1. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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2. |
- Bussy, Aurélie, et al.
(författare)
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Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia
- 2023
-
Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 44:7, s. 2684-2700
-
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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3. |
- Landqvist, Maria, 1989, et al.
(författare)
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Starting up a local energy system in Sweden: The story of technological collaboration between an Italian supplier and established Swedish energy company
- 2019
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Ingår i: The 35th IMP Conference 2019.
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Konferensbidrag (refereegranskat)abstract
- This paper focuses on the inter-organizational aspects of creating a local energy system in Sweden. Today the Swedish energy system faces a challenge of becoming 100 % renewable in 2040. To be able to manage the transformation the system needs to open up for new actors and new renewable technology. However, to embed new renewable technology into the existing system is difficult because of the already predefined infrastructure and regulations. Hence, there is need to explore how technological collaboration can facilitate the process of embedding new renewable technology into the energy system. Therefore, this study focuses on the technological collaboration between the energy company E.ON and the Italian supplier Loccioni and the embedding of new technology in the shape of a local energy system in Sweden. By relying on the Industrial Network Approach and in particular the resource layer this study aims to explore the impact of the collaboration on three levels; the dyadic level, the project level and the system level.
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4. |
- Manzoni, Claudia, et al.
(författare)
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Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia
- 2024
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Ingår i: American Journal of Human Genetics. - 0002-9297. ; 111:7, s. 1316-1329
-
Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10−12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10−12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10−8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.
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5. |
- Ulugut, Hulya, et al.
(författare)
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Clinical recognition of frontotemporal dementia with right anterior temporal predominance : A multicenter retrospective cohort study
- 2024
-
Ingår i: Alzheimer's and Dementia. - 1552-5260.
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. METHODS: Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments. RESULTS: Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations. DISCUSSION: This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients. Highlights: This project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.
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6. |
- Andersson, Elin Möller, et al.
(författare)
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Clinicopathological concordance in cognitive disease diagnostics
- 2020
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Ingår i: Clinical Neuropathology. - 0722-5091. ; 39:3, s. 99-104
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Tidskriftsartikel (refereegranskat)abstract
- Neurocognitive disorder encompasses many separate diagnoses, such as frontotemporal dementia (FTD), Alzheimer's disease (AD), Lewy body dementia (LBD), vascular dementia (VaD), and mixed dementia (MD). Because of the many variations between and within each subtype, it may be a challenge to clinically diagnose each condition. In a previous study on 176 dementia patients in a university hospital cohort between the years 1996 and 2006, a full diagnostic concordance of 49% was demonstrated between clinical diagnoses and pathological morphology [1]. The aims of this study were to do a follow-up on diagnostic concordance from the subsequent 10 years (2007 - 2016) and to compare the results with the previous study from 2009. In all cases of neuropathologically diagnosed dementia disorders (n = 324), the clinical records were searched for information on the clinical diagnosis of dementia, including on subtype. All individuals who had been diagnosed by a specialist were selected (n = 210). In this study, a full concordance between clinical diagnoses and neuropathological morphology was found in 61% of individuals, with marked variations between subgroups, including the lowest (31%) in the group of VaD. Vigilance in clinicopathological concordance is important for quality maintenance as well as the improvement of skills in diagnostic work. In light of the previous study, VaD one decade later remains elusive. The unmasking of this complicated and multifaceted disorder may be beneficial to the overall diagnostic accuracy in cognitive disease investigations.
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7. |
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8. |
- Bonham, LW, et al.
(författare)
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Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10854-
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Tidskriftsartikel (refereegranskat)abstract
- The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
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9. |
- Christidis, Maria, 1982-
(författare)
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Ämnesintegrering på vård- och omsorgsprogrammet utifrån ett verksamhetsteoretiskt perspektiv
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The study investigated subject integrated teaching and vocational knowledge in one Health and Social Care program. The material was collected ethnographically, during a period of a school semester (5 months), and analysed according to the Activity-Theoretical concepts actions, goals and tools.The results identified five goals for subject integrated teaching: the legitimacy of Swedish as a school subject; a focus on linguistic prescriptivism; the identity of vocational subjects; a predominant medical focus in vocational subjects; and a professional language. Further six recurrent tools were identified: a fictional book; a teacher-prepared hand-out; a teacher-constructed case report; teacher-examples from health care; and linguistic rules. There was a theoretical kind of vocational knowledge with focus on language issues, on medical aspects of care, and on a professional language.In conclusion, subject integrated teaching contributed with more than each of the specific subjects contributed with and simultaneously tensions between goals representing different subjects were found. However, tools were shared between subjects.
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10. |
- Ducharme, Simon, et al.
(författare)
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Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders
- 2020
-
Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:6, s. 1632-1650
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Tidskriftsartikel (refereegranskat)abstract
- The behavioural variant of frontotemporal dementia (bvFTD) is a frequent cause of early-onset dementia. The diagnosis of bvFTD remains challenging because of the limited accuracy of neuroimaging in the early disease stages and the absence of molecular biomarkers, and therefore relies predominantly on clinical assessment. BvFTD shows significant symptomatic overlap with non-degenerative primary psychiatric disorders including major depressive disorder, bipolar disorder, schizophrenia, obsessive-compulsive disorder, autism spectrum disorders and even personality disorders. To date, ∼50% of patients with bvFTD receive a prior psychiatric diagnosis, and average diagnostic delay is up to 5-6 years from symptom onset. It is also not uncommon for patients with primary psychiatric disorders to be wrongly diagnosed with bvFTD. The Neuropsychiatric International Consortium for Frontotemporal Dementia was recently established to determine the current best clinical practice and set up an international collaboration to share a common dataset for future research. The goal of the present paper was to review the existing literature on the diagnosis of bvFTD and its differential diagnosis with primary psychiatric disorders to provide consensus recommendations on the clinical assessment. A systematic literature search with a narrative review was performed to determine all bvFTD-related diagnostic evidence for the following topics: bvFTD history taking, psychiatric assessment, clinical scales, physical and neurological examination, bedside cognitive tests, neuropsychological assessment, social cognition, structural neuroimaging, functional neuroimaging, CSF and genetic testing. For each topic, responsible team members proposed a set of minimal requirements, optimal clinical recommendations, and tools requiring further research or those that should be developed. Recommendations were listed if they reached a ≥ 85% expert consensus based on an online survey among all consortium participants. New recommendations include performing at least one formal social cognition test in the standard neuropsychological battery for bvFTD. We emphasize the importance of 3D-T1 brain MRI with a standardized review protocol including validated visual atrophy rating scales, and to consider volumetric analyses if available. We clarify the role of 18F-fluorodeoxyglucose PET for the exclusion of bvFTD when normal, whereas non-specific regional metabolism abnormalities should not be over-interpreted in the case of a psychiatric differential diagnosis. We highlight the potential role of serum or CSF neurofilament light chain to differentiate bvFTD from primary psychiatric disorders. Finally, based on the increasing literature and clinical experience, the consortium determined that screening for C9orf72 mutation should be performed in all possible/probable bvFTD cases or suspected cases with strong psychiatric features.
