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  • Cavallin, L, et al. (författare)
  • Overtime reliability of medial temporal lobe atrophy rating in a clinical setting
  • 2012
  • Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 53:3, s. 318-323
  • Tidskriftsartikel (refereegranskat)abstract
    • Medial temporal lobe atrophy (MTA) is one of the first magnetic resonance imaging (MRI) signs in patients with Alzheimer's disease (AD) and used as a measure of disease progression. Visual assessment of MTA is easy to perform but the reliability of MTA rating over time has not been studied. Purpose To investigate what happens to the MTA rating scores if two radiologists rate the same MRI scans six times over a period of 1 year. Material and Methods One hundred outpatients were included in this study. All patients underwent MRI with a protocol and sequences used for geriatric patients, according to local clinical standards. One neuroradiologist and one general radiologist independently of each other performed retrospective visual assessments of MTA six times, using the same scans, over a period of 1 year. Results Intra-rater kappa varied between κ 0.65 and 0.84 for the neuroradiologist and κ 0.38 and 0.74 for the general radiologist. Intra-rater weighted kappa (wκ) values showed almost perfect agreement for both investigators (wκ 0.83–0.94). Inter-rater reliability showed fair to moderate agreement, with the kappa value varying from κ 0.29 to 0.48 and weighted kappa values ranging from wκ 0.72 to 0.84. There was a statistically significant difference in rating between the two investigators. Conclusion Visual assessment of MTA repeated over time has a high grade of reproducibility when performed by an experienced investigator. The reproducibility drops when assessment is rarely performed. Inter-rater reliability is low when two investigators not working together are compared.
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  • Goncalves-Pereira, M, et al. (författare)
  • [Needs for Care and Service Use in Dementia: Baseline Assessment of Portuguese Participants in the Actifcare Cohort Study]
  • 2019
  • Ingår i: Acta medica portuguesa. - : Ordem dos Medicos. - 1646-0758 .- 0870-399X. ; 32:5, s. 355-367
  • Tidskriftsartikel (refereegranskat)abstract
    • Introdução: As pessoas com demência e os seus familiares deveriam ter acesso atempado a cuidados formais na comunidade (centros de dia, apoio domiciliário). O projecto EU-Actifcare investigou o acesso/utilização destes serviços em países europeus. Descrevemos a implementação do estudo de coorte e a avaliação inicial em Portugal, com foco nas necessidades de cuidados e recurso aos serviços.Material e Métodos: Selecionámos uma amostra de conveniência de 66 pessoas com diagnóstico de demência ligeira a moderada (residindo na comunidade sem cuidados formais relevantes) e respetivos familiares-cuidadores. A avaliação (clínico-funcional e social) incluiu os instrumentos Camberwell Assessment of Need for the Elderly e Resource Utilization in Dementia.Resultados: Identificámos necessidades não-cobertas dos doentes (média 1,1; DP = 1,7), principalmente de companhia (23% dos casos), sofrimento psicológico (20%) e atividades diárias (14%). Os familiares-cuidadores dedicavam 150 minutos/dia (mediana) à prestação de cuidados e 44% apresentavam necessidades não-cobertas de sofrimento psicológico. Quando havia problemas de acesso/utilização dos serviços de saúde e sociais na comunidade, estes estavam frequentemente relacionados com recusa ou desconhecimento de utentes/familiares.Discussão: A seleção dos participantes não foi fácil, pela especificidade dos critérios adotados. Não almejando representatividade nacional, recrutámos uma amostra típica de pessoas em estádios ligeiros a moderados de demência, em serviços e regiões diferentes. Nalguns casos, encontrámos necessidades não-cobertas e repercussões familiares que já justificariam respostas de serviços na comunidade, não fossem os problemas de acesso/utilização.Conclusão: Na área das demências, existem dificuldades no acesso atempado e utilização efectiva de cuidados formais, coexistindo com uma cobertura menor de necessidades específicas.
