301 results on '"Borghammer P"'
Search Results
2. Sertraline treatment influences [18F]FE-PE2I PET imaging for Parkinsonism
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Justesen, Thomas E. H., Borghammer, Per, Aanerud, Joel, Hovind, Peter, and Marner, Lisbeth
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- 2023
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3. The heterogeneity of Parkinson’s disease
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Wüllner, Ullrich, Borghammer, Per, Choe, Chi-un, Csoti, Ilona, Falkenburger, Björn, Gasser, Thomas, Lingor, Paul, and Riederer, Peter
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- 2023
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4. The brain-first vs. body-first model of Parkinson’s disease with comparison to alternative models
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Borghammer, Per
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- 2023
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5. Thyroid [123I]MIBG uptake in Parkinson’s disease and diabetes mellitus
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Tatyana D. Fedorova, Karoline Knudsen, Thorsten K. Rasmussen, Jacob Horsager, Adjmal Nahimi, Casper Skjærbæk, Eva Schaeffer, Daniela Berg, Astrid J. Terkelsen, and Per Borghammer
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Parkinson’s disease ,Diabetes mellitus ,MIBG ,Thyroid gland ,Scintigraphy ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Thyroid [123I]MIBG uptake is proposed as a tool for differentiating between Parkinson’s disease (PD) and diabetes mellitus (DM) on [123I]MIBG scintigraphies since both patient groups show decreased cardiac uptake. One study compared thyroid [123I]MIBG uptake in DM and PD patients and reported reduced [123I]MIBG uptake only in the PD group. Here, we investigated thyroid [123I]MIBG uptake in patients with PD and DM and found severely reduced thyroid [123I]MIBG uptake in DM. Larger studies are needed to substantiate whether DM patients are more or less likely to exhibit decreased thyroid MIBG uptake compared to controls and PD patients.
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- 2023
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6. Sertraline treatment influences [18F]FE-PE2I PET imaging for Parkinsonism
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Thomas E. H. Justesen, Per Borghammer, Joel Aanerud, Peter Hovind, and Lisbeth Marner
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Dopamine transporter ,SSRI ,Blocking ,DAT ,Positron emission tomography ,Parkinson’s disease ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Abstract Background The dopamine transporter (DaT) PET ligand [18F]FE-PE2I is used to aid the diagnosis of Parkinson’s disease. After encountering four patients with a history of daily sertraline use, who all showed atypical findings on [18F]FE-PE2I PET, we suspected that the selective serotonin reuptake inhibitor (SSRI), sertraline, might interfere with the results and lead to globally reduced striatal [18F]FE-PE2I binding due to sertraline’s high affinity for DaT. Methods We rescanned the four patients with [18F]FE-PE2I PET after a 5-day sertraline pause. Sertraline plasma concentration was estimated based on body weight and dose, and specific binding ratios (SBR) in caudate nucleus, known to be more preserved in Parkinson’s, were used to estimate the effect on tracer binding. Comparison was made to a patient with [18F]FE-PE2I PET before and after a 7-day Modafinil pause. Results We found a significant effect of sertraline on caudate nucleus SBR (p = 0.029). The effect showed a linear dose-dependent relationship that corresponds to a reduction in SBR by 0.32 or 0.44 for a 75 kg male or a 65 kg female, respectively, taking a daily dose of 50 mg sertraline. Conclusion Sertraline is one of the most commonly used antidepressants and in contrast to other SSRI’s, sertraline show high affinity for DaT. We recommend that sertraline treatment is taken into account when patients are undergoing [18F]FE-PE2I PET especially in patients showing apparent globally reduced PE2I binding. If tolerable, pausing of the sertraline treatment should be considered, especially for doses above 50 mg/day.
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- 2023
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7. RBDtector: an open-source software to detect REM sleep without atonia according to visual scoring criteria
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Annika Röthenbacher, Matteo Cesari, Christopher E. J. Doppler, Niels Okkels, Nele Willemsen, Nora Sembowski, Aline Seger, Marie Lindner, Corinna Brune, Ambra Stefani, Birgit Högl, Stephan Bialonski, Per Borghammer, Gereon R. Fink, Martin Schober, and Michael Sommerauer
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Medicine ,Science - Abstract
Abstract REM sleep without atonia (RSWA) is a key feature for the diagnosis of rapid eye movement (REM) sleep behaviour disorder (RBD). We introduce RBDtector, a novel open-source software to score RSWA according to established SINBAR visual scoring criteria. We assessed muscle activity of the mentalis, flexor digitorum superficialis (FDS), and anterior tibialis (AT) muscles. RSWA was scored manually as tonic, phasic, and any activity by human scorers as well as using RBDtector in 20 subjects. Subsequently, 174 subjects (72 without RBD and 102 with RBD) were analysed with RBDtector to show the algorithm’s applicability. We additionally compared RBDtector estimates to a previously published dataset. RBDtector showed robust conformity with human scorings. The highest congruency was achieved for phasic and any activity of the FDS. Combining mentalis any and FDS any, RBDtector identified RBD subjects with 100% specificity and 96% sensitivity applying a cut-off of 20.6%. Comparable performance was obtained without manual artefact removal. RBD subjects also showed muscle bouts of higher amplitude and longer duration. RBDtector provides estimates of tonic, phasic, and any activity comparable to human scorings. RBDtector, which is freely available, can help identify RBD subjects and provides reliable RSWA metrics.
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- 2022
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8. A postmortem study suggests a revision of the dual-hit hypothesis of Parkinson’s disease
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Per Borghammer, Mie Kristine Just, Jacob Horsager, Casper Skjærbæk, Anna Raunio, Eloise H. Kok, Sara Savola, Shigeo Murayama, Yuko Saito, Liisa Myllykangas, and Nathalie Van Den Berge
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract The dual-hit hypothesis of Parkinson’s disease (PD) originally postulated that a neurotropic pathogen leads to formation of α-synuclein pathology in the olfactory bulb (OB) and dorsal motor nucleus of the vagus (DMV) and then invades the brain from these two entry points. Little work has been conducted to validate an important underlying premise for the dual-hit hypothesis, namely that the initial Lewy pathology does arise simultaneously in the OB and the enteric nervous system (ENS) plexuses and DMV at the earliest disease stage. We conducted a focused re-analysis of two postmortem datasets, which included large numbers of mild Lewy body disease (LBD) cases. We found that cases with α-synuclein pathology restricted to the peripheral autonomic nervous system and/or lower brainstem (early body-first LBD cases) very rarely had any OB pathology, suggesting that Lewy pathology commonly arises in the ENS without concomitant involvement of the OB. In contrast, cases with mild amygdala-predominant Lewy pathology (early brain-first LBD cases) nearly always showed OB pathology. This is compatible with the first pathology being triggered in the OB or amygdala followed by secondary spreading to connected structures, but without early involvement of the ENS or lower brainstem. These observations support that the pathologic process starts in either the olfactory bulb or the ENS, but rarely in the olfactory bulb and gut simultaneously. More studies on neuropathological datasets are warranted to reproduce these findings. The agreement between the revised single-hit hypothesis and the recently proposed brain-first vs. body-first model of LBD is discussed.