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11. |
- Gao, YX, et al.
(författare)
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Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 12184-
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Tidskriftsartikel (refereegranskat)abstract
- We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
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12. |
- Gorcenco, Sorina, et al.
(författare)
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Clinical and genetic analyses of a Swedish patient series diagnosed with ataxia
- 2024
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Ingår i: Journal of Neurology. - 0340-5354. ; 271:1, s. 526-542
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary ataxia is a heterogeneous group of complex neurological disorders. Next-generation sequencing methods have become a great help in clinical diagnostics, but it may remain challenging to determine if a genetic variant is the cause of the patient’s disease. We compiled a consecutive single-center series of 87 patients from 76 families with progressive ataxia of known or unknown etiology. We investigated them clinically and genetically using whole exome or whole genome sequencing. Test methods were selected depending on family history, clinical phenotype, and availability. Genetic results were interpreted based on the American College of Medical Genetics criteria. For high-suspicion variants of uncertain significance, renewed bioinformatical and clinical evaluation was performed to assess the level of pathogenicity. Thirty (39.5%) of the 76 families had received a genetic diagnosis at the end of our study. We present the predominant etiologies of hereditary ataxia in a Swedish patient series. In two families, we established a clinical diagnosis, although the genetic variant was classified as “of uncertain significance” only, and in an additional three families, results are pending. We found a pathogenic variant in one family, but we suspect that it does not explain the complete clinical picture. We conclude that correctly interpreting genetic variants in complex neurogenetic diseases requires genetics and clinical expertise. The neurologist’s careful phenotyping remains essential to confirm or reject a diagnosis, also by reassessing clinical findings after a candidate genetic variant is suggested. Collaboration between neurology and clinical genetics and combining clinical and research approaches optimizes diagnostic yield.
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13. |
- Hansson, Oskar, et al.
(författare)
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CSF placental growth factor – a novel candidate biomarker of frontotemporal dementia
- 2019
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 6:5, s. 863-872
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Diagnosis of frontotemporal dementia (FTD) is complicated by the overlap of clinical symptoms with other dementia disorders. Development of robust fluid biomarkers is critical to improve the diagnostic work-up of FTD. Methods: CSF concentrations of placental growth factor (PlGF) were measured in the discovery cohort including patients with FTD (n = 27), Alzheimer disease (AD) dementia (n = 75), DLB or PDD (n = 47), subcortical vascular dementia (VaD, n = 33), mild cognitive impairment that later converted to AD (MCI-AD, n = 34), stable MCI (sMCI, n = 62), and 50 cognitively healthy controls from the Swedish BioFINDER study. For validation, CSF PlGF was measured in additional independent cohort of FTD patients (n = 22) and controls (n = 18) from the Netherlands. Results: In the discovery cohort, MCI, MCI-AD, AD dementia, DLB-PDD, VaD, and FTD patients all showed increased CSF levels of PlGF compared with controls (sMCI P = 0.019; MCI-AD P = 0.005; AD dementia, DLB-PDD, VaD, and FTD all P < 0.001). PlGF levels were 1.8–2.1-fold higher in FTD than in AD, DLB-PDD and VaD (all P < 0.001). PlGF distinguished with high accuracy FTD from controls and sMCI performing better than tau/Aβ42 (AUC 0.954–0.996 versus 0.564–0.754, P < 0.001). A combination of PlGF, tau, and Aβ42 (tau/Aβ42/PlGF) was more accurate than tau/Aβ42 when differentiating FTD from a group of other dementias (AUC 0.972 vs. 0.932, P < 0.01). Increased CSF levels of PlGF in FTD compared with controls were corroborated in the validation cohort. Interpretation: CSF PlGF is increased in FTD compared with other dementia disorders, MCI, and healthy controls and might be useful as a diagnostic biomarker of FTD.
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14. |
- Harper, Luke, et al.
(författare)
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Prenatal Gyrification Pattern Affects Age at Onset in Frontotemporal Dementia
- 2022
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 32:18, s. 3937-3944
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Tidskriftsartikel (refereegranskat)abstract
- The paracingulate sulcus is a tertiary sulcus formed during the third trimester. In healthy individuals paracingulate sulcation is more prevalent in the left hemisphere. The anterior cingulate and paracingulate gyri are focal points of neurodegeneration in behavioral variant frontotemporal dementia (bvFTD). This study aims to determine the prevalence and impact of paracingulate sulcation in bvFTD. Structural magnetic resonance images of individuals with bvFTD (n = 105, mean age 66.9 years), Alzheimer's disease (n = 92, 73.3), and healthy controls (n = 110, 62.4) were evaluated using standard protocol for hemispheric paracingulate sulcal presence. No difference in left hemisphere paracingulate sulcal frequency was observed between groups; 0.72, 0.79, and 0.70, respectively, in the bvFTD, Alzheimer's disease, and healthy control groups, (P = 0.3). A significant impact of right (but not left) hemispheric paracingulate sulcation on age at disease onset was identified in bvFTD (mean 60.4 years where absent vs. 63.8 where present [P = 0.04, Cohen's d = 0.42]). This relationship was not observed in Alzheimer's disease. These findings demonstrate a relationship between prenatal neuronal development and the expression of a neurodegenerative disease providing a gross morphological example of brain reserve.
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15. |
- Jakabek, David, et al.
