168 results on '"Knudsen, Karoline"'
Search Results
2. Functional and 123I-MIBG scintigraphy assessment of cardiac adrenergic dysfunction in diabetes
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Rasmussen, Thorsten K., Borghammer, Per, Finnerup, Nanna B., Jensen, Troels S., Hansen, John, Knudsen, Karoline, Singer, Wolfgang, Lamotte, Guillaume, and Terkelsen, Astrid J.
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- 2024
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3. [18F]FEOBV positron emission tomography may not be a suitable method to measure parasympathetic denervation in patients with Parkinson's disease
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Horsager, Jacob, Okkels, Niels, Fedorova, Tatyana D., Knudsen, Karoline, Skjærbæk, Casper, Van Den Berge, Nathalie, Jacobsen, Jan, Munk, Ole Lajord, Danielsen, Erik Hvid, Bender, Dirk, Brooks, David J., and Borghammer, Per
- Published
- 2022
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4. Healthy brain aging assessed with [18F]FDG and [11C]UCB-J PET
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Andersen, Katrine B., Hansen, Allan K., Knudsen, Karoline, Schacht, Anna Christina, Damholdt, Malene F., Brooks, David J., and Borghammer, Per
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- 2022
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5. Imaging progressive peripheral and central dysfunction in isolated REM sleep behaviour disorder after 3 years of follow-up
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Fedorova, Tatyana D., Knudsen, Karoline, Andersen, Katrine B., Horsager, Jacob, Skjærbæk, Casper, Beier, Christoph P., Sommerauer, Michael, Svendsen, Kristina B., Otto, Marit, and Borghammer, Per
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- 2022
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6. Fasting gallbladder volume is increased in patients with Parkinson's disease
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Horsager, Jacob, Tiroke, Lasse Hubertus, Skjærbæk, Casper, Knudsen, Karoline, Fedorova, Tatyana D., Okkels, Niels, and Borghammer, Per
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- 2021
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7. Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes.
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Okkels, Niels, Grothe, Michel J, Taylor, John-Paul, Hasselbalch, Steen Gregers, Fedorova, Tatyana D, Knudsen, Karoline, van der Zee, Sygrid, Laar, Teus van, Bohnen, Nicolaas I, Borghammer, Per, and Horsager, Jacob
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LEWY body dementia ,SYMPTOMS ,ALZHEIMER'S disease ,BEHAVIOR disorders ,ALZHEIMER'S patients ,MOVEMENT disorders - Abstract
Cholinergic degeneration is significant in Lewy body disease, including Parkinson's disease, dementia with Lewy bodies, and isolated REM sleep behaviour disorder. Extensive research has demonstrated cholinergic alterations in the CNS of these disorders. More recently, studies have revealed cholinergic denervation in organs that receive parasympathetic denervation. This enables a comprehensive review of cholinergic changes in Lewy body disease, encompassing both central and peripheral regions, various disease stages and diagnostic categories. Across studies, brain regions affected in Lewy body dementia show equal or greater levels of cholinergic impairment compared to the brain regions affected in Lewy body disease without dementia. This observation suggests a continuum of cholinergic alterations between these disorders. Patients without dementia exhibit relative sparing of limbic regions, whereas occipital and superior temporal regions appear to be affected to a similar extent in patients with and without dementia. This implies that posterior cholinergic cell groups in the basal forebrain are affected in the early stages of Lewy body disorders, while more anterior regions are typically affected later in the disease progression. The topographical changes observed in patients affected by comorbid Alzheimer pathology may reflect a combination of changes seen in pure forms of Lewy body disease and those seen in Alzheimer's disease. This suggests that Alzheimer co-pathology is important to understand cholinergic degeneration in Lewy body disease. Thalamic cholinergic innervation is more affected in Lewy body patients with dementia compared to those without dementia, and this may contribute to the distinct clinical presentations observed in these groups. In patients with Alzheimer's disease, the thalamus is variably affected, suggesting a different sequential involvement of cholinergic cell groups in Alzheimer's disease compared to Lewy body disease. Patients with isolated REM sleep behaviour disorder demonstrate cholinergic denervation in abdominal organs that receive parasympathetic innervation from the dorsal motor nucleus of the vagus, similar to patients who experienced this sleep disorder in their prodrome. This implies that REM sleep behaviour disorder is important for understanding peripheral cholinergic changes in both prodromal and manifest phases of Lewy body disease. In conclusion, cholinergic changes in Lewy body disease carry implications for understanding phenotypes and the influence of Alzheimer co-pathology, delineating subtypes and pathological spreading routes, and for developing tailored treatments targeting the cholinergic system. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Altered sensorimotor cortex noradrenergic function in idiopathic REM sleep behaviour disorder – A PET study
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Andersen, Katrine B., Hansen, Allan K., Sommerauer, Michael, Fedorova, Tatyana D., Knudsen, Karoline, Vang, Kim, Van Den Berge, Nathalie, Kinnerup, Martin, Nahimi, Adjmal, Pavese, Nicola, Brooks, David J., and Borghammer, Per
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- 2020
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9. Objective intestinal function in patients with idiopathic REM sleep behavior disorder
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Knudsen, Karoline, Fedorova, Tatyana D., Hansen, Allan K., Sommerauer, Michael, Haase, Anne-Mette, Svendsen, Kristina B., Otto, Marit, Østergaard, Karen, Krogh, Klaus, and Borghammer, Per
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- 2019
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10. Gastric emptying in Parkinson's disease – A mini-review
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Knudsen, Karoline, Szwebs, Martha, Hansen, Allan K., and Borghammer, Per
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- 2018
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11. In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control study
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Knudsen, Karoline, Fedorova, Tatyana D, Hansen, Allan K, Sommerauer, Michael, Otto, Marit, Svendsen, Kristina B, Nahimi, Adjmal, Stokholm, Morten G, Pavese, Nicola, Beier, Christoph P, Brooks, David J, and Borghammer, Per
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- 2018
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12. Observations on muscle activity in REM sleep behavior disorder assessed with a semi-automated scoring algorithm
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Jeppesen, Jesper, Otto, Marit, Frederiksen, Yoon, Hansen, Allan K., Fedorova, Tatyana D., Knudsen, Karoline, Nahimi, Adjmal, Brooks, David J., Borghammer, Per, and Sommerauer, Michael
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- 2018
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13. Impaired cholinergic integrity of the colon and pancreas in dementia with Lewy bodies.
