| 1. |
- Bäckström, David C, M.D. 1978-
(author)
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The biology of cognitive decline and reduced survival in Parkinson disease : prognostic factors in a population-based cohort
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Parkinson disease (PD) is a progressive neurodegenerative disease that affects about 1% of the population over 60 years. The cardinal symptoms are motor disabilities but cognitive decline is also common. About 50% of all persons with PD develop dementia within 10 years after disease onset. Dementia in PD account for high social costs and has large, negative effects on quality of life. Aims. The aim of the study was to investigate clinical, neurobiological and genetic factors of importance for progression and for the prognosis in PD and parkinsonism. First, we aimed to describe mortality and risk factors for death, including possible associations with cognitive dysfunction, in patients with idiopathic parkinsonism. Second, we aimed to study if biomarkers in the cerebrospinal fluid (CSF) are useful for the diagnosis of different forms of idiopathic parkinsonism and prediction of cognitive decline in PD. Methods. A population-based cohort consisting of patients with new-onset, idiopathic parkinsonism was studied prospectively. After screening in a catchment area of ~142 000 inhabitants in Sweden, 182 patients with parkinsonism were included. The patients were investigated comprehensively, including neuropsychological testing, multimodal neuroimaging and genetic and biosample analyses. During follow up, 143 patients were diagnosed with PD, 13 with multiple system atrophy (MSA), and 18 with progressive supranuclear palsy (PSP). A total of 109 patients died. Results. Patients with MSA and PSP had the shortest life expectancy. PD patients who presented with normal cognitive function had a largely normal life expectancy. In contrast, the mortality was increased in PD patients with cognitive impairment, freezing of gait, hyposmia, and mildly elevated leukocytes in the CSF. Of importance for the prognosis, patients with PD with an early CSF pattern of high Neurofilament light protein, low β-amyloid, and high heart fatty acid binding protein had an 11.8 times increased risk of developing PD dementia (95% CI 3.3-42.1, p <0.001), compared with PD patients with a more ”normal” CSF pattern. Variation in genes associated with dopamine function was also associated with some effects on cognitive functions in PD. Conclusions. PD subtypes, for instance the subtype characterized by cognitive decline, have distinguishing clinical, neurochemical and neurobiological traits, which are of importance for the prognosis and the survival. An early CSF analysis is useful for predicting cognitive decline. The finding of a low-grade immune reaction in the CSF of patients with PD may have clinical implications. In clinical practice, CSF biomarkers could be useful for improving diagnosis and prognostication.
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| 2. |
- Ekman, Urban, et al.
(author)
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Increase of frontal neuronal activity in chronic neglect after training in virtual reality
- 2018
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In: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 138:4, s. 284-292
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Journal article (peer-reviewed)abstract
- Objectives: A third of patients with stroke acquire spatial neglect associated with poor rehabilitation outcome. New effective rehabilitation interventions are needed. Scanning training combined with multisensory stimulation to enhance the rehabilitation effect is suggested. In accordance, we have designed a virtual-reality based scanning training that combines visual, audio and sensori-motor stimulation called RehAtt((R)). Effects were shown in behavioural tests and activity of daily living. Here, we use fMRI to evaluate the change in brain activity during Posners Cuing Task (attention task) after RehAtt((R)) intervention, in patients with chronic neglect.Methods: Twelve patients (mean age=72.7years, SD=6.1) with chronic neglect (persistent symptoms >6months) performed the interventions 3 times/wk during 5weeks, in total 15hours. Training effects on brain activity were evaluated using fMRI task-evoked responses during the Posners cuing task before and after the intervention.Results: Patients improved their performance in the Posner fMRI task. In addition, patients increased their task-evoked brain activity after the VR interventions in an extended network including pre-frontal and temporal cortex during attentional cueing, but showed no training effects during target presentations.Conclusions: The current pilot study demonstrates that a novel multisensory VR intervention has the potential to benefit patients with chronic neglect in respect of behaviour and brain changes. Specifically, the fMRI results show that strategic processes (top-down control during attentional cuing) were enhanced by the intervention. The findings increase knowledge of the plasticity processes underlying positive rehabilitation effects from RehAtt((R)) in chronic neglect.
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| 3. |
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| 4. |
- Lenfeldt, Niklas, et al.
