| 1. |
- Palmqvist, Sebastian, et al.
(author)
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Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease
- 2015
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In: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 85:14, s. 1240-1249
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Journal article (peer-reviewed)abstract
- Objective:To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD).Methods:From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). -Amyloid (A) deposition in 9 brain regions was examined with [F-18]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study.Results:The best CSF measures for identifying MCI-AD were A42/total tau (t-tau) and A42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF A42/t-tau and A42/p-tau performed better than CSF A42 and A42/40 (AUC difference 0.03-0.12, p < 0.05). Using nonoptimized cutoffs, CSF A42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately.Conclusions:Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global A deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy.Classification of evidence:This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately.
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| 2. |
- Lewerin, Catharina, 1961, et al.
(author)
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Low holotranscobalamin and cobalamins predict incident fractures in elderly men: the MrOS Sweden.
- 2014
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In: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 25:1, s. 131-140
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Journal article (peer-reviewed)abstract
- In a population-based study on cobalamin status and incident fractures in elderly men (n=790) with an average follow-up of 5.9years, we found that low levels of metabolically active and total cobalamins predict incident fractures, independently of body mass index (BMI), bone mineral density (BMD), plasma total homocysteine (tHcy), and cystatin C.
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| 3. |
- Johansson, Per, 1966, et al.
(author)
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Reduced cerebrospinal fluid concentration of interleukin-12/23 subunit p40 in patients with cognitive impairment.
- 2017
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:5
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Journal article (peer-reviewed)abstract
- The role of inflammation in Alzheimer's disease (AD) and other cognitive disorders is unclear. In a well-defined mono-center population, we measured cytokines and chemokines in paired serum and cerebrospinal fluid (CSF) samples.Consecutive patients with AD (n = 30), stable mild cognitive impairment (SMCI, n = 11), other dementias (n = 11), and healthy controls (n = 18) were included. None of the subjects was treated with glucocorticoids, cholinesterase inhibitors, or non-steroidal anti-inflammatory drugs. Serum and CSF concentrations of interleukin-6 (IL-6), IL-8, IL-12/23 p40, IL-15, IL-16, vascular endothelial growth factor-A (VEGF-A), and three chemokines were measured using a multiplex panel.After correction for multiple comparisons, only CSF IL-12/23 p40 concentration differed significantly between the total patient group (n = 52) and controls (n = 18; p = 0.002). Further analyses showed that CSF IL-12/23 p40 concentration was decreased in all patient subgroups (AD, other dementias, and SMCI) compared to healthy controls (p < 0.01, p < 0.05, and p < 0.05, respectively). In the total study population (n = 70), CSF IL-12/23 p40 concentrations correlated positively with CSF concentrations of β-amyloid1-42 (Aβ1-42) and phosphorylated tau protein (P-tau) whereas in AD patients (n = 30), CSF IL-12/23 p40 only correlated positively with CSF P-Tau (r = 0.46, p = 0.01).Most cytokines and chemokines were similar in patients and controls, but CSF IL-12/23 subunit p40 concentration was decreased in patients with cognitive impairment, and correlated with markers of AD disease status. Further studies are needed to evaluate the role of CSF IL-12/23 p40 in other dementias and SMCI.
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| 4. |
- Pourhamidi, Kaveh, et al.
(author)
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Evaluation of clinical tools and their diagnostic use in distal symmetric polyneuropathy
- 2014
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In: Primary care diabetes. - : Elsevier. - 1878-0210 .- 1751-9918. ; 8:1, s. 77-84
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Journal article (peer-reviewed)abstract
- AIMS: To compare the diagnostic usefulness of tuning fork, monofilament, biothesiometer and skin biopsies in peripheral neuropathy in individuals with varying glucose metabolism.METHODS: Normoglycaemic, impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) individuals were recruited. Nerve conduction studies (NCS) and thermal threshold tests were performed. Vibrotactile sense was tested with a biothesiometer and a 128-Hz tuning fork. Touch/pressure perception was examined with a 10-g monofilament. Skin biopsies were performed and intraepidermal nerve fibres were quantified. Distal symmetric polyneuropathy (DSPN) was defined as neuropathy disability score ≥2 and abnormal NCS. Thermal threshold tests were used to define small nerve fibre neuropathy (sDSPN) in cases where NCS (large nerve fibres) were normal.RESULTS: The prevalence of DSPN and sDSPN in the whole group (n=119) was 18% and 23%, respectively. For the biothesiometer, a cut-off of ≥24.5V had a sensitivity of 82% and specificity of 70% (AUC=0.81, 95% CI 0.71-0.91) when evaluating DSPN. An intraepidermal nerve fibre density cut-off of ≤3.39fibres/mm showed a sensitivity of 74% and specificity of 70% in the detection of sDSPN, whereas the sensitivity of the tuning fork and the biothesiometer were relatively low, 46% and 67%, respectively. When combining skin biopsies with the tuning fork, 10 more sDSPN cases were identified. Adding skin biopsy to the combination of the tuning fork and biothesiometer increased the sensitivity of finding sDSPN cases, but not DSPN, from 81% to 93%.CONCLUSION: Using a biothesiometer in clinical routine might be a sensitive method to detect large nerve fibre dysfunction in the lower extremity, whereas skin biopsies in combination with methods measuring vibrotactile sense could increase the diagnostic sensitivity of detecting peripheral neuropathy at an early stage.
