| 1. |
- Adam, A, et al.
(författare)
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Abstracts from Hydrocephalus 2016.
- 2017
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Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
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| 4. |
- Ruti, P. M., et al.
(författare)
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The West African climate system: a review of the AMMA model inter-comparison initiatives
- 2011
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Ingår i: Atmospheric Science Letters. - : Wiley. - 1530-261X. ; 12:1, s. 116-122
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Tidskriftsartikel (refereegranskat)abstract
- We review the African Monsoon Multidisciplinary Analysis (AMMA) model inter-comparison activities for West Africa. The Model Inter-comparison Project is an evaluation exercise of how global and regional atmospheric models represent seasonal and intra-seasonal variations of the climate and rainfall over the Sahel. The Land surface Model Inter-comparison Project in turn focuses on modelling critical land surface processes over West Africa and on their link with the atmosphere. The CHEmistry Model Inter-comparison Project (CHEMIP) is a comparison of the tropospheric composition as simulated by a number of Chemical Transport Models (CTM) and Chemistry-Climate Models. We highlight the main model limitations and provide recommendations for future development. Copyright. (C) 2011 Royal Meteorological Society
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| 5. |
- Leinonen, V, et al.
(författare)
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Positron emission tomography with [18F]flutemetamol and [11C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients.
- 2013
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 20:7, s. 1043-52
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: This study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [(18) F]flutemetamol and amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical biopsy.METHODS: Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous brain biopsy obtained during intracranial pressure monitoring underwent [18F]flutemetamol PET. Seven of these patients also underwent [11C] Pittsburgh compound B (PiB) PET. [18F]Flutemetamol and [11C]PiB uptake was quantified using standardized uptake value ratio (SUVR) with the cerebellar cortex as a reference region. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain.RESULTS: [18F]Flutemetamol and [11C]PiB SUVRs correlated with biopsy specimen amyloid-β levels contralateral (r = 0.86, P < 0.0001; r = 0.96, P = 0.0008) and ipsilateral (r = 0.82, P = 0.0002; r = 0.87, P = 0.01) to the biopsy site. Association between cortical composite [(18) F]flutemetamol SUVRs and [11C]PiB SUVRs was highly significant (r = 0.97, P = 0.0003).CONCLUSIONS: [18F]Flutemetamol detects brain amyloid-β in vivo with moderate to high sensitivity and high specificity. This agent, therefore, represents a valuable new tool to study and verify the presence of amyloid-β pathology, both in patients with possible NPH and among the wider population.
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| 6. |
- Herukka, S. K., et al.
(författare)
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Amyloid-beta and Tau Dynamics in Human Brain Interstitial Fluid in Patients with Suspected Normal Pressure Hydrocephalus
- 2015
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 46:1, s. 261-269
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyloid-beta (A beta(1-42)), total tau (T-tau), and phosphorylated tau (P-tau(181)) in the cerebrospinal fluid (CSF) are the most promising biomarkers of Alzheimer's disease (AD). Still, little is known about the dynamics of these molecules in the living brain. In a transgenic mouse brain, soluble A beta decreases with increasing age and advanced A beta pathology as seen similarly in CSF. Objective: To assess the relationship between AD-related pathological changes in human brain tissue, ventricular and lumbar CSF, and brain interstitial fluid (ISF). Methods: Altogether 11 patients with suspected idiopathic normal pressure hydrocephalus underwent frontal cortical brain biopsy, 24-h intraventricular pressure monitoring, and a microdialysis procedure. AD-related biomarkers were analyzed from brain tissue, CSF, and ISF. Results: ISF T-tau levels decreased strongly within the first 12 h, then plateauing until the end of the experiment. A beta(1-42) and P-tau(181) remained stable during the experiment (n = 3). T-tau and P-tau were higher in the ISF than in ventricular or lumbar CSF, while A beta(1-42) levels were within similar range in both CSF and ISF samples. ISF P-tau correlated with the ventricular CSF T-tau (r = 0.70, p = 0.017) and P-tau(181) (r = 0.64, p = 0.034). Five patients with amyloid pathology in the brain biopsy tended to reveal lower ISF A beta(1-42) levels than those six without amyloid pathology. Conclusions: This is the first study to report ISF A beta and tau levels in the human brain without significant brain injury. The set-up used enables sampling from the brain ISF for at least 24 h without causing adverse effects due to the microdialysis procedure to follow the dynamics of the key molecules in AD pathogenesis in the living brain at various stages of the disease.