(författare)
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Structural and microstructural thalamocortical network disruption in sporadic behavioural variant frontotemporal dementia
- 2023
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Ingår i: NeuroImage: Clinical. - 2213-1582. ; 39, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Using multi-block methods we combined multimodal neuroimaging metrics of thalamic morphology, thalamic white matter tract diffusion metrics, and cortical thickness to examine changes in behavioural variant frontotemporal dementia. (bvFTD). Method: Twenty-three patients with sporadic bvFTD and 24 healthy controls underwent structural and diffusion MRI scans. Clinical severity was assessed using the Clinical Dementia Rating scale and behavioural severity using the Frontal Behaviour Inventory by patient caregivers. Thalamic volumes were manually segmented. Anterior and posterior thalamic radiation fractional anisotropy and mean diffusivity were extracted using Tract-Based Spatial Statistics. Finally, cortical thickness was assessed using Freesurfer. We used shape analyses, diffusion measures, and cortical thickness as features in sparse multi-block partial least squares (PLS) discriminatory analyses to classify participants within bvFTD or healthy control groups. Sparsity was tuned with five-fold cross-validation repeated 10 times. Final model fit was assessed using permutation testing. Additionally, sparse multi-block PLS was used to examine associations between imaging features and measures of dementia severity. Results: Bilateral anterior-dorsal thalamic atrophy, reduction in mean diffusivity of thalamic projections, and frontotemporal cortical thinning, were the main features predicting bvFTD group membership. The model had a sensitivity of 96%, specificity of 68%, and was statistically significant using permutation testing (p = 0.012). For measures of dementia severity, we found similar involvement of regional thalamic and cortical areas as in discrimination analyses, although more extensive thalamo-cortical white matter metric changes. Conclusions: Using multimodal neuroimaging, we demonstrate combined structural network dysfunction of anterior cortical regions, cortical-thalamic projections, and anterior thalamic regions in sporadic bvFTD.
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16. |
- Janelidze, Shorena, et al.
(författare)
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Cerebrospinal fluid neurogranin and YKL-40 as biomarkers of Alzheimer's disease.
- 2016
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Ingår i: Annals of clinical and translational neurology. - : Wiley. - 2328-9503. ; 3:1, s. 12-20
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Tidskriftsartikel (refereegranskat)abstract
- Widespread implementation of cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) in clinical settings requires improved accuracy for diagnosis of prodromal disease and for distinguishing AD from non-AD dementias. Novel and promising CSF biomarkers include neurogranin, a marker of synaptic degeneration, and YKL-40, a marker of neuroinflammation.
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17. |
- Javanshiri, Keivan, et al.
(författare)
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Atherosclerosis, Hypertension, and Diabetes in Alzheimer's Disease, Vascular Dementia, and Mixed Dementia : Prevalence and Presentation
- 2018
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877. ; 65:4, s. 1247-1258
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease (AD) is the most prevalent cause of dementia with vascular dementia (VaD) being second alongside with mixed AD and VaD, according to some. For some time, it has been proposed that cardiovascular disease (CaVD), hypertension, and diabetes mellitus (DM), which are known risk factors for VaD, also are associated with and contribute to the development of AD. Objective: The aim of this study was to investigate the prevalence of these proposed general risk factors, and to document presence of CaVD as evidenced from clinical records or from autopsy findings, further to correlate these with the diagnoses AD, VaD and mixed AD-VaD (MD), respectively. Methods: Autopsy reports at the Clinical Department of Pathology in Lund from 1992-2017 were analyzed. All cases with a complete autopsy report and a neuropathologically diagnosed dementia disorder (AD, VaD, or MD) were selected on the condition of a clinical diagnosis of dementia. Clinical data were retrieved through medical records and the Swedish National Diabetes Register (NDR). A total of 268 subjects were included. Results: In AD, there was less CaVD as significantly less organ/tissue findings (p < 0.05), significantly less hypertension (p < 0.001), and likewise significantly less DM (p = 0.0014) than in VaD, with the MD group results being set between these two in all aspects studied. Conclusion: AD and VaD exhibit such different profiles of organ and vascular damage as well as of hypertension and DM that they clearly point toward different pathogenic origin with low likelihood of shared risk factors.
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18. |
- Laage-Hellman, Jens, 1947, et al.
(författare)
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5 R&D Collaboration and Start-ups
- 2017
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Ingår i: Starting up in business networks: Why relationships matter. - London : Palgrave Macmillan UK. - 9781137527141 ; , s. 139-170
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- It is well known from previous studies that R&D collaboration is important to firms’ technological development, especially in business-to-business (B2B) markets. This includes empirical studies carried out in the Industrial Marketing and Purchasing (IMP) tradition focusing on the role and importance of interaction, business relationships and industrial networks (e.g. Baraldi, 2003; Baraldi, Gressetvold, & Harrison, 2012; Gressetvold, 2004; Håkansson, 1987; Håkansson & Waluszewski, 2002, 2007; Laage-Hellman, 1997; Wedin, 2001) as well as other types of innovation studies (e.g. McKelvey, Zaring, & Ljungberg, 2015; Melander, 2014; von Hippel, 1988). Innovation thus tends to be the outcome of interaction processes between different types of actors including, for example, selling and buying firms.
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19. |
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20. |
- Laage-Hellman, Jens, 1947, et al.
(författare)
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Business creation in networks: How a technology-based start-up collaborates with customers in product development
- 2018
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Ingår i: Industrial Marketing Management. - : Elsevier BV. - 0019-8501 .- 1873-2062. ; 70, s. 13-24
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Tidskriftsartikel (refereegranskat)abstract
- This paper deals with business creation in networks by setting the focus on how technology- based start-up companies collaborate with customers in product development. The aim is to analyze the pattern of customer collaboration by using the industrial network approach as theoretical point of departure. The method consists of a process-based single case study. The focal case is Oxeon, a Swedish rapidly growing university spin-off company commercializing a new technology for making carbon fiber composites. The development of products and applications has taken place in close collaboration with their customers. The paper addresses three research issues, which are related to the timing, mutuality and organizing of the collaboration. The analysis of the Oxeon case results in identification of five crucial aspects on the management of customer collaboration: (i) the need for involving customers early, (ii) the choice of application areas, (iii) the mutual process of choosing and getting chosen as collaboration partner, (iv) the external networking role of the start-up, and (v) the internal organizing of the start-up in relation to its ambitions for external interaction with customers. The results are summarized by formulating a set of propositions that can be taken as starting point for further research.