(author)
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Alterations in white matter microstructure are associated with goal-directed upper-limb movement segmentation in children born extremely preterm
- 2017
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In: Human Brain Mapping. - Hoboken : Wiley-Blackwell. - 1065-9471 .- 1097-0193. ; 38:10, s. 5051-5068
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Journal article (peer-reviewed)abstract
- Altered white matter microstructure is commonly found in children born preterm (PT), especially those born at an extremely low gestational age (GA). These children also commonly show disturbed motor function. This study explores the relation between white matter alterations and upperlimb movement segmentation in 41 children born PT (19 girls), and 41 children born at term (18 girls) at 8 years. The PT group was subdivided into extremely PT (E-PT; GA = 25–27 weeks, N = 10), very PT (V-PT; GA = 28–32 weeks, N = 13), and moderately PT (M-PT; GA = 33–35 weeks, N = 18). Arm/hand preference (preferred/non-preferred) was determined through object interactions and the brain hemispheres were designated accordingly. White matter alterations were assessed using diffusion tensor imaging in nine areas, and movement segmentation of the body-parts head, shoulder, elbow, and wrist were registered during a unimanual goal-directed task. Increased movement segmentation was demonstrated consistently on the preferred side in the E-PT group compared with the term born group. Also compared with the term born peers, the E-PT group demonstrated reduced fractional anisotropy (FA) in the cerebral peduncle (targeting the corticospinal tract) in the hemisphere on the non-preferred side and in the splenium of corpus callosum. In contrast, in the anterior internal capsule on the preferred side, the E-PT group had increased FA. Lower FA in the cerebral peduncle, but higher FA in the anterior internal capsule, was associated with increased movement segmentation across body-parts in a contralateral manner. The results suggest that impaired development of sensorimotor tracts in E-PT children could explain a sub-optimal spatiotemporal organization of upper-limb movements.
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| 5. |
- Lenfeldt, Niklas, et al.
(author)
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Fractional Anisotropy and Mean Diffusion as Measures of Dopaminergic Function in Parkinson's Disease : Challenging Results
- 2017
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In: Journal of Parkinson's Disease. - 1877-7171 .- 1877-718X. ; 7:1, s. 129-142
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Journal article (peer-reviewed)abstract
- Background: Diffusion tensor imaging (DTI) has been purported as an imaging technique to assess dopaminergic degeneration in Parkinson’s disease.Objective: To test if fractional anisotropy (FA) and mean diffusion (MD) in the basal ganglia as measured by DTI correlates with dopaminergic function as measured by dopamine transporter (DAT) and dopamine D2-receptor (D2R) SPECT.Methods: One-hundred and eleven patients with Parkinson’s disease (71±10 years) and thirty-one controls (68±7 years) performed DTI, DAT and D2R SPECT at baseline and four follow-ups (1-year: 89 patients/zero controls; 3-year: 72/11; 5-year: 48/17; and 8-year: 13/13). Four equipment combinations of MRI scanners/SPECT gamma cameras were used during the study. Data from each combination were analyzed separately. Regions-of-interest were outlined in the substantia nigra (three subareas, DTI only) and in the striatum (putamen and caudate). Side differences and bilateral averages were correlated using linear regression. The significance threshold was set at P < 0.001 and 0.001 < P< 0.05 was defined as a trend towards significance.Results: For side differences, no significant correlations were observed, but in patients, there was a trend towards a negative correlation between MD in the middle nigra and putaminal DAT uptake in two combinations (P = 0.04 and P = 0.03). For averages, in patients, striatal MD correlated negatively with striatal DAT uptake in one combination (P = 0.0005) and trended towards negative correlations with striatal D2R uptake (one combination, P = 0.03) and with the sum of striatal DAT and D2R uptake (two combinations P = 0.002 and P = 0.03). FA showed no correlations in patients, and no correlations were found in controls.Conclusions: The poor correlations between MD and dopamine activity –and absent correlations for FA – imply that additional diffusion measures must be developed to reliably assess the dopaminergic degeneration in Parkinson’s disease.
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| 6. |
- Lenfeldt, Niklas, et al.
