| 1. |
- E:son Jennersjö, Pär, 1956-
(författare)
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Risk factors in type 2 diabetes with emphasis on blood pressure, physical activity and serum vitamin D
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundType 2 diabetes is a common chronic disease with a two-fold increased risk for cardiovascular morbidity and mortality and has an increasing prevalence worldwide. This thesis is based on a study conducted in primary health care in Östergötland and Jönköping, Sweden. The aim of the thesis was to evaluate new risk markers to identify patients with high risk of developing cardiovascular disease in middle-aged men and women with type 2 diabetes.MethodsData from the cohort study CArdiovascular Risk in type 2 DIabetes – a Prospective study in Primary care (CARDIPP) was used. In paper III data were also used from CARDIPP-Revisited where all participants in the CARDIPP study were invited four years after the baseline investigation for a re-investigation. In paper IV data were used from CAREFUL which is a control group of 185 subjects without diabetes. The investigation included a standard medical history including data on diabetes duration and on-going medication. Anthropometric data were recorded and both office and ambulatory blood pressure were measured. The patients filled out a detailed questionnaire and physical activity was measured by using waist-mounted pedometers. Pedometer-determined physical activity was classified in four groups: Group 1: <5000 steps/day (‘sedentary’); Group 2: 5000-7499 steps/day (‘low active’); Group 3: 7500-9999 steps/day (‘somewhat active’); Group 4: and ≥10 000 steps/day (‘active’). Blood samples were drawn for routine analyses and also frozen for later analyses. The investigations at the departments of physiology included echocardiography, measurements of the carotid intima-media thickness, applanation tonometry and measurements of sagittal abdominal diameter.ResultsPaper 1:Patients with a non-dipping systolic blood pressure pattern showed higher left ventricular mass index and pulse wave velocity (PWV) compared with patients with ≥10% decline in nocturnal systolic blood pressure. Patients with <10% decline in nocturnal systolic blood pressure had higher BMI and sagittal abdominal diameter, lower GFR and higher albumin:creatinine ratio and also higher levels of NT-proBNP than patients with a dipping pattern of the nocturnal blood pressure.Paper 2:The number of steps/day were inversely significantly associated with BMI, waist circumference and sagittal abdominal diameter, levels of CRP, levels of interleukin-6 and PWV.Paper 3:At the 4-year follow-up the change in PWV (ΔPWV) from baseline was calculated. The group with the lowest steps/day had a significantly higher increase in ΔPWV compared with the group with the highest steps/day. The associations between baseline steps/day and ΔPWV remained after further adjustment in a multivariate linear regression statistically significant (p=0.005). 23% of the variation in the study could be explained by our model. Every 1000 extra steps at baseline reduced the change in ΔPWV by 0.103 m/s between baseline and follow-up.Paper 4:Low vitamin D levels were associated with significantly increased risk for premature mortality in men with type 2 diabetes. High levels of parathyroid hormone were associated with significantly increased risk for premature mortality in women with type 2 diabetes. These relationships were still statistically significant also when two other well-established risk markers for mortality, PWV and carotid intima-media thickness, were added to the analyses.ConclusionsAmbulatory blood pressure recording can by addressing the issue of diurnal blood pressure variation, explore early cardiovascular organ damage and microvascular complications that goes beyond effects of standardised office blood pressure measurements. Pedometer-determined physical activity may serve as a surrogate marker for inflammation and subclinical organ damage in patients with type 2 diabetes. There is novel support for the durable vascular protective role of a high level of daily physical activity, which is independent of BMI and systolic blood pressure. The use of pedometers is feasible in clinical practice and provides objective information not only about physical activity but also the future risk for subclinical organ damage in middle-aged people with type 2 diabetes. Our results indicate that low vitamin D levels in men or high parathyroid hormone levels in women give independent prognostic information of an increased risk for total mortality.