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21. |
- Landqvist, Hans, 1958, et al.
(författare)
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Inledning [till avdelningen Juridik på svenska i Finland]
- 2010
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Ingår i: Mattila, H.E.S., A. Piehl & S. Pajula (toim./red.), Oikeuskieli ja säädöstieto Suomenkielinen lakikirja 250 vuotta - Rättsspråk och författningsinformation Den finskspråkiga lagboken 250 år. - Helsinki/Helsingfors : Suomalainen Lakimiesyhdistys. - 9789518553017 ; , s. 31-33
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Bokkapitel (refereegranskat)
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22. |
- Landqvist, Hans, 1958, et al.
(författare)
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Juridik på svenska i Finland: bakgrund, introduktion och disposition
- 2016
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Ingår i: Juridik på svenska i Finland : perspektiv på språk och rätt / Hans Landqvist, Christer Laurén, Liselott Nordman, Marianne Nordman, Maria Kvist. - Vasa : Förlagsaktiebolaget Scriptum. - 9789527005347 ; , s. 12-39
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Bokkapitel (refereegranskat)
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23. |
- Landqvist, Hans, 1958, et al.
(författare)
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Juridik på svenska i Finland: historia, nutid och framtid
- 2016
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Ingår i: Landqvist, Hans, Christer Laurén, Lieselott Nordman, Marianne Nordman & Maria Kvist, Juridik på svenska i Finland. Perspektiv på språk och rätt. - Vasa : Förlagsaktiebolaget Scriptum. - 9789527005347 ; , s. 370-380
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Bokkapitel (refereegranskat)
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24. |
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25. |
- Landqvist, Hans, 1958, et al.
(författare)
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Summary
- 2016
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Ingår i: Juridik på svenska i Finland : perspektiv på språk och rätt / Hans Landqvist, Christer Laurén, Liselott Nordman, Marianne Nordman, Maria Kvist. - Vasa : Förlagsaktiebolaget Scriptum. - 9789527005347 ; , s. 387-391
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Bokkapitel (refereegranskat)
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26. |
- Landqvist, Maria, 1989, et al.
(författare)
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A start-up embedding in three business network settings: a matter of resource combining
- 2019
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Ingår i: Industrial Marketing Management. - : Elsevier BV. - 0019-8501 .- 1873-2062. ; 80, s. 160-171
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Tidskriftsartikel (refereegranskat)abstract
- This paper focuses on how newly established technology-based start-up companies become part of the business landscape. In more detail, the aim of the paper is to analyse how a start-up becomes embedded through its networking behaviours in a business network. To approach this phenomenon, the theoretical frame of reference is based on the industrial network approach to industrial markets separating a developing, producing and using setting. The business network settings are combined with networking behaviours consisting of both strong and weak ties. Importantly, for a start-up to become embedded through networking, resources of the start-up need to be combined with resources in the three business network settings. The paper relies on a case study methodology focusing on a start-up, founded at a technical university in Sweden, and its networking behaviours. The paper concludes that networking behaviours relying on strong ties are crucial to resource combining. However, the analysis also shows the importance of networking behaviours of weak ties, acquiring information and interaction to sensing new opportunities. The paper ends with managerial implications for start-up managers, pinpointing the need to work with both strong and weak ties as a platform to eventually become embedded in business networks.
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27. |
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28. |
- Landqvist, Maria, et al.
(författare)
-
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
-
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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29. |
- Landqvist, Maria, 1989, et al.
(författare)
-
Exploring renewal, heaviness and variety in the Swedish energy system
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In this paper the existing energy system will be analyzed as heavy resource structures with the aim to explore renewal in heavy resource structures. The energy system can be viewed as an industrial system and thus analytically be seen through the lens of the network model separating: activities, resources and actors (Håkansson, 1987). In order to understand renewal of the established structures, resources are in focus. Resources are seen as heterogeneous, referring to that the value of resources depend on how they are combined with other resources. Resource combining and resource re-combining will be important aspects of renewal in an industrial system characterized by heaviness (Håkansson & Waluszewski, 2002, 2018). Also the established resource structure as context (Bengtson, 2003) will be useful for analyzing possible ways of finding renewal. There is no doubt our modern society needs renewal and energy from renewable sources. Renewable energy refers to energy derived from wind, water, sun and waves, meaning energy from sources that are not consumed. What currently is more of a discussion is what kind of renewable energy sources that will dominate in the coming years. The view of the future is both diverging and uncertain (Melander, Dubois, Hedvall, & Lind, 2019). Many actors try to and will influence the development of future energy sources, including industry, university and government agencies. A starting point is that we will need several different renewable energy sources simultaneously. Developing the technology behind renewable energy is complex since it not only involves developing the technology per se but also infrastructure, systems, business interactions and models. Importantly, what is challenging is that the existing fossil fuel-based energy systems need to be changed and/or replaced, which at times hindering the development. The framework of the paper builds on the assumption of resource heterogeneity implying that the value of resources depends on how they are combined with other resources. Resources could be organizational and technological in nature (Baraldi, Gressetvold, & Harrison, 2012). The framework focuses on how resources are developed through interaction between the start-ups and different types of actors such as developing partners, users and suppliers. Building on this framework we will look at: (1) the resources and their features that are exchanged and developed in interaction, (2) how existing resources are changed, combined and recombined and (3) how resources impact one another, and are accepted or not as new resource combinations in broader contexts. The method of the paper is a case study methodology. The empirical data of the paper is centered on the resource network of the energy sector in Sweden. The case will be used to see the role of interaction between established firms as well as start-ups and in this way explore renewal in heavy resource structures. The paper has its empirical base in an ongoing project funded by the Swedish Energy Agency, where we are investigating the role taken by technology-based start-up companies in commercializing their technologies for renewable energy in Sweden. The start-ups in focus for the project have technologies for renewable energy as their commercial bases, for example, water-based energy solutions and creating renewable energy from algae. Practice and policy underline the importance of innovation in broad and start-ups for economic development and growth. Start-up managers are always foreseeing an uncertain future with limited resources and no established customer relationships (see e.g. Aaboen, Dubois, & Lind, 2011). When their context is characterized by diverse expectations on the fossil free alternatives to be used, we see needs for understanding established firms and start-ups roles for renewable energy in order to contributing insights that can be helpful for government as well as policy terms (Andersson, Vico, Hammar, & Sandén, 2017). We will be able to explain renewal with help of a theoretical approach emphasizing interaction, implying a potential for contribution to the innovation literature as well as opportunities for practical implications for managers in companies and representatives of universities and policy actors.