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- 2022
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9. Distribution of cholinergic nerve terminals in the aged human brain measured with [18F]FEOBV PET and its correlation with histological data
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Niels Okkels, Jacob Horsager, Miguel A. Labrador-Espinosa, Frederik O. Hansen, Katrine B. Andersen, Mie Kristine Just, Tatyana D. Fedorova, Casper Skjærbæk, Ole L. Munk, Kim V. Hansen, Hanne Gottrup, Allan K. Hansen, Michel J. Grothe, and Per Borghammer
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Brain ,Cholinergic Neurons ,VAChT Proteins ,PET-CT ,mRNA ,Healthy Volunteer ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Introduction: [18F]fluoroetoxybenzovesamicol ([18F]FEOBV) is a positron emission topography (PET) tracer for the vesicular acetylcholine transporter (VAChT), a protein located predominantly in synaptic vesicles in cholinergic nerve terminals. We aimed to use [18F]FEOBV PET to study the cholinergic topography of the healthy human brain. Materials and methods: [18F]FEOBV PET brain data volumes of healthy elderly humans were normalized to standard space and intensity-normalized to the white matter. Stereotactic atlases of regions of interest were superimposed to describe and quantify tracer distribution. The spatial distribution of [18F]FEOBV PET uptake was compared with histological and gene expression data. Results: Twenty participants of both sexes and a mean age of 73.9 ± 6.0 years, age-range [64; 86], were recruited. Highest tracer binding was present in the striatum, some thalamic nuclei, and the basal forebrain. Intermediate binding was found in most nuclei of the brainstem, thalamus, and hypothalamus; the vermis and flocculonodular lobe; and the hippocampus, amygdala, insula, cingulate, olfactory cortex, and Heschl's gyrus. Lowest binding was present in most areas of the cerebral cortex, and in the cerebellar nuclei and hemispheres. The spatial distribution of tracer correlated with immunohistochemical post-mortem data, as well as with regional expression levels of SLC18A3, the VAChT coding gene. Discussion: Our in vivo findings confirm the regional cholinergic distribution in specific brain structures as described post-mortem. A positive spatial correlation between tracer distribution and regional gene expression levels further corroborates [18F]FEOBV PET as a validated tool for in vivo cholinergic imaging. The study represents an advancement in the continued efforts to delineate the spatial topography of the human cholinergic system in vivo.
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- 2023
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10. A postmortem study suggests a revision of the dual-hit hypothesis of Parkinson’s disease
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Borghammer, Per, Just, Mie Kristine, Horsager, Jacob, Skjærbæk, Casper, Raunio, Anna, Kok, Eloise H., Savola, Sara, Murayama, Shigeo, Saito, Yuko, Myllykangas, Liisa, and Van Den Berge, Nathalie
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- 2022
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11. In vivo vesicular acetylcholine transporter density in human peripheral organs: an [18F]FEOBV PET/CT study
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Horsager, Jacob, Okkels, Niels, Van Den Berge, Nathalie, Jacobsen, Jan, Schact, Anna, Munk, Ole Lajord, Vang, Kim, Bender, Dirk, Brooks, David J., and Borghammer, Per
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- 2022
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12. RBDtector: an open-source software to detect REM sleep without atonia according to visual scoring criteria
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Röthenbacher, Annika, Cesari, Matteo, Doppler, Christopher E. J., Okkels, Niels, Willemsen, Nele, Sembowski, Nora, Seger, Aline, Lindner, Marie, Brune, Corinna, Stefani, Ambra, Högl, Birgit, Bialonski, Stephan, Borghammer, Per, Fink, Gereon R., Schober, Martin, and Sommerauer, Michael
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- 2022
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13. In vivo vesicular acetylcholine transporter density in human peripheral organs: an [18F]FEOBV PET/CT study
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Jacob Horsager, Niels Okkels, Nathalie Van Den Berge, Jan Jacobsen, Anna Schact, Ole Lajord Munk, Kim Vang, Dirk Bender, David J. Brooks, and Per Borghammer
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VAChT ,Vesicular acetylcholine transporter ,Cholinergic neurons ,Parasympathetic nervous system ,PET imaging ,[18F]FEOBV ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Abstract Background The autonomic nervous system is frequently affected in some neurodegenerative diseases, including Parkinson’s disease and Dementia with Lewy bodies. In vivo imaging methods to visualize and quantify the peripheral cholinergic nervous system are lacking. By using [18F]FEOBV PET, we here describe the peripheral distribution of the specific cholinergic marker, vesicular acetylcholine transporters (VAChT), in human subjects. We included 15 healthy subjects aged 53–86 years for 70 min dynamic PET protocol of peripheral organs. We performed kinetic modelling of the adrenal gland, pancreas, myocardium, renal cortex, spleen, colon, and muscle using an image-derived input function from the aorta. A metabolite correction model was generated from venous blood samples. Three non-linear compartment models were tested. Additional time-activity curves from 6 to 70 min post injection were generated for prostate, thyroid, submandibular-, parotid-, and lacrimal glands. Results A one-tissue compartment model generated the most robust fits to the data. Total volume-of-distribution rank order was: adrenal gland > pancreas > myocardium > spleen > renal cortex > muscle > colon. We found significant linear correlations between total volumes-of-distribution and standard uptake values in most organs. Conclusion High [18F]FEOBV PET signal was found in structures with known cholinergic activity. We conclude that [18F]FEOBV PET is a valid tool for estimating VAChT density in human peripheral organs. Simple static images may replace kinetic modeling in some organs and significantly shorten scan duration. Clinical Trial Registration Trial registration: NCT, NCT03554551. Registered 31 May 2018. https://clinicaltrials.gov/ct2/show/NCT03554551?term=NCT03554551&draw=2&rank=1 .
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- 2022
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14. Spinal cord stimulation therapy for patients with Parkinson’s disease and gait problems (STEP-PD): study protocol for an exploratory, double-blind, randomised, placebo-controlled feasibility trial
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Nicola Pavese, Jens Christian Hedemann Sørensen, Elena Moro, Andreas Nørgaard Glud, Victor S Hvingelby, Miriam Højholt Terkelsen, Erik L Johnsen, Mette Møller, Erik Hvid Danielsen, Tove Henriksen, Yen Tai, Anne Sofie Møller Andersen, Kaare Meier, and Per Borghammer
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Introduction Gait difficulties are common in Parkinson’s disease (PD) and cause significant disability. These symptoms are often resistant to treatment. Spinal cord stimulation (SCS) has been found to improve gait, including freezing of gait, in a small number of patients with PD. The mechanism of action is unclear, and some patients are non-responders. With this double-blind, placebo-controlled efficacy and feasibility clinical and imaging study, we aim to shed light on the mechanism of action of SCS and collect data to inform development of a scientifically sound clinical trial protocol. We also aim to identify clinical and imaging biomarkers at baseline that could be predictive of a favourable or a negative outcome of SCS and improve patient selection.Methods and analysis A total of 14 patients will be assessed with clinical rating scales and gait evaluations at baseline, and at 6 and 12 months after SCS implantation. They will also receive serial 18F-deoxyglucose and 18FEOBV PET scans to assess the effects of SCS on cortical/subcortical activity and brain cholinergic function. The first two patients will be included in an open pilot study while the rest will be randomised to receive active treatment or placebo (no stimulation) for 6 months. From this point, the entire cohort will enter an open label active treatment phase for a subsequent 6 months.Ethics and dissemination This study was reviewed and approved by the Committee on Health Research Ethics, Central Denmark RM. It is funded by the Danish Council for Independent Research. Independent of outcome, the results will be published in peer-reviewed journals and presented at national and international conferences.Trial registration number NCT05110053; ClinicalTrials.gov Identifier.
