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  • van der Lee, S. J., et al. (författare)
  • A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
  • 2019
  • Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 237-250
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLC gamma 2 pathway as drug-target.
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  • Sweeney, M. D., et al. (författare)
  • Vascular dysfunction-The disregarded partner of Alzheimer's disease
  • 2019
  • Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:1, s. 158-167
  • Tidskriftsartikel (refereegranskat)abstract
    • Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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  • Vermunt, L., et al. (författare)
  • Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype
  • 2019
  • Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:7, s. 888-898
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: We estimated the age-specific duration of the preclinical, prodromal, and dementia stages of Alzheimer's disease (AD) and the influence of sex, setting, apolipoprotein E (APOE) genotype, and cerebrospinal fluid tau on disease duration. Methods: We performed multistate modeling in a combined sample of 6 cohorts (n = 3268) with death as the end stage and estimated the preclinical, prodromal, and dementia stage duration. Results: The overall AD duration varied between 24 years (age 60) and 15 years (age 80). For individuals presenting with preclinical AD, age 70, the estimated preclinical AD duration was 10 years, prodromal AD 4 years, and dementia 6 years. Male sex, clinical setting, APOE epsilon 4 allele carriership, and abnormal cerebrospinal fluid tau were associated with a shorter duration, and these effects depended on disease stage. Discussion: Estimates of AD disease duration become more accurate if age, sex, setting, APOE, and cerebrospinal fluid tau are taken into account. This will be relevant for clinical practice and trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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  • Sachdev, P. S., et al. (författare)
  • STROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease
  • 2017
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 7, s. 11-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). Methods Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. Results Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3months to 21years. Discussion Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes. © 2016 The Authors
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  • Aguilar, C., et al. (författare)
  • Automated CT-based segmentation and quantification of total intracranial volume
  • 2015
  • Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 25:11, s. 3151-3160
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To develop an algorithm to segment and obtain an estimate of total intracranial volume (tICV) from computed tomography (CT) images. Materials and methods Thirty-six CT examinations from 18 patients were included. Ten patients were examined twice the same day and eight patients twice six months apart (these patients also underwent MRI). The algorithm combines morphological operations, intensity thresholding and mixture modelling. The method was validated against manual delineation and its robustness assessed from repeated imaging examinations. Using automated MRI software, the comparability with MRI was investigated. Volumes were compared based on average relative volume differences and their magnitudes; agreement was shown by a Bland-Altman analysis graph. Results We observed good agreement between our algorithm and manual delineation of a trained radiologist: the Pearson's correlation coefficient was r = 0.94, tICVml[manual] = 1.05 x tICVml[automated] - 33.78 (R-2 = 0.88). Bland-Altman analysis showed a bias of 31 mL and a standard deviation of 30 mL over a range of 1265 to 1526 mL. Conclusions tICV measurements derived from CT using our proposed algorithm have shown to be reliable and consistent compared to manual delineation. However, it appears difficult to directly compare tICV measures between CT and MRI.
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11.
  • Andersen, Oluf, 1941, et al. (författare)
  • Diffusion tensor imaging in multiple sclerosis at different final outcomes
  • 2018
  • Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 137:2, s. 165-173
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES:Methods to evaluate the relative contributions of demyelination vs axonal degeneration over the long-term course of MS are urgently needed. We used magnetic resonance diffusion tensor imaging (DTI) to estimate degrees of demyelination and axonal degeneration in the corpus callosum (CC) in cases of MS with different final outcomes.MATERIALS AND METHODS:We determined DTI measures mean diffusivity (MD), fractional anisotropy (FA), and axial (AD) and radial (RD) diffusivities in the CC of 31 MS patients, of whom 13 presented a secondary progressive course, 11 a non-progressive course, and seven a monophasic course. The study participants were survivors from an incidence cohort of 254 attack-onset MS patients with 50 years of longitudinal follow-up. As reference, we included five healthy individuals without significant morbidity.RESULTS:In patients with secondary progression, compared to all other groups, the corpus callosum showed increased RD and reduced FA, but no change in AD. None of the parameters exhibited differences among non-progressive and monophasic course groups and controls.CONCLUSION:Increased RD was observed in secondary progressive MS, indicating significant myelin loss. Normal RD values observed in the clinically isolated syndrome and non-progressive groups confirm their benign nature. AD was not a characterizing parameter for long-term outcome. Demyelination revealed by increased RD is a distinguishing trait for secondary progression.