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| 7. |
- Luikku, Antti J., et al.
(författare)
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Multimodal analysis to predict shunt surgery outcome of 284 patients with suspected idiopathic normal pressure hydrocephalus
- 2016
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Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 158:12, s. 2311-2319
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Tidskriftsartikel (refereegranskat)abstract
- Optimal selection of idiopathic normal pressure hydrocephalus (iNPH) patients for shunt surgery is challenging. Disease State Index (DSI) is a statistical method that merges multimodal data to assist clinical decision-making. It has previously been shown to be useful in predicting progression in mild cognitive impairment and differentiating Alzheimer's disease (AD) and frontotemporal dementia. In this study, we use the DSI method to predict shunt surgery response for patients with iNPH. In this retrospective cohort study, a total of 284 patients (230 shunt responders and 54 non-responders) from the Kuopio NPH registry were analyzed with the DSI. Analysis included data from patients' memory disorder assessments, age, clinical symptoms, comorbidities, medications, frontal cortical biopsy, CT/MRI imaging (visual scoring of disproportion between Sylvian and suprasylvian subarachnoid spaces, atrophy of medial temporal lobe, superior medial subarachnoid spaces), APOE genotyping, CSF AD biomarkers, and intracranial pressure. Our analysis showed that shunt responders cannot be differentiated from non-responders reliably even with the large dataset available (AUC = 0.58). Prediction of the treatment response in iNPH is challenging even with our extensive dataset and refined analysis. Further research of biomarkers and indicators predicting shunt responsiveness is still needed.
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| 8. |
- Luikku, Antti J., et al.
(författare)
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Predicting Development of Alzheimer's Disease in Patients with Shunted Idiopathic Normal Pressure Hydrocephalus
- 2019
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 71:4, s. 1233-1243
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Tidskriftsartikel (refereegranskat)abstract
- Background: Idiopathic normal pressure hydrocephalus (iNPH) patients often develop Alzheimer's disease (AD) related brain pathology. Disease State Index (DSI) is a method to combine data from various sources for differential diagnosis and progression of neurodegenerative disorders.Objective: To apply DSI to predict clinical AD in shunted iNPH-patients in a defined population.Methods: 335 shunted iNPH-patients (median 74 years) were followed until death (n = 185) or 6/2015 (n = 150). DSI model (including symptom profile, onset age of NPH symptoms, atrophy of medial temporal lobe in CT/MRI, cortical brain biopsy finding, and APOE genotype) was applied. Performance of DSI model was evaluated with receiver operating characteristic (ROC) curve analysis.Results: A total of 70 (21%) patients developed clinical AD during median follow-up of 5.3 years. DSI-model predicted clinical AD with moderate effectiveness (AUC= 0.75). Significant factors were cortical biopsy (0.69), clinical symptoms (0.66), and medial temporal lobe atrophy (0.66).Conclusion: We found increased occurrence of clinical AD in previously shunted iNPH patients as compared with general population. DSI supported the prediction of AD. Cortical biopsy during shunt insertion seems indicated for earlier diagnosis of comorbid AD.
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| 9. |
- Paeth, Heiko, et al.
(författare)
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Progress in regional downscaling of west African precipitation
- 2011
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Ingår i: Atmospheric Science Letters. - : Wiley. - 1530-261X. ; 12:1, s. 75-82
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Tidskriftsartikel (refereegranskat)abstract
- We review the recent progress in dynamical and statistical downscaling approaches for west African precipitation and perform a regional climate model (RCM) intercomparison using the novel multi-model RCM data set from the Ensembles-based Predictions of Climate Changes and Their Impacts (ENSEMBLES) and African Monsoon Multidisciplinary Analyses (AMMA) projects. Present RCMs have distinct systematic errors in terms of west African precipitation varying in amplitude and pattern across models. This is also reflected in a relatively large spread in projected future precipitation trends. Altogether, the ENSEMBLES RCMs indicate a prevailing drying tendency in sub-Saharan Africa. Statistical post-processing of simulated precipitation is a promising tool to reduce systematic model errors before application in impact studies.