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- 2022
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15. Prodromal Parkinson disease subtypes — key to understanding heterogeneity
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Berg, Daniela, Borghammer, Per, Fereshtehnejad, Seyed-Mohammad, Heinzel, Sebastian, Horsager, Jacob, Schaeffer, Eva, and Postuma, Ronald B.
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- 2021
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16. Impact of aging on animal models of Parkinson's disease
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Ida Hyllen Klæstrup, Mie Kristine Just, Karina Lassen Holm, Aage Kristian Olsen Alstrup, Marina Romero-Ramos, Per Borghammer, and Nathalie Van Den Berge
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Alpha-synuclein (a-Synuclein) ,Parkinson's disease ,gut-brain axis ,aging ,animal models ,autonomic nervous system ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Aging is the biggest risk factor for developing Parkinson's disease (PD), the second most common neurodegenerative disorder. Several animal models have been developed to explore the pathophysiology underlying neurodegeneration and the initiation and spread of alpha-synuclein-related PD pathology, and to investigate biomarkers and therapeutic strategies. However, bench-to-bedside translation of preclinical findings remains suboptimal and successful disease-modifying treatments remain to be discovered. Despite aging being the main risk factor for developing idiopathic PD, most studies employ young animals in their experimental set-up, hereby ignoring age-related cellular and molecular mechanisms at play. Consequently, studies in young animals may not be an accurate reflection of human PD, limiting translational outcomes. Recently, it has been shown that aged animals in PD research demonstrate a higher susceptibility to developing pathology and neurodegeneration, and present with a more disseminated and accelerated disease course, compared to young animals. Here we review recent advances in the investigation of the role of aging in preclinical PD research, including challenges related to aged animal models that are limiting widespread use. Overall, current findings indicate that the use of aged animals may be required to account for age-related interactions in PD pathophysiology. Thus, although the use of older animals has disadvantages, a model that better represents clinical disease within the elderly would be more beneficial in the long run, as it will increase translational value and minimize the risk of therapies failing during clinical studies. Furthermore, we provide recommendations to manage the challenges related to aged animal models.
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- 2022
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17. Alpha-Synuclein Strain Variability in Body-First and Brain-First Synucleinopathies
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Mie Kristine Just, Hjalte Gram, Vasileios Theologidis, Poul Henning Jensen, K. Peter R. Nilsson, Mikael Lindgren, Karoline Knudsen, Per Borghammer, and Nathalie Van Den Berge
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animal models ,synucleinopathies ,Lewy body disorders ,seed amplification assay ,oligothiophene ligands ,peripheral biomarkers ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Pathogenic alpha-synuclein (asyn) aggregates are a defining feature of neurodegenerative synucleinopathies, which include Parkinson's disease, Lewy body dementia, pure autonomic failure and multiple system atrophy. Early accurate differentiation between these synucleinopathies is challenging due to the highly heterogeneous clinical profile at early prodromal disease stages. Therefore, diagnosis is often made in late disease stages when a patient presents with a broad range of motor and non-motor symptoms easing the differentiation. Increasing data suggest the clinical heterogeneity seen in patients is explained by the presence of distinct asyn strains, which exhibit variable morphologies and pathological functions. Recently, asyn seed amplification assays (PMCA and RT-QuIC) and conformation-specific ligand assays have made promising progress in differentiating between synucleinopathies in prodromal and advanced disease stages. Importantly, the cellular environment is known to impact strain morphology. And, asyn aggregate pathology can propagate trans-synaptically along the brain-body axis, affecting multiple organs and propagating through multiple cell types. Here, we present our hypothesis that the changing cellular environments, an asyn seed may encounter during its brain-to-body or body-to-brain propagation, may influence the structure and thereby the function of the aggregate strains developing within the different cells. Additionally, we aim to review strain characteristics of the different synucleinopathies in clinical and preclinical studies. Future preclinical animal models of synucleinopathies should investigate if asyn strain morphology is altered during brain-to-body and body-to-brain spreading using these seeding amplification and conformation-specific assays. Such findings would greatly deepen our understanding of synucleinopathies and the potential link between strain and phenotypic variability, which may enable specific diagnosis of different synucleinopathies in the prodromal phase, creating a large therapeutic window with potential future applications in clinical trials and personalized therapeutics.
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- 2022
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18. Intestinal Transit in Early Moderate Parkinson’s Disease Correlates with Probable RBD: Subclinical Esophageal Dysmotility Does Not Correlate
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Casper Skjærbæk, Karoline Knudsen, Martin Kinnerup, Kim Vang Hansen, and Per Borghammer
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background. Nonmotor symptoms, including constipation and dysphagia, are very common in Parkinson’s disease (PD) and Lewy pathology is widespread in the gastrointestinal tract, particularly in the lower esophagus. Constipation and REM sleep behavior disorder (RBD) may present prior to clinical diagnosis. Yet, little is known about esophageal dysfunction and its connection to constipation in early PD. Objective. This study aimed to investigate esophageal and colonic transit in early moderate PD and to study correlations between symptoms and objective measures. Methods. Thirty early moderate PD patients and 28 healthy controls (HC) were included in this cross-sectional study. Esophageal transit times were determined by esophageal scintigraphy and colonic transit times by CT after radio-opaque marker ingestion. Olfaction tests, clinical evaluation, and nonmotor questionnaires were also performed. Results. Distal esophageal transit times and colonic transit times were both significantly prolonged in the PD group compared to HC (p
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- 2022
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19. Asymmetric amyloid deposition in preclinical Alzheimer’s disease: A PET study
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Pernille L. Kjeldsen, Peter Parbo, Kim V. Hansen, Joel F.A. Aanerud, Rola Ismail, Peter H. Nissen, Rikke B. Dalby, Malene F. Damholdt, Per Borghammer, and David J. Brooks
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Preclinical Alzheimer’s disease ,Positron emission tomography ,Amyloid deposition ,Asymmetry ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Introduction: The typical spatial pattern of amyloid-β (Aβ) in diagnosed Alzheimer’s disease (AD) is that of a symmetrical hemispheric distribution. However, Aβ may be asymmetrically distributed in early stages of AD. Aβ distribution on PET has previously been explored in MCI and AD, but it has yet to be directly investigated in preclinical AD (pAD). We examined how Aβ was distributed in individuals with pAD and MCI using 11C-Pittsburgh Compound B (PiB) PET. Methods: In this PET study, 79 subjects were retrospectively enrolled, including 34 controls, 24 pAD, and 21 MCI. All subjects underwent APOE genotyping, 11C-PiB PET, MRI, and cognitive testing. We explored differences in Aβ load, Aβ lateralisation, and Aβ distribution, as well as associations between Aβ distribution and cognition. Results: The Aβ asymmetry index (AI) differed between groups, with pAD having the highest Aβ AI as compared to both controls and MCI. There was no clear Aβ lateralisation in pAD, but there was a non-significant trend towards Aβ being more left-lateralised in MCI. There were no correlations between the cognitive scores and Aβ AI or Aβ lateralisation in pAD or MCI. Conclusion: The distribution of Aβ is most asymmetrical in pAD, as Aβ first starts accumulating, and it then becomes less asymmetrical in MCI, when Aβ has spread further, suggesting that more pronounced asymmetrical Aβ distribution may be a distinguishing factor in pAD. Longitudinal studies examining the distribution of Aβ across the AD continuum are needed.