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  • Mulrooney, Elisabeth, et al. (författare)
  • The associations of psychological symptoms and cognitive patterns with pain and pain sensitization in people with hand osteoarthritis
  • 2022
  • Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 4:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To examine whether psychological symptoms and cognitive patterns are associated with self-reported pain and pain sensitization in people with hand osteoarthritis (OA). Design: In the Nor-Hand study (n ​= ​300), people with hand OA self-reported psychological symptoms (Hospital Anxiety and Depression Scale), cognitive patterns (Pain catastrophizing Scale and Arthritis Self-Efficacy Scale) as well as their pain severity in hands, overall pain and multi-joint pain. Central pain sensitization was measured clinically by temporal summation and pressure pain threshold tests. We examined whether psychological symptoms and cognitive patterns were cross-sectionally associated with pain using linear regression. Beta coefficients (β) per one standard deviation of the independent variable were presented. Stratified analyses were performed in cases of significant interactions (p ​< ​0.10). Results: Higher levels of anxiety, depressive symptoms and pain catastrophizing and low levels of self-efficacy were statistically significantly associated with higher levels of hand pain by Numeric Rating Scale (β ​= ​0.43, 0.48 and −0.57, respectively). Similar associations were found for overall pain, but not for measures of central pain sensitization. In stratified analyses, anxiety and depressive symptoms were more strongly related with pain in subgroups with younger age and higher comorbidity burden. Pain catastrophizing was more strongly related with pain in subgroups with younger age, overweight/obesity, higher comorbidity burden and poor sleep. Conclusion: Psychological symptoms and cognitive patterns were associated with self-reported OA pain, especially in people with younger age, overweight/obesity, higher comorbidity burden and poor sleep. No associations were found for psychological symptoms and cognitive patterns with pain sensitization.
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  • Persson, K, et al. (författare)
  • Comparison of automated volumetry of the hippocampus using NeuroQuant® and visual assessment of the medial temporal lobe in Alzheimer's disease
  • 2018
  • Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 59:8, s. 997-1001
  • Tidskriftsartikel (refereegranskat)abstract
    • Different clinically feasible methods for evaluation of medial temporal lobe atrophy exists and are useful in diagnostic work-up of Alzheimer’s disease (AD). Purpose To compare the diagnostic properties of two clinically available magnetic resonance imaging (MRI)-based methods—an automated volumetric software, NeuroQuant® (NQ) (evaluation of hippocampus volume) and the Scheltens scale (visual evaluation of medial temporal lobe atrophy [MTA])—in patients with AD dementia, and subjective and mild cognitive impairment (non-dementia). Material and Methods MRIs from 56 patients (31 AD, 25 non-dementia) were assessed with both methods. Correlations between the methods were calculated and receiver operating curve (ROC) analyses that yield area under the curve (AUC) statistics were conducted. Results High correlations were found between the two MRI assessments for the total hippocampal volume measured with NQ and mean MTA score (–0.753, P < 0.001), for the right (–0.767, P < 0.001), and for the left (–0.675, P < 0.001) sides. The NQ total measure yielded somewhat higher AUC (0.88, “good”) compared to the MTA mean measure (0.80, “good”) in the comparison of patients with AD and non-dementia, but the accuracy was in favor of the MTA scale. Conclusion The two methods correlated highly and both methods reached equally “good” power.
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  • Persson, K, et al. (författare)
  • Visual Evaluation of Medial Temporal Lobe Atrophy as a Clinical Marker of Conversion from Mild Cognitive Impairment to Dementia and for Predicting Progression in Patients with Mild Cognitive Impairment and Mild Alzheimer's Disease
  • 2017
  • Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 44:1-2, s. 12-24
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background/Aims:</i></b> To evaluate whether visual assessment of medial temporal lobe atrophy (vaMTA) can predict 2-year conversion from mild cognitive impairment (MCI) to dementia and progression of MCI and Alzheimer's disease dementia as measured by the Clinical Dementia Rating Scale Sum of Boxes score (CDR-SB). <b><i>Methods:</i></b> vaMTA was performed in 94 patients with MCI according to the Winblad criteria and in 124 patients with AD according to ICD-10 and NINCDS-ADRDA criteria. Demographic data, the Consortium to Establish a Registry for Alzheimer's Disease 10-word delayed recall, APOE &#x025B;4 status, Cornell Scale for Depression in Dementia, and comorbid hypertension were used as covariates. <b><i>Results:</i></b> vaMTA was associated with MCI conversion in an unadjusted model but not in an adjusted model (<i>p</i> = 0.075), where delayed recall and APOE &#x025B;4 status were significant predictors. With CDR-SB change as the outcome, an interaction between vaMTA and diagnosis was found, but in the adjusted model only delayed recall and age were significant predictors. For vaMTA below 2, the association between vaMTA and CDR-SB change differed between diagnostic groups. Similar results were found based on a trajectory analysis. <b><i>Conclusion:</i></b> In adjusted models, memory function, APOE &#x025B;4 status and age were significant predictors of disease progression, not vaMTA. The association between vaMTA and CDR-SB change was different in patients with MCI and Alzheimer's disease dementia.
