Publications by authors named "Per Borghammer"

112 Publications

Asymmetric Distribution of Dopamine Transporters in Premorbid Corticobasal Syndrome-A Case Report.

Mov Disord Clin Pract 2021 May 1;8(4):607-609. Epub 2021 Apr 1.

Department of Nuclear Medicine and PET Aarhus University Hospital Aarhus Denmark.

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http://dx.doi.org/10.1002/mdc3.13192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088103PMC
May 2021

Fasting gallbladder volume is increased in patients with Parkinson's disease.

Parkinsonism Relat Disord 2021 Apr 30;87:56-60. Epub 2021 Apr 30.

Department of Nuclear Medicine and PET, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, J220, 8200, Aarhus N, Denmark.

Introduction: Autonomic denervation in patients with Parkinson's disease (PD) and isolated REM-sleep behavior disorder (iRBD) could impede gallbladder function leading to increased fasting gallbladder volume (fGBV) and higher risk of gallstones. We aimed to determine fGBV in patients with PD, iRBD, and healthy controls (HCs).

Methods: We included 189 subjects; 100 patients with PD, 21 with iRBD, and 68 HCs. fGBV was determined from abdominal CT scans, and radiopaque gallstone frequency was evaluated.

Results: Median fGBV was 35.7 ml in patients with PD, 31.8 ml in iRBD, and 27.8 ml in HCs (Kruskal-Wallis test: P = 0.0055). Post-tests adjusted for multiple comparison revealed a significant group difference between patients with PD and HCs (P = 0.0038). In the PD group, 23% had enlarged fGBV (cut-off at mean + 2 x standard deviation (SD) in the HC group). No difference in fGBV was observed between iRBD and the other two groups. The total prevalence of gallstones was 6.4% with no differences between the three groups.

Conclusion: Almost a quarter of patients with PD in our cohort exhibited increased fGBV. This study illuminates a potentially overlooked topic in PD research and calls for more studies on biliary dysfunction.
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http://dx.doi.org/10.1016/j.parkreldis.2021.04.027DOI Listing
April 2021

Reduced Synaptic Density in Patients with Lewy Body Dementia: An [ C]UCB-J PET Imaging Study.

Mov Disord 2021 Apr 25. Epub 2021 Apr 25.

Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark.

Background: Patients with Parkinson's disease (PD) often develop dementia, but the underlying substrate is incompletely understood. Generalized synaptic degeneration may contribute to dysfunction and cognitive decline in Lewy body dementias, but in vivo evidence is lacking.

Objective: The objective of this study was to assess the density of synapses in non-demented PD (nPD) subjects (N = 21), patients with PD-dementia or Dementia with Lewy bodies (DLB) (N = 13), and age-matched healthy controls (N = 15).

Method: Using in vivo PET imaging and the novel synaptic-vesicle-glycoprotein 2A (SV2A) radioligand [11C]UCB-J, SUVR-1 values were obtained for 12 pre-defined regions. Volumes-of-interest were defined on MRI T1 scans. Voxel-level between-group comparisons of [11C]UCB-J SUVR-1 were performed. All subjects underwent neuropsychological assessment. Correlations between [11C]UCB- J PET and domain-specific cognitive functioning were examined.

Results: nPD patients only demonstrated significantly reduced SUVR-1 values in the substantia nigra (SN) compared to HC. DLB/PDD patients demonstrated reduced SUVR-1 values in SN and all cortical VOIs except for the hippocampus and amygdala. The voxel-based analysis supported the VOI results. Significant correlation was seen between middle frontal gyrus [11C]UCB-J SUVR-1 and performance on tests of executive function.

Conclusion: Widespread cortical reduction of synaptic density was documented in a cohort of DLB/PDD subjects using in vivo [11C]UCB-J PET. Our study confirms previously reported synaptic loss in SN of nPD patients. [11C]UCB-J binding in selected cortical VOIs of the DLB/PDD patients correlated with their levels of cognitive function across relevant neuropsychological domains. These findings suggest that the loss of synaptic density contributes to cognitive impairment in nPD and DLB/PDD. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28617DOI Listing
April 2021

Impaired cerebral microcirculation in isolated REM sleep behaviour disorder.

Brain 2021 Apr 20. Epub 2021 Apr 20.

Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark.