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| 10. |
- Pyykkö, O. T., et al.
(författare)
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APOE4 predicts amyloid-β in cortical brain biopsy but not idiopathic normal pressure hydrocephalus
- 2012
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 83:11, s. 1119-1124
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the association of apolipoprotein E (APOE) genotype, especially the APOE4 allele, to (1) idiopathic normal pressure hydrocephalus (iNPH) and (2) amyloid-β (Aβ) plaques in cortical brain biopsies of presumed NPH patients with and without a final clinical diagnosis of Alzheimer's disease (AD). Methods: 202 patients with presumed NPH were evaluated by intraventricular pressure monitoring and frontal cortical biopsy immunostained against Aβ (134 semiquantified by Aβ plaques/mm 2). The 202 patients and 687 cognitively healthy individuals were genotyped for APOE. The final clinical diagnoses in a median follow-up of 3.9 years were: 113 iNPH (94 shunt responsive, 16 shunt non-responsive, three not shunted); 36 AD (12 mixed iNPH + AD); 53 others. Results: The APOE genotypes distributed similarly in the 94 shunt responsive and 16 non-responsive iNPH patients and healthy controls. In multivariate analysis, the APOE4 allele correlated independently with Aβ plaques in the cortical biopsies (OR 8.7, 95% CI 3.6 to 20, p<0.001). The APOE4 allele in presumed NPH predicted later AD as follows: sensitivity 61%; specificity 77%; positive predictive value 37%; negative predictive value 90%. Conclusion: In presumed NPH patients, APOE4 associates independently with the presence of Aβ plaques in the frontal cortical biopsy. APOE4 is not a risk factor for iNPH and does not predict the response to shunt. Our data further support the view that the iNPH syndrome is a distinct dementing disease.
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| 11. |
- Rummukainen, M., et al.
(författare)
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The Swedish Regional Climate Modelling Programme, SWECLIM: A review
- 2004
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Ingår i: Ambio. - 0044-7447. ; 33:4-5, s. 176-182
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Regional Climate Modelling Programme, SWECLIM, was a 6.5-year national research network for regional climate modeling, regional climate change projections and hydrological impact assessment and information to a wide range of stakeholders. Most of the program activities focussed on the regional climate system of Northern Europe. This led to the establishment of an advanced, coupled atmosphere-ocean-hydrology regional climate model system, a suite of regional climate change projections and progress on relevant data and process studies. These were, in turn, used for information and educational purposes, as a starting point for impact analyses on different societal sectors and provided contributions also to international climate research.
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| 12. |
- Seppala, T. T., et al.
(författare)
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CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings
- 2012
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 78:20, s. 1568-1575
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD. Methods: In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), A beta plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF A beta 42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia. Results: The patients with A beta 42 plaques in the cortical biopsy had lower (p = 0.009) CSF A beta 42 levels than those with no A beta plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) A beta 42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest A beta 42 and highest tau and p-tau 181 levels in CSF. The A beta 42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical A beta was independently predicted by the APOE epsilon 4 carrier status and age but not by CSF A beta 42 or tau levels. Conclusions: Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF A beta 42 and high CSF tau and p-tau levels, respectively. Neurology (R) 2012;78:1568-1575
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| 13. |
- Tengborn, Elisabeth, 1978, et al.
(författare)
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Effect of the misorientation of the 4H-SiC substrate on the open volume defects in GaN grown by metal-organic chemical vapor deposition
- 2006
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Ingår i: Applied Physics Letters. ; 89:091905, s. 3-
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Tidskriftsartikel (refereegranskat)abstract
- Positron annihilation spectroscopy has been used to study GaN grown by metal-organic chemical vapor deposition on misoriented 4H-SiC substrates. Two kinds of vacancy defects are observed: Ga vacancies and larger vacancy clusters in all the studied layers. In addition to vacancies, positrons annihilate at shallow traps that are likely to be dislocations. The results show that the vacancy concentration increases and the shallow positron trap concentration decreases with the increasing substrate misorientation.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Herukka, Sanna-Kaisa, et al.