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  • Stephan, Astrid, et al. (författare)
  • Barriers and facilitators to the access to and use of formal dementia care : findings of a focus group study with people with dementia, informal carers and health and social care professionals in eight European countries
  • 2018
  • Ingår i: BMC Geriatrics. - : BioMed Central. - 1471-2318. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: People with dementia and informal carers often access formal care late in the process of dementia. The barriers and facilitators to service use from the perspectives of different stakeholders involved are not well understood. Thus, we aimed to explore the barriers and facilitators of access to and utilisation of formal care from the perspectives of people with dementia, their informal carers and health and social care professionals.METHOD: Focus groups with people with dementia, informal carers and professionals were conducted in eight European countries. Recruitment targeted people with dementia, informal carers with experience of formal care and professionals involved in providing (access to) formal care. Qualitative content analysis using open coding was used on a national level. Cross-national synthesis was based on the translated national reports.RESULTS: Overall, 55 focus groups with 261 participants were conducted, involving 51 people with dementia, 96 informal carers and 114 professionals. Sixteen categories describing barriers and facilitators were identified, referring to three global themes: Aspects related to 1) individuals involved, 2) the system or 3) overarching aspects. The attitudes and beliefs of people with dementia and their carers may have a major impact, and they often serve as barriers. Formal care was perceived as a threat to the individual independence of people with dementia and was thus avoided as long as possible. A healthcare professional serving as a constant key contact person could be an essential facilitator to overcome these barriers. Contact should be initiated proactively, as early as possible, and a trusting and consistent relationship needs to be established. Beyond that, the findings largely confirm former research and show that barriers to accessing and using formal care still exist across Europe despite a number of national and European initiatives.CONCLUSION: Further investigations are needed to elaborate how the concept of a key contact person could be integrated with existing case management approaches and how the independence and autonomy of people with dementia can be strengthened when formal care needs to be accessed and used. These may be meaningful facilitators regarding enhanced access to formal care for people with dementia and their families.
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  • Witoelar, A, et al. (författare)
  • Meta-analysis of Alzheimer's disease on 9,751 samples from Norway and IGAP study identifies four risk loci
  • 2018
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 18088-
  • Tidskriftsartikel (refereegranskat)abstract
    • A large fraction of genetic risk factors for Alzheimer’s Disease (AD) is still not identified, limiting the understanding of AD pathology and study of therapeutic targets. We conducted a genome-wide association study (GWAS) of AD cases and controls of European descent from the multi-center DemGene network across Norway and two independent European cohorts. In a two-stage process, we first performed a meta-analysis using GWAS results from 2,893 AD cases and 6,858 cognitively normal controls from Norway and 25,580 cases and 48,466 controls from the International Genomics of Alzheimer’s Project (IGAP), denoted the discovery sample. Second, we selected the top hits (p < 1 × 10−6) from the discovery analysis for replication in an Icelandic cohort consisting of 5,341 cases and 110,008 controls. We identified a novel genomic region with genome-wide significant association with AD on chromosome 4 (combined analysis OR = 1.07, p = 2.48 x 10-8). This finding implicated HS3ST1, a gene expressed throughout the brain particularly in the cerebellar cortex. In addition, we identified IGHV1-68 in the discovery sample, previously not associated with AD. We also associated USP6NL/ECHDC3 and BZRAP1-AS1 to AD, confirming findings from a follow-up transethnic study. These new gene loci provide further evidence for AD as a polygenic disorder, and suggest new mechanistic pathways that warrant further investigation.
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  • Arsland, D, et al. (författare)
  • [Antipsychotic agents--not to patients with dementia?]
