| 1. |
- Almkvist, Ove, et al.
(författare)
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Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer's Disease
- 2017
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Ingår i: Journal of the International Neuropsychological Society. - : CAMBRIDGE UNIV PRESS. - 1355-6177 .- 1469-7661. ; 23:3, s. 195-203
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to investigate cognitive performance including preclinical and clinical disease course in carriers and non-carriers of autosomal-dominant Alzheimer's disease (adAD) in relation to multiple predictors, that is, linear and non-linear estimates of years to expected clinical onset of disease, years of education and age. Methods: Participants from five families with early-onset autosomal-dominant mutations (Swedish and Arctic APP, PSEN1 M146V, H163Y, and I143T) included 35 carriers (28 without dementia and 7 with) and 44 non-carriers. All participants underwent a comprehensive clinical evaluation, including neuropsychological assessment at the Memory Clinic, Karolinska University Hospital at Huddinge, Stockholm, Sweden. The time span of disease course covered four decades of the preclinical and clinical stages of dementia. Neuropsychological tests were used to assess premorbid and current global cognition, verbal and visuospatial functions, short-term and episodic memory, attention, and executive function. Results: In carriers, the time-related curvilinear trajectory of cognitive function across disease stages was best fitted to a formulae with three predictors: years to expected clinical onset (linear and curvilinear components), and years of education. In non-carriers, the change was minimal and best predicted by two predictors: education and age. The trajectories for carriers and non-carriers began to diverge approximately 10 years before the expected clinical onset in episodic memory, executive function, and visuospatial function. Conclusions: The curvilinear trajectory of cognitive functions across disease stages was mimicked by three predictors in carriers. In episodic memory, executive and visuospatial functions, the point of diverging trajectories occurred approximately 10 years ahead of the clinical onset compared to non-carriers.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- Moller, Anders Pape, et al.
(författare)
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Clutch-size variation in Western Palaearctic secondary hole-nesting passerine birds in relation to nest box design
- 2014
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Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 5:4, s. 353-362
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Tidskriftsartikel (refereegranskat)abstract
- Secondary hole-nesting birds that do not construct nest holes themselves and hence regularly breed in nest boxes constitute important model systems for field studies in many biological disciplines with hundreds of scientists and amateurs involved. Those research groups are spread over wide geographic areas that experience considerable variation in environmental conditions, and researchers provide nest boxes of varying designs that may inadvertently introduce spatial and temporal variation in reproductive parameters. We quantified the relationship between mean clutch size and nest box size and material after controlling for a range of environmental variables in four of the most widely used model species in the Western Palaearctic: great tit Parus major, blue tit Cyanistes caeruleus, pied flycatcher Ficedula hypoleuca and collared flycatcher F.albicollis from 365 populations and 79610 clutches. Nest floor area and nest box material varied non-randomly across latitudes and longitudes, showing that scientists did not adopt a random box design. Clutch size increased with nest floor area in great tits, but not in blue tits and flycatchers. Clutch size of blue tits was larger in wooden than in concrete nest boxes. These findings demonstrate that the size of nest boxes and material used to construct nest boxes can differentially affect clutch size in different species. The findings also suggest that the nest box design may affect not only focal species, but also indirectly other species through the effects of nest box design on productivity and therefore potentially population density and hence interspecific competition.
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| 5. |
- Moller, Anders P., et al.
(författare)
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Variation in clutch size in relation to nest size in birds
- 2014
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:18, s. 3583-3595
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Tidskriftsartikel (refereegranskat)abstract
- Nests are structures built to support and protect eggs and/or offspring from predators, parasites, and adverse weather conditions. Nests are mainly constructed prior to egg laying, meaning that parent birds must make decisions about nest site choice and nest building behavior before the start of egg-laying. Parent birds should be selected to choose nest sites and to build optimally sized nests, yet our current understanding of clutch size-nest size relationships is limited to small-scale studies performed over short time periods. Here, we quantified the relationship between clutch size and nest size, using an exhaustive database of 116 slope estimates based on 17,472 nests of 21 species of hole and non-hole-nesting birds. There was a significant, positive relationship between clutch size and the base area of the nest box or the nest, and this relationship did not differ significantly between open nesting and hole-nesting species. The slope of the relationship showed significant intraspecific and interspecific heterogeneity among four species of secondary hole-nesting species, but also among all 116 slope estimates. The estimated relationship between clutch size and nest box base area in study sites with more than a single size of nest box was not significantly different from the relationship using studies with only a single size of nest box. The slope of the relationship between clutch size and nest base area in different species of birds was significantly negatively related to minimum base area, and less so to maximum base area in a given study. These findings are consistent with the hypothesis that bird species have a general reaction norm reflecting the relationship between nest size and clutch size. Further, they suggest that scientists may influence the clutch size decisions of hole-nesting birds through the provisioning of nest boxes of varying sizes.
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| 6. |
- af Bjerkén, Sara, et al.