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| 2. |
- Pellas, Johnny
(författare)
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Assessment and psychological treatment of depression in older adults
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Depression is one of the leading causes of disability in older adults worldwide. Many older adults with depression are undetected, and there is a need for brief, scalable psychological treatments for depression that can be delivered remotely.The aims of this thesis were 1) to investigate the diagnostic accuracy of two rating scales (PHQ-9 and GDS-15) for the detection of depression in older adults, and 2) to investigate the feasibility, preliminary efficacy and patients’ experiences of a telephone-based psychological intervention, Behavioral activation with mental imagery (BA-MI), for the treatment of depression in older adults in the context of the covid-19 pandemic. Study I showed that a cutoff of ≥6 on the GDS-15 and ≥5 on the PHQ-9 were optimal to identify major depressive disorder. When identifying both major depressive disorder and subthreshold depression, the optimal cutoff on the GDS-15 was ≥5. Study II was a randomized clinical pilot trial, CoviDep, with a treatment group receiving the BA-MI intervention, and a control group. The drop-out rate was low. Compared to the control group, the treatment group reported a decrease in depressive symptoms throughout the treatment, with a large effect-size at posttreatment. Study III was a long-term follow-up of participants in CoviDep that received the BA-MI intervention. The drop-out rate over time was low, and compared to baseline, decreases in depressive symptoms were observed with a medium effect-size at posttreatment that was maintained 1- and 3 months post-treatment but lower after 6 months. Study IV was a qualitative study. The BA-MI intervention in CoviDep was described as increasing activities and improving mood. Telephone-delivery reduced barriers due to pandemic restrictions but felt less personal and lacking non-verbal communication. Being recognized and talking to a therapist every week was healing, but the manualized mode of treatment seemed to impair the relationship.In sum, this thesis shows that both the GDS-15 and the PHQ-9 are useful tools for the detection of depression in older adults, and adds to the support for telephone-delivered BA for the treatment of depression and indicates that MI-interventions are feasible as an augmentation of BA in older adults.
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| 3. |
- Malmgren, Linnea
(författare)
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Kidney Function During Ageing and its Association with Bone Mass, Fracture and Mortality
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Osteoporosis and osteoporosis related fractures are a major health care challenge both in Sweden and globally. The cost and suffering from osteoporosis are expected to increase since the population of elderly is increasing. Bone health can be affected by altered mineral homeostasis, which in its turn can be affected by reduced kidney function. However, the course of age-related decline in kidney function and its association to osteoporosis andfracture in the very elderly need further investigation since longitudinal data are scarce. Therefore, this thesis has two main aims; 1) to investigate kidney function during ageing and 2) its association to bone health in a cohort ofelderly women.Data was collected through the Malmö Osteoporosis Prospective Risk Assessment (OPRA) cohort, a prospective cohort of 1044 community dwelling women, all aged 75 and followed for ten years with reinvestigations at age 80and 85. Data on BMD, fracture and blood biochemistry was available at all three time points.Estimated kidney function greatly depends on which marker and study equation is used. The discrepancies are to such an extent that could affect whether a person is diagnosed with chronic kidney disease (CKD) or not, of particular importance in the elderly. Only women with the worst kidney function, corresponding to CKD stage 3b-5, had continuously increased mortality risk. This indicates that an age-dependent CKD definition would be of valuein elderly women.Kidney function in elderly women was associated with markers of mineral homeostasis, bone loss and BMD, but the effect size was relatively small compared to other risk factors. Also, fracture risk was increased only in womenwith mild-moderate reduction of kidney function (CKD stage 3a) and not in women with the worst kidney function (CKD stage 3b-5). Low BMD was associated with increased fracture risk independent of kidney function. Havingboth reduced kidney function and osteoporosis could present an additional risk increase.In conclusion, estimated kidney function in elderly women greatly depends on method of estimation and the results advocate for an age-adapted CKD definition. Maintaining adequate kidney function is important formaintaining bone health, although in old age it is probable that the effect size of any single specific risk factor is smaller compared with younger individuals.
