| 1. |
- Kirsebom, B. E., et al.
(författare)
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Stable cerebrospinal fluid neurogranin and beta-site amyloid precursor protein cleaving enzyme 1 levels differentiate predementia Alzheimer's disease patients
- 2022
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:5
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Tidskriftsartikel (refereegranskat)abstract
- Kirsebom & Richter et al. report that levels of the CSF synapse markers neurogranin and BACE1 remain stable in Alzheimer's disease A/T/N subgroups, even when progressing to dementia. Their results suggest that CSF levels may differentiate pathomechanistic Alzheimer's disease subtypes, putatively with different options for treatment. Cerebrospinal fluid (CSF) beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), neurogranin and the neurogranin/BACE1 ratio are proposed markers for Alzheimer's disease. BACE1 is also a drug target. However, CSF levels may differ between early-stage amyloid plaque formation (A) and later stage downstream tau-tangle pathology (T) and neurodegeneration (N) and may be expressed as an A/T/N stage (e.g. A+/T-/N or A+/T+/N+). Whether BACE1 and neurogranin levels are persistent traits or change with disease progression is unknown. The aim of this study was to investigate whether CSF neurogranin and BACE1 concentrations differ between A/T/N stages, whether these change over time and correlate with memory decline. This may have implications for patient selection in future trials. We used CSF markers to determine A/T/N stage using amyloid beta42/40 ratio, p-tau181 and total-tau respectively in predementia Alzheimer's disease cases (n = 176) [including cases that progressed to dementia (n = 10)] and controls (n = 74) from the Norwegian Dementia Disease Initiation cohort. We selected cases at the presumed early (A+/T-/N-, n = 86) and late stages (A+/T+/N+, n = 90) of the Alzheimer's disease continuum and controlled with normal markers (A-/T-/N-, n = 74). A subset of subjects in all A/T/N groups underwent repeat CSF sampling at approximately 2-year intervals up to 6 years from baseline. Using linear mixed models, longitudinal measurements of CSF BACE1 and neurogranin levels in A+/T-/N- and A+/T+/N+ as compared to A-/T-/N- healthy controls were performed. Next, we measured changes in CSF BACE1 and neurogranin levels in cases that progressed from A-/T-/N- to A+/T-/N- (n = 12), from A+/T-/N- to A+/T or N+ (n = 12), remained stable A+/T-/N- (n = 26), remained stable A+/T+/N+ (n = 28) compared with controls remaining stable A-/T-/N- (n = 33). Lastly, associations between these markers and memory decline were assessed. Compared with A-/T-/N- healthy controls, neurogranin was unaltered in A+/T-/N- (n.s.) but higher in A+/T+/N+ (P < 0.0001). In contrast, BACE1 was lower in A+/T-/N- (P < 0.05) and higher in A+/T+/N+ (P < 0.0001). The neurogranin/BACE1 ratio was increased in both A+/T-/N- (P < 0.05) and A+/T+/N+ (P < 0.0001) groups as compared to A-/T-/N- healthy controls and was more strongly associated with memory decline (b = -0.29, P = 0.0006) than neurogranin (b = -0.20, P = 0.002) and BACE1 (b = -0.13, P = 0.046). Neurogranin and BACE1 level differences remained stable over time not only within A/T/N groups but also in patients progressing to more pathological A/T/N stages (e.g. progressing from A+/T-/N- to A + T or N+) and in cases progressing to dementia. Our results suggest that neurogranin and BACE1 levels may differentiate pathomechanistic Alzheimer's disease subgroups, putatively with different options for treatment.
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| 2. |
- Espenes, J., et al.
(författare)
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Demographically adjusted trail making test norms in a Scandinavian sample from 41 to 84 years
- 2020
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Ingår i: Clinical Neuropsychologist. - : Informa UK Limited. - 1385-4046 .- 1744-4144. ; 34:suppl. 1, s. 110-126
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Tidskriftsartikel (refereegranskat)abstract
- Objective The trail making test (TMT) is one of the most widely used neuropsychological tests. TMT-A provides measures of visual scanning/visuomotor speed and TMT-B involves additional demands on executive functions. Derived scores TMT B-A and TMT B/A enhance measures of executive functioning. However, simple B-A subtraction may lead to false estimates of executive dysfunction in clinical samples. Norms for TMT have been published in several countries but are currently lacking for Scandinavia. Methods A total of 292 healthy controls between age 41 and 84 years were included from the Norwegian "Dementia Disease Initiation" (DDI) study (n = 170) and the Gothenburg Mild Cognitive Impairment (MCI) study (n = 122). We used a regression-based procedure to develop demographically adjusted norms for basic (TMT-A and TMT-B) and derived measures (TMT B-A and B/A). We also propose a regression-based alternative to the TMT B-A measure named "TMT-beta". The proposed norms were compared to norms from Heaton et al. and Tombaugh. Results Due to differences in the estimated normative effects of demographics on performance, the proposed norms for TMT were better suited in the Scandinavian sample compared with published non-Scandinavian norms. The proposed TMT-beta measure was highly correlated to TMT B-A (r = 0.969,p < 0.001). Conclusion We here propose demographically adjusted norms for the TMT for ages 41 through 84 years based on a Scandinavian sample. We also present the regression-based derived measure TMT-beta which may resolve issues with the conventional TMT B-A measure.