(författare)
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Amyloid-beta and Tau Dynamics in Human Brain Interstitial Fluid in Patients with Suspected Normal Pressure Hydrocephalus
- 2015
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 46:1, s. 261-269
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Amyloid-beta (A beta(1-42)), total tau (T-tau), and phosphorylated tau (P-tau(181)) in the cerebrospinal fluid (CSF) are the most promising biomarkers of Alzheimer's disease (AD). Still, little is known about the dynamics of these molecules in the living brain. In a transgenic mouse brain, soluble A beta decreases with increasing age and advanced A beta pathology as seen similarly in CSF. Objective: To assess the relationship between AD-related pathological changes in human brain tissue, ventricular and lumbar CSF, and brain interstitial fluid (ISF). Methods: Altogether 11 patients with suspected idiopathic normal pressure hydrocephalus underwent frontal cortical brain biopsy, 24-h intraventricular pressure monitoring, and a microdialysis procedure. AD-related biomarkers were analyzed from brain tissue, CSF, and ISF. Results: ISF T-tau levels decreased strongly within the first 12 h, then plateauing until the end of the experiment. A beta(1-42) and P-tau(181) remained stable during the experiment (n = 3). T-tau and P-tau were higher in the ISF than in ventricular or lumbar CSF, while A beta(1-42) levels were within similar range in both CSF and ISF samples. ISF P-tau correlated with the ventricular CSF T-tau (r = 0.70, p = 0.017) and P-tau(181) (r = 0.64, p = 0.034). Five patients with amyloid pathology in the brain biopsy tended to reveal lower ISF A beta(1-42) levels than those six without amyloid pathology. Conclusions: This is the first study to report ISF A beta and tau levels in the human brain without significant brain injury. The set-up used enables sampling from the brain ISF for at least 24 h without causing adverse effects due to the microdialysis procedure to follow the dynamics of the key molecules in AD pathogenesis in the living brain at various stages of the disease.
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| 18. |
- Koivisto, Anne M, et al.
(författare)
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Poor Cognitive Outcome in Shunt-Responsive Idiopathic Normal Pressure Hydrocephalus
- 2013
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Ingår i: Neurosurgery. - 0148-396X .- 1524-4040. ; 72:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:: Idiopathic normal pressure hydrocephalus (iNPH) causes cognitive decline that can be alleviated by shunting, but long-term outcome studies are scarce. OBJECTIVE:: To elucidate the long-term cognitive condition of shunt-responsive iNPH patients. METHODS:: The follow-up data (Kuopio University Hospital NPH Registry) of 146 patients diagnosed with iNPH by clinical and radiological examination, 24-hour intraventricular pressure monitoring, frontal cortical biopsy, and response to the shunt were analyzed for signs of dementia. The Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, and specified memory disorder criteria were used. Median follow-up was 4.8 years. RESULTS:: At the end of follow-up, 117 (80%) of the 146 iNPH patients had cognitive decline and 67 (46%) had clinical dementia. The most common clinical diagnoses were Alzheimer disease and vascular dementia. In multivariate analysis of the 146 iNPH patients, memory deficit as a first symptom before shunt (odds ratio [OR] 18.3; 95% confidence interval [CI] 1.9-175), male sex (OR 3.29; 95% CI 1.11-9.73), age (OR 1.17 year; 95% CI 1.07-1.28), and follow-up time (OR 1.20 year; 95% CI 1.02-1.40) predicted dementia. Interestingly, 8 (5%) iNPH patients had dementia without any signs of other neurodegenerative diseases in clinical, neuroradiological, or brain biopsy evaluation. These patients initially presented a full triad of symptoms, with gait disturbance being the most frequent initial symptom followed by deterioration in cognition. CONCLUSION:: The novel findings were (a) a significant risk of dementia in iNPH initially responsive to cerebrospinal fluid shunt, (b) cognitive impairment most commonly due to iNPH-related dementia followed by concurrent degenerative brain disease, and (c) a subgroup with dementia related to iNPH without comorbidities. ABBREVIATIONS:: Aβ, amyloid betaAD, Alzheimer diseaseCI, confidence intervalHPτ, hyperphosphorylated tauICP, intracranial pressureiNPH, idiopathic normal pressure hydrocephalusKUH, Kuopio University HospitalNPH, normal pressure hydrocephalusVaD, vascular dementia.