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| 5. |
- Sundell, Anna Lena, 1970-
(author)
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Children with orofacial clefts : dental caries and health-related quality of life
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Background. The current understanding on caries and enamel developmental defects prevalence and frequency, caries risk, health-related quality life (HRQoL) and stress response in young children with cleft lip and/or palate (CL/P) are sparse. In this thesis these aspects were investigated in 5- and 10- year-old children with CL/P in comparison to non-cleft children in the same ages.Design. The studies in this thesis have a cross-sectional case-control design. Participants. The study group consisted of 139 children with CL/P (80 children aged 5 years and 59 aged 10 years) and 313 non-cleft controls (144 children aged 5 years and 169 aged 10 years).Method. Caries was scored according to International Caries Detection and Assessment System (ICDAS II) and developmental enamel defects were measured as presence and frequency of hypoplasia and hypomineralization. Oral hygiene was assessed using Quigley-Hein plaque index. Stimulated saliva samples were analyzed for mutans streptococci, lactobacilli, buffering capacity and secretion rates. Information regarding children’s oral hygiene routines, dietary habits and fluoride exposure were collected with questionnaires. Caries risk was evaluated with algorithm-based software, Cariogram while HRQoL was perceived with KIDSCREEN-52. Stress response was analyzed with cortisol concentration in saliva at three different time points using a commercial competitive radioimmunoassay.Results. Caries prevalence (36% versus 18%) and caries frequency (1.2 dmfs versus 0.9 dmfs) was significantly higher in 5-year-old children with CL/P in comparison to non-cleft controls. In 10-yearolds no significant difference was found between children with CL/P and non-cleft controls in caries prevalence (47% versus 38%) or in caries frequency (0.7 DMFS versus 0.5 DMFS). Children with CL/P had significantly higher prevalence of enamel defects, higher counts of salivary lactobacilli and less good oral hygiene. The odds of being categorized with high caries risk were elevated in children with CL/P. Children with CL/P had similar HRQoL and salivary cortisol concentrations as non-cleft controls. However, 10-year-old boys with CL/P had significantly higher cortisol concentrations in the evening than non-cleft boys.Conclusions. Preschool children with CL/P seem to have more caries in the primary dentition than non-cleft controls. Children with CL/P had increased odds of being categorized as high caries risk individuals compared to controls. Some of the contributing factors seem to be higher prevalence of enamel defects, impaired oral hygiene and elevated salivary lactobacilli. Furthermore, as measured with the help of cortisol concentrations in saliva, children with CL/P were not more stressed than noncleft controls and their HRQoL was comparable to a European norm population. It appears that regular comprehensive preventive oral care in children with CL/P is effective in preventing caries development in permanent teeth. However, children with CL/P are at risk of caries development and preventive oral care should be implemented and started earlier than today.
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| 6. |
- Trägårdh, Karin, et al.
(author)
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Risk Profiles of Female Perpetrators of Severe Violence
- 2019
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In: 13th Nordic Symposium on Forensic Psychiatry. August 20-22, Gothenburg, Sweden.