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| 3. |
- Hyldegaard, S., et al.
(författare)
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Precise branching ratios to unbound 12C states from 12N and 12B [beta]-decays
- 2009
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 678:5, s. 459 - 464
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Tidskriftsartikel (refereegranskat)abstract
- Two complementary experimental techniques have been used to extract precise branching ratios to unbound states in 12C from 12N and 12B [beta]-decays. In the first the three [alpha]-particles emitted after [beta]-decay are measured in coincidence in separate detectors, while in the second method 12N and 12B are implanted in a detector and the summed energy of the three [alpha]-particles is measured directly. For the narrow states at 7.654 MeV (0+) and 12.71 MeV (1+) the resulting branching ratios are both smaller than previous measurements by a factor of [similar, equals]2. The experimental results are compared to no-core shell model calculations with realistic interactions from chiral perturbation theory, and inclusion of three-nucleon forces is found to give improved agreement.
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| 4. |
- Hyldegaard, S., et al.
(författare)
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R-matrix analysis of the beta decays of 12N and 12B
- 2010
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Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 81:2
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Tidskriftsartikel (refereegranskat)abstract
- The β decays of 12N and 12B have been studied at KVI and JYFL to resolve the composition of the broad and interfering 0+ and 2+ strengths in the triple-α continuum. For the first time a complete treatment of 3α decay is presented including all major breakup channels. A multilevel, many-channel R-matrix formalism has been developed for the complete description of the breakup in combination with the recently published separate analysis of angular correlations. We find that, in addition to the Hoyle state at 7.65 MeV, more than one 0+ and 2+ state is needed to reproduce the spectra. Broad 03+ and 22+ states are found between 10.5 and 12 MeV in this work. The presence of β strength up to the 12N Q-value window suggests the presence of additional 0+ and 2+ components in the 12C structure at energies above 12.7 MeV.
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| 5. |
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| 6. |
- Roger, T., et al.
(författare)
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Precise Determination of the Unperturbed B8 Neutrino Spectrum
- 2012
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Ingår i: Phys. Rev. Lett.. ; 108:16, s. Art. no. 162502-
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Tidskriftsartikel (refereegranskat)abstract
- A measurement of the final state distribution of the 8B beta decay, obtained by implanting a 8B beam in a double-sided silicon strip detector, is reported here. The present spectrum is consistent with a recent independent precise measurement performed by our collaboration at the IGISOL facility, Jyvaskyla [O. S.Kirsebom et al., Phys. Rev. C 83, 065802 (2011)]. It shows discrepancies with previously measuredspectra, leading to differences in the derived neutrino spectrum. Thanks to a low detection threshold, theneutrino spectrum is for the first time directly extracted from the measured final state distribution, thusavoiding the uncertainties related to the extrapolation of R-matrix fits. Combined with the IGISOL data,this leads to an improvement of the overall errors and the extension of the neutrino spectrum at highenergy. The new unperturbed neutrino spectrum represents a benchmark for future measurements of thesolar neutrino flux as a function of energy.
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| 7. |
- Siafarikas, N., et al.
(författare)
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Cerebrospinal fluid markers for synaptic function and Alzheimer type changes in late life depression
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- To explore markers for synaptic function and Alzheimer disease (AD) pathology in late life depression (LLD), predementia AD and normal controls (NC). A cross-sectional study to compare cerebrospinal fluid (CSF) levels of neurogranin (Ng), Beta-site amyloid-precursor-protein cleaving enzyme1 (BACE1), Ng/BACE1 ratio and Amyloid-beta 42/40 ratio, phosphorylated-tau and total-tau in LLD with (LLD AD) or without (LLD NoAD) AD pathology, predementia AD and normal controls (NC). We included 145 participants (NC = 41; predementia AD = 66 and LLD = 38). LLD comprised LLD AD (n = 16), LLD NoAD (n = 19), LLD with non-AD typical changes (n = 3, excluded). LLD AD (p(ADJ) < 0.05) and predementia AD (p(ADJ) < 0.0001) showed significantly higher Ng than NC. BACE1 and Ng/BACE1 ratio were altered similarly. Compared to LLD NoAD, LLD AD showed significantly higher Ng (p(ADJ) < 0.001), BACE1 (p(ADJ) < 0.05) and Ng/BACE1 ratio (p(ADJ) < 0.01). All groups had significantly lower A beta 42/40 ratio than NC (predementia AD and LLD AD, p < 0.0001; LLD NoAD, p < 0.05). Both LLD groups performed similarly on tests of memory and executive function, but significantly poorer than NC. Synaptic function in LLD depended on AD pathology. LLD showed an association to Amyloid dysmetabolism. The LLD groups performed poorer cognitively than NC. LLD AD may be conceptualized as "predementia AD with depression".