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Okkels, Niels, Horsager, Jacob, Fedorova, Tatyana D, Knudsen, Karoline, Skjærbæk, Casper, Andersen, Katrine B, Labrador-Espinosa, Miguel, Vestergaard, Karsten, Mortensen, Janne K, Klit, Henriette, Møller, Mette, Danielsen, Erik H, Johnsen, Erik L, Bekan, Goran, Hansen, Kim V, Munk, Ole L, Damholdt, Malene F, Kjeldsen, Pernille L, Hansen, Allan K, and Gottrup, Hanne
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LEWY body dementia ,PARASYMPATHETIC nervous system ,ORTHOSTATIC intolerance ,PANCREAS ,COLON (Anatomy) ,DYSAUTONOMIA ,SYMPATHETIC nervous system - Abstract
Dementia with Lewy bodies is characterized by a high burden of autonomic dysfunction and Lewy pathology in peripheral organs and components of the sympathetic and parasympathetic nervous system. Parasympathetic terminals may be quantified with
18 F-fluoroetoxybenzovesamicol, a PET tracer that binds to the vesicular acetylcholine transporter in cholinergic presynaptic terminals. Parasympathetic imaging may be useful for diagnostics, improving our understanding of autonomic dysfunction and for clarifying the spatiotemporal relationship of neuronal degeneration in prodromal disease. Therefore, we aimed to investigate the cholinergic parasympathetic integrity in peripheral organs and central autonomic regions of subjects with dementia with Lewy bodies and its association with subjective and objective measures of autonomic dysfunction. We hypothesized that organs with known parasympathetic innervation, especially the pancreas and colon, would have impaired cholinergic integrity. To achieve these aims, we conducted a cross-sectional comparison study including 23 newly diagnosed non-diabetic subjects with dementia with Lewy bodies (74 ± 6 years, 83% male) and 21 elderly control subjects (74 ± 6 years, 67% male). We obtained whole-body images to quantify PET uptake in peripheral organs and brain images to quantify PET uptake in regions of the brainstem and hypothalamus. Autonomic dysfunction was assessed with questionnaires and measurements of orthostatic blood pressure. Subjects with dementia with Lewy bodies displayed reduced cholinergic tracer uptake in the pancreas (32% reduction, P = 0.0003) and colon (19% reduction, P = 0.0048), but not in organs with little or no parasympathetic innervation. Tracer uptake in a region of the medulla oblongata overlapping the dorsal motor nucleus of the vagus correlated with autonomic symptoms (rs = −0.54, P = 0.0077) and changes in orthostatic blood pressure (rs = 0.76, P < 0.0001). Tracer uptake in the pedunculopontine region correlated with autonomic symptoms (rs = −0.52, P = 0.0104) and a measure of non-motor symptoms (rs = −0.47, P = 0.0230). In conclusion, our findings provide the first imaging-based evidence of impaired cholinergic integrity of the pancreas and colon in dementia with Lewy bodies. The observed changes may reflect parasympathetic denervation, implying that this process is initiated well before the point of diagnosis. The findings also support that cholinergic denervation in the brainstem contributes to dysautonomia. [ABSTRACT FROM AUTHOR]- Published
- 2024
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14. Severe cholinergic terminal loss in newly diagnosed dementia with Lewy bodies.
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Okkels, Niels, Horsager, Jacob, Labrador-Espinosa, Miguel, Kjeldsen, Pernille L, Damholdt, Malene F, Mortensen, Janne, Vestergård, Karsten, Knudsen, Karoline, Andersen, Katrine B, Fedorova, Tatyana D, Skjærbæk, Casper, Gottrup, Hanne, Hansen, Allan K, Grothe, Michel J, and Borghammer, Per
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LEWY body dementia ,BRAIN metabolism ,LIMBIC system ,BRAIN diseases ,CEREBRAL cortex ,SENILE dementia ,BRAIN degeneration - Abstract
Cholinergic changes play a fundamental role in the natural history of dementia with Lewy bodies and Lewy body disease in general. Despite important achievements in the field of cholinergic research, significant challenges remain. We conducted a study with four main objectives: (i) to examine the integrity of cholinergic terminals in newly diagnosed dementia with Lewy bodies; (ii) to disentangle the cholinergic contribution to dementia by comparing cholinergic changes in Lewy body patients with and without dementia; (iii) to investigate the in vivo relationship between cholinergic terminal loss and atrophy of cholinergic cell clusters in the basal forebrain at different stages of Lewy body disease; and (iv) to test whether any asymmetrical degeneration in cholinergic terminals would correlate with motor dysfunction and hypometabolism. To achieve these objectives, we conducted a comparative cross-sectional study of 25 newly diagnosed dementia with Lewy bodies patients (age 74 ± 5 years, 84% male), 15 healthy control subjects (age 75 ± 6 years, 67% male) and 15 Parkinson's disease patients without dementia (age 70 ± 7 years, 60% male). All participants underwent
18 F-fluoroetoxybenzovesamicol PET and high-resolution structural MRI. In addition, we collected clinical18 F-fluorodeoxyglucose PET images. Brain images were normalized to standard space and regional tracer uptake and volumetric indices of basal forebrain degeneration were extracted. Patients with dementia showed spatially distinct reductions in cholinergic terminals across the cerebral cortex, limbic system, thalamus and brainstem. Also, cholinergic terminal binding in cortical and limbic regions correlated quantitatively and spatially with atrophy of the basal forebrain. In contrast, patients without dementia showed decreased cholinergic terminal binding in the cerebral cortex despite preserved basal forebrain volumes. In patients with dementia, cholinergic terminal reductions were most severe in limbic regions and least severe in occipital regions compared to those without dementia. Interhemispheric asymmetry of cholinergic terminals correlated with asymmetry of brain metabolism and lateralized motor function. In conclusion, this study provides robust evidence for severe cholinergic terminal loss in newly diagnosed dementia with Lewy bodies, which correlates with structural imaging measures of cholinergic basal forebrain degeneration. In patients without dementia, our findings suggest that loss of cholinergic terminal function occurs 'before' neuronal cell degeneration. Moreover, the study supports that degeneration of the cholinergic system is important for brain metabolism and may be linked with degeneration in other transmitter systems. Our findings have implications for understanding how cholinergic system pathology contributes to the clinical features of Lewy body disease, changes in brain metabolism and disease progression patterns. [ABSTRACT FROM AUTHOR]- Published
- 2023
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15. Mitochondrial function-associated genes underlie cortical atrophy in prodromal synucleinopathies.