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Conference paper (other academic/artistic)abstract
- Female offenders without a severe mental disorder show more criminogenic factors than those with. Both groups are characterized by mental health problems. We need to further characterize female offenders. Background Offenders of lethal/severe violence are in a majority of cases male, about 90% (Falk et al., 2014), and research has to a considerable extent focused on male violent offenders. Although less is known about female violent offenders than male offenders, previous research has indicated significant differences between male and female offenders of lethal/severe violence (Trägårdh et al., 2016; Yourstone et al., 2008). Since a majority of female perpetrators of lethal violence undergo a forensic psychiatric investigation (RPU/FPI), these documents contains important information about this group. Purpose The aim of this ongoing study is to characterize female perpetrators of severe violent crimes, and to compare female perpetrators sentenced to forensic psychiatric compulsory care with those sentenced to correctional treatment. Method This is an exploratory and descriptive study with a cross-sectional design. All forensic evaluations (FPI) made in Sweden between 2000-2014 (from The National Board of Forensic Medicine/RMV), and the subsequent court verdicts, in cases where women had used lethal/severe violence (n≈180) where used as the basis for data collection in this study. The present preliminary analyses (2-tests and ANOVA) contains approx. 26% (n=47) of the total group. Group differences were investigated regarding: Mental health (FPI) Risk factors (HCR-20 and PCL-R) Victim relation (FPI) Criminal behavior (FPI) Results Female offenders with and without a Severe mental disorder (SMD) seems to differ in some respects. For female offenders with a SMD, the crime was more likely to have been conducted in a less criminal context (see Table). For female offenders without a SMD, the following characteristics were more frequently present: Victim gender – male Substance abuse + Under the influence of substance (offender and victim) Previous violence between victim and offender Previous registered criminality Also, several common features between the SMD and non-SMD group of female offenders were found. The majority of all female offenders had: Previous psychiatric contact and diagnoses Previously attempted suicide No previously registered criminality Conclusions Preliminary results of the female perpetrators who had underwent a FPI seems to identify both substantial differences and similarities between those with versus without a SMD, where those without show more criminogenic factors. Both groups were also characterized by a high amount of mental illness. Also, these results supports previous research that female and male offenders of severe violence differ in important ways. Since a majority of female perpetrators of lethal violence undergo a forensic psychiatric investigation, these results should be generalizable to this group as a whole in Sweden. Based on these results, a great need to further characterize female offenders of severe/lethal violence remain.
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| 7. |
- Lundin, Anna-Carin
(author)
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Tendinosis in Trigger Finger
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Trigger finger is one of the most common hand conditions, with a prevalence of almost 3%. The aetiology remains unclear even though many causes have been suggested. The prevailing paradigm is that the pathogenesis of trigger finger is ascribed to primary changes in the first fibrous condensation of the tendon sheath (A1-pulley). Several studies have investigated pathology in the pulley, but few have investigated the tendon. The general aim of this thesis was to find out if there is pathology in the trigger finger tendon and to define it.We first looked at trigger finger tendon biopsies in a light microscope, and found that they were histologically different from healthy tendons. They showed signs of micro-ruptures, collagen degradation, increased amounts of ground substance, both hyper- and hypo-cellular areas, round active cell nuclei and absence of inflammatory cells, all similar to tendinosis. The histological picture was further assessed by using a scoring system for Achilles tendinosis. The trigger finger tendons scored high, suggesting a similar histopathology.Next, we performed a quantitative real-time polymerase chain reaction (qPCR) on trigger finger tendons. We assessed the mRNA expression of 10 genes, which have been described to be differently expressed in Achilles tendinosis (collagen 1 and 3, versican, decorin, biglycan, aggrecan, MMP-2, MMP-3, ADAMTS-5, and TIMP-3). The overall expression pattern agreed with previous studies on Achilles tendinosis, suggesting that the cellular function in trigger finger tendons is disturbed in a similar way as in Achilles tendinosis.Recent experimental and observational research has suggested potential side effects of statin treatment on tendons, but firm evidence was lacking. We performed an epidemiological study on two large population-based cohorts. Statin use was found to increase the risk of both trigger finger and tendinosis in the shoulder and Achilles tendons, especially among men. This suggests a similar pathology in trigger finger and tendinosis.We have also studied the time to treatment effect after a single injection of glucocorticoid in trigger finger. Our results suggest that 60-80% of patients can expect resolution of the triggering within 14 days, and half of them within seven days. This result allows correct information to be given to the patient and proper planning of follow-ups.In conclusion, the pathology in trigger finger tendons is similar to tendinosis in other tendons.
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| 8. |
- Schöll, Michael, 1980, et al.
(author)
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Biomarkers for tau pathology.