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30. |
- Landqvist, Maria, et al.
(författare)
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Frontotemporal demens heterogen sjukdomsgrupp.
- 2009
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Ingår i: Läkartidningen. - 0023-7205. ; 106:20, s. 1381-1385
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) or frontotemporal dementia (FTD) is a clinically and neuropathologically heterogeneous group of primary degenerative dementia diseases. The clinical representation consists of progressive psychiatric and/or neurological symtoms such as behavioural changes, language or motor dysfunction. FTD is usually divided into the following subgroups: Behavioural variant FTD (FTD-bv), semantic dementia (SD), progressive non-fluent aphasia (PNFA) and FTD with motor neuron disease (FTD-MND). Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) show both clinical and neuropathological similarities to FTD, and therefore are often considered being part of the FTD complex. Knowledge about the great diversity in phenotype of FTD facilitates early refererral and diagnosis of patients, which is necessary for adequate support and treatment.
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31. |
- Landqvist, Maria
(författare)
-
Frontotemporal dementia - symptoms and brain pathology
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Frontotemporal dementia (FTD) is the clinical term for a heterogeneous group of dementia disorders with symptoms emerging from frontotemporal lobar degeneration (FTLD). FTD encompasses the behavioural variant (bvFTD) and the progressive aphasias: progressive non-fluent aphasia (PNFA) and semantic dementia (SD). Neuropathological classification is based on protein pathology with three major subgroups: Tau, TDP-43 and FUS. Early clinical diagnosis is challenging and prediction of neuropathological subtype is often not possible. The objective was to identify clinical markers (biomarkers or specific symptoms), of possible diagnostic value. In paper I potential cerebrospinal fluid biomarkers were examined. Increased neurofilament light protein (NFL) was seen in FTD compared to Alzheimer’s disease and healthy controls, particularly in the clinical subtype SD and in tau-negative cases. In paper II clinical and neuropathological characteristics in a large bvFTD family with a newly identified mutation (C9ORF72 expansion) were analysed. Despite age variations at onset and duration, symptomatology was strikingly homogenous. Unexpectedly, psychotic symptoms and extensive somatic complaints, not included in current FTD criteria, were common. These symptoms were further analysed in an extended neuropathologically verified cohort (paper III, IV) and both symptom categories were found in about 1/3 of all cases. There was no clear correlation with protein pathology. Psychotic symptoms correlated strongly with right-predominant brain pathology. Clinical misdiagnosis, often psychiatric, was especially common among young patients and in those with psychotic symptoms. Our findings highlight the clinical importance of recognizing symptoms not included in current criteria to achieve a better understanding of these phenomena and to improve diagnostics.
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32. |
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33. |
- Landqvist, Maria, 1989
(författare)
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Patterns of resource interaction in resource constellations: The case of start-ups approaching the Swedish energy system
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This doctoral thesis deals with resource interaction in business networks. Interactive resource development is based on a combination of new and existing resources. However, interactions with specific resource constellations will look different depending on the context in which a new resource is to be embedded. Consequently, to support technological development and innovation it is important to understand how resources interact in a resource constellation and how changes evolve when to make new resources useful in the business network. Therefore, the aim of this thesis is to develop the understanding of resource interaction in business networks. The theoretical starting point is the Industrial Network Approach to industrial markets, especially resource development through interaction. Particular attention is devoted to the resource interfaces that are created between the resources of start-ups and those of other actors in the business network, and the way these are combined to create value for the involved parties over time. The empirical setting of the study is the Swedish energy system, which is characterised by long-term business relationships and investments and an urgent need for transformation. The method used is a single case study that describes the innovation journey of three start-ups when approaching resource constellations. The three start-ups focus on novel approaches to renewable energy. The results of this thesis are manifold. Firstly, the study contributes an analytical model to capture connected resource interfaces in business networks and identify potential hindrances and enablers when embedding new resources into a resource constellation. Consequently, different sequences of connected resource interfaces will occur, forming different resource interaction patterns. Five patterns are identified that can help in estimating the effects of attempting to embed a new resource into a resource constellation. Secondly, the study reveals that exploring the potential versatility of a resource in a resource constellation is a matter of exploring and exploiting resource interfaces within it. Thirdly, the study emphasises the importance of considering not only the known use(s) of a resource but also its potential use(s). Regarding policy implications, it is important to consider the network of the start-up when investing in start-ups that could be part of transforming the Swedish energy system. It is important to assess the resource collections of a start-up and the potential resource constellation it would be part of to see if any existing resources could act as a ‘bridge’ to the energy system. From a start-up manager’s perspective, it is important to have an awareness of the process of working with certain resource interfaces and how they are connected in order to allow for a start-up’s resources to be embedded into the business network. It is also necessary to find collaboration partners that are willing to make adaptations to their own resource collections.
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34. |
- Landqvist, Maria, et al.
(författare)
-
Psychotic symptoms in frontotemporal dementia: a diagnostic dilemma?
- 2015
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Ingår i: International Psychogeriatrics. - 1741-203X. ; 27:4, s. 531-539
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Background: Frontotemporal dementia (FTD) constitutes a spectrum of neurodegenerative disorders associated with degeneration of, predominantly, the frontal and temporal lobes. The clinical heterogeneity is evident, and early diagnosis is a challenge. The primary objectives were to characterize psychotic symptoms, initial clinical diagnoses and family history in neuropathologically verified FTD-patients and to analyze possible correlations with different neuropathological findings. Methods: The medical records of 97 consecutive patients with a neuropathological diagnosis of frontotemporal lobar degeneration (FTLD) were reevaluated. Psychotic symptoms (hallucinations, delusions, paranoid ideas), initial diagnosis and family history for psychiatric disorders were analyzed. Results: Psychotic symptoms were present in 31 patients (32%). There were no significant differences in age at onset, disease duration or gender between patients with and without psychotic symptoms. Paranoid ideas were seen in 20.6%, and hallucinations and delusions in 17.5% in equal measure. Apart from a strong correlation between psychotic symptoms and predominantly right-sided brain degeneration, the majority of patients (77.4%) were tau-negative. Only 14.4% of the patients were initially diagnosed as FTD, while other types of dementia were seen in 34%, other psychiatric disorders in 42%, and 9.2% with other cognitive/neurological disorders. The patients who were initially diagnosed with a psychiatric disorder were significantly younger than the patients with other initial clinical diagnoses. A positive heredity for dementia or other psychiatric disorder was seen in 42% and 26% of the patients respectively. Conclusions: Psychotic symptoms, not covered by current diagnostic criteria, are common and may lead to clinical misdiagnosis in FTD.