During the prodromal period of Parkinson's disease and other α-synucleinopathy-related parkinsonisms, neurodegeneration is thought to progressively affect deep brain nuclei, such as the locus coeruleus, caudal raphe nucleus, substantia nigra, and the forebrain nucleus basalis of Meynert. Besides their involvement in the regulation of mood, sleep, behaviour, and memory functions, these nuclei also innervate parenchymal arterioles and capillaries throughout the cortex, possibly to ensure that oxygen supplies are adjusted according to the needs of neural activity. The aim of this study was to examine whether patients with isolated REM sleep behaviour disorder, a parasomnia considered to be a prodromal phenotype of α-synucleinopathies, reveal microvascular flow disturbances consistent with disrupted central blood flow control. We applied dynamic susceptibility contrast MRI to characterize the microscopic distribution of cerebral blood flow in the cortex of 20 polysomnographic-confirmed patients with isolated REM sleep behaviour disorder (17 males, age range: 54-77 years) and 25 healthy matched controls (25 males, age range: 58-76 years). Patients and controls were cognitively tested by Montreal Cognitive Assessment and Mini Mental State Examination. Results revealed profound hypoperfusion and microvascular flow disturbances throughout the cortex in patients compared to controls. In patients, the microvascular flow disturbances were seen in cortical areas associated with language comprehension, visual processing and recognition and were associated with impaired cognitive performance. We conclude that cortical blood flow abnormalities, possibly related to impaired neurogenic control, are present in patients with isolated REM sleep behaviour disorder and associated with cognitive dysfunction. We hypothesize that pharmacological restoration of perivascular neurotransmitter levels could help maintain cognitive function in patients with this prodromal phenotype of parkinsonism.
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http://dx.doi.org/10.1093/brain/awab054DOI Listing
April 2021

Ageing promotes pathological alpha-synuclein propagation and autonomic dysfunction in wild-type rats.

Brain 2021 Apr 20. Epub 2021 Apr 20.

Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Neuronal aggregates of misfolded alpha-synuclein protein are found in the brain and periphery of patients with Parkinson's disease. Braak and colleagues have hypothesized that the initial formation of misfolded alpha-synuclein may start in the gut, and then spread to the brain via peripheral autonomic nerves hereby affecting several organs, including the heart and intestine. Age is considered the greatest risk factor for Parkinson's disease, but the effect of age on the formation of pathology and its propagation has not been studied in detail. We aimed to investigate whether propagation of alpha-synuclein pathology from the gut to the brain is more efficient in old versus young wild-type rats, upon gastrointestinal injection of aggregated alpha-synuclein. Our results demonstrate a robust age-dependent gut-to-brain and brain-to-gut spread of alpha-synuclein pathology along the sympathetic and parasympathetic nerves, resulting in age-dependent dysfunction of the heart and stomach, as observed in patients with Parkinson's disease. Moreover, alpha-synuclein pathology is more densely packed and resistant to enzymatic digestion in old rats, indicating an age-dependent maturation of alpha-synuclein aggregates. Our study is the first to provide a detailed investigation of alpha-synuclein pathology in several organs within one animal model, including the brain, skin, heart, intestine, spinal cord and autonomic ganglia. Taken together, our findings suggest that age is a crucial factor for alpha-synuclein aggregation and complete propagation to heart, stomach and skin, similar to patients. Given that age is the greatest risk factor for human Parkinson's disease, it seems likely that older experimental animals will yield the most relevant and reliable findings. These results have important implications for future research to optimize diagnostics and therapeutics in Parkinson's disease and other age-associated synucleinopathies. Increased emphasis should be placed on using aged animals in preclinical studies and to elucidate the nature of age-dependent interactions.
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http://dx.doi.org/10.1093/brain/awab061DOI Listing
April 2021

Prodromal Parkinson disease subtypes - key to understanding heterogeneity.

Nat Rev Neurol 2021 Jun 20;17(6):349-361. Epub 2021 Apr 20.

Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.

In Parkinson disease (PD), pathological processes and neurodegeneration begin long before the cardinal motor symptoms develop and enable clinical diagnosis. In this prodromal phase, risk and prodromal markers can be used to identify individuals who are likely to develop PD, as in the recently updated International Parkinson and Movement Disorders Society research criteria for prodromal PD. However, increasing evidence suggests that clinical and prodromal PD are heterogeneous, and can be classified into subtypes with different clinical manifestations, pathomechanisms and patterns of spatial and temporal progression in the CNS and PNS. Genetic, pathological and imaging markers, as well as motor and non-motor symptoms, might define prodromal subtypes of PD. Moreover, concomitant pathology or other factors, including amyloid-β and tau pathology, age and environmental factors, can cause variability in prodromal PD. Patients with REM sleep behaviour disorder (RBD) exhibit distinct patterns of α-synuclein pathology propagation and might indicate a body-first subtype rather than a brain-first subtype. Identification of prodromal PD subtypes and a full understanding of variability at this stage of the disease is crucial for early and accurate diagnosis and for targeting of neuroprotective interventions to ensure efficacy.
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http://dx.doi.org/10.1038/s41582-021-00486-9DOI Listing
June 2021

Constipation is Associated with Development of Cognitive Impairment in de novo Parkinson's Disease: A Longitudinal Analysis of Two International Cohorts.