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- 2022
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20. Neuropathological evidence of body-first vs. brain-first Lewy body disease
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Per Borghammer, Jacob Horsager, Katrine Andersen, Nathalie Van Den Berge, Anna Raunio, Shigeo Murayama, Laura Parkkinen, and Liisa Myllykangas
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Lewy body ,Parkinson's disease ,Alpha-synuclein ,Dementia with Lewy bodies ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Aggregation of alpha-synuclein into inclusion bodies, termed Lewy pathology, is a defining feature of Parkinson's disease (PD) and Dementia with Lewy bodies (DLB). In the majority of post mortem cases, the distribution of Lewy pathology seems to follow two overarching patterns: a caudo-rostral pattern with relatively more pathology in the brainstem than in the telencephalon, and an amygdala-centered pattern with the most abundant pathology in the “center of the brain”, including the amygdala, entorhinal cortex, and substantia nigra, and relatively less pathology in the lower brainstem and spinal autonomic nuclei. The recent body-first versus brain-first model of Lewy Body Disorders proposes that the initial pathogenic alpha-synuclein in some patients originates in the enteric nervous system with secondary spreading to the brain; and in other patients originates inside the CNS with secondary spreading to the lower brainstem and peripheral autonomic nervous system. Here, we use two existing post mortem datasets to explore the possibility that clinical body-first and brain-first subtypes are equivalent to the caudo-rostral and amygdala-centered patterns of Lewy pathology seen at post mortem.
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- 2021
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21. Imaging dopamine function and microglia in asymptomatic LRRK2 mutation carriers
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Gersel Stokholm, Morten, Garrido, Alicia, Tolosa, Eduardo, Serradell, Mónica, Iranzo, Alex, Østergaard, Karen, Borghammer, Per, Møller, Arne, Parbo, Peter, Stær, Kristian, Brooks, David J., Martí, Maria José, and Pavese, Nicola
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- 2020
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22. Cortical Activity During an Attack of Ménière's Disease—A Case Report
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Louise Devantier, Allan K. Hansen, Jens-Jacob Mølby-Henriksen, Michael Pedersen, Per Borghammer, Therese Ovesen, and Måns Magnusson
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case report ,Menière's disease ,neuroimaging ,PET ,cortical activity ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Ménière's disease (MD) is a chronic peripheral vestibular disorder with recurrent episodes of vertigo accompanied by fluctuating hearing loss, tinnitus and aural fullness in the affected ear. There are several unanswered fundamental questions regarding MD, one of these being cortical activity during a MD attack. However, it is not possible to plan an investigation in an episodic disease as MD.Objective: To visualize cortical activity during an attack of MD.Method:18F-FDG PET scans were used to visualize cortical activity in a 62 years old male suffering from definite MD. Two 18F-FDG PET scans were performed. One to show activity during the attack and one to show normal baseline brain activity 7 days after the attack.Results: A number of low-magnitude fluctuations in the 18F-FDG FDG uptake were found in 18F-FDG PET examination following the MD attack compared to the patient's own baseline 18F-FDG FDG scan. Across both hemispheres no significant changes were seen. However, reduced activity was observed in most of the orbitofrontal, frontal cortices as well as Heschl's gyrus and insula.Conclusion: This is the first neuroimaging showing alteration of brain activity during an attack in a patient with MD. No strong focal alterations was seen. It is noteworthy that the decreased activity observed was in the insula and Heschl's gyrus that seems to be core areas for processing information from the labyrinth. It is also of interest that decreased activity rather than hyperactivity was observed.
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- 2021
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23. Vagus Nerve Cross-Sectional Area in Patients With Parkinson's Disease—An Ultrasound Case-Control Study
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Jacob Horsager, Uwe Walter, Tatyana D. Fedorova, Katrine B. Andersen, Casper Skjærbæk, Karoline Knudsen, Niels Okkels, Paul von Weitzel-Mudersbach, Stig Eric Dyrskog, Bo Bergholt, and Per Borghammer
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parkinson's disease ,vagus nerve ,ultrasound ,parasympathetic ,cross-sectional area ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Vagal parasympathetic neurons are prone to degeneration in Parkinson's disease (PD). High-resolution ultrasound can precisely estimate the cross-sectional (CSA) area of peripheral nerves. Here, we tested the hypothesis that vagus CSA is reduced in PD.Methods: We included 56 healthy controls (HCs) and 63 patients with PD. Using a high-end ultrasound system equipped with a high-frequency transducer, five images were obtained of each nerve. The hypoechoic neuronal tissue was delineated offline with dedicated software and the CSA extracted.Results: In the initial PD vs. HC comparison, no statistically significant differences were observed in mean left vagus CSA (HC: 1.97 mm2, PD: 1.89 mm2, P = 0.36) nor in mean right vagus CSA (HC: 2.37 mm2, PD: 2.23 mm2, P = 0.17). The right vagus CSA was significantly larger than the left vagus CSA in both groups (P < 0.0001). Females were overrepresented in the HC group and presented with generally smaller vagus CSAs. Consequently, sex-adjusted CSA was significantly smaller for the right vagus nerve of the PD group (P = 0.041), but not for the left.Conclusion: A small but significant reduction in sex-adjusted right vagus CSA was observed in patients with PD. The left vagus CSA was not significantly reduced in patients with PD. Ultrasound may not be a suitable method to detecting vagal axonal loss in individual patients.
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- 2021
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24. Preserved noradrenergic function in Parkinson's disease patients with rest tremor
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Martin B. Kinnerup, Michael Sommerauer, Malene F. Damholdt, Jeppe L. Schaldemose, Rola Ismail, Astrid J. Terkelsen, Kristian Stær, Allan Hansen, Tatyana D. Fedorova, Karoline Knudsen, Casper Skjærbæk, Per Borghammer, Nicola Pavese, David J. Brooks, and Adjmal Nahimi
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Parkinson's disease ,Tremor ,11C-MeNER ,Positron emission tomography (PET) ,Noradrenaline transporter ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Noradrenergic neurotransmission may play an important role in tremor modulation through its innervation of key structures of the central tremor circuits. Here, Parkinson's disease (PD) patients with (PDT+) or without (PDT-) rest tremor had 11C-methylreboxetine(11C-MeNER) positron emission tomography (PET) to test the hypothesis that noradrenaline terminal function was relatively preserved in PDT+ compared to PDT-. Methods: Sixty-five PD patients and 28 healthy controls (HC) were scanned with 11C-MeNER PET. Patients were categorized as PDT+ if subscores in UPDRS-III item 3 or MDS-UPDRS-III item 17 was ≥2; remaining were categorized as PDT-. Simplified reference tissue model 2 distribution volume ratios (DVR) for 11C-MeNER were calculated for thalamus, dorsal and median raphe, locus coeruleus (LC) and red nucleus using time activity curves (TACs) obtained from volumes of interest (VOI). Data were statistically interrogated with a general linear mixed model using ‘region’, and ‘group’ as factors and the interaction of ‘region x group’ was examined. Results: Tremor positive PD patients had a significantly higher mean 11C-MeNER DVR compared to PDT- in LC and thalamus. The PDT+ mean LC DVR was similar to that of HC. PDT+ mean 11C-MeNER DVRs were significantly lower than HC in the dorsal raphe while the PDT- group showed significantly lower mean 11C-MeNER DVR across all regions compared to HC. Conclusion: While both PD T+ and PD T- groups showed a significant loss of noradrenaline terminal function compared to controls, noradrenergic neurons were relatively preserved in PDT+ in LC and thalamus. The greater loss of noradrenergic transporters in PDT- in LC and thalamus compared with PDT+ is in line with earlier in-vitro studies and could potentially contribute to their tremor negative phenotype.