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35. |
- Landqvist, Maria, 1989, et al.
(författare)
-
Resource renewal in heavy business networks: the case of Modvion starting up in the Swedish wind energy context
- 2023
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Ingår i: Journal of Business and Industrial Marketing. - : Emerald Group Holdings Ltd.. - 0885-8624 .- 2052-1189. ; 38:3, s. 507-519
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Taking the perspective of a start-up company, the purpose of this paper is to analyse resource renewal in heavy business networks. Design/methodology/approach: The theoretical framework is based on the Industrial Network Approach and, especially, the resource interaction framework, business network settings and studies of starting up in business networks. The basis for the paper is a case study of a start-up in the Swedish wind energy context. Findings: Resource renewal in this case means replacing one resource, having implications for the resource interfaces in the three business network settings. Research limitations/implications: The paper contributes to the area of studies of starting up in business networks by identifying a distinct form of resource renewal in heavy business networks enabled by development of resource interfaces in three business network settings. Practical implications: Managers in start-ups as well as established firms need to interact to create and develop the resource interfaces that are needed to achieve resource renewal. Resource renewal not only is in the hands of start-ups but also requires interactive resource development with various collaboration partners. Originality/value: This study takes a start-up’s perspective to resource renewal of heavy business networks and analyses heaviness based on resource interfaces in three business network settings.
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36. |
- Landqvist, Maria, et al.
(författare)
-
Somatic complaints in frontotemporal dementia.
- 2014
-
Ingår i: American Journal of Neurodegenerative Disease. - 2165-591X. ; 3:2, s. 84-92
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is associated with a broad spectrum of clinical characteristics. The objective of this study was to analyze the prevalence of unexplained somatic complaints in neuropathologically verified FTD. We also examined whether the somatic presentations correlated with protein pathology or regional brain pathology and if the patients with these somatic features showed more depressive traits. Ninety-seven consecutively neuropathologically verified FTLD patients were selected. All 97 patients were part of a longitudinal study of FTD and all medical records were systematically reviewed. The somatic complaints focused on were headache, musculoskeletal, gastro/urogenital and abnormal pain response. Symptoms of somatic character (either somatic complaints and/or abnormal pain response) were found in 40.2%. These patients did not differ from the total group with regard to gender, age at onset or duration. Six patients showed exaggerated reactions to sensory stimuli, whereas three patients showed reduced response to pain. Depressive traits were present in 38% and did not correlate with somatic complaints. Suicidal behavior was present in 17 patients, in 10 of these suicidal behavior was concurrent with somatic complaints. No clear correlation between somatic complaints and brain protein pathology, regional pathology or asymmetric hemispherical atrophy was found. Our results show that many FTD patients suffer from unexplained somatic complaints before and/or during dementia where no clear correlation can be found with protein pathology or regional degeneration. Somatic complaints are not covered by current diagnostic criteria for FTD, but need to be considered in diagnostics and care. The need for prospective studies with neuropathological follow up must be stressed as these phenomena remain unexplained, misinterpreted, bizarre and, in many cases, excruciating.
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37. |
- Landqvist, Maria, 1989, et al.
(författare)
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Start-ups developing business relationships in the Swedish energy system
- 2018
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Ingår i: Proceedings of the IMP Asia 2018 Conference, Sri Lanka, December 2-5.
-
Konferensbidrag (refereegranskat)abstract
- This paper focuses on the process of starting up in the Swedish energy system and in particular how existing resource structures both facilitate and hinder commercialization of new innovations that may contribute to renewable energy solutions. The Swedish energy system is an outcome of many years of investments being made in both public and private infrastructures that can be seen as a ‘heavy resource structure’. However, the current ‘heavy resource structure’ containing for example refineries that generate products from fossil fuels is now subject to huge challenges and must open up for new actors and resources to meet the new demands. By using a case methodology this paper aims to explore how to capture the starting up process in the Swedish energy system and specifically the interplay between organizational and technical resources as a way to embed new technical solutions in already established resource structures. The theoretical starting point is the Industrial Network Approach and especially the concepts of resource interaction and resource interfaces.
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38. |
- Landqvist, Maria, 1989
(författare)
-
Start-ups in Business Networks: Resource Development through Interaction
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This licentiate thesis deals with start-ups’ processes of relating to existing components in the business network in order to develop their innovations and become embedded in it. Previous research has shown that technology-based start-ups rely on external resources through collaborative business partners in order to create innovation. However, how this is done and what effects these collaborations have on the innovation and network itself is an area that needs further study. This licentiate thesis therefore aims to contribute to extending the knowledge of the interactive innovation process for technology-based start-ups by taking the starting point in the start-ups’ resources and how they are combined in the business network. The theoretical starting point is taken in the Industrial Network Approach to industrial markets and, more specifically, the process of resource development through interaction in the business network by seeing the innovations as a result of a number of resource combinations taking place in it. The method used is a case study of three cases that illustrate three different innovation processes for technology-based start-ups to capture resource development in business networks over time. This study shows that these start-ups are in great need of adapting their resource features to fit into the existing resource constellations in the developing, producing and using settings in order to innovate. It is also relevant to approach collaboration partners that are willing to adapt their own resource collections to allow the start-up’s resources to fit into their existing resource structures. Furthermore, the adaptations made in one resource interface impacts other connected resource interfaces, causing friction. Specifically, and as this study reveals, relating in business networks is a way of handling friction, which is a continuous interplay between triggers and changes in the resource interfaces. As a result, the important part lies in creating an understanding of how a specific change in one specific resource interface triggers a new change in a connected resource interface over time. From a managerial point of view, the start-up needs to be aware of the importance of working with proximity of the three settings of developing, producing and using to allow it to embed its resources into the business network. Furthermore, it is relevant to find collaboration partners that are willing to make adaptations to their own resource collections. From a theoretical point of view, this study contributes additional knowledge to the study of resource development as a process by exhibiting the underlying mechanisms of why changes in resource interfaces take place and their consequences.