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Rahayel, Shady, Tremblay, Christina, Vo, Andrew, Misic, Bratislav, Lehéricy, Stéphane, Arnulf, Isabelle, Vidailhet, Marie, Corvol, Jean-Christophe, Group, the ICEBERG Study, Gagnon, Jean-François, Postuma, Ronald B, Montplaisir, Jacques, Lewis, Simon, Matar, Elie, Martens, Kaylena Ehgoetz, Borghammer, Per, Knudsen, Karoline, Hansen, Allan K, Monchi, Oury, and Gan-Or, Ziv
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GENE ontology ,RAPID eye movement sleep ,CEREBRAL atrophy ,LEWY body dementia ,PARTIAL least squares regression ,ALZHEIMER'S disease - Abstract
Isolated rapid eye movement sleep behaviour disorder (iRBD) is a sleep disorder characterized by the loss of rapid eye movement sleep muscle atonia and the appearance of abnormal movements and vocalizations during rapid eye movement sleep. It is a strong marker of incipient synucleinopathy such as dementia with Lewy bodies and Parkinson's disease. Patients with iRBD already show brain changes that are reminiscent of manifest synucleinopathies including brain atrophy. However, the mechanisms underlying the development of this atrophy remain poorly understood. In this study, we performed cutting-edge imaging transcriptomics and comprehensive spatial mapping analyses in a multicentric cohort of 171 polysomnography-confirmed iRBD patients [67.7 ± 6.6 (49–87) years; 83% men] and 238 healthy controls [66.6 ± 7.9 (41–88) years; 77% men] with T
1 -weighted MRI to investigate the gene expression and connectivity patterns associated with changes in cortical thickness and surface area in iRBD. Partial least squares regression was performed to identify the gene expression patterns underlying cortical changes in iRBD. Gene set enrichment analysis and virtual histology were then done to assess the biological processes, cellular components, human disease gene terms, and cell types enriched in these gene expression patterns. We then used structural and functional neighbourhood analyses to assess whether the atrophy patterns in iRBD were constrained by the brain's structural and functional connectome. Moreover, we used comprehensive spatial mapping analyses to assess the specific neurotransmitter systems, functional networks, cytoarchitectonic classes, and cognitive brain systems associated with cortical changes in iRBD. All comparisons were tested against null models that preserved spatial autocorrelation between brain regions and compared to Alzheimer's disease to assess the specificity of findings to synucleinopathies. We found that genes involved in mitochondrial function and macroautophagy were the strongest contributors to the cortical thinning occurring in iRBD. Moreover, we demonstrated that cortical thinning was constrained by the brain's structural and functional connectome and that it mapped onto specific networks involved in motor and planning functions. In contrast with cortical thickness, changes in cortical surface area were related to distinct genes, namely genes involved in the inflammatory response, and to different spatial mapping patterns. The gene expression and connectivity patterns associated with iRBD were all distinct from those observed in Alzheimer's disease. In summary, this study demonstrates that the development of brain atrophy in synucleinopathies is constrained by specific genes and networks. [ABSTRACT FROM AUTHOR]- Published
- 2023
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16. 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
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- 2017
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17. Evaluation of the noradrenergic system in Parkinson’s disease: an 11C-MeNER PET and neuromelanin MRI study
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Sommerauer, Michael, Fedorova, Tatyana D, Hansen, Allan K, Knudsen, Karoline, Otto, Marit, Jeppesen, Jesper, Frederiksen, Yoon, Blicher, Jakob U, Geday, Jacob, Nahimi, Adjmal, Damholdt, Malene F, Brooks, David J, and Borghammer, Per
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- 2018
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18. 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
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LEWY body dementia , *PARKINSON'S disease , *POSITRON emission tomography computed tomography , *POSITRON emission tomography - Abstract
Background: 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-first Lewy body disease. We have hypothesized that most patients with dementia with Lewy bodies (DLB) belong to the body-first subtype, whereas patients with Parkinson's disease (PD) more often belong to the brain-first subtype. Objective: To compare asymmetry of striatal dopaminergic dysfunction in DLB and PD patients using [18F]-FE-PE2I positron emission tomography (PET). Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]
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- 2023
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19. 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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20. 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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21. Decreased intestinal acetylcholinesterase in early Parkinson disease: An 11C-donepezil PET study
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Fedorova, Tatyana D., Seidelin, Louise B., Knudsen, Karoline, Schacht, Anna C., Geday, Jacob, Pavese, Nicola, Brooks, David J., and Borghammer, Per
- Published
- 2017
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22. Constipation in parkinsonʼs disease: Subjective symptoms, objective markers, and new perspectives
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Krack, Paul, Volkmann, Jens, Knudsen, Karoline, Krogh, Klaus, Østergaard, Karen, and Borghammer, Per
- Published
- 2017
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23. Imaging Parkinson’s disease below the neck
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Borghammer, Per, Knudsen, Karoline, Fedorova, Tatyana D., and Brooks, David J.
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- 2017
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24. Disruption of Sleep Microarchitecture Is a Sensitive and Early Marker of Parkinson's Disease.
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Doppler, Christopher E.J., Smit, Julia, Hommelsen, Maximilian, Seger, Aline, Okkels, Niels, Horsager, Jacob, Kinnerup, Martin, Hansen, Allan K., Fedorova, Tatyana D., Knudsen, Karoline, Otto, Marit, Nahimi, Adjmal, Fink, Gereon R., Borghammer, Per, and Sommerauer, Michael
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SLEEP interruptions ,PARKINSON'S disease ,CAPITALIZATION rate ,RAPID eye movement sleep - Abstract
Background: Although sleep disturbances are highly prevalent in patients with Parkinson's disease, sleep macroarchitecture metrics show only minor changes. Objective: To assess alterations of the cyclic alternating pattern (CAP) as a critical feature of sleep microarchitecture in patients with prodromal, recent, and established Parkinson's disease. Methods: We evaluated overnight polysomnography for classic sleep macroarchitecture and CAP metrics in 68 patients at various disease stages and compared results to 22 age- and sex-matched controls. Results: Already at the prodromal stage, patients showed a significantly reduced CAP rate as a central characteristic of sleep microarchitecture. Temporal characteristics of CAP showed a gradual change over disease stages and correlated with motor performance. In contrast, the sleep macroarchitecture metrics did not differ between groups. Conclusion: Data suggest that alterations of sleep microarchitecture are an early and more sensitive characteristic of Parkinson's disease than changes in sleep macroarchitecture. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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25. Imaging acetylcholinesterase density in peripheral organs in Parkinsonʼs disease with 11C-donepezil PET
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Gjerløff, Trine, Fedorova, Tatyana, Knudsen, Karoline, Munk, Ole L., Nahimi, Adjmal, Jacobsen, Steen, Danielsen, Erik H., Terkelsen, Astrid J., Hansen, John, Pavese, Nicola, Brooks, David J., and Borghammer, Per
- Published
- 2015
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26. Brain atrophy in prodromal synucleinopathy is shaped by structural connectivity and gene expression.