  • 1999
  • Ingår i: Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke. - 0029-2001. ; 119:2, s. 263-4
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Engedal, K, et al. (författare)
  • Quantitative EEG Applying the Statistical Recognition Pattern Method: A Useful Tool in Dementia Diagnostic Workup
  • 2015
  • Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 40:1-2, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background/Aim:</i></b> The aim of this study was to examine the discriminatory power of quantitative EEG (qEEG) applying the statistical pattern recognition (SPR) method to separate Alzheimer's disease (AD) patients from elderly individuals without dementia and from other dementia patients. <b><i>Methods:</i></b> The participants were recruited from 6 Nordic memory clinics: 372 unselected patients [mean age 71.7 years (SD 8.6), 54% women] and 146 healthy elderly individuals [mean age 66.5 years (SD 7.7), 60% women]. After a standardized and comprehensive assessment, clinical diagnoses were made according to internationally accepted criteria by at least 2 clinicians. EEGs were recorded in a standardized way and analyzed independently of the clinical diagnoses, using the SPR method. <b><i>Results:</i></b> In receiver operating characteristic curve analyses, the qEEGs separated AD patients from healthy elderly individuals with an area under the curve (AUC) of 0.90, representing a sensitivity of 84% and a specificity of 81%. The qEEGs further separated patients with Lewy body dementia or Parkinson's disease dementia from AD patients with an AUC of 0.9, a sensitivity of 85% and a specificity of 87%. <b><i>Conclusion:</i></b> qEEG using the SPR method could be a useful tool in dementia diagnostic workup.
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  • Engedal, K, et al. (författare)
  • The Power of EEG to Predict Conversion from Mild Cognitive Impairment and Subjective Cognitive Decline to Dementia
  • 2020
  • Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 49:1, s. 38-47
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Introduction:</i></b> The aim of this study was to examine if quantitative electroencephalography (qEEG) using the statistical pattern recognition (SPR) method could predict conversion to dementia in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). <b><i>Methods:</i></b> From 5 Nordic memory clinics, we included 47 SCD patients, 99 MCI patients, and 67 healthy controls. EEGs analyzed with the SPR method together with clinical data recorded at baseline were evaluated. The patients were followed up for a mean of 62.5 (SD 17.6) months and reexamined. <b><i>Results:</i></b> Of 200 participants with valid clinical information, 70 had converted to dementia, and 52 had developed Alzheimer’s disease. Receiver-operating characteristic analysis of the EEG results as defined by a dementia index (DI) ranging from 0 to 100 revealed that the area under the curve was 0.78 (95% CI 0.70–0.85), corresponding to a sensitivity of 71%, specificity of 69%, and accuracy of 69%. A logistic regression analysis showed that by adding results of a cognitive test at baseline to the EEG DI, accuracy could improve. <b><i>Conclusion:</i></b> We conclude that applying qEEG using the automated SPR method can be helpful in identifying patients with SCD and MCI that have a high risk of converting to dementia over a 5-year period. As the discriminant power of the method is of moderate degree, it should be used in addition to routine diagnostic methods.
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  • Ferreira, D, et al. (författare)
  • Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers
  • 2016
  • Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 42:1-2, s. 80-92
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background/Aims:</i></b> Dementia biomarkers that are accessible and easily applicable in nonspecialized clinical settings are urgently needed. Quantitative electroencephalography (qEEG) is a good candidate, and the statistical pattern recognition (SPR) method has recently provided promising results. We tested the diagnostic value of qEEG-SPR in comparison to cognition, structural imaging, and cerebrospinal fluid (CSF) biomarkers. <b><i>Methods:</i></b> A total of 511 individuals were recruited from the multicenter NORD EEG study [141 healthy controls, 64 subjective cognitive decline, 124 mild cognitive impairment, 135 Alzheimer's disease (AD), 15 dementia with Lewy bodies/Parkinson's disease with dementia (DLB/PDD), 32 other dementias]. The EEG data were recorded in a standardized way. Structural imaging data were visually rated using scales of atrophy in the medial temporal, frontal, and posterior cortex. <b><i>Results:</i></b> qEEG-SPR outperformed structural imaging, cognition, and CSF biomarkers in DLB/PDD diagnosis, outperformed structural imaging in AD diagnosis, and improved the differential diagnosis of AD. In addition, qEEG-SPR allowed differentiation of two clinically different AD subtypes. <b><i>Conclusion:</i></b> Adding qEEG to the diagnostic workup substantially increases the detection of AD pathology even in pre-dementia stages and improves differential diagnosis. EEG could serve as a good complement to currently established dementia biomarkers since it is cheap, noninvasive, and extensively applied outside academic centers.
