| 21. |
- Oliveira, F., et al.
(author)
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Data driven diagnostic classification in Alzheimer's disease based on different reference regions for normalization of PiB-PET images and correlation with CSF concentrations of A beta species
- 2018
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In: Neuroimage-Clinical. - : Elsevier BV. - 2213-1582. ; 20, s. 603-610
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Journal article (peer-reviewed)abstract
- Positron emission tomography (PET) neuroimaging with the Pittsburgh Compound_B (PiB) is widely used to assess amyloid plaque burden. Standard quantification approaches normalize PiB-PET by mean cerebellar gray matter uptake. Previous studies suggested similar pons and white-matter uptake in Alzheimer's disease (AD) and healthy controls (HC), but lack exhaustive comparison of normalization across the three regions, with data-driven diagnostic classification. We aimed to compare the impact of distinct reference regions in normalization, measured by data-driven statistical analysis, and correlation with cerebrospinal fluid (CSF) amyloid beta (A beta) species concentrations. 243 individuals with clinical diagnosis of AD, HC, mild cognitive impairment (MCI) and other dementias, from the Biomarkers for Alzheimer's/Parkinson's Disease (BIOMARKAPD) initiative were included. PiB-PET images and CSF concentrations of A beta(38), A beta(40) and A beta(42) were submitted to classification using support vector machines. Voxel-wise group differences and correlations between normalized PiB-PET images and CSF A beta concentrations were calculated. Normalization by cerebellar gray matter and pons yielded identical classification accuracy of AD (accuracy-96%, sensitivity-96%, specificity-95%), and significantly higher than A beta concentrations (best accuracy 91%). Normalization by the white-matter showed decreased extent of statistically significant multivoxel patterns and was the only method not outperforming CSF biomarkers, suggesting statistical inferiority. A beta(38) and A beta(40) correlated negatively with PiB-PET images normalized by the white-matter, corroborating previous observations of correlations with non-AD-specific subcortical changes in white-matter. In general, when using the pons as reference region, higher voxel-wise group differences and stronger correlation with A beta(42), the A beta(42)/A beta(40) or A beta(42)/A beta(38) ratios were found compared to normalization based on cerebellar gray matter.
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| 22. |
- Pyykkö, O. T., et al.
(author)
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APOE4 predicts amyloid-β in cortical brain biopsy but not idiopathic normal pressure hydrocephalus
- 2012
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In: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 83:11, s. 1119-1124
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Journal article (peer-reviewed)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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| 23. |
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| 24. |
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| 25. |
- Kaprio, J, et al.
(author)
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The Older Finnish Twin Cohort - 45 Years of Follow-up
- 2019
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In: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 22:4, s. 240-254
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Journal article (peer-reviewed)abstract
- The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945–1957 in 2011–2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938–1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes.
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| 26. |
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| 27. |
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| 28. |
- Osterwalder, S., et al.
(author)
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A dual-inlet, single detector relaxed eddy accumulation system for long-term measurement of mercury flux
- 2016
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In: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 9:2, s. 509-524
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Journal article (peer-reviewed)abstract
- The fate of anthropogenic emissions of mercury (Hg) to the atmosphere is influenced by the exchange of elemental Hg with the earth surface. This exchange holds the key to a better understanding of Hg cycling from local to global scales, which has been difficult to quantify. To advance research about land-atmosphere Hg interactions, we developed a dual-inlet, single detector relaxed eddy accumulation (REA) system. REA is an established technique for measuring turbulent fluxes of trace gases and aerosol particles in the atmospheric surface layer. Accurate determination of gaseous elemental mercury (GEM) fluxes has proven difficult due to technical challenges presented by extremely small concentration differences (typically < 0.5 ngm(-3)) between updrafts and downdrafts. We present an advanced REA design that uses two inlets and two pairs of gold cartridges for continuous monitoring of GEM fluxes. This setup reduces the major uncertainty created by the sequential sampling in many previous designs. Additionally, the instrument is equipped with a GEM reference gas generator that monitors drift and recovery rates. These innovations facilitate continuous, autonomous measurement of GEM flux. To demonstrate the system performance, we present results from field campaigns in two contrasting environments: an urban setting with a heterogeneous fetch and a boreal peatland during snowmelt. The observed average emission rates were 15 and 3 n gm(-2) h(-1), respectively. We believe that this dual-inlet, single detector approach is a significant improvement of the REA system for ultra-trace gases and can help to advance our understanding of long-term land-atmosphere GEM exchange.
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| 29. |
- Rinne, J., et al.
(author)
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Effect of the 2018 European drought on methane and carbon dioxide exchange of northern mire ecosystems
- 2020
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In: Philosophical Transactions of the Royal Society B-Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1810
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Journal article (peer-reviewed)abstract
- We analysed the effect of the 2018 European drought on greenhouse gas (GHG) exchange of five North European mire ecosystems. The low precipitation and high summer temperatures in Fennoscandia led to a lowered water table in the majority of these mires. This lowered both carbon dioxide (CO2) uptake and methane (CH4) emission during 2018, turning three out of the five mires from CO(2)sinks to sources. The calculated radiative forcing showed that the drought-induced changes in GHG fluxes first resulted in a cooling effect lasting 15-50 years, due to the lowered CH(4)emission, which was followed by warming due to the lower CO(2)uptake. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
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| 30. |
- Seppala, T. T., et al.
(author)
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CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings
- 2012
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In: Neurology. - 0028-3878 .- 1526-632X. ; 78:20, s. 1568-1575
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Journal article (peer-reviewed)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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