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Rahayel, Shady, Tremblay, Christina, Vo, Andrew, Zheng, Ying Qiu, Lehéricy, Stéphane, Arnulf, Isabelle, Vidailhet, Marie, Corvol, Jean Christophe, Group, ICEBERG Study, Gagnon, Jean François, Postuma, Ronald B, Montplaisir, Jacques, Lewis, Simon, Matar, Elie, Martens, Kaylena Ehgoetz, Borghammer, Per, Knudsen, Karoline, Hansen, Allan, Monchi, Oury, and Misic, Bratislav
- Abstract
Isolated REM sleep behaviour disorder (iRBD) is a synucleinopathy characterized by abnormal behaviours and vocalizations during REM sleep. Most iRBD patients develop dementia with Lewy bodies, Parkinson's disease, or multiple system atrophy over time. Patients with iRBD exhibit brain atrophy patterns that are reminiscent of those observed in overt synucleinopathies. However, the mechanisms linking brain atrophy to the underlying alpha-synuclein pathophysiology are poorly understood. Our objective was to investigate how the prion-like and regional vulnerability hypotheses of alpha-synuclein might explain brain atrophy in iRBD. Using a multicentric cohort of 182 polysomnography-confirmed iRBD patients who underwent T1-weighted MRI, we performed vertex-based cortical surface and deformation-based morphometry analyses to quantify brain atrophy in patients (67.8 years, 84% men) and 261 healthy controls (66.2 years, 75%) and investigated the morphological correlates of motor and cognitive functioning in iRBD. Next, we applied the agent-based Susceptible-Infected-Removed model (i.e., a computational model that simulates in silico the spread of pathologic alpha-synuclein based on structural connectivity and gene expression) and tested if it recreated atrophy in iRBD by statistically comparing simulated regional brain atrophy to the atrophy observed in patients. The impact of SNCA and GBA gene expression and brain connectivity was then evaluated by comparing the model fit to the one obtained in null models where either gene expression or connectivity was randomized. The results showed that iRBD patients present with cortical thinning and tissue deformation, which correlated with motor and cognitive functioning. Next, we found that the computational model recreated cortical thinning (r = 0.51, p = 0.0007) and tissue deformation (r = 0.52, p = 0.0005) in patients, and that the connectome's architecture along with SNCA and GBA gene expression contributed to shaping atrophy in iRBD. We further demonstrated that the full agent-based model performed better than network measures or gene expression alone in recreating the atrophy pattern in iRBD. In summary, atrophy in iRBD is extensive, correlates with motor and cognitive function, and can be recreated using the dynamics of agent-based modelling, structural connectivity, and gene expression. These findings support the concepts that both prion-like spread and regional susceptibility account for the atrophy observed in prodromal synucleinopathies. Therefore, the agent-based Susceptible-Infected-Removed model may be a useful tool for testing hypotheses underlying neurodegenerative diseases and new therapies aimed at slowing or stopping the spread of alpha-synuclein pathology. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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27. Intestinal Transit in Early Moderate Parkinson's Disease Correlates with Probable RBD: Subclinical Esophageal Dysmotility Does Not Correlate.
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Skjærbæk, Casper, Knudsen, Karoline, Kinnerup, Martin, Hansen, Kim Vang, and Borghammer, Per
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GASTROINTESTINAL motility , *CROSS-sectional method , *CONSTIPATION , *RAPID eye movement sleep , *DEGLUTITION disorders , *SLEEP disorders , *RISK assessment , *RADIONUCLIDE imaging , *PARKINSON'S disease , *ESOPHAGEAL motility disorders , *QUESTIONNAIRES , *COMPUTED tomography , *DISEASE risk factors ,ESOPHAGEAL radiography - 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 < 0.05 and p < 0.01 , respectively) and a moderate-strong positive correlation was found between colonic transit time (CTT) and RBDSQ score (r = 0.61, p < 0.001). Significant correlations were also found between CTT and SCOPA-AUT scores as well as between CTT and ROME III functional constipation scores. Conclusion. Colonic transit correlates with probable RBD and is more severely prolonged in early moderate PD than is the distal esophageal transit time. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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28. Alpha-Synuclein Strain Variability in Body-First and Brain-First Synucleinopathies.
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Just, Mie Kristine, Gram, Hjalte, Theologidis, Vasileios, Jensen, Poul Henning, Nilsson, K. Peter R., Lindgren, Mikael, Knudsen, Karoline, Borghammer, Per, and Van Den Berge, Nathalie
- Subjects
BIOMARKERS ,BIOLOGICAL models ,LEWY body dementia ,SYNUCLEINS ,NEURODEGENERATION ,LUMINESCENCE spectroscopy - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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29. ARadionuclide imaging of the gut-brain axis in Parkinson’s disease.
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Horsager, Jacob, Knudsen, Karoline, and Borghammer, Per
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- 2021
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30. Asymmetric Dopaminergic Dysfunction in Brain-First versus Body-First Parkinson's Disease Subtypes.
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Knudsen, Karoline, Fedorova, Tatyana D., Horsager, Jacob, Andersen, Katrine B., Skjærbæk, Casper, Berg, Daniela, Schaeffer, Eva, Brooks, David J., Pavese, Nicola, Van Den Berge, Nathalie, and Borghammer, Per
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PARKINSON'S disease , *POSITRON emission tomography , *DISTRIBUTION (Probability theory) , *RAPID eye movement sleep , *BEHAVIOR disorders - Abstract
Background: We have hypothesized that Parkinson's disease (PD) comprises two subtypes. Brain-first, where pathogenic α-synuclein initially forms unilaterally in one hemisphere leading to asymmetric nigrostriatal degeneration, and body-first with initial enteric pathology, which spreads through overlapping vagal innervation leading to more symmetric brainstem involvement and hence more symmetric nigrostriatal degeneration. Isolated REM sleep behaviour disorder has been identified as a strong marker of the body-first type. Objective: To analyse striatal asymmetry in [18F]FDOPA PET and [123I]FP-CIT DaT SPECT data from iRBD patients, de novo PD patients with RBD (PD+RBD) and de novo PD patients without RBD (PD-RBD). These groups were defined as prodromal body-first, de novo body-first, and de novo brain-first, respectively. Methods: We included [18F]FDOPA PET scans from 21 iRBD patients, 11 de novo PD+RBD, 22 de novo PD-RBD, and 18 controls subjects. Also, [123I]FP-CIT DaT SPECT data from iRBD and de novo PD patients with unknown RBD status from the PPPMI dataset was analysed. Lowest putamen specific binding ratio and putamen asymmetry index (AI) was defined. Results: Nigrostriatal degeneration was significantly more symmetric in patients with RBD versus patients without RBD or with unknown RBD status in both FDOPA (p = 0.001) and DaT SPECT (p = 0.001) datasets. Conclusion: iRBD subjects and de novo PD+RBD patients present with significantly more symmetric nigrostriatal dopaminergic degeneration compared to de novo PD-RBD patients. The results support the hypothesis that body-first PD is characterized by more symmetric distribution most likely due to more symmetric propagation of pathogenic α-synuclein compared to brain-first PD. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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31. A Radionuclide imaging of the gut-brain axis in Parkinson’s disease.
- Author
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Horsager, Jacob, Knudsen, Karoline, and Borghammer, Per
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- 2021
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32. Regional locus coeruleus degeneration is uncoupled from noradrenergic terminal loss in Parkinson's disease.