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  • Gaarden, T. L., et al. (författare)
  • Exploration of 27 plasma immune markers: a cross-sectional comparison of 64 old psychiatric inpatients having unipolar major depression and 18 non-depressed old persons
  • 2018
  • Ingår i: BMC Geriatr. - : Springer Science and Business Media LLC. - 1471-2318. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prevalence of major depression (MD) according to population studies is the same for old (65 years and older) and younger adults. In contrast, an elevated proportion of old MD patients are hospitalized compared to younger adults with MD, indicating a need to expand the characteristics of old inpatients with MD. To illustrate this point, the association between inflammation and MD in old psychiatric inpatients is sparsely investigated even though an association between inflammation and treatment resistance among younger adults with MD has been reported. In this study, we aimed to explore the plasma concentrations of 27 immune markers in old inpatients with MD, and our purpose was to expand the understanding of inflammatory mechanisms in these patients. Methods: Prior to electroconvulsive treatment of MD, we compared 64 inpatients with unipolar MD (mean age 75.2 years) and 18 non-depressed controls (mean age 78.0 years). Symptoms characterizing MD were assessed by the Hamilton Rating Scale of Depression (HRSD)-17, and the immune markers from peripheral blood plasma were analysed using multiplex assay technology. For statistical analysis of data, we used the independent samples median test, independent samples t-test, chi(2)-test, receiver operating characteristic curve analyses, stepwise discriminant analysis, and multivariate linear regression. Results: Twenty-two immune markers representing pro-and anti-inflammatory, adaptive and trophic signalling had higher concentrations in the inpatients compared to the controls. Only the four immune markers IL-1 beta, IL-5, IL-10 and IL-15 had concentrations below the lower detection limit in a considerable portion (above 20%) of the patient cases. A combination of the concentration in plasma of TNF, vascular endothelial growth factor (VEGF), IL-1 beta, IL-7 and monocyte chemotactic protein (MCP)-1, correctly classified 98.4% of the depressed patients and 83.3% of the non-depressed controls. Plasma concentration of TNF and VEGF were associated with the HRSD-17 scores (p = 0.017 and 0.005, respectively). Conclusions: Our results indicate that several inflammatory mechanisms may be highly activated in old psychiatric inpatients with MD, and indicate that immune markers may contribute to a more comprehensive understanding of MD in old persons.
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  • Ommundsen, N, et al. (författare)
  • Validity of the quantitative EEG statistical pattern recognition method in diagnosing Alzheimer's disease
  • 2011
  • Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 31:3, s. 195-201
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Aims:</i> To evaluate the use of quantitative EEG (qEEG) statistical pattern recognition in diagnosing Alzheimer’s disease (AD). <i>Methods:</i> qEEG was performed on 104 patients referred to a memory clinic. The qEEG results were compared to the clinical diagnosis made without access to the EEG results. <i>Results:</i> Of 30 patients with a clinical diagnosis of AD, 22 were test positive. Of the 74 patients without AD, 34 were test negative. The qEEG result was found to correlate with atrophy of the medial temporal lobe demonstrated on cerebral MRI (p = 0.002) and with scores on neuropsychological tests. <i>Conclusion:</i> The qEEG was poor at diagnosing AD, as it produced many false-positive results.
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  • Schjønning Nielsen, M, et al. (författare)
  • Quantitative Electroencephalography Analyzed by Statistical Pattern Recognition as a Diagnostic and Prognostic Tool in Mild Cognitive Impairment: Results from a Nordic Multicenter Cohort Study
  • 2018
  • Ingår i: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 8:3, s. 426-438
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Aim:</i></b> To examine diagnostic and prognostic potential of quantitative electroencephalography (qEEG) analyzed by the statistical pattern recognition (SPR) method in patients with cognitive impairment. We compared the differential diagnostic ability of SPR to visual EEG analysis. Correlation between SPR findings and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers were evaluated. <b><i>Methods:</i></b> It is a multicenter cohort study involving 129 patients, (mild cognitive impairment [MCI], AD, and healthy controls). Standardized EEG was performed at baseline. Patients were continuously clinically evaluated. <b><i>Results:</i></b> Receiver Operating Characteristic curves showed a low discriminative ability of SPR and no ability to predict clinical progression in patients with MCI. Moderate correlation between SPR analysis and CSF AD biomarkers was found. <b><i>Conclusion:</i></b> The diagnostic and prognostic abilities of qEEG were low. The SPR method was superior to the visual EEG analysis. The qEEG method correlates well to CSF AD biomarkers, suggesting association with pathology in AD.