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  • Chibnik, L. B., et al. (författare)
  • Trends in the incidence of dementia: design and methods in the Alzheimer Cohorts Consortium
  • 2017
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 32:10, s. 931-938
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies have reported a decline in incidence of dementia which may have large implications for the projected burden of disease, and provide important guidance to preventive efforts. However, reports are conflicting or inconclusive with regard to the impact of gender and education with underlying causes of a presumed declining trend remaining largely unidentified. The Alzheimer Cohorts Consortium aggregates data from nine international population-based cohorts to determine changes in the incidence of dementia since 1990. We will employ Poisson regression models to calculate incidence rates in each cohort and Cox proportional hazard regression to compare 5-year cumulative hazards across study-specific epochs. Finally, we will meta-analyse changes per decade across cohorts, and repeat all analysis stratified by sex, education and APOE genotype. In all cohorts combined, there are data on almost 69,000 people at risk of dementia with the range of follow-up years between 2 and 27. The average age at baseline is similar across cohorts ranging between 72 and 77. Uniting a wide range of disease-specific and methodological expertise in research teams, the first analyses within the Alzheimer Cohorts Consortium are underway to tackle outstanding challenges in the assessment of time-trends in dementia occurrence.
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  • Fyhrquist, N, et al. (författare)
  • Microbe-host interplay in atopic dermatitis and psoriasis
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4703-
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.
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14.
  • Ganguli, M., et al. (författare)
  • Population Neuroscience: Dementia Epidemiology Serving Precision Medicine and Population Health
  • 2018
  • Ingår i: Alzheimer Disease and Associated Disorders. - 0893-0341. ; 32:1, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Over recent decades, epidemiology has made significant contributions to our understanding of dementia, translating scientific discoveries into population health. Here, we propose reframing dementia epidemiology as "population neuroscience," blending techniques and models from contemporary neuroscience with those of epidemiology and biostatistics. On the basis of emerging evidence and newer paradigms and methods, population neuroscience will minimize the bias typical of traditional clinical research, identify the relatively homogenous subgroups that comprise the general population, and investigate broader and denser phenotypes of dementia and cognitive impairment. Long-term follow-up of sufficiently large study cohorts will allow the identification of cohort effects and critical windows of exposure. Molecular epidemiology and omics will allow us to unravel the key distinctions within and among subgroups and better understand individuals' risk profiles. Interventional epidemiology will allow us to identify the different subgroups that respond to different treatment/prevention strategies. These strategies will inform precision medicine. In addition, insights into interactions between disease biology, personal and environmental factors, and social determinants of health will allow us to measure and track disease in communities and improve population health. By placing neuroscience within a real-world context, population neuroscience can fulfill its potential to serve both precision medicine and population health. © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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  • Kern, Silke, et al. (författare)
  • Association of Cerebrospinal Fluid Neurofilament Light Protein With Risk of Mild Cognitive Impairment Among Individuals Without Cognitive Impairment.
  • 2019
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 76:2, s. 187-193
  • Tidskriftsartikel (refereegranskat)abstract
    • Accumulating data suggest that elevated cerebrospinal fluid (CSF) neurofilament light (NfL) and neurogranin (Ng) levels are associated with cognitive decline and may be useful markers of neurodegeneration. However, to our knowledge, previous studies have not assessed these CSF markers in the community, evaluated them with regards to risk of mild cognitive impairment (MCI), or compared their prognostic value with CSF total tau (T-tau) or phosphorylated tau (P-tau).To determine (1) whether CSF NfL and Ng levels were associated with risk of MCI, (2) the effect size of these markers compared with CSF T-tau or P-tau for risk of MCI, and (3) whether CSF amyloid-β (Aβ42) modified these associations.The analyses included 648 participants without cognitive impairment who were enrolled into the prospective population-based Mayo Clinic Study of Aging between January 2004 and December 2015 with available CSF data and at least 1 follow-up visit. Participants were followed up for a median of 3.8 years (interquartile range, 2.6-5.4 years). The CSF NfL and Ng levels were measured using an in-house sandwich enzyme-linked immunosorbent assay. The CSF Aβ42, T-tau, and P-tau levels were measured with automated electrochemiluminescence immunoassays. Cox proportional hazards models, with age as the timescale, were used to assess the association between CSF NfL, Ng, Aβ42, T-tau, or P-tau with risk of MCI after adjusting for sex, education, apolipoprotein E genotype, and the Charlson comorbidity index. To examine CSF Aβ42 as an effect modifier, it was categorized into tertiles; the bottom tertile was defined as having elevated brain amyloid.Risk of MCI.At baseline, the median age of the 648 participants without cognitive impairment was 72.3 years (range, 50.7-95.3 years) and 366 (56.5%) were men; 96 (14.8%) developed incident MCI. Compared with the bottom quartile, the top quartile of CSF NfL was associated with a 3.1-fold increased risk of MCI (hazard ratio, 3.13; 95% CI, 1.36-7.18) in multivariate models. Neither CSF T-tau, P-tau, nor Ng was associated with risk of MCI. There was no interaction between Aβ42 and CSF NfL for risk of MCI.Elevated CSF NfL levels but not CSF T-tau, P-tau or Ng are a risk factor for MCI in a community population and are independent of brain amyloid.
