 1409 persons who fully participated in the first re-examination and the third study on the 1511 persons who participated in one or both re-examinations. In the first two studies logistic regression was the main statistical method with any cognitive impairment versus no cognitive impairment as outcome. In addition we performed analyses with mild cognitive impairment and Alzheimer’s disease as separate outcomes. In Study 1 and 2 we also analysed how apolipoprotein epsilon 4 (ApoE4) status affected the associations with Alzheimer’s disease. The statistical method in Study 3 was survival model analysis (Kaplan-Meyer and Cox regression) and the outcome variable was dementia, without subtyping. We compared the results from the analysis on the 1511 participants with the results when we used the total sample (by including register linked data on dementia diagnoses). We adjusted the associations for several potential confounding variables in all three studies.In Study 4 we used 19 elderly healthy volunteers who were between 65 and 80 years (mean = 70.8 years). They performed three different activities during 35 minutes on separate occasions, i.e. a within-subject cross-over experimental design where we randomized the order of the three conditions between the participants. We sampled blood from a suitablelower arm vein directly before and after each activity session and in addition at 20 and 60 minutes after the session had ended. After the serum had been analysed for BDNF levels, we used repeated measures ANOVA to calculate the differences in the effect of BDNF levels between the three conditions.MAIN RESULTSWe found that living alone in midlife was associated with approximately a doubled risk of cognitive impairment during the re-examination. Among the non-cohabitants the risk increase was especially high for persons who were widowed in midlife and who had continued to live alone until the re-examination (odds ratio (OR) 7.67, 95% confidence interval (CI) 1.6 – 40.0). Feelings of loneliness were common both among cohabitants and non-cohabitants, but we found that such feelings were only associated with an increased dementia risk if these persons had also been living alone. Feelings of hopelessness in midlife, but not at follow-up, were associated with increased risk of cognitive impairment at the re-examination, especially of Alzheimer’s disease (OR 2.90, CI 1.4 – 5.9). When we adjusted the association from midlife also for depression and hopelessness at the re-examination, this association was still statistically significant. Participants with a diagnosis of cognitive impairment had higher feelings of hopelessness at the re-examination, compared to the cognitively healthy group, but this difference between the groups existed already when they were in midlife. When we stratified the participants with reference to ApoE4 status, we found that participants who were also ApoE4 carriers had a dramatically increased risk of Alzheimer’s disease compared to non-carriers without feelings of hopelessness, even after final adjustment for depression (OR 6.48, CI 2.4 –17.5). A similar stratification for ApoE4 status in Study 1 showed an even more dramatic increase in the association for persons who had lost their partner (widowed or divorced/separated) if they in addition were ApoE4 carriers.In Study 4 we found that physical exercise, but not cognitive training or mindfulness, led to a statistically significant increase in BDNF levels of around 25%, compared to baseline. We also found that the individual differences in BDNF levels after the physical exercise correlated with working memory performance, measured on a separate occasion.CONCLUSIONSSocial and emotional factors can have long-term consequences for cognitive health in later life. The long follow-up time in Study 1-3 suggests that the associations we found with dementia could reflect a causal, rather than a prodromal, relation. As other studies have found a range of adverse ill health consequences from both living alone and from depressive feelings, a possible mechanism behind the associations we found could be related to a systemic biological impact, and that the specific ill health outcome could be a result of individual vulnerability where genetic dispositions could play an important role. This conclusion seems consistent with the dramatic risk increases we found for AD when ApoE4status was combined with the social factor of living alone and with the emotional dimension of hopelessness. At the micro level, as synaptic dysfunction and loss is characteristic of Alzheimer’s disease, and as BDNF has a central role for synaptogenesis, impaired BDNF functionality could play a role in the development of Alzheimer’s disease. More research is needed to further explore the role of BDNF in Alzheimer’s disease and if the disease can be prevented, or the disease process halted, by activities that stimulate BDNF expression in the brain.
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