(author)
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Fractional anisotropy in the substantia nigra in Parkinson's disease : a complex picture
- 2015
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In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 22:10, s. 1410-1416
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Journal article (peer-reviewed)abstract
- Background and purpose: This study employs magnetic resonance imaging (MRI) diffusion tensor imaging to compare diffusion measures in the brains of patients with Parkinson's disease (PD) with healthy controls using longitudinal data. Methods: One-hundred and twenty-two patients and 34 controls were included at baseline. The MRI investigations were repeated after 1, 3 and 5 years. The diffusion measures were quantified using fractional anisotropy and mean, radial and axial diffusion (FA, MD, RD, AD). Regions of interest included the anterior, middle and posterior substantia nigra (SN), but also other areas. Linear models were used to test for the effect of disease and hemispheric lateralization. The P value was set at 0.05 (Bonferroni corrected). Results: Fractional anisotropy and AD were increased in the three nigral subareas in PD (P < 0.01), but MD and RD were unaltered. The right SN had higher FA than the left in all subareas (P < 0.01). MD and AD were increased in the right anterior part (P < 0.04), whereas MD and RD were decreased in the right middle and posterior parts (P < 0.001). The left middle cerebellar peduncle had increased FA and AD (P < 0.001) and decreased MD and RD (P < 0.01) compared to the right. Diffusion measures did not progress over time and side differences were not related to disease or lateralization of symptoms. Conclusions: Increased FA in the SN in PD indicates gliosis and inflammation in the nuclei, but possibly also intrusion of surrounding fibres into the shrinking structure. The hemispheric side differences of diffusion might reflect natural lateralization of connectivity, but their relation to PD must be studied further.
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| 7. |
- Lenfeldt, Niklas, et al.
(author)
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Frontal white matter injuries predestine gait difficulties in Parkinson's disease
- 2016
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In: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 134:3, s. 210-218
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Journal article (peer-reviewed)abstract
- Objectives: This study applies diffusion tensor imaging (DTI) to determine differences in neuronal integrity between motor phenotypes in Parkinson's disease. Material and Methods: One hundred and twenty-two patients (47 females, mean age = 70.3 years) were included at baseline. Forty patients were tremor dominant (TD), 64 had postural imbalance and gait difficulty (PIGD), and 18 patients were indeterminate. The DTI was repeated after one, three and 5 years, including reassessment of phenotype. DTI was quantified using fractional anisotropy (FA), and mean, radial and axial diffusion. Targeted white matter involved six regions of interests (ROIs) in prefrontal cortex (PFC), the entrance to the external capsule (EEC) and lateral to the horn of the anterior ventricle (LVAH). Grey matter involved the basal ganglia. Data were analysed using mixed linear models with P < 0.05 (Bonferroni corrected) as significance threshold. Results: PIGD and Indeterminate had reduced FA and axial diffusion in PFC, EEC and LVAH compared to Tremor dominant (P < 0.05). Basal ganglia showed no differences. Post hoc analysis showed that FA correlated negatively, and mean and radial diffusion positively, to PIGD symptoms in EEC, LVAH and four ROIs in PFC (P < 0.05). Tremor symptoms showed no correlations. Patients converting to PIGD and Indeterminate had lower FA, and higher mean and radial diffusion, at baseline in EEC, LVAH and four areas in PFC compared to non-converting patients (P < 0.05). Conclusion: Degeneration in frontal white matter is connected to PIGD symptoms in Parkinson's disease and if present at an early stage, the risk for conversion to the PIGD phenotype increases.
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| 8. |
- Rönnqvist, Louise, et al.
(author)
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Assessment of myelin and brain volumes at early school-age: long-term effects of a preterm birth
- 2018
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In: Developmental Medicine & Child Neurology. - : John Wiley & Sons. - 0012-1622 .- 1469-8749. ; 60:S2, s. 20-20
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Journal article (peer-reviewed)abstract
- Introduction: Structural and functional alterations in white matter architecture are common described in children born preterm (PT) and associated to behavioral implications. Still, how critical gestational immaturity may associate with later myelination is less studied. This study aimed to explore the influence and associations between gestational age (GA) and birthweight (BW) in children born PT compared with fullterm (FT), on quantitative values of brain myelin and volumes.Patients and methods: Participants included 60 children (mean age = 8.2 years) categorized based on GA (weeks); ranging from 25 - 35.4 in PTs (N=27); 38 - 41.9 in FTs (N=33). Volumetric brain measures were conducted by a 3.0-Tesla MRI-scanner and synthetic MRI (SyMRI) acquisition sequence, including synthesis of contrast weighted images. Automatic segmentation of total brain tissues (intracranial [ICV] and parenchymal [BPV] volume [ml]) generated gray-matter (GM), white-matter (WM), cerebrospinal fluid (CSF), and total myelin volume.Result: Children born extremely PT (<27GW) displayed reductions of total BPV and WM compared to FTs, less myelinated content than very PT (VPT; < 32GW) and moderately PT (MPT; <36GW), and significant more CSF than FT-born. Significant positive correlation between respectively increasing GA (r= .48) and BW (r= .53) and amount of myelinated content were found for the PT-born.Conclusion: Detection of diversity regarding myelination and brain-volumes and associations to risk factors related to gestational immaturity may be useful for increased understanding of long-term effects of degree of prematurity and allowing future investigations of how interventions effects brain myelination (and plasticity) in children born PT.