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39. |
- Landqvist, Maria
(författare)
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The Frontotemporal Dementias.
- 2015
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Ingår i: Psychiatric Clinics of North America. - : Elsevier BV. - 1558-3147 .- 0193-953X. ; 38:2, s. 193-193
-
Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a heterogeneous group of hereditary and sporadic neurodegenerative disorders affecting frontotemporal areas. FTD, a leading cause of young-onset dementia, is often initially mistaken for primary psychiatric disorders. Based on early and predominant symptoms, different clinical syndromes can be distinguished: the behavioral variant and 2 variants of progressive aphasia; semantic dementia and progressive nonfluent aphasia. Neuropathological classification is based on protein accumulation in the brain. Pathogenic mutations in different genes have been identified. Specific pharmacological treatment is the main research goal. Meanwhile the management must focus on early correct diagnosis, symptom alleviation, caregiver support and educational interventions.
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40. |
- Liljegren, Madeleine, et al.
(författare)
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Association of Neuropathologically Confirmed Frontotemporal Dementia and Alzheimer Disease With Criminal and Socially Inappropriate Behavior in a Swedish Cohort
- 2019
-
Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805.
-
Tidskriftsartikel (refereegranskat)abstract
- Importance Criminal and socially inappropriate behavior is encountered among patients with dementia, and it is sometimes the first sign of a dementing disorder. This behavior constitutes a significant burden to society, patients’ relatives, and patients themselves. Objectives To investigate and compare the prevalence and type of criminal and socially inappropriate behavior, as well as recurrence of criminal behavior, associated with Alzheimer disease (AD) and frontotemporal dementia (FTD) neuropathologically verified post mortem, and to assess whether there is a specific type of protein pathology more closely associated with criminal behavior in patients with FTD. Design, Setting, and Participants Cohort study using medical record review of 220 Swedish patients with a postmortem neuropathologic diagnosis of AD (n = 101) or frontotemporal lobar degeneration (n = 119) (hereinafter referred to as FTD) diagnosed between January 1, 1967, and December 31, 2017. Main Outcomes and Measures Patient notes containing reports of criminal and socially inappropriate behavior, as well as data on dominant protein pathology for patients with FTD, were duly reviewed and recorded. The Fisher exact test or logistic regression was used to assess possible differences between groups. Results Of the 220 patients studied, 128 (58.2%) were female, the median (range) age at disease onset was 63 (30-88) years and at death was 72 (34-96) years, and the median (range) disease duration was 9 (1-28) years. Instances of criminal behavior were found in 65 of the 220 patients (29.5%): in 15 of the 101 patients (14.9%) with AD and 50 of the 119 patients (42.0%) with FTD (P < .001). Recurrence of criminal behavior was significantly higher in the FTD group (89.0%) than in the AD group (53.3%) (P = .04). Instances of socially inappropriate behavior were found in 57 patients (56.4%) with AD and 89 (74.8%) with FTD (P = .004). An expression of non-tau pathology increased the odds for criminal behavior by a factor of 9.0 (95% CI, 3.4-24.0) among patients with FTD. Conclusions and Relevance These results suggest that criminal and socially inappropriate behaviors may be more prevalent and criminal behaviors may be more recurrent in patients with FTD than in those with AD. Non-tau pathology, but not tau pathology, appears to be associated with criminal behavior. These findings may help with the clinical diagnostic process.
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41. |
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42. |
- Liljegren, Madeleine, et al.
(författare)
-
Physical aggression among patients with dementia, neuropathologically confirmed post-mortem
- 2018
-
Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 33:2, s. 242-248
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo investigate the prevalence of physical aggression among patients with dementia of different types and to analyze potential differences in clinical traits, in terms of singular or repetitive behavior and occurrence in early or late stage of the disease. We also aimed at examining against whom the physical aggression was exerted.MethodsWe included 281 cases with a neuropathological dementia diagnosis from the brain bank at the Department of Pathology, Lund University, for this retrospective medical records review. The study covers cases with a post-mortem examination performed between 1967 and 2013.ResultsOf the 281 patients studied, 97 (35%) patients had a history of exerting physical aggression during the course of their disease. The patients with frontotemporal dementia exerted physical aggression earlier in the course of their disease than Alzheimer's disease patients. The most frequent victims of the patients' physical aggression were health staff and other patients. The aggression also affected family members as well as (to the demented patient) unknown people. The frequency of the physical aggression differed among the different diagnostic groups; frontotemporal dementia patients exhibiting a higher physical aggression frequency score than did Alzheimer's disease patients.ConclusionsThe patterns of manifested physical aggression thus differ between the frontotemporal dementia and Alzheimer's disease patient groups in this study. Knowledge about such differences may be of value in decision making in patient care.
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43. |
- Liljegren, Madeleine, et al.
(författare)
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Police Interactions Among Neuropathologically Confirmed Dementia Patients: Prevalence and Cause
- 2018
-
Ingår i: Alzheimer Disease and Associated Disorders. - 1546-4156. ; 32:4, s. 346-350
-
Tidskriftsartikel (refereegranskat)abstract
- Objective:The aim of this study was to investigate and compare the prevalence and recurrence of police interaction (PI) with patients diagnosed with dementia. We also aimed to study the reason behind the PI, the time of occurrence of PI, and potential consequences of the PI.Methods:For this retrospective medical records’ review, we included 281 cases with a neuropathologic dementia diagnosis from the Department of Pathology, Region Skane/Lund University, between 1967 and 2013. The diagnoses were Alzheimer disease, frontotemporal lobar degeneration, vascular dementia, and mixed dementia. A prerequisite was that extensive clinical investigation and follow-up had been conducted at the Department of Geriatric Psychiatry in Lund.Results:Of the 281 patients studied, 50 (18%) had a history of interacting with the police during the course of their disease. Frontotemporal dementia patients had a relatively higher prevalence of PI and more often due to criminal behavior. The recurrence of PIs differed among the groups; frontotemporal dementia patients exhibited a higher PI recurrence compared with the other groups.Conclusions:The patterns of PIs differ between the frontotemporal dementia and Alzheimer disease patients. Knowledge about such differences may be of value for the police, the judiciary system, and the society in general.