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| 4. |
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| 5. |
- Vikström Eckevall, Josefin, 1984-
(författare)
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The influence of infertility and in vitro fertilization treatment on postpartum and long-term mental health in women
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: It is estimated that about 10-15% of couples suffer from infertility, i.e. the inability to achieve a clinical pregnancy after at least one year of regular, unprotected intercourse and that between 2-5% of births are a result of in vitro fertilization (IVF) treatment. Infertility and its treatment can have adverse effects on psychological well-being. While previous studies on postpartum depression (PPD) in IVF women suffer some methodological issues, there are no published studies on the risk of postpartum psychosis (PPP) after IVF pregnancies. Long-term, most women adjust well emotionally after IVF treatment but some, especially the childless, still suffer negative consequences. Meanwhile, few studies have extended beyond the first decade after treatment. Some studies have found that the childless elderly have social networks of less support potential but most show that psychological well-being is not affected by parental status. None of the studies have focused on the oldest old (≥85 years) and many have excluded those who live in institutional care, thus the frailest.Objective: The overall aim of this thesis was to study postpartum mental health in women who have undergone IVF treatment, using psychiatric diagnoses as outcomes, while controlling for major PPD and PPP risk factors as well as to determine the influences of childlessness, infertility and IVF treatment on long-term mental health in women. Materials and methods: Studies I-II are register-based, case control studies of 3532 (I) and 10,412 (II) primiparous women included in the Swedish IVF register. A control group of 8,553 (I) and 18,624 (II) primiparous women with spontaneous conceptions was selected from the Medical Birth Register. The main outcomes were PPD and PPP diagnoses the 1st year postpartum collected from the National Patient Register. Studies III-IV are cross-sectional. Study III included 470 women who had undergone IVF treatment 20-23 years previously. The Symptom Checklist-90 was used to investigate self-reported mental health. The results were compared with those from a population-based study and by parental status group. Study IV included 496 85-year olds. Psychological well-being, living situation, demographics and social network was investigated through a questionnaire and an interview.Results: Study I-II: There were no differences between the IVF and control group in the risk of receiving a PPD or PPP diagnosis. Having previously been diagnosed with any psychiatric, an affective or personality disorder increased the risk of PPD while any previous psychiatric, psychotic, bipolar, depressive, anxiety or personality disorder diagnosis increased the risk of PPP. None of the women had committed suicide. Study III: The IVF women reported symptoms of higher intensity and were at increased risk of symptoms of depression, obsessive-compulsion and somatisation compared with the reference group. Childless women, compared with parents, reported a higher level of mental health problems as well as symptoms of depression and phobic anxiety. Study IV: No differences in psychological wellbeing, living situation or having friends close by were found across parental status groups. The childless 85-year olds were less likely to have relatives close by and to receive help.Discussion: This thesis indicates that the risk of receiving a PPD or PPP diagnosis from in- or outpatient psychiatric care or of committing suicide during the first year postpartum is not increased in women who have undergone IVF treatment. Any negative effects of infertility and its treatment might have been mitigated by the “healthy patient effect”; those who choose to enter treatment are generally psychologically robust. A history of mental illness is a major risk factor for PPD and PPP. The risk of some adverse symptoms of mental illness might be increased in women who have undergone IVF treatment twenty years previously, especially in those who have remained childless. The childless elderly appear to have social networks of less support potential but are not more likely to live in institutional care and do not experience more adverse effects on psychological well-being than the elderly who are parents.