(författare)
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Reliability and validity of visual analysis of [18F]FE-PE2I PET/CT in early Parkinsonian disease
- 2023
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Ingår i: Nuclear medicine communications. - : Wolters Kluwer. - 0143-3636 .- 1473-5628. ; 44:5, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- Objective: [18F]FE-PE2I (FE-PE2I) is a new radiotracer for dopamine transporter (DAT) imaging with PET. The aim of this study was to evaluate the visual interpretation of FE-PE2I images for the diagnosis of idiopathic Parkinsonian syndrome (IPS). The inter-rater variability, sensitivity, specificity, and diagnostic accuracy for visual interpretation of striatal FE-PE2I compared to [123I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) was evaluated.Methods: Thirty patients with newly onset parkinsonism and 32 healthy controls with both an FE-PE2I and FP-CIT were included in the study. Four patients had normal DAT imaging, of which three did not fulfil the IPS criteria at the clinical reassessment after 2 years. Six raters evaluated the DAT images blinded to the clinical diagnosis, interpreting the image as being ‘normal’ or ‘pathological’, and assessed the degree of DAT-reduction in the caudate and putamen. The inter-rater agreement was assessed with intra-class correlation and Cronbach’s α. For calculation of sensitivity and specificity, DAT images were defined as correctly classified if categorized as normal or pathological by ≥4/6 raters.Results: The overall agreement in visual evaluation of the FE-PE2I- and FP-CIT images was high for the IPS patients (α = 0.960 and 0.898, respectively), but lower in healthy controls (FE-PE2I: α = 0.693, FP-CIT: α = 0.657). Visual interpretation gave high sensitivity (both 0.96) but lower specificity (FE-PE2I: 0.86, FP-CIT: 0.63) with an accuracy of 90% for FE-PE2I and 77% for FP-CIT.Conclusion: Visual evaluation of FE-PE2I PET imaging demonstrates high reliability and diagnostic accuracy for IPS.
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| 7. |
- Bussy, Aurélie, et al.
(författare)
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Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia
- 2023
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 44:7, s. 2684-2700
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.
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| 8. |
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| 9. |
- Hartikainen, Päivi, et al.
(författare)
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Cortical thickness in frontotemporal dementia, mild cognitive impairment, and Alzheimer's disease
- 2012
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 30:4, s. 857-874
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Tidskriftsartikel (refereegranskat)abstract
- Cortical thickness analysis has been proposed as a potential diagnostic measure in memory disorders. In this retrospective study, we compared the cortical thickness values of 24 patients with frontotemporal dementia (FTD) to those of 25 healthy controls, 45 symptomatic subjects with stable mild cognitive impairment (S-MCI), 15 subjects with progressive mild cognitive impairment (P-MCI), and 36 patients with Alzheimer's disease (AD). The patterns of regions of thinning in FTD when compared to controls and also S-MCI patients showed similar trends; thinning of the bilateral frontal poles and bilateral medial temporal lobe structures, especially the anterior part of the gingulum, the uncus, and parahippocampal gyri. Cortical thinning in FTD was also found on the boundary regions of parietal and occipital lobes. In the P-MCI group compared to FTD, the trend of thinning in small distinct areas of the parietal and occipital lobes was observed. The FTD and AD groups did not differ statistically, but we found trends toward thinning in FTD of the left cingulate gyrus, and the left occipitotemporal gyri, and in AD of the inferior parietal, occipitoparietal, and the pericalcarine regions, more in the right hemisphere. In FTD, increased slowness in the executive test (Trail-Making A) correlated with the thinner cortex, whereas the language tests showed the lower scores, the thinner cortex in the left hemisphere. Cortical thickness might be a tool for detecting subtle changes in brain atrophy in screening of dementia prior to the development of diffuse or lobar atrophies.
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| 10. |
- Johnsen, Hans E., et al.
(författare)
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Multiparametric Flow Cytometry Profiling of Neoplastic Plasma Cells in Multiple Myeloma
- 2010
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Ingår i: Cytometry Part B - Clinical Cytometry. - : Wiley. - 1552-4949. ; 78B:5, s. 338-347
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim: The clinical impact of multiparametric flow cytometry (MFC) in multiple myeloma (MM) is still unclear and under evaluation. Further progress relies on multiparametric profiling of the neoplastic plasma cell (PC) compartment to provide an accurate image of the stage of differentiation. The primary aim of this study was to perform global analysis of CD expression on the PC compartment and subsequently to evaluate the prognostic impact. Secondary aims were to study the diagnostic and predictive impact. Design and methods: The design included a retrospective analysis of MFC data generated from diagnostic bone marrow (BM) samples of 109 Nordic patients included in clinical trials within NMSG. Whole marrow were analyzed by MFC for identification of end-stage CD45(-)/CD38(++) neoplastic PC and registered the relative numbers of events and mean fluorescence intensity (MFI) staining for CD19, CD20, CD27, CD28, CD38, CD44, CD45, CD56, and isotypes for cluster analysis. Results: The median MFC-PC number was 15%, and the median light microscopy (LM)-PC number was 35%. However, the numbers were significant correlated and the prognostic value with an increased relative risk (95% Cl) of 3.1 (1.7-5.5) and 2.9 (1.4-6.2), P < 0.0003 and P < 0.004 of MFC-PC and LM-PC counts, respectively. Unsupervised clustering based on global MFI assessment on PC revealed two clusters based on CD expression profiling. Cluster I with high intensity for CD56, CD38, CD45, right-angle light-scatter signal (SSC), forward-angle light-scatter signal (FSC), and low for CD28, CD19, and a Cluster II, with low intensity of CD56, CD38, CD45, SSC, FSC, and high for CD28, CD19 with a median survival of 39 months and 19 months, respectively (P = 0.02). Conclusions: The MFC analysis of MM BM samples produces diagnostic, prognostic, and predictive information useful in clinical practice, which will be prospectively validated within the European Myeloma Network (EMN). (C) 2010 International Clinical Cytometry Society
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