| 21. |
- Gustafson, Lars, et al.
(författare)
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The accuracy of short clinical rating scales in neuropathologically diagnosed dementia.
- 2010
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Ingår i: The American journal of geriatric psychiatry. - 1064-7481 .- 1545-7214. ; 18:9, s. 810-820
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The overall aim was to evaluate to what extent the diagnosis of dementia subtypes, obtained by three clinical rating scales, concurred with postmortem neuropathologic (NP) diagnosis of Alzheimer disease (AD), frontotemporal dementia (FTD), vascular dementia (VaD) and mixed AD/VaD. Design: A prospective longitudinal clinical work-up with postmortem NP examination. Participants: Two hundred nine patients with dementia referred for clinical evaluation and follow-up. Methods: The diagnostic scores in a set of three short clinical rating scales for AD, FTD, and VaD were evaluated against NP diagnoses. Results: The sensitivity and specificity of the AD scale were 0.80 and 0.87, respectively, of the FTD scale 0.93 and 0.92, respectively, and of the Hachinski Ischemic Score (HIS, VaD diagnosis) 0.69 and 0.92, respectively. Cases with mixed AD/VaD generally presented a combination of high AD and ischemic scores. A preferred cutoff score of six was identified for both the AD and FTD scales. Conclusions: All three clinical rating scales showed a high sensitivity and specificity, in close agreement with final NP diagnosis-for the HIS a moderate sensitivity. These scales may thus be considered good diagnostic tools and are recommended for clinical and research center settings.
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| 22. |
- Hagel, Sofia, et al.
(författare)
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Trends in 21st century Health Care Utilization in a Rheumatoid Arthritis Cohort Compared to the General Population
- 2012
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Ingår i: Arthritis and Rheumatism. - Hoboken, NJ : John Wiley & Sons. - 0004-3591 .- 1529-0131. ; 64:S10, s. S31-S32
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Tidskriftsartikel (refereegranskat)abstract
- Statement of purpose: To study twenty-first century trends in health care utilization by rheumatoid arthritis (RA) patients compared to the general population. Methods: Observational cohort study; using Swedish health care register data, we identified 3977 Region Skåne residents (mean age year 2001, 62.7 years and 73% women) consulting for RA (ICD-10 codes M05 or M06) in 1998-2001. We randomly sampled two referents from the general population per RA patient matched for age, sex, and area of residence. We calculated the year 2001-2010 trends for the annual ratio (RA cohort/referents) of the mean number of hospitalizations and outpatient clinic visits. Results: By the end of the 10-year period 62% of RA patients and 74% of referents were still alive and resident in the region. From 2001 to 2010 the ratio (RA cohort/referents) of the mean number of hospitalizations for men and women decreased by 27% (p=0.01) and 28% (p=0.004), respectively. The corresponding decrease was 29% (p=0.005), and 16% (p=0.004) for outpatient physician care, 34% (p=0.009) and 18% (p=0.01) for nurse visits, and 34% (p=0.01) and 28% (p=0.004) for physiotherapy (Figure 1 and 2). Figure 1.Health care utilization during the first decade of the twenty-first century by patients in a closed rheumatoid arthritis cohort and their matched referents from the general population. The y-axes show the mean number of visits per subject per calendar year. Figure 2.Health care utilization during the first decade of the twenty-first century by patients in a closed rheumatoid arthritis cohort and their matched referents from the general population. The y-axes show the mean number of visits per subject per calendar year. Conclusions: During the twenty-first century, coinciding with increasing use of earlier and more active RA treatment including biological treatment, the overall inpatient and outpatient health care utilization by a cohort of RA patients decreased relative to the general population.
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| 23. |
- Hagel, Sofia, et al.
(författare)
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Trends in the first decade of 21st century healthcare utilisation in a rheumatoid arthritis cohort compared with the general population.