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18.
  • Makenzius, Marlene, et al. (författare)
  • Health disparities based on neighbourhood and social conditions : Open Comparisons-an indicator-based comparative study in Sweden
  • 2019
  • Ingår i: Public Health. - 0033-3506 .- 1476-5616. ; 174, s. 97-101
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The overarching goal of the Swedish public health policy is to create the right societal conditions for good and equitable health throughout the population and to reduce avoidable health inequalities within a generation. The objective of this article is to highlight the main findings of the Open Comparisons in Public Health (OCPH) 2019 study. STUDY DESIGN: The OCPH is a longitudinal indicator-based comparative study, encompassing 39 public health indicators with results from Sweden's 21 regions and 290 municipalities. METHODS: Descriptive statistics and 95% confidence intervals were used to compare results between municipalities, regions and time points. Correlation analysis was used to study the strength of the relationship between the results of municipalities and their socio-economic conditions. RESULTS: Across the population, levels of health are good and have, in some areas, improved over recent decades. However, some significant health disparities remain according to neighbourhood, sex, age and educational background. Health disparities related to the level of education are often larger than those between women and men, and there are larger differences within a region than between regions. Health disparities have, in some cases, increased, such as for life expectancy. CONCLUSION: If health equity is to be achieved, leaders at all levels must collaborate and advocate for political action and local efficient public health interventions to eliminate health disparities as a result of neighbourhood and social conditions.
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  • Sadeghi, Mitra, 1982-, et al. (författare)
  • The use of aortic balloon occlusion in traumatic shock : first report from the ABO trauma registry
  • 2018
  • Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Berlin/Heidelberg. - 1863-9933 .- 1863-9941 .- 1615-3146. ; 44:4, s. 491-501
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a technique for temporary stabilization of patients with non-compressible torso hemorrhage. This technique has been increasingly used worldwide during the past decade. Despite the good outcomes of translational studies, clinical studies are divided. The aim of this multicenter-international study was to capture REBOA-specific data and outcomes.METHODS: REBOA practicing centers were invited to join this online register, which was established in September 2014. REBOA cases were reported, both retrospective and prospective. Demographics, injury patterns, hemodynamic variables, REBOA-specific data, complications and 30-days mortality were reported.RESULTS: Ninety-six cases from 6 different countries were reported between 2011 and 2016. Mean age was 52 ± 22 years and 88% of the cases were blunt trauma with a median injury severity score (ISS) of 41 (IQR 29-50). In the majority of the cases, Zone I REBOA was used. Median systolic blood pressure before balloon inflation was 60 mmHg (IQR 40-80), which increased to 100 mmHg (IQR 80-128) after inflation. Continuous occlusion was applied in 52% of the patients, and 48% received non-continuous occlusion. Occlusion time longer than 60 min was reported as 38 and 14% in the non-continuous and continuous groups, respectively. Complications, such as extremity compartment syndrome (n = 3), were only noted in the continuous occlusion group. The 30-day mortality for non-continuous REBOA was 48%, and 64% for continuous occlusion.CONCLUSIONS: This observational multicenter study presents results regarding continuous and non-continuous REBOA with favorable outcomes. However, further prospective studies are needed to be able to draw conclusions on morbidity and mortality.
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21.