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| 19. |
- Leinonen, Ville, et al.
(författare)
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Amyloid and Tau Proteins in Cortical Brain Biopsy and Alzheimer's Disease
- 2010
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 68:4, s. 446-453
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Amyloid-beta(A beta) aggregates are presumed to be found in the brain at an early stage of Alzheimer's disease (AD) but have seldom been assessed by brain biopsy during life in often elderly patients. Methods: Between 1991 and 2006 we evaluated 468 patients with suspected normal pressure hydrocephalus with intraventricular pressure monitoring and a right frontal cortical biopsy sample immunostained for A beta and hyperphosphorylated tau (HP tau). Adequate samples and the clinical follow-up data until death or the end of 2008, available in 433 cases, were reviewed for the clinical signs of dementia, including AD. Logistic regression analysis was used to analyze whether A beta and/or HP tau in the biopsy samples obtained during life predicted development of cognitive impairment, in particular, AD. Results: Of the 433 frontal cortical samples, 42 (10%) displayed both A beta and HP tau, 144 (33%) A beta only, and 247 (57%) neither A beta nor HP tau. In a median follow-up time of 4.4 years, 94 patients (22%) developed clinical AD. The presence of both A beta and HP tau was strongly associated (odds ratio [OR], 68.2; 95% confidence interval [Cl], 22.1-210) and A beta alone significantly associated (OR, 10.8; 95% Cl, 4.9-23.8) with the clinical diagnosis of AD. Interpretation: This is the largest follow-up study of patients assessed for the presence of A beta and HP tau in frontal cortical brain biopsy samples. 1) The presence of A beta and HP tau spoke strongly for the presence or later development of clinical AD; 2) A beta alone was suggestive of AD; and 3) the absence of A beta and HP tau spoke against a later clinical diagnosis of AD.
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| 20. |
- Leinonen, Ville, et al.
(författare)
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Cortical Brain Biopsy in Long-Term Prognostication of 468 Patients with Possible Normal Pressure Hydrocephalus
- 2012
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Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 10:1-4, s. 166-169
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Tidskriftsartikel (refereegranskat)abstract
- Normal pressure hydrocephalus (NPH) can be alleviated by cerebrospinal fluid shunting but the differential diagnosis and patient selection are challenging. Intraventricular intracranial pressure monitoring as part of the diagnostic workup as well as shunting enable to obtain cortical brain biopsies to detect amyloid-β (Aβ) and hyperphosphorylated tau (HPτ), the hallmark lesions of Alzheimer's disease (AD). In possible NPH, Aβ alone indicates an increased risk of AD and when present with HPτ probable AD, but the effect of those brain lesions on survival is not known. The aim of this study was to evaluate the predictive value of brain biopsy for the long-term outcome of possible NPH. Between 1991 and 2006, the Neurosurgery Department of the Kuopio University Hospital evaluated 468 patients for possible NPH by intraventricular intracranial pressure monitoring and frontal cortical brain biopsy immunostained against Aβ and HPτ. All patients were followed up until the end of 2008 (n = 201) or death (n = 267) with a median follow-up of 4.6 years (range 0-17). Logistic regression analysis with Cox models was applied. Out of the 468 cases, Aβ was detected in 197 (42%) cortical biopsies, and together with HPτ in 44 (9%). Aβ alone indicated increased risk of AD and with HPτ probable AD, but it did not affect survival. Vascular aetiology was the most frequent cause of death. Cortical biopsy findings indicate that NPH is at present a heterogeneous syndrome and has notable overlapping with AD. Brain biopsy did not predict survival but may open a novel research window to study the pathobiology of neurodegeneration.
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| 21. |
- Leinonen, Ville, et al.