- 2013
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ. - 1468-2060 .- 0003-4967. ; 72:7, s. 1212-1216
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study 21st century trends in healthcare utilisation by patients with rheumatoid arthritis (RA) compared with the general population. METHODS: Observational cohort study. Using Swedish healthcare register data, we identified 3977 Region Skåne residents (mean age in 2001, 62.7 years; 73% women) presenting with RA (International Classification of Diseases-10 codes M05 or M06) in 1998-2001. We randomly sampled two referents from the general population per RA patient matched for age, sex and area of residence. We calculated the year 2001-2010 trends for the annual ratio (RA cohort/referents) of the mean number of hospitalisations and outpatient clinic visits. RESULTS: By the end of the 10-year period, 62% of patients and 74% of referents were still alive and resident in the region. From 2001 to 2010, the ratio (RA cohort/referents) of the mean number of hospitalisations for men and women decreased by 27% (p=0.01) and 28% (p=0.004), respectively. The corresponding decrease was 29% (p=0.005) and 16% (p=0.004) for outpatient physician care, 34% (p=0.009) and 18% (p=0.01) for nurse visits, and 34% (p=0.01) and 28% (p=0.004) for physiotherapy. The absolute reduction in number of hospitalisations was from an annual mean of 0.79 to 0.69 in male patients and from 0.71 to 0.59 in female patients. The corresponding annual mean number of consultations in outpatient physician care by male and female RA patients changed from 9.2 to 7.7 and from 9.9 to 8.7, respectively. CONCLUSIONS: During the first decade of the 21st century, coinciding with increasing use of earlier and more active RA treatment including biological treatment, overall inpatient and outpatient healthcare utilisation by a cohort of patients with RA decreased relative to the general population.
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| 24. |
- Hertwig, Falk, et al.
(författare)
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Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells.
- 2012
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Ingår i: Cancer Research. - 1538-7445. ; 72:13, s. 3381-3392
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Tidskriftsartikel (refereegranskat)abstract
- Although brain tumors are classified and treated based upon their histology, the molecular factors involved in the development of various tumor types remain unknown. In this study, we show that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells (NSC/NPC). We found that the overexpression of specific genes led to the development of these three different brain tumors from NSC/NPCs, and manipulation of the order of genetic events was able to convert one established tumor type into another. In addition, loss of the nuclear chromatin-remodeling factor SMARCB1 in rhabdoid tumors led to increased phosphorylation of eIF2α, a central cytoplasmic unfolded protein response (UPR) component, suggesting a role for the UPR in these tumors. Consistent with this, application of the proteasome inhibitor bortezomib led to an increase in apoptosis of human cells with reduced SMARCB1 levels. Taken together, our findings indicate that the order of genetic events determines the phenotypes of brain tumors derived from a common precursor cell pool, and suggest that the UPR may represent a therapeutic target in atypical teratoid/rhabdoid tumors. Cancer Res; 72(13); 3381-92. ©2012 AACR.
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| 25. |
- Huttner, Hagen B, et al.
(författare)
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The age and genomic integrity of neurons after cortical stroke in humans
- 2014
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 17:6, s. 801-803
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Tidskriftsartikel (refereegranskat)abstract
- It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA rearrangements in the human neocortex. Using immunohistochemistry; transcriptome, genome and ploidy analyses; and determination of nuclear bomb test-derived (14)C concentration in neuronal DNA, we found neither to be the case. A large proportion of cortical neurons displayed DNA fragmentation and DNA repair a short time after stroke, whereas neurons at chronic stages after stroke showed DNA integrity, demonstrating the relevance of an intact genome for survival.
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| 26. |
- Ihara, Masafumi, et al.
(författare)
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Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer's disease, and dementia with Lewy bodies
- 2010
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 119:5, s. 579-589
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to characterize myelin loss as one of the features of white matter abnormalities across three common dementing disorders. We evaluated post-mortem brain tissue from frontal and temporal lobes from 20 vascular dementia (VaD), 19 Alzheimer's disease (AD) and 31 dementia with Lewy bodies (DLB) cases and 12 comparable age controls. Images of sections stained with conventional luxol fast blue were analysed to estimate myelin attenuation by optical density. Serial adjacent sections were then immunostained for degraded myelin basic protein (dMBP) and the mean percentage area containing dMBP (%dMBP) was determined as an indicator of myelin degeneration. We further assessed the relationship between dMBP and glutathione S-transferase (a marker of mature oligodendrocytes) immunoreactivities. Pathological diagnosis significantly affected the frontal but not temporal lobe myelin attenuation: myelin density was most reduced in VaD compared to AD and DLB, which still significantly exhibited lower myelin density compared to ageing controls. Consistent with this, the degree of myelin loss was correlated with greater %dMBP, with the highest %dMBP in VaD compared to the other groups. The %dMBP was inversely correlated with the mean size of oligodendrocytes in VaD, whereas it was positively correlated with their density in AD. A two-tier regression model analysis confirmed that the type of disorder (VaD or AD) determines the relationship between %dMBP and the size or density of oligodendrocytes across the cases. Our findings, attested by the use of three markers, suggest that myelin loss may evolve in parallel with shrunken oligodendrocytes in VaD but their increased density in AD, highlighting partially different mechanisms are associated with myelin degeneration, which could originate from hypoxic-ischaemic damage to oligodendrocytes in VaD whereas secondary to axonal degeneration in AD.