  • Tani, E, et al. (författare)
  • A Review of the Use of Fine-Needle Aspiration Biopsy of Mammary Tumors for Diagnosis and Research
  • 2017
  • Ingår i: Acta cytologica. - : S. Karger AG. - 1938-2650 .- 0001-5547. ; 61:4-5, s. 305-315
  • Tidskriftsartikel (refereegranskat)abstract
    • The article “Aspiration Biopsy of Mammary Tumors in Diagnosis and Research - A Critical Review of 2,200 Cases” by Zajicek et al. [Acta Cytol 1967;11:169-175] is composed of two separate parts as can be seen from the title. Both are, however, of great historical interest. The first describes the early days of fine-needle aspiration cytology diagnosis of breast lesions in particular carcinomas. The results are still impressive with a diagnostic accuracy close to 90%. The second deals with the effect of negative pressure on cell viability during the aspiration procedure. These studies were aimed at evaluating the usefulness of aspirated tumor cells to analyze the effects of therapy and the origin of tumor cells.
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  • Tervaniemi, MH, et al. (författare)
  • NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis
  • 2016
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 22745-
  • Tidskriftsartikel (refereegranskat)abstract
    • Psoriatic skin differs distinctly from normal skin by its thickened epidermis. Most gene expression comparisons utilize full-thickness biopsies, with substantial amount of dermis. We assayed the transcriptomes of normal, lesional and non-lesional psoriatic epidermis, sampled as split-thickness skin grafts, with 5′-end RNA sequencing. We found that psoriatic epidermis contains more mRNA per total RNA than controls and took this into account in the bioinformatic analysis. The approach highlighted innate immunity-related pathways in psoriasis, including NOD-like receptor (NLR) signaling and inflammasome activation. We demonstrated that the NLR signaling genes NOD2, PYCARD, CARD6 and IFI16 are upregulated in psoriatic epidermis and strengthened these findings by protein expression. Interestingly, PYCARD, the key component of the inflammasome, showed an altered expression pattern in the lesional epidermis. The profiling of non-lesional skin highlighted PSORS4 and mitochondrially encoded transcripts, suggesting that their gene expression is altered already before the development of lesions. Our data suggest that all components needed for the active inflammasome are present in the keratinocytes of psoriatic skin. The characterization of inflammasome pathways provides further opportunities for therapy. Complementing previous transcriptome studies, our approach gives deeper insight into the gene regulation in psoriatic epidermis.
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24.
  • Vakkilainen, S, et al. (författare)
  • The human long non-coding RNA gene RMRP has pleiotropic effects and regulates cell-cycle progression at G2
  • 2019
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 13758-
  • Tidskriftsartikel (refereegranskat)abstract
    • RMRP was the first non-coding nuclear RNA gene implicated in a disease. Its mutations cause cartilage-hair hypoplasia (CHH), an autosomal recessive skeletal dysplasia with growth failure, immunodeficiency, and a high risk for malignancies. This study aimed to gain further insight into the role of RNA Component of Mitochondrial RNA Processing Endoribonuclease (RMRP) in cellular physiology and disease pathogenesis. We combined transcriptome analysis with single-cell analysis using fibroblasts from CHH patients and healthy controls. To directly assess cell cycle progression, we followed CHH fibroblasts by pulse-labeling and time-lapse microscopy. Transcriptome analysis identified 35 significantly upregulated and 130 downregulated genes in CHH fibroblasts. The downregulated genes were significantly connected to the cell cycle. Multiple other pathways, involving regulation of apoptosis, bone and cartilage formation, and lymphocyte function, were also affected, as well as PI3K-Akt signaling. Cell-cycle studies indicated that the CHH cells were delayed specifically in the passage from G2 phase to mitosis. Our findings expand the mechanistic understanding of CHH, indicate possible pathways for therapeutic intervention and add to the limited understanding of the functions of RMRP.
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25.
  • Wang, JW, et al. (författare)
  • Investigation of rare and low-frequency variants using high-throughput sequencing with pooled DNA samples
  • 2016
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 33256-
  • Tidskriftsartikel (refereegranskat)abstract
    • High-throughput sequencing using pooled DNA samples can facilitate genome-wide studies on rare and low-frequency variants in a large population. Some major questions concerning the pooling sequencing strategy are whether rare and low-frequency variants can be detected reliably, and whether estimated minor allele frequencies (MAFs) can represent the actual values obtained from individually genotyped samples. In this study, we evaluated MAF estimates using three variant detection tools with two sets of pooled whole exome sequencing (WES) and one set of pooled whole genome sequencing (WGS) data. Both GATK and Freebayes displayed high sensitivity, specificity and accuracy when detecting rare or low-frequency variants. For the WGS study, 56% of the low-frequency variants in Illumina array have identical MAFs and 26% have one allele difference between sequencing and individual genotyping data. The MAF estimates from WGS correlated well (r = 0.94) with those from Illumina arrays. The MAFs from the pooled WES data also showed high concordance (r = 0.88) with those from the individual genotyping data. In conclusion, the MAFs estimated from pooled DNA sequencing data reflect the MAFs in individually genotyped samples well. The pooling strategy can thus be a rapid and cost-effective approach for the initial screening in large-scale association studies.