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| 6. |
- Alassaad, Anna, 1977-
(författare)
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Improving the Quality and Safety of Drug Use in Hospitalized Elderly : Assessing the Effects of Clinical Pharmacist Interventions and Identifying Patients at Risk of Drug-related Morbidity and Mortality
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Older people admitted to hospital are at high risk of rehospitalization and medication errors. We have demonstrated, in a randomized controlled trial, that a clinical pharmacist intervention reduces the incidence of revisits to hospital for patients aged 80 years or older admitted to an acute internal medicine ward. The aims of this thesis were to further study the effects of the intervention and to investigate possibilities of targeting the intervention by identifying predictors of treatment response or adverse health outcomes.The effect of the pharmacist intervention on the appropriateness of prescribing was assessed, by using three validated tools. This study showed that the quality of prescribing was improved for the patients in the intervention group but not for those in the control group. However, no association between the appropriateness of prescribing at discharge and revisits to hospital was observed.Subgroup analyses explored whether the clinical pharmacist intervention was equally effective in preventing emergency department visits in patients with few or many prescribed drugs and in those with different levels of inappropriate prescribing on admission. The intervention appeared to be most effective in patients taking fewer drugs, but the treatment effect was not altered by appropriateness of prescribing.The most relevant risk factors for rehospitalization and mortality were identified for the same study population, and a score for risk-estimation was constructed and internally validated (the 80+ score). Seven variables were selected. Impaired renal function, pulmonary disease, malignant disease, living in a nursing home, being prescribed an opioid and being prescribed a drug for peptic ulcer or gastroesophageal reflux disease were associated with an increased risk, while being prescribed an antidepressant drug (tricyclic antidepressants not included) was linked with a lower risk. These variables made up the components of the 80+ score. Pending external validation, this score has potential to aid identification of high-risk patients.The last study investigated the occurrence of prescription errors when patients with multi-dose dispensed (MDD) drugs were discharged from hospital. Twenty-five percent of the MDD orders contained at least one medication prescription error. Almost half of the errors were of moderate or major severity, with potential to cause increased health-care utilization.
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| 7. |
- Andin, Ulla
(författare)
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Vascular dementia - classification and clinical correlates
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the period (1976-1995) a total of 175 consecutive patients (m 88/f 87) with neuropathologically verified vascular dementia (VaD) were examined. 22 patients with pure Alzheimer's Disease (AD) were also studied. All patients were diagnosed and followed at the Department of Psychogeriatrics (Lund University Hospital). The neuropathological examination revealed VaD, sometimes with additional contribution of Alzheimer pathology. The cases were classified as Large Vessel Dementia (LVD), Small Vessel Dementia (SVD) and Hypoperfusive Hypoxic-ischemic Dementia (HHD). The mean age at death was 80 years (range 54-100) and almost identical in the three groups.The results show that VaD is neuropathologically heterogeneous, characterized by one, two or all three types of vascular pathology. The majority of cases (126/175), showed more than one type of brain pathology (vascular or in combination with Alzheimer pathology). There was a large coexistence with Alzheimer pathology (65% of the total 175 cases). 49 cases were pure, with only one type of vascular pathology. SVD was the largest pure group (21% of the total 175 cases). Post mortem verified heart pathology, was twice as common in SVD as in LVD and HHD.Cardio-cerebrovascular features (arrhythmia, congestive heart failure, cardiac infarction, hypertension, orthostatic hypotension and TIA/stroke) were more common in LVD and SVD, than in HHD. The coexistence of Alzheimer pathology did not change these results.Dizziness and unsteadiness or falls were reported in 102 of the 175 VaD patients. Dizziness correlated with hypertension and orthostatic hypotension while unsteadiness correlated only with hypertension. Falls correlated strongly to the use of neuroleptics and hypnotics.Hallucinations/delusions and delirium were reported in many patients and most common in the groups with pure LVD, pure SVD and especially in the SVD with combined Alzheimer pathology.Cardio-cerebrovascular features were more common in patients with AD combined with white matter pathology than those with pure AD. This study illustrates the neuropathological and clinical heterogeneity in VaD. This is of great importance for the understanding, treatment and care of the individual suffering from VaD.