(författare)
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Post-mortem findings in 10 patients with presumed normal pressure hydrocephalus and review of the literature
- 2011
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Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 38:1, s. 72-86
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Neuropathological features of idiopathic normal pressure hydrocephalus (iNPH) are poorly characterized. Brain biopsy during life may help in the differential diagnosis of dementia but post-mortem validation of biopsy findings is scarce. Here we review and report brain biopsy and post-mortem neuropathological findings in patients with presumed NPH. Methods: We evaluated 10 patients initially investigated by intraventricular pressure monitoring and a frontal cortical biopsy for histological and immunohistochemical assessment as a diagnostic procedure for presumed NPH. Results: Out of the 10 patients, eight were shunted and seven benefited. Until death, six had developed severe and two mild cognitive impairment. One was cognitively unimpaired, and one was mentally retarded. Three subjects displayed Ab aggregates in their frontal cortical biopsy obtained at the initial procedure. One of these patients developed Alzheimer's disease during a follow-up time of nearly 10 years. One patient with cognitive impairment and NPH suffered from corticobasal degeneration. In six patients various vascular lesions were seen at the final neuropathological investigation. Five of them were cognitively impaired, and in four vascular lesions were seen sufficient in extent to be considered as causative regarding their symptoms. Conclusions: The frequent finding of vascular pathology in NPH is intriguing suggesting that vascular alterations might be causative of cognitive impairment in a notable number of patients with NPH and dementia. Brain biopsy can be used to detect Ab aggregates but neuropathological characteristics of iNPH as a distinct disease still need to be discovered.
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| 22. |
- Pyykkö, Okko T, et al.
(författare)
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Cerebrospinal fluid biomarker and brain biopsy findings in idiopathic normal pressure hydrocephalus
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3, s. e91974-
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the role of soluble APP (sAPP) and amyloid beta (Ab) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy Ab and hyperphosphorylated tau (HPt) findings. Methods: The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Ab and HPt. CSF levels of AD-related biomarkers (Ab42, p-tau, total tau), non-AD-related Ab isoforms (Ab38, Ab40), sAPP isoforms (sAPPa, sAPPb), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results: Lumbar CSF levels of sAPP alpha were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPb showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Ab or HPt in the brain biopsy. Quantified Ab load in the brain biopsy showed a negative correlation with CSF levels of Ab42 in ventricular (r = 20.295, p = 0.003) and lumbar (r = 20.356, p = 0.01) samples, while the levels of Ab38 and Ab40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure. Conclusions: The role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD.
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| 23. |
- Rinne, Juha O., et al.
(författare)
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[C-11]PIB PET Is Associated with the Brain Biopsy Amyloid-beta Load in Subjects Examined for Normal Pressure Hydrocephalus
- 2019
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 67:4, s. 1343-1351
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Tidskriftsartikel (refereegranskat)abstract
- Background: Idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with concomitant amyloid-beta (A beta) pathology. Objective: To compare the [C-11]PIB PET uptake in the patients with suspected iNPH to A beta and hyperphosphorylated-tau (HP tau) in the right frontal cortical biopsy, the cerebrospinal fluid (CSF) A beta, the response to a CSF shunt, and the final clinical diagnosis of Alzheimer's disease (AD). Methods: Patients (n = 21) from Kuopio NPH Registry (http://www.uef.fi/nph) with intraventricular pressure monitoring, immunostaining for A beta and HP tau in the right frontal cortical biopsies, and a Mini-Mental State Examination and a Clinical Dementia Rating underwent [C-1(1)]PIB PET. A beta, total tau, and P tau(181) were measured by ELISA from the ventricular (n= 15) and the lumbar (n = 9) CSF. Response to the shunt was seen in 13 out of the 15 shunted patients. AD was diagnosed in 8 patients during a median follow-up of 6 years (mean 7.3 +/- 2.4 years, range 3-1). Results: [C-11]PIB uptake in the right frontal cortex (rho = 0.60, p < 0.01) and the combined neocortical [C-11]PIB uptake score (rho = 0.61, p < 0.01) were associated with a higher A beta load in the right frontal cortical biopsy. Excluding one (1/15) outlier, [C-11]PIB uptake was also associated with the ventricular CSF A beta (rho = -0.58, p = 0.03). Conclusions: The findings show that [C-11]PIB PET can reliably detect simultaneous amyloid pathology among the iNPH patients. Further studies will show whether amyloid PET could predict a clinical response to the shunt operation. In addition, the presence of A beta pathology in the patients with iNPH might also warrant treatment with current AD drugs.