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| 27. |
- Kurowska, Zuzanna, et al.
(författare)
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Signs of Degeneration in 12-22-Year Old Grafts of Mesencephalic Dopamine Neurons in Patients with Parkinson's Disease
- 2011
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Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 1:1, s. 83-92
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that grafted human fetal mesencephalic neurons can survive and extend axons for 22 years in the brain of a patient with Parkinson's disease (PD). In this patient, the overall survival and fiber outgrowth of the grafts were, however, relatively poor, which is consistent with the lack of significant clinical graft-induced benefit. We have compared the morphology of neurons in the 22-year old grafts with those in two younger grafts (16- and 12-year old), which were sequentially implanted in another PD patient. In the case with the 22-year-old transplant, a high proportion (up to 38%) of the grafted dopaminergic (pigment-granule containing) neurons do not express tyrosine hydroxylase and dopamine transporter and their perikarya appear atrophic. The proportion of pigmented neurons not expressing these markers is lower in the 12-16 year old grafts. Furthermore, in the 22-year-old graft, 49% of the pigmented neurons display alpha-synuclein immunoreactivity in the cell body and 1.2% of them contain Lewy bodies. In conclusion, our results show that grafted dopaminergic neurons can survive for more than two decades. However, over time an increasing proportion of grafted neurons exhibit signs of degeneration.
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| 28. |
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| 29. |
- Landqvist, Maria, et al.
(författare)
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Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia
- 2013
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Frontotemporal dementia (FTD) is recognised as a clinically and morphologically heterogeneous group of interrelated neurodegenerative conditions. One of the subtypes within this disease spectrum is the behavioural variant FTD (bvFTD). This is known to be a varied disorder with a mixture of tau-positive and tau-negative underlying pathologies. The other subtypes include semantic dementia (SD), which generally exhibits tau-negative pathology, and progressive non-fluent aphasia (PNFA), which is usually tau-positive. As the clinical presentation of these subtypes may overlap, a specific diagnosis can be difficult to attain and today no specific biomarker can predict the underlying pathology. Neurofilament light chain protein (NFL), a cytoskeletal constituent of intermediate filaments, is thought to reflect neuronal and axonal death when appearing in the cerebrospinal fluid (CSF). NFL has been shown to be elevated in CSF in patients with FTD compared with AD and controls. Our hypothesis was that the levels of NFL also differ between the subtypes of FTD and may indicate the underlying pathological subtype. Methods: We retrospectively analysed data from previous CSF analyses in 34 FTD cases (23 bvFTD, seven SD, four PNFA), 20 AD cases, and 26 healthy controls. A separate group of 10 neuropathologically verified and subtyped FTD cases (seven tau-negative, three tau-positive) were also analysed. Result: NFL levels were significantly higher in FTD compared with both AD (p<0.001) and controls (p<0.001). The NFL levels of SD and bvFTD were significantly higher (p<0.001) compared with AD. The biomarker profiles of PNFA and AD were similar. In the neuropathologically verified FTD cases, NFL was higher in the tau-negative than in the tau-positive cases (exact p=0.017). Conclusions: The marked NFL elevation in some but not all FTD cases is likely to reflect the different underlying pathologies. The highest NFL values found in the SD group as well as in the neuropathologically verified tau-negative cases may be of subtype diagnostic value, if corroborated in larger patient cohorts. In bvFTD, a mixture of tau-positive and tau-negative underlying pathologies could possibly explain the intermediate NFL values.
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| 30. |
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