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Doppler, Christopher E J, Kinnerup, Martin B, Brune, Corinna, Farrher, Ezequiel, Betts, Matthew, Fedorova, Tatyana D, Schaldemose, Jeppe L, Knudsen, Karoline, Ismail, Rola, Seger, Aline D, Hansen, Allan K, Stær, Kristian, Fink, Gereon R, Brooks, David J, Nahimi, Adjmal, Borghammer, Per, and Sommerauer, Michael
- Subjects
LOCUS coeruleus ,PARKINSON'S disease ,SOCIAL degeneration - Abstract
Previous studies have reported substantial involvement of the noradrenergic system in Parkinson's disease. Neuromelanin-sensitive MRI sequences and PET tracers have become available to visualize the cell bodies in the locus coeruleus and the density of noradrenergic terminal transporters. Combining these methods, we investigated the relationship of neurodegeneration in these distinct compartments in Parkinson's disease. We examined 93 subjects (40 healthy controls and 53 Parkinson's disease patients) with neuromelanin-sensitive turbo spin-echo MRI and calculated locus coeruleus-to-pons signal contrasts. Voxels with the highest intensities were extracted from published locus coeruleus coordinates transformed to individual MRI. To also investigate a potential spatial pattern of locus coeruleus degeneration, we extracted the highest signal intensities from the rostral, middle, and caudal third of the locus coeruleus. Additionally, a study-specific probabilistic map of the locus coeruleus was created and used to extract mean MRI contrast from the entire locus coeruleus and each rostro-caudal subdivision. Locus coeruleus volumes were measured using manual segmentations. A subset of 73 subjects had 11C-MeNER PET to determine noradrenaline transporter density, and distribution volume ratios of noradrenaline transporter-rich regions were computed. Patients with Parkinson's disease showed reduced locus coeruleus MRI contrast independently of the selected method (voxel approaches: P < 0.0001, P < 0.001; probabilistic map: P < 0.05), specifically on the clinically-defined most affected side (P < 0.05), and reduced locus coeruleus volume (P < 0.0001). Reduced MRI contrast was confined to the middle and caudal locus coeruleus (voxel approach, rostral: P = 0.48, middle: P < 0.0001, and caudal: P < 0.05; probabilistic map, rostral: P = 0.90, middle: P < 0.01, and caudal: P < 0.05). The noradrenaline transporter density was lower in patients with Parkinson's diseasein all examined regions (group effect P < 0.0001). No significant correlation was observed between locus coeruleus MRI contrast and noradrenaline transporter density. In contrast, the individual ratios of noradrenaline transporter density and locus coeruleus MRI contrast were lower in Parkinson's disease patients in all examined regions (group effect P < 0.001). Our multimodal imaging approach revealed pronounced noradrenergic terminal loss relative to cellular locus coeruleus degeneration in Parkinson's disease; the latter followed a distinct spatial pattern with the middle-caudal portion being more affected than the rostral part. The data shed first light on the interaction between the axonal and cell body compartments and their differential susceptibility to neurodegeneration in Parkinson's disease, which may eventually direct research towards potential novel treatment approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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33. Microsleep disturbances are associated with noradrenergic dysfunction in Parkinson's disease.
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Doppler, Christopher E J, Smit, Julia A M, Hommelsen, Maximilian, Seger, Aline, Horsager, Jacob, Kinnerup, Martin B, Hansen, Allan K, Fedorova, Tatyana D, Knudsen, Karoline, Otto, Marit, Nahimi, Adjmal, Borghammer, Per, and Sommerauer, Michael
- Published
- 2021
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34. Gastric Emptying Time and Volume of the Small Intestine as Objective Markers in Patients With Symptoms of Diabetic Enteropathy.
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Klinge, Mette W., Sutter, Nanna, Mark, Esben B., Haase, Anne-Mette, Borghammer, Per, Schlageter, Vincent, Lund, Sten, Fleischer, Jesper, Knudsen, Karoline, Drewes, Asbjørn M., and Krogh, Klaus
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GASTRIC emptying ,GASTROPARESIS ,SMALL intestine ,COMPUTED tomography ,PEOPLE with diabetes ,INTESTINAL diseases - Abstract
Background/Aims Patients with diabetes mellitus (DM) often suffer from gastrointestinal (GI) symptoms, but these correlate poorly to established objective GI motility measures. Our aim is to perform a detailed evaluation of potential measures of gastric and small intestinal motility in patients with DM type 1 and severe GI symptoms. Methods Twenty patients with DM and 20 healthy controls (HCs) were included. GI motility was examined with a 3-dimensional-Transit capsule, while organ volumes were determined by CT scans. Results Patients with DM and HCs did not differ with regard to median gastric contraction frequency (DM: 3.0 contractions/minute [interquartile range {IQR}, 2.9-3.0]; HCs: 2.9 [IQR, 2.8-3.1]; P = 0.725), amplitude of gastric contractions (DM: 9 mm [IQR, 8-11]; HCs: 11 mm (IQR, 9-12); P = 0.151) or fasting volume of the stomach wall (DM: 149 cm3 [IQR, 112-187]; HCs: 132 cm3 [IQR, 107-154]; P = 0.121). Median gastric emptying time was prolonged in patients (DM: 3.3 hours [IQR, 2.6-4.6]; HCs: 2.4 hours [IQR, 1.8-2.7]; P = 0.002). No difference was found in small intestinal transit time (DM: 5 hours [IQR, 3.7-5.6]; HCs: 4.8 hours [IQR, 3.9-6.0]; P = 0.883). However, patients with DM had significantly larger volume of the small intestinal wall (DM: 623 cm3 [IQR, 487-766]; HCs: 478 cm3 [IQR, 393-589]; P = 0.003). Among patients, 13 (68%) had small intestinal wall volume and 9 (50%) had gastric emptying time above the upper 95% percentile of HCs. Conclusion In our study, gastric emptying time and volume of the small intestinal wall appeared to be the best objective measures in patients with DM type 1 and symptoms and gastroenteropathy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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35. Vagus Nerve Cross-Sectional Area in Patients With Parkinson's Disease—An Ultrasound Case-Control Study.
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Horsager, Jacob, Walter, Uwe, Fedorova, Tatyana D., Andersen, Katrine B., Skjærbæk, Casper, Knudsen, Karoline, Okkels, Niels, von Weitzel-Mudersbach, Paul, Dyrskog, Stig Eric, Bergholt, Bo, and Borghammer, Per
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PARKINSON'S disease ,VAGUS nerve ,ULTRASONIC imaging ,PERIPHERAL nervous system ,CASE-control method - 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 mm
2 , 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. [ABSTRACT FROM AUTHOR]- Published
- 2021
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36. Brain-first versus body-first Parkinson's disease: a multimodal imaging case-control study.