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| 9. |
- Rönnqvist, Louise, et al.
(author)
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Associations between brain volumes, myelin and upper-limb kinematics in children born preterm
- 2019
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In: Developmental Medicine & Child Neurology. - : Wiley-Blackwell. - 0012-1622 .- 1469-8749. ; 61:S2, s. 53-54
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Journal article (peer-reviewed)abstract
- Introduction: Long-term outcomes linked to preterm (PT) births have generally found an increased amount of neuromotor-developmental delays and/or disabilities. Few studies have addressed how upper-limb kinematics associates with brain volumes and myelination. This study aimed to investigate such possible relationships within children born PT compared with term-born controls at early school age, in relation to gestational age (GA) and birth-weight (BW).Material and methods: This sub-study, part of a multidisciplinary project exploring long-term effects of PT births, included 27 children (Mean age= 8.2y) born PT (Mean GA= 32-weeks, range 22-35), and 33 age-matched born term. Kinematics of task-specific head and bi-/uni-manual upper-limb-movements was measured by a 3D-registration system (ProReflex). Brain volumes and myelin content were investigated by a 3-Tesla, magnetic resonance imaging (MRI)-scanner with a 7-min Synthetic MRI (SyMRI) acquisition-sequence.Results: Significantly (p < .05) less efficient upper-limb kinematics with more segmented and longer movement paths was found in PT-born compared with term-born, particularly evident for those extremely-/very PT-born (<32 GA). Smaller total brain volumes and regional white-matter reduction with less myelin were significantly correlated with more segmented and longer arm- and head-trajectories, and with lower GA and BW.Discussion-conclusion: The present findings show that an extremely- and very-PT-birth may cause long-term effects on neuromotor-mechanisms involved in goal-directed movements and that these effects are associated with generally delayed brain development and myelination. Additionally, SyMRI stands out as a suitable and cost-effective method for longitudinal/follow-up of brain development and changes, reducing distress in children due to a decreased scan time.
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| 10. |
- Wåhlin, Anders, et al.
(author)
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Rehabilitation in chronic spatial neglect strengthens resting-state connectivity
- 2019
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In: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 139:3, s. 254-259
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Journal article (peer-reviewed)abstract
- Objectives: Rehabilitation of patients with chronic visuospatial neglect is underexplored, and little is known about neural mechanisms that can be exploited to promote recovery. In this study, we present data on resting-state functional connectivity within the dorsal attention network (DAN) in chronic neglect patients as they underwent training in a virtual reality (VR) environment that improved left-side awareness.Methods: The study included 13 patients with visuospatial neglect persisting more than six months after a right-sided stroke. The patients underwent resting-state functional magnetic resonance imaging (fMRI). Scans were collected at baseline and after five weeks of intense training. We specifically examined resting-state functional connectivity within the DAN. In addition, using spatial concordance correlation, we compared changes in the spatial topology of the DAN with that of other networks.Results: We found a longitudinal increase in interhemispheric functional connectivity between the right frontal eye field and the left intraparietal sulcus following training (before: 0.33 +/- 0.17 [mean +/- SD]; after: 0.45 +/- 0.13; P = 0.004). The spatial concordance analyses indicated that training influenced the DAN connectivity more than any of the other networks.Conclusion: Intense VR training that improved left-sided awareness in chronic stroke patients also increased sporadic interhemispheric functional connectivity within the DAN. Specifically, a region responsible for saccadic eye movement to the left became more integrated with the left posterior parietal cortex. These results highlight a mechanism that should be exploited in the training of patients with chronic visuospatial neglect.
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