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  • Vdovikova, Svitlana, et al. (författare)
  • A Novel Role of Listeria monocytogenes Membrane Vesicles in Inhibition of Autophagy and Cell Death
  • 2017
  • Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Bacterial membrane vesicle (MV) production has been mainly studied in Gram-negative species. In this study, we show that Listeria monocytogenes, a Gram-positive pathogen that causes the food-borne illness listeriosis, produces MVs both in vitro and in vivo. We found that a major virulence factor, the pore-forming hemolysin listeriolysin O (LLO), is tightly associated with the MVs, where it resides in an oxidized, inactive state. Previous studies have shown that LLO may induce cell death and autophagy. To monitor possible effects of LLO and MVs on autophagy, we performed assays for LC3 lipidation and LDH sequestration as well as analysis by confocal microscopy of HEK293 cells expressing GFP-LC3. The results revealed that MVs alone did not affect autophagy whereas they effectively abrogated autophagy induced by pure LLO or by another pore-forming toxin from Vibrio cholerae, VCC. Moreover, Listeria monocytogenes MVs significantly decreased Torin1-stimulated macroautophagy. In addition, MVs protected against necrosis of HEK293 cells caused by the lytic action of LLO. We explored the mechanisms of LLO-induced autophagy and cell death and demonstrated that the protective effect of MVs involves an inhibition of LLO-induced pore formation resulting in inhibition of autophagy and the lytic action on eukaryotic cells. Further, we determined that these MVs help bacteria to survive inside eukaryotic cells (mouse embryonic fibroblasts). Taken together, these findings suggest that intracellular release of MVs from L. monocytogenes may represent a bacterial strategy to survive inside host cells, by its control of LLO activity and by avoidance of destruction from the autophagy system during infection.
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  • Vossius, C., et al. (författare)
  • Cost analysis of day care centres in Norway
  • 2019
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 14:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Day care services aim to offer meaningful activities and a safe environment for the attendees and a respite for family caregivers while being cost effective. This study compares the use of formal and informal care in users and non-users of day care centres designed for persons with dementia. Method Users of day care designed for dementia (DC group) and non-users (NDC group) were followed over a period of 24 months or until nursing home admission (NHA) respectively death. Demographic and clinical characteristics were collected at baseline and after 12 and 24 months. The use of care was recorded by Resource Utilization in Dementia (RUD). Results A total of 257 persons with dementia participated in the study, 181 in the DC group and 76 in the NDC group. Users of day care centres cause higher costs due to the expenses for day care, while neither the use of home nursing, secondary care, informal care nor the time until NHA did show any differences between users and non-users. The overall costs were higher in the DC group at baseline and after 12 months, but this difference was no longer present at the end of the two-year study period. Conclusion Our results indicate no potential cost-saving effect of day care designed for people with dementia, as the use of day care did neither result in a reduced use of care nor in a delay of NHA. Future research should balance the non-monetary benefits of day care against its costs for a full cost-effectiveness analysis, most favourable in a RCT-design.
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  • Wimo, A, et al. (författare)
  • An economic evaluation of donepezil in mild to moderate Alzheimer's disease: results of a 1-year, double-blind, randomized trial
  • 2003
  • Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 15:1, s. 44-54
  • Tidskriftsartikel (refereegranskat)abstract
    • The costs and consequences of donepezil versus placebo treatment in patients with mild to moderate Alzheimer’s disease (AD) were evaluated as part of a 1-year prospective, double-blind, randomized, multinational clinical trial. Patients received either donepezil (n = 142; 5 mg/day for 28 days followed by 10 mg/day according to the clinician’s judgement) or placebo (n = 144). Unit costs were assessed in 1999 Swedish kronas (SEK) and converted to US dollars (USD). Donepezil-treated patients gained functional benefits relative to placebo on the Progressive Deterioration Scale (p = 0.042) and Instrumental Activities of Daily Living scale (p = 0.025) at week 52. Caregivers of donepezil-treated patients spent an average of 400 h less annually providing care than caregivers of placebo-treated patients. Mean annual healthcare costs were SEK 137,752 (USD 16,438) per patient for the donepezil group and SEK 135,314 (USD 16,147) in the placebo group. With the average annual cost of donepezil at SEK 10,723 (USD 1,280) per patient, the SEK 2,438 (USD 291) cost difference represented a 77% cost offset. When caregiver time and healthcare costs were included, mean annual costs were SEK 209,244 (USD 24,969) per patient in the donepezil group and SEK 218,434 (USD 26,066) in the placebo group, a total saving associated with donepezil treatment of SEK 9,190 (USD 1,097) per patient [95% CI of SEK –43,959 (USD –5,246), SEK 25,581 (USD 3,053); p = 0.6]. The positive effects on the efficacy outcome measures combined with no additional costs from a societal perspective indicate that donepezil is a cost-effective treatment, representing an improved strategy for the management of patients with AD.