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Horsager, Jacob, Andersen, Katrine B, Knudsen, Karoline, Skjærbæk, Casper, Fedorova, Tatyana D, Okkels, Niels, Schaeffer, Eva, Bonkat, Sarah K, Geday, Jacob, Otto, Marit, Sommerauer, Michael, Danielsen, Erik H, Bech, Einar, Kraft, Jonas, Munk, Ole L, Hansen, Sandra D, Pavese, Nicola, Göder, Robert, Brooks, David J, and Berg, Daniela
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PARKINSON'S disease ,PERIPHERAL nervous system ,AUTONOMIC nervous system ,LOCUS coeruleus ,CASE-control method - Abstract
Parkinson's disease is characterized by the presence of abnormal, intraneuronal α-synuclein aggregates, which may propagate from cell-to-cell in a prion-like manner. However, it remains uncertain where the initial α-synuclein aggregates originate. We have hypothesized that Parkinson's disease comprises two subtypes. A brain-first (top-down) type, where α-synuclein pathology initially arises in the brain with secondary spreading to the peripheral autonomic nervous system; and a body-first (bottom-up) type, where the pathology originates in the enteric or peripheral autonomic nervous system and then spreads to the brain. We also hypothesized that isolated REM sleep behaviour disorder (iRBD) is a prodromal phenotype for the body-first type. Using multimodal imaging, we tested the hypothesis by quantifying neuronal dysfunction in structures corresponding to Braak stages I, II and III involvement in three distinct patient groups. We included 37 consecutive de novo patients with Parkinson's disease into this case-control PET study. Patients with Parkinson's disease were divided into 24 RBD-negative (PDRBD-) and 13 RBD-positive cases (PDRBD+) and a comparator group of 22 iRBD patients. We used 11C-donepezil PET/CT to assess cholinergic (parasympathetic) innervation, 123I-metaiodobenzylguanidine (MIBG) scintigraphy to measure cardiac sympathetic innervation, neuromelanin-sensitive MRI to measure the integrity of locus coeruleus pigmented neurons, and 18F-dihydroxyphenylalanine (FDOPA) PET to assess putaminal dopamine storage capacity. Colon volume and transit times were assessed with CT scans and radiopaque markers. Imaging data from the three groups were interrogated with ANOVA and Kruskal-Wallis tests corrected for multiple comparisons. The PDRBD- and PDRBD+ groups showed similar marked reductions in putaminal FDOPA-specific uptake, whereas two-thirds of iRBD patients had normal scans (P < 10-13, ANOVA). When compared to the PDRBD- patients, the PDRBD+ and iRBD patients showed reduced mean MIBG heart:mediastinum ratios (P < 10-5, ANOVA) and colon 11C-donepezil standard uptake values (P = 0.008, ANOVA). The PDRBD+ group trended towards a reduced mean MRI locus coeruleus: pons ratio compared to PDRBD- (P = 0.07, t-test). In comparison to the other groups, the PDRBD+ group also had enlarged colon volumes (P < 0.001, ANOVA) and delayed colonic transit times (P = 0.01, Kruskal-Wallis). The combined iRBD and PDRBD+ patient data were compatible with a body-first trajectory, characterized by initial loss of cardiac MIBG signal and 11C-colonic donepezil signal followed by loss of putaminal FDOPA uptake. In contrast, the PDRBD- data were compatible with a brain-first trajectory, characterized by primary loss of putaminal FDOPA uptake followed by a secondary loss of cardiac MIBG signal and 11C-donepezil signal. These findings support the existence of brain-first and body-first subtypes of Parkinson's disease. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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37. Skin Temperature in Parkinson's Disease Measured by Infrared Thermography.
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Purup, Mathias Møller, Knudsen, Karoline, Karlsson, Pall, Terkelsen, Astrid Juhl, and Borghammer, Per
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AUTONOMIC nervous system diseases , *STATISTICAL correlation , *FOOT , *HAND , *MEDICAL thermography , *NERVE tissue proteins , *PARKINSON'S disease , *QUESTIONNAIRES , *TOES , *SKIN temperature , *TORSO , *BODY mass index - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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38. A Screening-Based Method for Identifying Patients with REM Sleep Behaviour Disorder in a Danish Community Setting.
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Fedorova, Tatyana D., Knudsen, Karoline, Sommerauer, Michael, Svendsen, Kristina B., Otto, Marit, and Borghammer, Per
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RAPID eye movement sleep , *BEHAVIOR disorders , *SLEEP disorders , *SYMPTOMS , *DISEASE prevalence - Abstract
Isolated REM sleep behaviour disorder (iRBD) is a predictive marker of prodromal Lewy body disease. iRBD prevalence in the general population is around 1%, but it remains under-diagnosed, even though symptoms are alleviated by medication. We developed a population screening strategy and identified 16 iRBD patients by conducting telephone interviews and polysomnography examinations. We compared our population-screened cohort with sleep-center referred patients and found higher MoCA scores and lower MDS-UPDRS-III scores in our patients. In conclusion, screening can be used to identify iRBD patients in a cost-effective manner with the benefit of identifying patients at a very early disease stage. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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39. Normative values for gastric motility assessed with the 3D‐transit electromagnetic tracking system.
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Sutter, Nanna, Klinge, Mette Winther, Mark, Esben Bolvig, Nandhra, Gursharan, Haase, Anne‐Mette, Poulsen, Jakob, Knudsen, Karoline, Borghammer, Per, Schlageter, Vincent, Birch, Malcolm, Scott, S. Mark, Drewes, Asbjørn Mohr, and Krogh, Klaus
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GASTROINTESTINAL motility ,GASTRIC emptying ,GASTROINTESTINAL system ,PYLORUS ,DEFINITIONS - Abstract
Background: The Motilis 3D‐Transit system allows ambulatory description of transit patterns throughout the gastrointestinal tract and offers an alternative method for studying gastric motility. We aimed to establish normative values for gastric motility assessed with the method. Method: A total of 132 healthy volunteers ingested the 3D‐Transit capsule for assessment of gastrointestinal transit times. Recordings from 125 subjects were used for definition of normative values. Forty‐six subjects were studied on two consecutive days. Recordings were reanalyzed using newly developed software providing information on gastric emptying (GE) as well as contraction frequency and movement during gastric contractions. Results: The median GE time was 2.7 hours (range 0.1‐21.2). In 89% of subjects, the capsule passed the pylorus within a postingestion period of 6 hours. The median frequency of gastric contractions was 3.1 per minute (range 2.6‐3.8). The frequency was higher in women (3.2, range 2.7‐3.8) than in men (3.0, range 2.6‐3.5) and increased with age (0.004 per year) (P <.05). The median amplitudes were 35° (range 4‐85) when based on rotation of the capsule and 11 mm (range 6‐31) when based on capsule change in position. The rotation amplitude was higher in women and decreased with increasing BMI (P <.05). The position amplitude was also higher in women and increased with the amount of calories in the test meal, but decreased with increasing BMI and age (P <.05). Day‐to‐day variation (P >.05) was considerable while inter‐rater variability was small. Conclusion and Inferences: We have established normative values for gastric motility assessed with the 3D‐Transit system. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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40. In vivo positron emission tomography imaging of decreased parasympathetic innervation in the gut of vagotomized patients.
