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  • Wallin, A.K., et al. (författare)
  • Donepezil in Alzheimer's disease : What to expect after 3 years of treatment in a routine clinical setting
  • 2007
  • Ingår i: Dementia and Geriatric Cognitive Disorders. - Basel : S. Karger. - 1420-8008 .- 1421-9824. ; 23:3, s. 150-160
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aims: Clinical short-term trails have shown positive effects of donepezil treatment in patients with Alzheimer's disease. The outcome of continuous long-term treatment in the routine clinical settings remains to be investigated. Methods: The Swedish Alzheimer Treatment Study (SATS) is a descriptive, prospective, longitudinal, multicentre study. Four hundred and thirty-five outpatients with the clinical diagnosis of Alzheimer's disease, received treatment with donepezil. Patients were assessed with Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), global rating (CIBIC) and Instrumental Activities of Daily Living (IADL) at baseline and every 6 months for a total period of 3 years. Results: The mean MMSE change from baseline was positive for more than 6 months and in subgroups of patients for 12 months. After 3 years of treatment the mean change from baseline in MMSE-score was 3.8 points (95% CI, 3.0-4.7) and the ADAS-cog rise was 8.2 points (95% CI, 6.4-10.1). This is better than expected in untreated historical cohorts, and better than the ADAS-cog rise calculated by the Stern equation (15.6 points, 95% CI, 14.5-16.6). After 3 years with 38% of the patients remaining, 30% of the them were unchanged or improved in the global assessment. Conclusion: Three-year donepezil treatment showed a positive global and cognitive outcome in the routine clinical setting. Copyright © 2007 S. Karger AG.
  • Vos, Stephanie J. B., et al. (författare)
  • Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage
  • 2015
  • Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 138:5, s. 1327-1338
  • Tidskriftsartikel (refereegranskat)abstract
    • Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer's disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer's disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer's disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer's disease at the mild cognitive impairment stage and progression to Alzheimer's disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer's disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer's disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer's disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer's disease likelihood group. The 3-year progression rate to Alzheimer's disease-type dementia was 59% in the high Alzheimer's disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer's disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer's disease likelihood group or the International Working Group-2 prodromal Alzheimer's disease group could be considered.
  • Abraham-Nordling, Mirna, et al. (författare)
  • Incidence of Hyperthyroidism in Sweden.
  • 2011
  • Ingår i: European journal of endocrinology. - : Society of the European Journal of Endocrinology. - 1479-683X .- 0804-4643. ; 165, s. 899-905
  • Tidskriftsartikel (refereegranskat)abstract
    • AbstractIntroduction: The incidence of hyperthyroidism has been reported in various countries to be 23 - 93/100 000 inhabitants/year. This extended study has evaluated the incidence for approximately 40% of the Swedish population of 9 million inhabitants. Sweden is considered iodine sufficient.Methods: All patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003-2005, were prospectively registered in a multicenter study. Inclusion criteria: clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below < 0.2 mIE/l, increased plasma levels of free/total T3 and/or free/total T4. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid associated eye symptoms/-signs and demographic data were registered.Results: 2916 patients were diagnosed with de novo hyperthyroidism giving the total incidence of 27.6 / 100000 inhabitants/year. The incidence of GD was 21.0/100000 and toxic nodular goiter (TNG=STA + TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5 /100 000. The incidence was higher in women compared to men (4.2:1). 75% of the patients were diagnosed as GD, in whom thyroid associated eye symptoms/-signs occurred at diagnosis in every fifth patient. Geographical differences were observed. Conclusion: The incidence of hyperthyroidism in Sweden is in a lower range compared to international reports. Patients with hyperthyroidism had GD in 75% and 20% of them had thyroid associated eye symptoms/-signs at diagnosis. The observed geographical differences require further studies.
  • Bos, Isabelle, et al. (författare)
  • The frequency and influence of dementia risk factors in prodromal Alzheimer's disease
  • 2017
  • Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 56, s. 33-40
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of 10 risk factors between the subgroups, and used Cox-regression to examine the effect of risk factors on cognitive decline. Depression, obesity, and hypercholesterolemia occurred more often in individuals with low-AD-likelihood, compared with those with a high-AD-likelihood. Only alcohol use increased the risk of cognitive decline, regardless of AD pathology. These results suggest that traditional risk factors for AD are not associated with prodromal AD or with progression to dementia, among subjects with mild cognitive impairment. Future studies should validate these findings and determine whether risk factors might be of influence at an earlier stage (i.e., preclinical) of AD.