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- 2021
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25. Evidence for bidirectional and trans-synaptic parasympathetic and sympathetic propagation of alpha-synuclein in rats
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Van Den Berge, Nathalie, Ferreira, Nelson, Gram, Hjalte, Mikkelsen, Trine Werenberg, Alstrup, Aage Kristian Olsen, Casadei, Nicolas, Tsung-Pin, Pai, Riess, Olaf, Nyengaard, Jens Randel, Tamgüney, Gültekin, Jensen, Poul Henning, and Borghammer, Per
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- 2019
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26. Skin Temperature in Parkinson’s Disease Measured by Infrared Thermography
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Mathias Møller Purup, Karoline Knudsen, Pall Karlsson, Astrid Juhl Terkelsen, and Per Borghammer
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background. Patients with Parkinson’s disease (PD) often show peripheral autonomic dysfunction and depositions of pathological alpha-synuclein aggregates in the skin. However, functional consequences of this skin involvement have received little attention. Objective. To determine thermographic differences in the skin between healthy controls (HCs) and PD patients on hands, feet, and trunk and to correlate findings with symptoms and signs of dysautonomia. Between-group differences in autonomic parameters and questionnaires were explored. Methods. Twenty-one PD patients and 19 HCs were examined by thermographic infrared imaging of standardized anatomical locations on the trunk and upper and lower extremities at baseline and after exposure to cold stress test (CST). Thermal recovery rates (RRs) were determined on the basis of thermograms. Correlation analyses between alterations in skin temperature and autonomic dysfunction were performed. Results. The most significant RR difference between PD patients and HCs was seen on the fifth distal phalanx 10 minutes post-CST (mean RR ± SD: 51 ± 18% vs. 70 ± 23%, p = 0.003). No between-group differences were seen in baseline or post-CST values of the feet. No correlations were seen between thermal parameters and clinical and autonomic data. In the HC group, a positive, moderate correlation was seen between post-CST recovery values on the 3rd and 5th phalanx and body mass index (BMI) (r = 0.661, p = 0.002). Conclusions. The PD patients exhibited significant reduction in RR compared to HC and patients also displayed altered thermal responses in multiple anatomical locations. Thus, infrared thermography could become an important future tool in investigation of autonomic deficiency in PD.
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- 2020
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27. PET Visualized Stimulation of the Vestibular Organ in Menière's Disease
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Louise Devantier, Allan K. Hansen, Jens-Jacob Mølby-Henriksen, Christian Bech Christensen, Tina Lildal, Michael Pedersen, Måns Magnusson, Per Borghammer, and Therese Ovesen
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Menière's disease ,central vestibular system ,vestibular cortex ,positron emission tomography ,neuroimaging ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Introduction: The cortical metabolic activity in patients with Menière's disease has not been investigated. The aim of this study was to investigate the 18F-FDG cerebral uptake in Menière's patients compared to healthy controls.Method: Eight patients with right-sided Menière's disease and fourteen healthy controls underwent a video head impulse test (vHIT), test of utricular function with ocular vestibular evoked myogenic potentials (oVEMP) and three 18F-FDG-based PET examinations of the brain. Participants were seated in a self-propelled chair, injected with 18F-FDG and then exposed to 35 min of chair motion stimulation, followed by a PET scan. Two types of natural vestibular stimuli were applied, predominantly toward the right horizontal semicircular canal (angular acceleration) and right utriculus (linear acceleration). For baseline scans, participants were injected with 18F-FDG while seated without movement.Results: Analyses of baseline scans revealed decreased 18F-FDG-uptake in the medial part of Heschl's gyrus in the left hemisphere in patients with Menière's disease compared to healthy controls. During angular vestibular stimulation there was also a significantly decreased 18F-FDG uptake in the intersection between the medial part of Heschl's gyrus and the parietal operculum in the left hemisphere and bilaterally in the posterior part of insula. During linear stimulation, Menière's patients showed decreased 18F-FDG uptake in the medial part of Heschl's gyrus in the right hemisphere and also bilaterally in the posterior insula. In addition, decreased 18F-FDG uptake was seen in the thalamus during vestibular stimulation.Conclusion: Heschl's gyrus, the posterior part of insula, and thalamus have previously been shown to be core areas for processing vestibular inputs. Patients with Menière's disease solely differed from the healthy controls with lower cortical activity in these areas at baseline and during natural vestibular stimulation.
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- 2020
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28. Passive Immunization in Alpha-Synuclein Preclinical Animal Models
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Jonas Folke, Nelson Ferreira, Tomasz Brudek, Per Borghammer, and Nathalie Van Den Berge
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alpha-synuclein ,passive immunization ,disease stratification ,Microbiology ,QR1-502 - Abstract
Alpha-synucleinopathies include Parkinson’s disease, dementia with Lewy bodies, pure autonomic failure and multiple system atrophy. These are all progressive neurodegenerative diseases that are characterized by pathological misfolding and accumulation of the protein alpha-synuclein (αsyn) in neurons, axons or glial cells in the brain, but also in other organs. The abnormal accumulation and propagation of pathogenic αsyn across the autonomic connectome is associated with progressive loss of neurons in the brain and peripheral organs, resulting in motor and non-motor symptoms. To date, no cure is available for synucleinopathies, and therapy is limited to symptomatic treatment of motor and non-motor symptoms upon diagnosis. Recent advances using passive immunization that target different αsyn structures show great potential to block disease progression in rodent studies of synucleinopathies. However, passive immunotherapy in clinical trials has been proven safe but less effective than in preclinical conditions. Here we review current achievements of passive immunotherapy in animal models of synucleinopathies. Furthermore, we propose new research strategies to increase translational outcome in patient studies, (1) by using antibodies against immature conformations of pathogenic αsyn (monomers, post-translationally modified monomers, oligomers and protofibrils) and (2) by focusing treatment on body-first synucleinopathies where damage in the brain is still limited and effective immunization could potentially stop disease progression by blocking the spread of pathogenic αsyn from peripheral organs to the brain.