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Fedorova, Tatyana Dmitrievna, Knudsen, Karoline, Hartmann, Bolette, Holst, Jens J., Viborg Mortensen, Frank, Krogh, Klaus, and Borghammer, Per
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POSITRON emission tomography , *PARASYMPATHETIC nervous system , *GASTROINTESTINAL system , *INNERVATION , *SMALL intestine - Abstract
Background: Parasympathetic neuropathy is a key feature in many common disorders, including diabetes, neurological disorders, and cancers, but few objective methods exist for assessing damage to the parasympathetic nervous system, particularly in the gastrointestinal system. This study aimed to validate the use of 11C‐donepezil positron emission tomography (PET) to assess parasympathetic integrity in a group of vagotomized patients. Methods: Sixteen healthy controls and 12 patients, vagotomized due to esophagectomy, underwent 11C‐donepezil PET, measurement of colonic transit time, quantification of plasma pancreatic polypeptide (PP), and assessment of subjective long‐term symptoms. Key Results: Vagotomized patients had significantly decreased PET signal in the small intestine and colon compared with healthy controls (5.7 [4.4‐7.9] vs 7.4 [4.5‐11.3], P =.01 and 1.4 [1.1‐2.1] vs 1.6 [1.4‐2.4], P <.01, respectively). Vagotomized patients also displayed a significantly increased colonic transit time (2.9 ± 0.9 h vs 1.9 ± 0.8 h), P <.01 and increased volumes of the small intestine and colon (715 ccm [544‐1177] vs 443 ccm [307‐613], P <.01 and 971 ccm [713‐1389] vs 711 ccm [486‐1394], P =.01, respectively). Patients and controls did not differ in PP ratio levels after sham feeding, but PP ratio at 10 minutes. after sham feeding and PET signal intensity in the small intestine was positively correlated (P =.03). Conclusions and Inferences: We found significantly decreased 11C‐donepezil signal in the intestine of vagotomized patients, supporting that 11C‐donepezil PET is a valid measure of intestinal parasympathetic denervation. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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41. Cardiac 11C-Donepezil Binding Increases With Age in Healthy Humans: Potentially Signifying Sigma-1 Receptor Upregulation.
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Horsager, Jacob, Fedorova, Tatyana D., Berge, Nathalie V.D., Klinge, Mette W., Knudsen, Karoline, Hansen, Allan K., Alstrup, Aage K.O., Krogh, Klaus, Gormsen, Lars, and Borghammer, Per
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FLUORODEOXYGLUCOSE F18 ,REGRESSION analysis ,LINEAR statistical models ,PARKINSON'S disease ,AGE ,INTERPERSONAL relations ,HEART metabolism ,BIOCHEMISTRY ,RESEARCH ,SIGMA-1 receptor ,PREDICTIVE tests ,HEART ,AGE distribution ,PHENOMENOLOGICAL biology ,RESEARCH methodology ,CASE-control method ,EVALUATION research ,COMPARATIVE studies ,RADIOPHARMACEUTICALS - Abstract
Background: Donepezil may have cardioprotective properties, but the mechanism is unclear. Using positron-emission tomography (PET), we explored 11C-donepezil uptake in the heart of humans in relation to age. The results are discussed in the context of the cardioprotective property of donepezil.Methods: We included data from 57 patients with cardiac 11C-donepezil PET scans. Linear regression analyses were performed to explore the correlation between cardiac 11C-donepezil standardized uptake value (SUV) and age. Subgroup analyses were performed for healthy controls, patients with prodromal or diagnosed Parkinson disease (PD), males, and females.Results: In the total group of 57 patients, linear regression analysis revealed a significant positive correlation between cardiac 11C-donepezil uptake and age ( r2 = .63, P < .0001). The average increase was ≈1.25 SUV per decade and a 2-fold increase in SUV from age 30 to 65 years. Subgroup analyses also showed significant correlations: healthy control patients alone (n = 28, r2 = .73, P < .0001), prodromal or diagnosed PD (n = 29, r2 = .28, P = .03), male patients (n = 34, r2 = .49, P < .0001), and female patients (n = 23, r2 = .82, P < .0001). No other organs showed increased 11C-donepezil binding with age.Conclusions: 11C-donepezil SUV increases robustly with age in the normal human heart. We speculate that the increased donepezil binding is caused primarily by sigma-1 receptor upregulation. If our interpretation is correct, it shows that sigma-1 receptors are dynamically regulated and may represent an overlooked target for pharmacological intervention studies. [ABSTRACT FROM AUTHOR]- Published
- 2019
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42. F26. Automated chin EMG analysis for quantification of REM sleep without atonia
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Jeppesen, Jesper, Otto, Marit, Frederiksen, Yoon, Hansen, Allan, Fedorova, Tatyana, Knudsen, Karoline, Nahimi, Adjmal, Brooks, David, Borghammer, Per, and Sommerauer, Michael
- Published
- 2018
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43. Decreased noradrenaline transporter density in the motor cortex of Parkinson's disease patients.
- Author
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Sommerauer, Michael, Hansen, Allan K., Parbo, Peter, Fedorova, Tatyana D., Knudsen, Karoline, Frederiksen, Yoon, Nahimi, Adjmal, Barbe, Michael T., Brooks, David J., and Borghammer, Per
- Abstract
Reduced noradrenaline levels have been reported to occur in the motor cortices of PD patients postmortem. Imaging techniques have recently become available to specifically study noradrenergic terminal function in vivo using PET. The objective of this study was to evaluate cortical 11 C-MeNER binding in PD patients. Thirty PD patients and 12 healthy control subjects comparable in age, sex, and cognitive performance underwent PET imaging with 11 C-MeNER, a specific ligand of the noradrenaline transporter. Cortical noradrenaline transporter binding was compared at a voxel level using Statistical Parametric Mapping, whereas cortical thickness was assessed using FreeSurfer software with MRI. PD patients showed reduced 11 C-MeNER binding in the primary motor cortex unrelated to cortical thickness; other cortical regions did not differ between groups. In a subgroup analysis, patients with higher Hoehn & Yahr stage exhibited more pronounced 11 C-MeNER binding reductions. Loss of cortical noradrenergic projections to the primary motor cortex occurs in PD associated with disease stage. © 2018 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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44. Gastrointestinal transit time and heart rate variability in patients with mild acquired brain injury.
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Enevoldsen, Johannes, Vistisen, Simon T., Krogh, Klaus, Nielsen, Jørgen F., Knudsen, Karoline, Borghammer, Per, and Andersen, Henning
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HEART beat ,BRAIN injuries ,FUNCTIONAL independence measure ,DYSAUTONOMIA ,INTRACRANIAL pressure - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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45. P365 Automated chin EMG analysis for quantification of REM sleep without atonia
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Jeppesen, Jesper, Otto, Marit, Frederiksen, Yoon, Hansen, Allan, Fedorova, Tatyana, Knudsen, Karoline, Borghammer, Per, and Sommerauer, Michael
- Published
- 2017
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46. Pancreatic Polypeptide in Parkinson's Disease: A Potential Marker of Parasympathetic Denervation.