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  • Winblad, B, et al. (författare)
  • 3-year study of donepezil therapy in Alzheimer's disease: effects of early and continuous therapy
  • 2006
  • Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 21:5-6, s. 353-363
  • Tidskriftsartikel (refereegranskat)abstract
    • Delays in the diagnosis of Alzheimer’s disease, and, therefore, delays in treatment, may have a detrimental effect on a patient’s long-term well-being. This studyassessed the effects of postponing donepezil treatment for 1 year by comparing patients treated continuously for 3 years with those who received placebo for 1 year followed by open-label donepezil for 2 years. Patients (n = 286) with possible or probable Alzheimer’s disease (according to DSM-IV, NINCDS-ADRDA, and Mini-Mental State Examination criteria; see text) were randomized to receive donepezil (5 mg/day for 4 weeks, 10 mg/day thereafter) or placebo (delayed-start group) for 1 year. Of the 192 completers, 157 began a 2-year, open-label phase of donepezil treatment. Outcome measures were the Gottfries-Bråne-Steen scale, the Mini-Mental State Examination, the Global Deterioration Scale, the Progressive Deterioration Scale, the Neuropsychiatric Inventory, and safety (adverse events). Mixed regression analysis was used to compare changes between the groups over 3 years on the efficacy measures. There was a trend for patients receiving continuous therapy to have less global deterioration (Gottfries-Bråne-Steen scale) than those who had delayed treatment (p = 0.056). Small but statistically significant differences between the groups were observed for the secondary measures of cognitive function (Mini-Mental State Examination; p<i> = </i>0.004) and cognitive and functional abilities (Global Deterioration Scale; p = 0.0231) in favor of continuous donepezil therapy. Over 90% of the patients in both cohorts experienced one treatment-emergent adverse event; most were considered mild or moderate. In conclusion, patients in whom the start of treatment is delayed may demonstrate slightly reduced benefits as compared with those seen in patients starting donepezil therapy early in the course of Alzheimer’s disease. These data support the long-term efficacy and safety of donepezil.
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46.
  • Winblad, B, et al. (författare)
  • A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD
  • 2001
  • Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 57:3, s. 489-495
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate the long-term clinical efficacy and safety of donepezil versus placebo over 1 year in patients with mild to moderate AD.Methods: Patients (n = 286; mean age, 72.5 years) with possible or probable AD from five Northern European countries were randomized to receive either donepezil (n = 142; 5 mg/day for 28 days, followed by 10 mg/day) or placebo (n = 144) for 1 year.Results: The study was completed by 66.9% of the donepezil- and 67.4% of the placebo-treated patients. The benefit of donepezil over placebo was demonstrated by the Gottfries-Bråne-Steen (a global assessment for rating dementia symptoms) total score at weeks 24, 36, and 52 (p < 0.05) and at the study end point (week 52, last observation carried forward; p = 0.054). Advantages of donepezil over placebo were also observed in cognition and activities of daily living (ADL) assessed by the Mini-Mental State Examination at weeks 24, 36, and 52, and the end point (p < 0.02) and by the Progressive Deterioration Scale at week 52 and the end point (p < 0.05). Adverse events (AE) were recorded for 81.7% of donepezil- and 75.7% of placebo-treated patients, with 7% of donepezil- and 6.3% of placebo-treated patients discontinuing because of AE. Treatment response to donepezil was not predicted by APOE genotype or sex in this population.Conclusion: As the first 1-year, multinational, double-blinded, placebo-controlled study of a cholinesterase inhibitor in AD, these data support donepezil as a well tolerated and effective long-term treatment for patients with AD, with benefits over placebo on global assessment, cognition, and ADL.
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