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- 2022
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29. Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study
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Peter Parbo, Rola Ismail, Michael Sommerauer, Morten G. Stokholm, Allan K. Hansen, Kim V. Hansen, Ali Amidi, Jeppe L. Schaldemose, Hanne Gottrup, Hans Brændgaard, Simon F. Eskildsen, Per Borghammer, Rainer Hinz, Joel Aanerud, and David J. Brooks
- Subjects
Alzheimer's disease ,Positron emission tomography ,Microglial activation ,Amyloid PET ,Tau PET ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Objective: Our aim was to assess with positron emission tomography (PET) the temporal and spatial inter-relationships between levels of cortical microglial activation and the aggregated amyloid-β and tau load in mild cognitive impairment (MCI) and early Alzheimer's disease (AD).Methods: Six clinically probable AD and 20 MCI subjects had inflammation (11C-(R)-PK11195), amyloid (11C-PiB) and tau (18F-flortaucipir) PET, magnetic resonance imaging (MRI) and a neuropsychological assessment. Parametric images of tracer binding were interrogated at a voxel level and by region of interest analyses.Results: 55% of MCI and 83% of AD subjects had a high amyloid-β load. We have previously reported that clusters of correlated amyloid and inflammation levels are present in cortex. Here we found no correlation between levels of inflammation (11C-(R)-PK11195 BPND) and tau (18F-flortaucipir SUVR) or MMSE scores in high amyloid-β cases.Interpretation: While correlated levels of amyloid-β and inflammation can be seen in MCI, we did not detect an association between levels of cortical tau tangles and inflammation in our series of high amyloid-β cases. High levels of inflammation could be seen in amyloid-β positive MCI cases where 18F-flortaucipir signals were low suggesting microglial activation precedes tau tangle formation. Inflammation levels were higher in high amyloid-β MCI than in early AD cases, compatible with it initially playing a protective role.
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- 2018
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30. Extrastriatal monoaminergic dysfunction and enhanced microglial activation in idiopathic rapid eye movement sleep behaviour disorder
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Morten Gersel Stokholm, Alex Iranzo, Karen Østergaard, Mónica Serradell, Marit Otto, Kristina Bacher Svendsen, Alicia Garrido, Dolores Vilas, Peter Parbo, Per Borghammer, Joan Santamaria, Arne Møller, Carles Gaig, David J. Brooks, Eduardo Tolosa, and Nicola Pavese
- Subjects
Idiopathic rapid-eye-movement sleep behaviour disorder ,Positron emission tomography ,18F-DOPA ,11C-PK11195 ,PD ,Dementia with Lewy bodies ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Background: The majority of patients diagnosed with idiopathic rapid eye movement sleep behaviour disorder (iRBD) progress over time to a Lewy-type α-synucleinopathy such as Parkinson's disease or dementia with Lewy bodies. This in vivo molecular imaging study aimed to investigate if extrastriatal monoaminergic systems are affected in iRBD patients and if this coincides with neuroinflammation. Methods: We studied twenty-one polysomnography-confirmed iRBD patients with 18F-DOPA and 11C-PK11195 positron emission tomography (PET) to investigate extrastriatal monoaminergic function and microglial activation. Twenty-nine healthy controls (n = 9 18F-DOPA and n = 20 11C-PK11195) were also investigated. Analyses were performed within predefined regions of interest and at voxel-level with Statistical Parametric Mapping. Results: Regions of interest analysis detected monoaminergic dysfunction in iRBD thalamus with a 15% mean reduction of 18F-DOPA Ki values compared to controls (mean difference = −0.00026, 95% confidence interval [−0.00050 to −0.00002], p-value = 0.03). No associated thalamic changes in 11C-PK11195 binding were observed. Other regions sampled showed no 18F-DOPA or 11C-PK11195 PET differences between groups. Voxel-level interrogation of 11C-PK11195 binding identified areas with significantly increased binding within the occipital lobe of iRBD patients. Conclusion: Thalamic monoaminergic dysfunction in iRBD patients may reflect terminal dysfunction of projecting neurons from the locus coeruleus and dorsal raphe nucleus, two structures that regulate REM sleep and are known to be involved in the early phase of PD. The observation of significantly raised microglial activation in the occipital lobe of these patients might suggest early local Lewy-type α-synuclein pathology and possibly an increased risk for later cognitive dysfunction.
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- 2018
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31. MAO-B Inhibitors Do Not Block In Vivo Flortaucipir([18F]-AV-1451) Binding
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Hansen, Allan K., Brooks, David J., and Borghammer, Per
- Published
- 2018
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32. Imaging Parkinson’s disease below the neck
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Per Borghammer, Karoline Knudsen, Tatyana D. Fedorova, and David J. Brooks
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Parkinson’s disease is a systemic disorder with widespread and early α-synuclein pathology in the autonomic and enteric nervous systems, which is present throughout the gastrointestinal canal prior to diagnosis. Gastrointestinal and genitourinary autonomic symptoms often predate clinical diagnosis by several years. It has been hypothesized that progressive α-synuclein aggregation is initiated in hyperbranched, non-myelinated neuron terminals, and may subsequently spread via retrograde axonal transport. This would explain why autonomic nerves are so prone to formation of α-synuclein pathology. However, the hypothesis remains unproven and in vivo imaging methods of peripheral organs may be essential to study this important research field. The loss of sympathetic and parasympathetic nerve terminal function in Parkinson’s disease has been demonstrated using radiotracers such as 123I-meta-iodobenzylguanidin, 18F-dopamine, and 11C-donepezil. Other radiotracer and radiological imaging methods have shown highly prevalent dysfunction of pharyngeal and esophageal motility, gastric emptying, colonic transit time, and anorectal function. Here, we summarize the methodology and main findings of radio-isotope and radiological modalities for imaging peripheral pathology in Parkinson’s disease.
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- 2017
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33. Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives
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Ditte S. Kornum, Astrid J. Terkelsen, Davide Bertoli, Mette W. Klinge, Katrine L. Høyer, Huda H. A. Kufaishi, Per Borghammer, Asbjørn M. Drewes, Christina Brock, and Klaus Krogh
- Subjects
autonomic dysfunction ,gastrointestinal ,motility ,investigations ,manometry ,breath test ,Medicine - Abstract
The autonomic nervous system delicately regulates the function of several target organs, including the gastrointestinal tract. Thus, nerve lesions or other nerve pathologies may cause autonomic dysfunction (AD). Some of the most common causes of AD are diabetes mellitus and α-synucleinopathies such as Parkinson’s disease. Widespread dysmotility throughout the gastrointestinal tract is a common finding in AD, but no commercially available method exists for direct verification of enteric dysfunction. Thus, assessing segmental enteric physiological function is recommended to aid diagnostics and guide treatment. Several established assessment methods exist, but disadvantages such as lack of standardization, exposure to radiation, advanced data interpretation, or high cost, limit their utility. Emerging methods, including high-resolution colonic manometry, 3D-transit, advanced imaging methods, analysis of gut biopsies, and microbiota, may all assist in the evaluation of gastroenteropathy related to AD. This review provides an overview of established and emerging assessment methods of physiological function within the gut and assessment methods of autonomic neuropathy outside the gut, especially in regards to clinical performance, strengths, and limitations for each method.
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- 2021
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34. Gastrointestinal Dysfunction in Parkinson’s Disease
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Casper Skjærbæk, Karoline Knudsen, Jacob Horsager, and Per Borghammer
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Parkinson’s disease ,autonomic ,gastrointestinal ,constipation ,alpha-synuclein ,parasympathetic ,Medicine - Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease. Patients show deposits of pathological, aggregated α-synuclein not only in the brain but throughout almost the entire length of the digestive tract. This gives rise to non-motor symptoms particularly within the gastrointestinal tract and patients experience a wide range of frequent and burdensome symptoms such as dysphagia, bloating, and constipation. Recent evidence suggests that progressive accumulation of gastrointestinal pathology is underway several years before a clinical diagnosis of PD. Notably, constipation has been shown to increase the risk of developing PD and in contrast, truncal vagotomy seems to decrease the risk of PD. Animal models have demonstrated gut-to-brain spreading of pathological α-synuclein and it is currently being intensely studied whether PD begins in the gut of some patients. Gastrointestinal symptoms in PD have been investigated by the use of several different questionnaires. However, there is limited correspondence between subjective gastrointestinal symptoms and objective dysfunction along the gastrointestinal tract, and often the magnitude of dysfunction is underestimated by the use of questionnaires. Therefore, objective measures are important tools to clarify the degree of dysfunction in future studies of PD. Here, we summarize the types and prevalence of subjective gastrointestinal symptoms and objective dysfunction in PD. The potential importance of the gastrointestinal tract in the etiopathogenesis of PD is briefly discussed.