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  • Wu, Yu-Tzu, et al. (författare)
  • Dementia in western Europe : epidemiological evidence and implications for policy making
  • 2016
  • Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 15:1, s. 116-124
  • Tidskriftsartikel (refereegranskat)abstract
    • Dementia is receiving increasing attention from governments and politicians. Epidemiological research based on western European populations done 20 years ago provided key initial evidence for dementia policy making, but these estimates are now out of date because of changes in life expectancy, living conditions, and health profiles. To assess whether dementia occurrence has changed during the past 20-30 years, investigators of five different studies done in western Europe (Sweden [Stockholm and Gothenburg], the Netherlands [Rotterdam], the UK [England], and Spain [Zaragoza]) have compared dementia occurrence using consistent research methods between two timepoints in well-defined geographical areas. Findings from four of the five studies showed non-significant changes in overall dementia occurrence. The only significant reduction in overall prevalence was found in the study done in the UK, powered and designed explicitly from its outset to detect change across generations (decrease in prevalence of 22%; p=0.003). Findings from the study done in Zaragoza (Spain) showed a significant reduction in dementia prevalence in men (43%; p=0.0002). The studies estimating incidence done in Stockholm and Rotterdam reported non-significant reductions. Such reductions could be the outcomes from earlier population-level investments such as improved education and living conditions, and better prevention and treatment of vascular and chronic conditions. This evidence suggests that attention to optimum health early in life might benefit cognitive health late in life. Policy planning and future research should be balanced across primary (policies reducing risk and increasing cognitive reserve), secondary (early detection and screening), and tertiary (once dementia is present) prevention. Each has their place, but upstream primary prevention has the largest effect on reduction of later dementia occurrence and disability.
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27.
  • Wu, Y. T., et al. (författare)
  • Dementia in western Europe: epidemiological evidence and implications for policy making
  • 2016
  • Ingår i: Lancet Neurology. - : Elsevier BV. - 1474-4422. ; 15:1, s. 116-124
  • Forskningsöversikt (refereegranskat)abstract
    • Dementia is receiving increasing attention from governments and politicians. Epidemiological research based on western European populations done 20 years ago provided key initial evidence for dementia policy making, but these estimates are now out of date because of changes in life expectancy, living conditions, and health profiles. To assess whether dementia occurrence has changed during the past 20-30 years, investigators of five different studies done in western Europe (Sweden [Stockholm and Gothenburg], the Netherlands [Rotterdam], the UK [England], and Spain [Zaragoza]) have compared dementia occurrence using consistent research methods between two timepoints in well-defined geographical areas. Findings from four of the five studies showed non-significant changes in overall dementia occurrence. The only significant reduction in overall prevalence was found in the study done in the UK, powered and designed explicitly from its outset to detect change across generations (decrease in prevalence of 22%; p=0.003). Findings from the study done in Zaragoza (Spain) showed a significant reduction in dementia prevalence in men (43%; p=0.0002). The studies estimating incidence done in Stockholm and Rotterdam reported non-significant reductions. Such reductions could be the outcomes from earlier population-level investments such as improved education and living conditions, and better prevention and treatment of vascular and chronic conditions. This evidence suggests that attention to optimum health early in life might benefit cognitive health late in life. Policy planning and future research should be balanced across primary (policies reducing risk and increasing cognitive reserve), secondary (early detection and screening), and tertiary (once dementia is present) prevention. Each has their place, but upstream primary prevention has the largest effect on reduction of later dementia occurrence and disability.
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28.
  • Wu, Yu-Tzu, et al. (författare)
  • The changing prevalence and incidence of dementia over time - current evidence.
  • 2017
  • Ingår i: Nature reviews. Neurology. - : Springer Science and Business Media LLC. - 1759-4766 .- 1759-4758. ; 13:6, s. 327-339
  • Tidskriftsartikel (refereegranskat)abstract
    • Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individual's life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.
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