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| 8. |
- Eliassen, I. V., et al.
(författare)
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Predictive and diagnostic utility of brief neuropsychological assessment in detecting Alzheimer's pathology and progression to dementia
- 2020
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Ingår i: Neuropsychology. - : American Psychological Association (APA). - 1931-1559 .- 0894-4105. ; 34:8, s. 851-861
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the role of brief neuropsychological assessments in prediction and identification of Alzheimer's disease (AD) pathology and progression to AD dementia. Method: Adults (N = 255; range = 40-81 years) with self-reported cognitive decline underwent baseline and 2-year follow-up clinical assessment, including a brief neuropsychological screening and lumbar puncture. Five different mild cognitive impairment (MCI) algorithms were applied on baseline cognitive test results: one conventional, three amnestic (lenient, stringent, multidomain), and one comprehensive criterion. We compared predictive and diagnostic accuracy of these MCI criteria by performing logistic regression analyses and calculating diagnostic accuracy measures for 2-year outcomes of (1) clinical diagnosis of AD dementia and (2) cerebrospinal fluid biomarkers in the Alzheimer's continuum. Results: The lenient amnestic MCI criterion showed the largest effect size for predicting progression to AD dementia (OR = 13.762, 99% CI = 1.969-96.194, p = .001) and AD biomarkers (OR = 4.855, 99% CI = 1.974-11.924, p < .001) after 2 years. This criterion was sensitive for progression to dementia (sensitivity = 92.0%, specificity = 54.8%, positive likelihood ratio [LR+] = 2.03, LR- = 0.15) and showed the highest overall diagnostic accuracy for AD biomarkers (sensitivity = 72.7%, specificity = 59.1%, LR+ = 1.78, negative likelihood ratio [LR-] = 0.46). The multidomain amnestic MCI criterion produced the highest specificity for dementia (sensitivity = 76.0%, specificity = 73.0%, LR+ = 2.82, LR- = 0.33) and AD biomarkers (sensitivity = 46.8% specificity = 70.9% LR+ = 1.61, LR- = 0.75). Conclusions: Defining MCI using a brief neuropsychological battery provided limited accuracy for progression to AD dementia and cerebrospinal fluid Aβ. The lenient amnestic MCI criterion identified the highest number of individuals who progressed to clinical AD or showed biomarker pathology, but this approach included a substantial number of false positives. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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| 9. |
- Espenes, J., et al.
(författare)
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Regression-based normative data for the Rey Auditory Verbal Learning Test in Norwegian and Swedish adults aged 49-79 and comparison with published norms
- 2023
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Ingår i: Clinical Neuropsychologist. - : Informa UK Limited. - 1385-4046 .- 1744-4144. ; 37:6, s. 1276-1301
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Rey Auditory Verbal Learning Test (RAVLT) is a widely used measure of episodic verbal memory. To our knowledge, culturally adapted and demographically adjusted norms for the RAVLT are currently not available for Norwegian and Swedish adults, and imported North American norms are often used. We here develop regression-based norms for Norwegian and Swedish adults and compare our norms to North American norms in an independent sample of cognitively healthy adults. Method: Participants were 244 healthy adults from Norway and Sweden between the aged 49 and 79 years, with between 6 and 24 years of education. Using a multiple multivariate regression-based norming procedure, we estimated effects of age, sex, and years of education on basic and derived RAVLT test scores. The newly developed norms were assessed in an independent comparison group of cognitively healthy adults (n = 145) and compared to recently published North American regression-based norms. Results: Lower age, female sex and more years of education predicted higher performance on the RAVLT. The new norms adequately adjusted for age, education, and sex in the independent comparison group. The American norms corrected for demographics on all RAVLT trials except trials 4, 7, list B, and trials 1-5 total. Test-retest (M = 2.55 years) reliability varied from poor to good. Conclusion: We propose regression-based norms for the RAVLT adjusting for pertinent demographics. The norms may be used for assessment of Norwegian and Swedish adults between the aged of 49 and 79 years, with between 6 and 24 years of education.
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| 10. |
- Fynbo, H. O. U., et al.
(författare)
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The β-decay approach for studying 12C
- 2008
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 111:1
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Tidskriftsartikel (refereegranskat)abstract
- The β-decays of the mirror nuclei 12B and 12N both populate states in 12C and they are therefore a precious source of information about this nucleus. Due to the selection rules of β-decay only 0+, 1+ and 2+ states are populated. This allows a very clean study of unbound states just above the 3α-threshold with those spin and parities. This probe has been applied in two experiments using two complementary experimental techniques: in the first the three α-particles emitted after β-decay are measured in coincidence in separate detectors using the ISOL method, while in the second method 12B and 12N are implanted in a detector and the summed energy of the three α-particles is measured directly. Preliminary results from the two approaches are presented. © 2008 IOP Publishing Ltd.
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