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- 2021
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35. Parkinson’s Disease and Dementia with Lewy Bodies: One and the Same
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Borghammer, Per, Okkels, Niels, and Weintraub, Daniel
- Abstract
The question whether Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) are expressions of the same underlying disease has been vigorously debated for decades. The recently proposed biological definitions of Lewy body disease, which do not assign any particular importance to the dopamine system over other degenerating neurotransmitter systems, has once more brought the discussion about different types of Lewy body disease to the forefront. Here, we briefly compare PDD and DLB in terms of their symptoms, imaging findings, and neuropathology, ultimately finding them to be indistinguishable. We then present a conceptual framework to demonstrate how one can view different clinical syndromes as manifestations of a shared underlying Lewy body disease. Early Parkinson’s disease, isolated RBD, pure autonomic failure and other autonomic symptoms, and perhaps even psychiatric symptoms, represent diverse manifestations of the initial clinical stages of Lewy body disease. They are characterized by heterogeneous and comparatively limited neuronal dysfunction and damage. In contrast, Lewy body dementia, an encompassing term for both PDD and DLB, represents a more uniform and advanced stage of the disease. Patients in this category display extensive and severe Lewy pathology, frequently accompanied by co-existing pathologies, as well as multi-system neuronal dysfunction and degeneration. Thus, we propose that Lewy body disease should be viewed as a single encompassing disease entity. Phenotypic variance is caused by the presence of individual risk factors, disease mechanisms, and co-pathologies. Distinct subtypes of Lewy body disease can therefore be defined by subtype-specific disease mechanisms or biomarkers.
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- 2024
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36. The Body, the Brain, the Environment, and Parkinson’s Disease
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Dorsey, E. Ray, De Miranda, Briana R., Horsager, Jacob, and Borghammer, Per
- Abstract
The brain- and body-first models of Lewy body disorders predict that aggregated alpha-synuclein pathology usually begins in either the olfactory system or the enteric nervous system. In both scenarios the pathology seems to arise in structures that are closely connected to the outside world. Environmental toxicants, including certain pesticides, industrial chemicals, and air pollution are therefore plausible trigger mechanisms for Parkinson’s disease and dementia with Lewy bodies. Here, we propose that toxicants inhaled through the nose can lead to pathological changes in alpha-synuclein in the olfactory system that subsequently spread and give rise to a brain-first subtype of Lewy body disease. Similarly, ingested toxicants can pass through the gut and cause alpha-synuclein pathology that then extends via parasympathetic and sympathetic pathways to ultimately produce a body-first subtype. The resulting spread can be tracked by the development of symptoms, clinical assessments, in vivoimaging, and ultimately pathological examination. The integration of environmental exposures into the brain-first and body-first models generates testable hypotheses, including on the prevalence of the clinical conditions, their future incidence, imaging patterns, and pathological signatures. The proposed link, though, has limitations and leaves many questions unanswered, such as the role of the skin, the influence of the microbiome, and the effects of ongoing exposures. Despite these limitations, the interaction of exogenous factors with the nose and the gut may explain many of the mysteries of Parkinson’s disease and open the door toward the ultimate goal –prevention.
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- 2024
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37. Brain atrophy in REM sleep behavior disorder is shaped by gene expression and structural connectivity
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Rahayel, S., primary, Tremblay, C., additional, Vo, A., additional, Lehéricy, S., additional, Arnulf, I., additional, Vidailhet, M., additional, Corvol, J.-C., additional, Study Group, I., additional, Gagnon, J.-F., additional, Postuma, R., additional, Montplaisir, J., additional, Lewis, S., additional, Matar, E., additional, Ehgoetz Martens, K., additional, Borghammer, P., additional, Knudsen, K., additional, Monchi, O., additional, Misic, B., additional, and Dagher, A., additional
- Published
- 2022
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38. Synaptic Density and Glucose Consumption in Patients with Lewy Body Diseases: An [11C]UCB-J and [18F]FDG PET Study
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Andersen KB, Hansen AK, Schacht AC, Horsager J, Gottrup H, Klit H, Danielsen EH, Pavese N, Brooks DJ, Borghammer P
- Published
- 2023
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39. Cholinergic PET imaging in infections and inflammation using 11C-donepezil and 18F-FEOBV
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Jørgensen, Nis Pedersen, Alstrup, Aage K. O., Mortensen, Frank V., Knudsen, Karoline, Jakobsen, Steen, Madsen, Line Bille, Bender, Dirk, Breining, Peter, Petersen, Mikkel Steen, Schleimann, Mariane Høgsberg, Dagnæs-Hansen, Frederik, Gormsen, Lars C., and Borghammer, Per
- Published
- 2017
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40. A dual tracer 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT pilot study for detection of cardiac sarcoidosis
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Gormsen, Lars C., Haraldsen, Ate, Kramer, Stine, Dias, Andre H., Kim, Won Yong, and Borghammer, Per
- Published
- 2016
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41. Gastrointestinal transit time and heart rate variability in patients with mild acquired brain injury
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Johannes Enevoldsen, Simon T. Vistisen, Klaus Krogh, Jørgen F. Nielsen, Karoline Knudsen, Per Borghammer, and Henning Andersen
- Subjects
Gastrointestinal transit ,Constipation ,Autonomic function ,Brain injury ,Heart rate variability ,Rehabilitation ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background Constipation is suspected to occur frequently after acquired brain injury (ABI). In patients with ABI, heart rate variability (HRV) is reduced suggesting autonomic dysfunction. Autonomic dysfunction may be associated with prolonged gastrointestinal transit time (GITT). The primary aim of this study was to investigate if GITT is prolonged in patients with ABI. Secondarily, HRV and its correlation with GITT was investigated. Methods We included 25 patients with ABI (18 men, median age: 61.3 years, range [30.7–74.5]). GITT was assessed using radio-opaque markers and HRV was calculated from 24-hour electrocardiograms. Medical records were reviewed for important covariates, including primary diagnosis, time since injury, functional independence measure, and use of medication. The GITT assessed in patients was compared to a control group of 25 healthy subjects (18 men, median age: 61.5 years, range [34.0–70.9]). Results In ABI patients, the mean GITT was significantly longer than in healthy controls (2.68 days, 95% CI [2.16–3.19] versus (1.92 days, 95% CI [1.62–2.22], p = 0.011)). No correlation was found between HRV and GITT. Conclusion Patients with mild to moderate ABI have prolonged GITT unrelated to the HRV.