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44. |
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45. |
- Prenkert, Frans, 1969-, et al.
(författare)
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Resource interaction: Key concepts, relations and representations
- 2022
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Ingår i: Industrial Marketing Management. - : Elsevier BV. - 0019-8501 .- 1873-2062. ; 105, s. 48-59
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Tidskriftsartikel (refereegranskat)abstract
- Value co-creation is a core focus area in both B2B marketing and strategy research, necessitating resource utilization within and across organizational boundaries. In the Industrial Marketing and Purchasing (IMP) group, scholars have focused on the interactions among resources as one important way to analyze central questions about resources in business relationships and networks. This has produced a breadth of investigations and concepts that are locally defined and utilized. This may hamper further theoretical development and inhibit analytical precision. The purpose of this paper is to develop a more general shared understanding of resource interaction by identifying and explicating the key concepts used, and to assess its status as an approach. The paper synthesizes 20 years of research to identify key concepts and the relationships across concepts. This provides both a platform for further conceptual and empirical research within IMP and potential for crossfertilization with parallel B2B areas.
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46. |
- Santillo, Alexander F., et al.
(författare)
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[18F]RO948 tau positron emission tomography in genetic and sporadic frontotemporal dementia syndromes
- 2023
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 50:5, s. 1371-1383
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine [18F]RO948 retention in FTD, sampling the underlying protein pathology heterogeneity. Methods: A total of 61 individuals with FTD (n = 35), matched cases of AD (n = 13) and Aβ-negative cognitively unimpaired individuals (n = 13) underwent [18F]RO948PET and MRI. FTD included 21 behavioral variant FTD (bvFTD) cases, 11 symptomatic C9orf72 mutation carriers, one patient with non-genetic bvFTD-ALS, one individual with bvFTD due to a GRN mutation, and one due to a MAPT mutation (R406W). Tracer retention was examined using a region-of-interest and voxel-wise approaches. Two individuals (bvFTD due to C9orf72) underwent postmortem neuropathological examination. Tracer binding was additionally assessed in vitro using [3H]RO948 autoradiography in six separate cases. Results: [18F]RO948 retention across ROIs was clearly lower than in AD and comparable to that in Aβ-negative cognitively unimpaired individuals. Only minor loci of tracer retention were seen in bvFTD; these did not overlap with the observed cortical atrophy in the cases, the expected pattern of atrophy, nor the expected or verified protein pathology distribution. Autoradiography analyses showed no specific [3H]RO948 binding. The R406W MAPT mutation carriers were clear exceptions with AD-like retention levels and specific in-vitro binding. Conclusion: [18F]RO948 uptake is not significantly increased in the majority of FTD patients, with a clear exception being specific MAPT mutations.
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47. |
- Santillo, Alexander Frizell, et al.
(författare)
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Diffusion Tensor Tractography versus Volumetric Imaging in the Diagnosis of Behavioral Variant Frontotemporal Dementia
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7, s. e66932-
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Tidskriftsartikel (refereegranskat)abstract
- MRI diffusion tensor imaging (DTI) studies of white matter integrity in behavioral variant frontotemporal dementia have consistently shown involvement of frontal and temporal white matter, corresponding to regional loss of cortical volume. Volumetric imaging has a suboptimal sensitivity as a diagnostic tool and thus we wanted to explore if DTI is a better method to discriminate patients and controls than volumetric imaging. We examined the anterior cingulum bundle in 14 patients with behavioral variant frontotemporal dementia and 22 healthy controls using deterministic manual diffusion tensor tractography, and compared DTI parameters with two measures of cortical atrophy, VBM and cortical thickness, of the anterior cingulate cortex (ACC). Statistically significant changes between patients and controls were detected in all DTI parameters, with large effect sizes. ROC-AUC was for the best DTI parameters: 0.92 (fractional anisotropy) to 0.97 (radial diffusivity), 0.82 for the best cortical parameter, VBM of the ACC. Results from the AUC were confirmed with binary logistic regression analysis including demographic variables, but only for fractional anisotropy and mean diffusivity. Ability to classify patient/nonpatient status was significantly better for mean diffusivity vs. VBM (p = 0.031), and borderline significant for fractional anisotropy vs. VBM (p = 0.062). The results indicate that DTI could offer advantages in comparison with the assessment of cortical volume in differentiating patients with behavioral variant frontotemporal dementia and controls.
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48. |
- Santillo, Alexander Frizell, et al.
(författare)
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Grey and white matter clinico-anatomical correlates of disinhibition in neurodegenerative disease
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico- anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information- based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insularorbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the prefrontal syndrome and the central role attributed to the ventromedial prefrontal cortex in inhibitory control.
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- Spotorno, Nicola, et al.
(författare)
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Plasma neurofilament light protein correlates with diffusion tensor imaging metrics in frontotemporal dementia
- 2020
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilaments are structural components of neurons and are particularly abundant in highly myelinated axons. The levels of neurofilament light chain (NfL) in both cerebrospinal fluid (CSF) and plasma have been related to degeneration in several neurodegenerative conditions including frontotemporal dementia (FTD) and NfL is currently considered as the most promising diagnostic and prognostic fluid biomarker in FTD. Although the location and function of filaments in the healthy nervous system suggests a link between increased NfL and white matter degeneration, such a claim has not been fully elucidated in vivo, especially in the context of FTD. The present study provides evidence of an association between the plasma levels of NfL and white matter involvement in behavioral variant FTD (bvFTD) by relating plasma concentration of NfL to diffusion tensor imaging (DTI) metrics in a group of 20 bvFTD patients. The results of both voxel-wise and tract specific analysis showed that increased plasma NfL concentration is associated with a reduction in fractional anisotropy (FA) in a widespread set of white matter tracts including the superior longitudinal fasciculus, the fronto-occipital fasciculus the anterior thalamic radiation and the dorsal cingulum bundle. Plasma NfL concentration also correlated with cortical thinning in a portion of the right medial prefrontal cortex and of the right lateral orbitofrontal cortex. These results support the hypothesis that blood NfL levels reflect the global level of neurodegeneration in bvFTD and help to advance our understanding of the association between this blood biomarker for FTD and the disease process.
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