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| 24. |
- Rummukainen, Markku, et al.
(författare)
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Klimatet
- 2006
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Ingår i: Klimatet och skogen - underlag för nationell forskning (Kungliga skogs- och lantbruksakademiens tidskrift). - 9185205427 ; 9, s. 35-41
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 25. |
- Rummukainen, M, et al.
(författare)
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Vacancy-impurity pairs in n-type Si1-xGex studied by positron spectroscopy
- 2006
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Ingår i: Physica. B, Condensed matter. - : Elsevier BV. - 0921-4526 .- 1873-2135. ; 376, s. 208-211
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Tidskriftsartikel (refereegranskat)abstract
- Positron annihilation spectroscopy was applied to study relaxed P-doped n-type Si1-xGex layers with Ge concentrations up to 30%. As-grown SiGe layers were defect-free and annihilations are superpositions from bulk Si and Ge. Proton irradiation at 2 MeV energy with a 1.6 x 10(15) cm(-2) fluence was used to produce saturated positron trapping in monovacancy related defects. The defects were identified as V-P pairs, the E-center. The distribution of Si and Ge atoms surrounding the E-center is the same as in the host lattice. The vacancy migration process leading to the formation of V-P pairs therefore does not seem to have a preference for either Si or Ge atoms. (c) 2005 Elsevier B.V. All rights reserved.
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| 26. |
- Rummukainen, M, et al.
(författare)
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Vacancy-impurity pairs in relaxed Si1-xGex layers studied by positron annihilation spectroscopy
- 2006
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 73:16
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Tidskriftsartikel (refereegranskat)abstract
- Positron annihilation spectroscopy was applied to study relaxed P-doped n-type and undoped Si1-xGex layers with x up to 0.30. The as-grown SiGe layers were found to be defect free and annihilation parameters in a random SiGe alloy could be represented as superpositions of annihilations in bulk Si and Ge. A 2 MeV proton irradiation with a 1.6x10(15) cm(-2) fluence was used to produce saturated positron trapping in monovacancy related defects in the n-type layers. The defects were identified as V-P pairs, the E center. The distribution of Si and Ge atoms surrounding the E center was the same as in the host lattice. The process leading to the formation of V-P pairs therefore does not seem to have a significant preference for either Si or Ge atoms. In undoped Si1-xGex we find that a similar irradiation produces a low concentration of divacancies or larger vacancy defects and found no evidence of monovacancies surrounded by several Ge atoms.
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| 27. |
- Seneviratne, Sonia I., et al.
(författare)
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Impact of soil moisture-climate feedbacks on CMIP5 projections: First results from the GLACE-CMIP5 experiment
- 2013
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 1944-8007 .- 0094-8276. ; 40:19, s. 5212-5217
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Tidskriftsartikel (refereegranskat)abstract
- The Global Land-Atmosphere Climate Experiment-Coupled Model Intercomparison Project phase 5 (GLACE-CMIP5) is a multimodel experiment investigating the impact of soil moisture-climate feedbacks in CMIP5 projections. We present here first GLACE-CMIP5 results based on five Earth System Models, focusing on impacts of projected changes in regional soil moisture dryness (mostly increases) on late 21st century climate. Projected soil moisture changes substantially impact climate in several regions in both boreal and austral summer. Strong and consistent effects are found on temperature, especially for extremes (about 1-1.5K for mean temperature and 2-2.5K for extreme daytime temperature). In the Northern Hemisphere, effects on mean and heavy precipitation are also found in most models, but the results are less consistent than for temperature. A direct scaling between soil moisture-induced changes in evaporative cooling and resulting changes in temperature mean and extremes is found in the simulations. In the Mediterranean region, the projected soil moisture changes affect about 25% of the projected changes in extreme temperature.
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| 28. |
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| 29. |
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