- Published
- 2018
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42. The Effect of 40-Hz Light Therapy on Amyloid Load in Patients with Prodromal and Clinical Alzheimer’s Disease
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Rola Ismail, Allan K. Hansen, Peter Parbo, Hans Brændgaard, Hanne Gottrup, David J. Brooks, and Per Borghammer
- Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Geriatrics ,RC952-954.6 - Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. AD pathology is characterized by abnormal aggregation of the proteins amyloid-β (Aβ) and hyperphosphorylated tau. No effective disease modifying therapies are currently available. A short-duration intervention with 40 Hz light flicker has been shown to reduce brain Aβ load in transgenic mice. We aimed to test the effect of a similar short-duration 40 Hz light flicker regime in human AD patients. We utilized a Light Emitting Diode (LED) light bulb with a 40 Hz flicker. Six Aβ positive patients received 10 days of light therapy, had 2 hours of daily exposure, and underwent a postintervention PiB PET on day 11. After 10 days of light therapy, no significant decrease of PiB SUVR values was detected in any volumes of interest tested (primary visual cortex, visual association cortex, lateral parietal cortex, precuneus, and posterior cingulate) or in the total motor cortex, and longer treatments may be necessary to induce amyloid removal in humans.
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- 2018
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43. Imaging the Autonomic Nervous System in Parkinson’s Disease
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Knudsen, Karoline and Borghammer, Per
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- 2018
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44. Imaging Systemic Dysfunction in Parkinson’s Disease
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Borghammer, Per, Knudsen, Karoline, and Brooks, David J.
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- 2016
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45. Molecular imaging of cholinergic processes in prostate cancer using 11C-donepezil and 18F-FEOBV
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Stokholm, Morten Gersel, Høyer, Søren, Borre, Michael, Bender, Dirk, Jakobsen, Steen, Frøkiær, Jørgen, and Borghammer, Per
- Published
- 2016
- Full Text
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46. Healthy brain aging assessed with [18F]FDG and [11 C]UCB-J PET
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Andersen KB, Hansen AK, Knudsen K, Schacht AC, Damholdt MF, Brooks DJ, Borghammer P
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- 2022
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47. Imaging Parkinson’s disease below the neck
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Borghammer, Per, Knudsen, Karoline, Fedorova, Tatyana D., and Brooks, David J.
- Published
- 2017
- Full Text
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48. Dopaminergic Dysfunction Is More Symmetric in Dementia with Lewy Bodies Compared to Parkinson’s Disease
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Fedorova, Tatyana Dmitrievna, Knudsen, Karoline, Horsager, Jacob, Hansen, Allan K., Okkels, Niels, Gottrup, Hanne, Vang, Kim, and Borghammer, Per
- Abstract
The α-syn Origin site and Connectome model (SOC) proposes that α-synucleinopathies can be divided into two categories: the asymmetrical brain-first,and more symmetrical body-firstLewy body disease. We have hypothesized that most patients with dementia with Lewy bodies (DLB) belong to the body-firstsubtype, whereas patients with Parkinson’s disease (PD) more often belong to the brain-firstsubtype. To compare asymmetry of striatal dopaminergic dysfunction in DLB and PD patients using [18F]-FE-PE2I positron emission tomography (PET). We analyzed [18F]-FE-PE2I PET data from 29 DLB patients and 76 PD patients who were identified retrospectively during a 5-year period at Dept. of Neurology, Aarhus University Hospital. Additionally, imaging data from 34 healthy controls was used for age-correction and visual comparison. PD patients showed significantly more asymmetry in specific binding ratios between the most and least affected putamen (p < 0.0001) and caudate (p = 0.003) compared to DLB patients. PD patients also had more severe degeneration in the putamen compared to the caudate in comparison to DLB patients (p < 0.0001) who had a more universal pattern of striatal degeneration. Patients with DLB show significantly more symmetric striatal degeneration on average compared to PD patients. These results support the hypothesis that DLB patients may be more likely to conform to the body-first subtype characterized by a symmetrical spread of pathology, whereas PD patients may be more likely to conform to the brain-first subtype with more lateralized initial propagation of pathology.
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- 2023
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49. Evaluation of Active Brown Adipose Tissue by the Use of Hyperpolarized [1-13C]Pyruvate MRI in Mice
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Mette Ji Riis-Vestergaard, Peter Breining, Steen Bønløkke Pedersen, Christoffer Laustsen, Hans Stødkilde-Jørgensen, Per Borghammer, Niels Jessen, and Bjørn Richelsen
- Subjects
brown adipose tissue ,UCP1 expression ,cold exposure ,hyperpolarized pyruvate MRI ,FDG PET ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The capacity to increase energy expenditure makes brown adipose tissue (BAT) a putative target for treatment of metabolic diseases such as obesity. Presently, investigation of BAT in vivo is mainly performed by fluoro-d-glucose positron emission tomography (FDG PET)/CT. However, non-radioactive methods that add information on, for example, substrate metabolism are warranted. Thus, the aim of this study was to evaluate the potential of hyperpolarized [1-13C]pyruvate Magnetic Resonance Imaging (HP-MRI) to determine BAT activity in mice following chronic cold exposure. Cold (6 °C) and thermo-neutral (30 °C) acclimated mice were scanned with HP-MRI for assessment of the interscapular BAT (iBAT) activity. Comparable mice were scanned with the conventional method FDG PET/MRI. Finally, iBAT was evaluated for gene expression and protein levels of the specific thermogenic marker, uncoupling protein 1 (UCP1). Cold exposure increased the thermogenic capacity 3–4 fold (p < 0.05) as measured by UCP1 gene and protein analysis. Furthermore, cold exposure as compared with thermo-neutrality increased iBAT pyruvate metabolism by 5.5-fold determined by HP-MRI which is in good agreement with the 5-fold increment in FDG uptake (p < 0.05) measured by FDG PET/MRI. iBAT activity is detectable in mice using HP-MRI in which potential changes in intracellular metabolism may add useful information to the conventional FDG PET studies. HP-MRI may also be a promising radiation-free tool for repetitive BAT studies in humans.
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- 2018
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50. Salivary Acetylcholinesterase Activity Is Increased in Parkinson’s Disease: A Potential Marker of Parasympathetic Dysfunction
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Tatyana Fedorova, Cindy Soendersoe Knudsen, Kim Mouridsen, Ebba Nexo, and Per Borghammer
- Subjects
Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Introduction. Decreased salivary flow and xerostomia are frequent findings in Parkinson’s disease (PD), possibly caused by alterations in the parasympathetic tonus. Here we explore salivary acetylcholinesterase (AChE) activity as a potential biomarker in PD. Methods. We measured salivary flow, AChE activity, and total protein concentration in 30 PD patients and 49 healthy controls. We also performed exploratory correlation analyses with disease duration, motor symptom severity, autonomic complaints, and other nonmotor symptoms. Results. PD patients displayed significantly decreased salivary flow rate, significantly increased salivary AChE activity, and total protein concentration. Importantly, the AChE activity/total protein ratio was significantly increased in PD patients, suggesting that increased AChE activity cannot be explained solely by upconcentration of saliva. The Unified PD Rating Scale (UPDRS) score displayed significant correlation with total salivary protein (P=0.002) and near-significant correlation with salivary flow (P=0.07). Color vision test scores were also significantly correlated with AChE activity (P=0.04) and total protein levels (P=0.002). Conclusion. Salivary AChE activity is increased in PD patients compared to healthy controls. Future studies are needed to elucidate whether this parameter reflects the extent of neuronal damage and parasympathetic denervation in the salivary glands of PD patients.
- Published
- 2015
- Full Text
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