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Knudsen, Karoline, Hartmann, Bolette, Fedorova, Tatyana D., Østergaard, Karen, Krogh, Klaus, Møller, Niels, Holst, Jens J., and Borghammer, Per
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- *
PARKINSON'S disease , *POLYPEPTIDES , *PANCREATIC proteins , *SYMPTOMS , *GASTROINTESTINAL system , *DENERVATION - Abstract
Background and Objectives: Parkinson's disease (PD) patients experience several non-motor symptoms from the gastrointestinal tract that may partly be caused by parasympathetic deficiency. The pancreas is densely innervated by the vagus nerve, which mediates early meal-induced secretion of pancreatic polypeptide (PP). Early secretion after sham feeding has been validated as a marker of vagal integrity. Thus, the aim was to evaluate the ratio of increased PP plasma levels after sham feeding in PD and correlate findings with gastrointestinal transit time (GITT). Methods: Twenty-five PD patients and 17 controls were included. PP, insulin, and blood glucose levels were measured before, during, and after sham feeding with white bread and chocolate spread. GITT was measured using radiopaque markers. Furthermore, faeces samples were analyzed for pancreatic elastase enzyme as a marker of exocrine pancreatic function. Results: PD patients showed significantly lower PP ratio levels after sham feeding, whichwas most pronounced at 10 minutes. No significant association was seen between attenuated PP response and GITT in PD patients. No between-group differences were seen in glucose or insulin levels over time, but PD patients showed generally lower insulin levels compared to controls. No difference was found in faeces pancreatic elastase. Conclusions: Early-to-moderate stage PD patients demonstrated significantly decreased PP response after sham feeding suggestive of vagal denervation. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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47. Gastrointestinal Transit Time in Parkinson's Disease Using a Magnetic Tracking System.
- Author
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Knudsen, Karoline, Haase, Anne-Mette, Fedorov, Tatyana D., Bekker, Anne Charlotte, Østergaard, Karen, Krogh, Klaus, and Borghammer, Per
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- *
DISEASE risk factors , *PARKINSON'S disease , *GASTROINTESTINAL diseases , *CECUM , *CONSTIPATION , *SYMPTOMS - Abstract
Background: Symptoms from the gastrointestinal tract are highly prevalent in Parkinson's disease (PD), but knowledge of the underlying pathology is incomplete and valid objective markers on regional gastrointestinal function are limited. Objective: The aims were to evaluate gastrointestinal transit time and motility in PD patients and controls. Methods: Twenty-two PD patients and 15 controls were included. Gastric-, small intestinal-, and caecum-ascending colonic transit times as well as colonic motility, defined as mass- and fastmovements, were performed using the ambulatory 3D-Transit system. Gastrointestinal transit time with radio opaque markers, gastric emptying scintigraphy, and subjective non-motor symptoms were also evaluated. Results: Using the 3D-Transit system, the patient group displayed significantly longer small intestinal- and caecum-ascending transit times (p = 0.030 and p = 0.0063). No between-group difference was seen in gastric transit time (p = 0.91). Time to first mass- and fast colonic movement were significantly increased in PD (p = 0.023 and p = 0.006). Radio opaque marker gastrointestinal transit time was significantly increased in the patient group (p < 0.0001), whereas no difference was seen in scintigraphic gastric emptying time (p = 0.68). Prevalence of constipation symptoms on the NMSQuest was 41% in PD and 7% in controls. Conclusions: Significantly increased small intestinal- and caecum-ascending 3D-Transit times were detected in PD patients. Also, time to first propagating colonic movement was increased. Radio opaque marker gastrointestinal transit time was significantly delayed, but no difference was seen in gastric transit time and gastric emptying time. The present findings highlight widespread intestinal involvement in PD increasing throughout the gastrointestinal tract. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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48. In Vivo cortical tau in Parkinson's disease using 18F-AV-1451 positron emission tomography.
- Author
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Hansen, Allan K., Damholdt, Malene Flensborg, Fedorova, Tatyana D., Knudsen, Karoline, Parbo, Peter, Ismail, Rola, Østergaard, Karen, Brooks, David J., Borghammer, Per, and Østergaard, Karen
- Abstract
Background: Alzheimer's disease copathology is common in PD at autopsy. In non-PD subjects with mild cognitive impairment, tau depositions can be detected using 18F-AV-1451 PET. We hypothesized that 18F-AV-1451 PET would show tau aggregation in PD with mild cognitive impairment and correlate with cognitive dysfunction.Objectives: To describe tau aggregation in PD patients.Methods: Twenty-six PD patients and 23 controls had 18F-AV-1451 PET and neuropsychological assessment to detect mild cognitive impairment.Results: Nine PD patients (35%) were identified with mild cognitive impairment. Regional analyses showed no significant differences between groups. Voxel-wise analyses showed no correlation with cognitive domain z-scores within patients. One patient with mild cognitive impairment was estimated Braak tau stage 5; all other patients were stage 0.Conclusion: Our results indicate that tau pathology, as detected by 18F-AV-1451, is uncommon in PD with mild cognitive impairment and shows no significant correlation with cognitive dysfunction at this stage. © 2017 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]- Published
- 2017
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49. Reply to the letter to the Editor: Comment to Barichella and colleagues.
- Author
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Knudsen, Karoline, Krogh, Klaus, Östergaard, Karen, and Borghammer, Per
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- 2017
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50. Objective Colonic Dysfunction is Far more Prevalent than Subjective Constipation in Parkinson's Disease: A Colon Transit and Volume Study.
- Author
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Knudsen, Karoline, Fedorova, Tatyana D., Bekker, Anne C., Iversen, Peter, Østergaard, Karen, Krogh, Klaus, and Borghammer, Per
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CONSTIPATION , *PARKINSON'S disease patients , *GASTROINTESTINAL diseases , *QUESTIONNAIRES , *GASTRIC emptying , *PREVENTION - Abstract
Background: Gastrointestinal function has received increased interest in the context of Parkinson's disease (PD). Constipation is among the most frequent non-motor symptoms, but our understanding of the underlying pathology is limited. Subjective constipation correlates poorly with objective markers. Objective: The aims were to evaluate colonic transit time and volume in PD and to correlate these measures with subjective symptoms and gastric emptying. Methods: Thirty-two PD patients and 26 controls were included. Colonic transit time, computed tomography-based volume estimation, and gastric emptying were performed as objective markers of gastrointestinal function. Subjective gastrointestinal symptoms were evaluated by three different questionnaires. Results: Seventy-nine percent of PD patients displayed prolonged colonic transit time (p < 0.0001) and 66% of patients had significantly increased colonic volume (p = 0.0002). Particularly the transverse and rectosigmoid segments were affected. There was no difference in gastric emptying time between groups. The prevalence of subjective constipation in PD patients was significantly lower and ranged from 3% to 38% depending on the type of questionnaire. Conclusions: Significantly delayed colonic transit time and increased volume were frequent findings in PD patients, and objective dysfunction was considerably more prevalent than subjective constipation symptoms. Also, the prevalence of subjective constipation varied widely depending upon which questionnaire was employed. These findings highlight the need for more research on how to define constipation in PD and also the need for improved understanding of the relationship between subjective symptoms and objective dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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