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| 8. |
- Ballin, Marcel, 1993-
(författare)
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Physical activity, visceral adipose tissue, and cardiovascular disease in older adults : associations and effects
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Cardiovascular disease (CVD) poses a substantial public health burden and is the leading cause of mortality in older adults. With the population aging rapidly, interventions aimed at improving modifiable risk factors for CVD, such as physical inactivity and visceral obesity, could play an important role in reducing its burden, provided they are proven effective.PURPOSE AND AIMS: The overall purpose of this thesis was to create a deeper understanding of the links between physical activity, visceral adipose tissue (VAT), and CVD in older adults, by studying it from both an observational and an interventional perspective. The specific aims were to investigate the associations of objectively measured physical activity and VAT with the risk of CVD and all-cause mortality, to investigate the effect of structured physical activity (exercise) on VAT, and to review the effects of exercise on CVD and all-cause mortality based on evidence from randomized controlled trials (RCTs).METHODS: This thesis comprised two prospective cohort studies, one RCT, and one narrative review of evidence from RCTs. The cohort studies included about 3,300 men and women aged 70 years with baseline data on physical activity and VAT mass, as obtained using accelerometry and dual-energy X-ray absorptiometry, respectively. Cases of stroke, myocardial infarction, and all-cause mortality during follow-up were collected from Swedish nationwide registers. The RCT included 77 men and women aged 70 years with visceral obesity who were randomly allocated to either 10 weeks of supervised vigorous-intensity exercise or to no exercise, with VAT mass measured before and after the intervention. In the review, evidence from published RCTs and meta-analyses of RCTs reporting on the effects of exercise on CVD (N=19,162) and all-cause mortality (N=37,443) in general older adults and in individuals with chronic conditions (such as obesity, type 2 diabetes, and preexisting CVD) were reviewed.MAIN FINDINGS: In the cohort studies, greater amounts of physical activity of any intensity, but especially that of moderate to vigorous intensity, were associated with lower risk of stroke, myocardial infarction, and all-cause mortality. Conversely, greater VAT mass was associated with higher risk of stroke or myocardial infarction. In the RCT, short-term vigorous-intensity exercise seemed to decrease VAT mass slightly, but the effect was not statistically significant. Finally, the review showed that there is currently no convincing evidence from RCTs that exercise effectively reduces the risk of CVD or all-cause mortality, which stands in sharp contrast to the strong associations typically reported in observational studies. The reasons for the conflicting findings are likely complex and multifactorial. In the RCTs, a lack of statistical power could partly explain why no effects have been detected in the general population of older adults, but it is unlikely to explain the null findings in clinical populations, as some of these trials, including meta-analyses of such trials, have been large. Other potential explanations could be a ceiling effect due to the inclusion of participants who were healthier and more physically active than the general population, or that an effect of exercise was masked by the use of effective medications such as antihypertensives and lipid-lowering agents. On the other hand, observational studies have likely overestimated the benefits of physical activity, because these studies are vulnerable to selection bias, reverse causation, and unmeasured confounding, such as from heritable influences.CONCLUSIONS AND IMPLICATIONS: Despite strong associations, the protective effect of physical activity as a single intervention against CVD and all-cause mortality in older adults is probably not as substantial as is commonly presumed. To uncover the true role of physical activity in preventing CVD, further high-quality trials would be valuable. However, because these trials are very difficult and resource demanding, they should be complemented by innovative observational studies that seek to strengthen causal inference through addressing sources of bias and confounding that are often incompletely accounted for in conventional observational studies. This could include a variety of methodologies, such as utilizing negative control outcomes, instrumental variables, sibling comparisons, and other genetically informed designs. As the aging population continues to grow, it becomes increasingly important to take these scientific steps in order to provide a more definitive answer to the question of the extent to which physical activity alone can reduce the risk of CVD.