  • Mattsson, Niklas, et al. (författare)
  • Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
  • 2018
  • Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
  • Bergenfelz, Anders, et al. (författare)
  • Scandinavian quality register for thyroid and parathyroid surgery: audit of surgery for primary hyperparathyroidism.
  • 2007
  • Ingår i: Langenbeck's Archives of Surgery. - : Springer. - 1435-2451. ; 392:4, s. 445-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aim Scandinavian Quality Register for Thyroid and Parathyroid Surgery is an on-line web-based database with the aim to improve the quality of thyroid and parathyroid surgery. Preliminary data from surgery for primary hyperparathyroidism are reported here. Materials and methods Fifteen departments registered 806 operations, with 639 women (79.7%) and 167 men. The median age of the patients was 62 years. Results Approximately 95.4% of the patients had sporadic disease and first time operation was performed in 93.8% of the patients. Localization examinations were performed in 524 patients (65%); sestamibi scintigraphy in 413 patients, with a true positive adenoma localization in 64.4% and ultrasound in 293 patients with adenoma localization in 61.1%. Bilateral neck exploration was performed in 66.8%, unilateral exploration in 16.1%, and focused minimal invasive surgery in 17.1%. In 301 patients planned for limited parathyroid exploration, conversion to bilateral neck surgery occurred in 11%. The cure rate, based on short follow-up, was 91.9%. Postoperative hypocalcemia occurred in 11.4% of the patients, and was associated with reoperation, concomitant thyroid operation, and the weight of excised parathyroid tissue. Conclusion Localization examinations are performed in 2/3 of the patients, but limited neck exploration was performed in only approximately 1/3 of the operations. The cure rate was lower and postoperative hypocalcemia was more frequent than expected.
  • Jansen, Willemijn J, et al. (författare)
  • Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
  • 2018
  • Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P < .001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P < .001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
  • Al-Adwani, S., et al. (författare)
  • Studies on citrullinated LL-37: detection in human airways, antibacterial effects and biophysical properties
  • 2020
  • Ingår i: Scientific Reports. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Arginine residues of the antimicrobial peptide LL-37 can be citrullinated by peptidyl arginine deiminases, which reduce the positive charge of the peptide. Notably, citrullinated LL-37 has not yet been detected in human samples. In addition, functional and biophysical properties of citrullinated LL-37 are not fully explored. The aim of this study was to detect citrullinated LL-37 in human bronchoalveolar lavage (BAL) fluid and to determine antibacterial and biophysical properties of citrullinated LL-37. BAL fluid was obtained from healthy human volunteers after intra-bronchial exposure to lipopolysaccharide. Synthetic peptides were used for bacterial killing assays, transmission electron microscopy, isothermal titration calorimetry, mass-spectrometry and circular dichroism. Using targeted proteomics, we were able to detect both native and citrullinated LL-37 in BAL fluid. The citrullinated peptide did not kill Escherichia coli nor lysed human red blood cells. Both peptides had similar α-helical secondary structures but citrullinated LL-37 was more stable at higher temperatures, as shown by circular dichroism. In conclusion, citrullinated LL-37 is present in the human airways and citrullination impaired bacterial killing, indicating that a net positive charge is important for antibacterial and membrane lysing effects. It is possible that citrullination serves as a homeostatic regulator of AMP-function by alteration of key functions. © 2020, The Author(s).
  • Bergenfelz, Anders O J, et al. (författare)
  • Impact of modern techniques on short-term outcome after surgery for primary hyperparathyroidism: a multicenter study comprising 2,708 patients.
  • 2009
  • Ingår i: Langenbeck's archives of surgery / Deutsche Gesellschaft für Chirurgie. - : Springer. - 1435-2451. ; 394:5, s. 851-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Preoperative localization procedures and the use of intraoperative parathyroidism (iOPTH) have led to a shift of paradigm from bilateral neck exploration to focused parathyroidectomy in primary hyperparathyroidism (pHPT). However, only a small number of randomized trials from specialized centers have been published. The main purpose of the study was to analyze the impact of localization procedures and iOPTH on short-term outcome after pHPT surgery in a multi-institutional setting.
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