- 2019
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In: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 97, s. 18-33
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Research review (peer-reviewed)abstract
- The aggregation of fibrils of hyperphosphorylated and C-terminally truncated microtubule-associated tau protein characterizes 80% of all dementia disorders, the most common neurodegenerative disorders. These so-called tauopathies are hitherto not curable and their diagnosis, especially at early disease stages, has traditionally proven difficult. A keystone in the diagnosis of tauopathies was the development of methods to assess levels of tau protein in vivo in cerebrospinal fluid, which has significantly improved our knowledge about these conditions. Tau proteins have also been measured in blood, but the importance of tau-related changes in blood is still unclear. The recent addition of positron emission tomography ligands to visualize, map and quantify tau pathology has further contributed with information about the temporal and spatial characteristics of tau accumulation in the living brain. Together, the measurement of tau with fluid biomarkers and positron emission tomography constitutes the basis for a highly active field of research. This review describes the current state of biomarkers for tau biomarkers derived from neuroimaging and from the analysis of bodily fluids and their roles in the detection, diagnosis and prognosis of tau-associated neurodegenerative disorders, as well as their associations with neuropathological findings, and aims to provide a perspective on how these biomarkers might be employed prospectively in research and clinical settings.
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| 9. |
- Nord, Maria, et al.
(author)
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Levodopa Pharmacokinetics in Brain after Both Oral and Intravenous Levodopa in One Patient with Advanced Parkinson’s Disease
- 2017
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In: Advances in Parkinsons Disease. - : Scientific Research Publishing Inc. - 2169-9712 .- 2169-9720. ; 6:2, s. 52-66
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Journal article (peer-reviewed)abstract
- Objective: One patient received oral levodopa during a study aiming for better understanding of the basal ganglia and of the mechanisms of deep brain stimulation of the subthalamic nucleus (STN DBS) with and without intravenous (IV) levodopa infusion in patients with Parkinson’s disease (PD). The results from oral and IV levodopa treatment are presented.Methods: Five patients with advanced PD were included in the original study. During planned STN DBS surgery microdialysis probes were implanted in the right putamen and in the right and left globus pallidus interna (Gpi). During the study, microdialysis was performed continuously and STN DBS, with and without IV levodopa infusion, was performed according to a specific protocol. After DBS surgery, but before STN DBS was started, one patient received oral levodopa/ benserazide and entacapone tablets out of protocol due to distressing parkinsonism.Results: The levodopa levels increased prompt in the central nervous system after the first PD medication intakes but declined after the last. Immediately the levodopa seemed to be metabolized to dopamine (DA) since the levels of DA correlated well with levodopa concentrations. Left STN DBS seemed to further increase DA levels in left Gpi while right STN DBS seemed to increase DA levels in the right putamen and right Gpi. There was no obvious effect on levodopa levels.Conclusions: The results indicate that PD patients still have capacity to metabolize levodopa to DA despite advanced disease with on-off symptoms and probably pronounced nigral degeneration. STN DBS seems to increase DA levels with a more pronounced effect on ipsilateral structures in striatum.
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| 10. |
- Björkman, Kristoffer, et al.
(author)
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Genotype-phenotype correlations in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1
- 2014
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In: Euromit 2014, 15-19 juni, Tampere, Finland.
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Conference paper (other academic/artistic)abstract
- Objectives: To study genotype-phenotype correlations in genes encoding complex I electron input module subunits. Materials and methods: We studied five patients with isolated complex I deficiency, three with NDUFS1 mutations and two with NDUFV1 mutations. A literature review of all reported cases of mutations in the affected genes was performed. Results: The literature review revealed pathological mutations in NDUFS1 for 18 patients in 17 families and correspondingly in NDUFV1 for 26 patients in 19 families. Unpublished clinical data for our five patients were added. Our study showed quite variable clinical courses; death before two years of age was seen in 41% of patients while 18% were alive at seven years. There was a significant difference between the NDUFS1 and NDUFV1 groups for clinical onset and life-span. Mutations in NDUFS1 were linked to a worse clinical course with earlier onset and earlier death. Conclusions: Genotype-phenotype correlations in patients with mutations affecting the genes that encode the electron input module of complex I vary, but patients with NDUFS1 mutation tend to have a worse clinical course than patients with NDUFV1 mutation. Identifying the mutations is of importance for accurate prognostic information and genetic counseling.
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