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| 9. |
- Bergman, Birgitta, 1941
(författare)
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On vision in old age. A longitudinal study of subjects 70 to 97 years old
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims. The main purpose of this study was to investigate different aspects of vision and visual function in old people, like change in vision and visual ability, to study the natural course of eye diseases, assess needs of visual intervention, investigate risk factors for ocular disorders late in life, and also to investigate coexistence between visual and hearing impairments. Materials and Methods. Within the framework of the Gerontological and Geriatric Population Studies, the H70 Study , launched 1971 in Göteborg, Sweden, a cohort comprising 958 subjects at the start of the study was eye-examined longitudinally at ages 70, 82, 88, 95, and 97 years. At ages 95 and 97, cross-sectional groups were added to extend the sample. Audiological and laboratory data were analysed in connection with the ophthalmological examinations.Results. At age 70, best-corrected normal vision (VA ³0.8) was found in 86%, at age 82 in 48%, at age 88 in 24%, and at age 95 in 8% of subjects. At age 97, severe visual impairment (VA £0.1) was found in every third subject. The deterioration rate (i.e., logMAR change per year) was faster in the highest age interval. At age 82, the visual ability score correlated with distance VA (r = 0.62). In subjects with no pathological findings, median VA was 0.9 at age 82 and 0.8 at age 88. Geographic atrophy was more common than exudative late ARM. At 97 years 30% had undergone cataract surgery. The benefit of regular eye examinations, improvement of glasses, and early cataract surgery was assessed. At age 70, blood folate levels, and physical activity earlier, correlated positively, and body mass index (BMI) correlated negatively, to VA ³0.8 at ages 82 and 88. Higher BMI at 70 correlated to cataract disease at age 88, and smoking at age 70 correlated to early ARM at age 82. Mild impairments of vision and hearing increased from 2% at age 70 to 22% at age 82.Conclusions. In old age, gradual deterioration of vision is encountered. Regular eye screening, with improvement of glasses, and/or cost-effective cataract surgery, should be performed early to increase the time of improved vision. Lifestyle variables may prospectively correlate to future eye health and vision. Combined visual and hearing impairment can result in pronounced problems in everyday activities.
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| 10. |
- Emami Khoonsari, Payam
(författare)
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Proteomics Studies of Subjects with Alzheimer’s Disease and Chronic Pain
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Alzheimer’s disease (AD) is a neurodegenerative disease and the major cause of dementia, affecting more than 50 million people worldwide. Chronic pain is long-lasting, persistent pain that affects more than 1.5 billion of the world population. Overlapping and heterogenous symptoms of AD and chronic pain conditions complicate their diagnosis, emphasizing the need for more specific biomarkers to improve the diagnosis and understand the disease mechanisms.To characterize disease pathology of AD, we measured the protein changes in the temporal neocortex region of the brain of AD subjects using mass spectrometry (MS). We found proteins involved in exo-endocytic and extracellular vesicle functions displaying altered levels in the AD brain, potentially resulting in neuronal dysfunction and cell death in AD.To detect novel biomarkers for AD, we used MS to analyze cerebrospinal fluid (CSF) of AD patients and found decreased levels of eight proteins compared to controls, potentially indicating abnormal activity of complement system in AD.By integrating new proteomics markers with absolute levels of Aβ42, total tau (t-tau) and p-tau in CSF, we improved the prediction accuracy from 83% to 92% of early diagnosis of AD. We found increased levels of chitinase-3-like protein 1 (CH3L1) and decreased levels of neurosecretory protein VGF (VGF) in AD compared to controls.By exploring the CSF proteome of neuropathic pain patients before and after successful spinal cord stimulation (SCS) treatment, we found altered levels of twelve proteins, involved in neuroprotection, synaptic plasticity, nociceptive signaling and immune regulation.To detect biomarkers for diagnosing a chronic pain state known as fibromyalgia (FM), we analyzed the CSF of FM patients using MS. We found altered levels of four proteins, representing novel biomarkers for diagnosing FM. These proteins are involved in inflammatory mechanisms, energy metabolism and neuropeptide signaling.Finally, to facilitate fast and robust large-scale omics data handling, we developed an e-infrastructure. We demonstrated that the e-infrastructure provides high scalability, flexibility and it can be applied in virtually any fields including proteomics. This thesis demonstrates that proteomics is a promising approach for gaining deeper insight into mechanisms of nervous system disorders and find biomarkers for diagnosis of such diseases.
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