J Parkinsons Dis 2021 Apr 2. Epub 2021 Apr 2.

King's College London, Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, London, United Kingdom.

Background: Constipation is regarded as one of the prodromal features of Parkinson's disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD.

Objective: We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n = 196 from the Non-motor International Longitudinal Study [NILS] and n = 423 from the Parkinson's Progression Markers Initiative [PPMI] study).

Methods: Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI]. We assessed baseline group differences (PD with or without constipation) in CI, global non-motor symptoms burden, motor dysfunction, and striatal dopaminergic denervation. Kaplan-Meier method estimated group differences in cumulative proportion of patients with incident CI over three years. In PPMI, we subsequently performed univariate and multivariate Cox survival analyses to evaluate whether constipation predicts incident mild cognitive impairment or dementia over a 6-year period, including constipation and other known predictors of CI as covariates.

Results: Patients with constipation had greater motor and global non-motor burden in both cohorts at baseline (p <  0.05). Kaplan-Meier plots showed faster conversion to CI in patients with constipation in both cohorts (p <  0.05). In PPMI, 37 subjects developed dementia during a mean follow-up of 4.9 years, and constipation was an independent predictor of dementia onset (hazard ratio = 2.311; p = 0.02).

Conclusion: Constipation in de novo PD patients is associated with development of cognitive decline and may serve as a clinical biomarker for identification of patients at risk for cognitive impairment.
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http://dx.doi.org/10.3233/JPD-212570DOI Listing
April 2021

Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives.

J Clin Med 2021 Mar 31;10(7). Epub 2021 Mar 31.

Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark.

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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http://dx.doi.org/10.3390/jcm10071392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037288PMC
March 2021

The Logic and Pitfalls of Parkinson's as Brain- Versus Body-First Subtypes.

Mov Disord 2021 03;36(3):785-786

Department of Nuclear Medicine & PET, Aarhus University Hospital, Aarhus, Denmark.

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http://dx.doi.org/10.1002/mds.28526DOI Listing
March 2021

The α-Synuclein Origin and Connectome Model (SOC Model) of Parkinson's Disease: Explaining Motor Asymmetry, Non-Motor Phenotypes, and Cognitive Decline.

Authors:
Per Borghammer

J Parkinsons Dis 2021 ;11(2):455-474

Department of Nuclear Medicine & PET, Aarhus University Hospital, Aarhus, Denmark.

A new model of Parkinson's disease (PD) pathogenesis is proposed, the α-Synuclein Origin site and Connectome (SOC) model, incorporating two aspects of α-synuclein pathobiology that impact the disease course for each patient: the anatomical location of the initial α-synuclein inclusion, and α-synuclein propagation dependent on the ipsilateral connections that dominate connectivity of the human brain. In some patients, initial α-synuclein pathology occurs within the CNS, leading to a brain-first subtype of PD. In others, pathology begins in the peripheral autonomic nervous system, leading to a body-first subtype. In brain-first cases, it is proposed that the first pathology appears unilaterally, often in the amygdala. If α-synuclein propagation depends on connection strength, a unilateral focus of pathology will disseminate more to the ipsilateral hemisphere. Thus, α-synuclein spreads mainly to ipsilateral structures including the substantia nigra. The asymmetric distribution of pathology leads to asymmetric dopaminergic degeneration and motor asymmetry. In body-first cases, the α-synuclein pathology ascends via the vagus to both the left and right dorsal motor nuclei of the vagus owing to the overlapping parasympathetic innervation of the gut. Consequently, the initial α-synuclein pathology inside the CNS is more symmetric, which promotes more symmetric propagation in the brainstem, leading to more symmetric dopaminergic degeneration and less motor asymmetry. At diagnosis, body-first patients already have a larger, more symmetric burden of α-synuclein pathology, which in turn promotes faster disease progression and accelerated cognitive decline. The SOC model is supported by a considerable body of existing evidence and may have improved explanatory power.
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http://dx.doi.org/10.3233/JPD-202481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150555PMC
January 2021

Monocyte markers correlate with immune and neuronal brain changes in REM sleep behavior disorder.

Proc Natl Acad Sci U S A 2021 Mar;118(10)

Department of Biomedicine and Danish Research Institute of Translational Neuroscience (DANDRITE), Aarhus University, 8000 Aarhus, Denmark;

Synucleinopathies are neurodegenerative diseases with both central and peripheral immune responses. However, whether the peripheral immune changes occur early in disease and their relation to brain events is yet unclear. Isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD) can precede synucleinopathy-related parkinsonism and provides a prodromal phenotype to study early Parkinson's disease events. In this prospective case-control study, we describe monocytic markers in a cohort of iRBD patients that were associated with the brain-imaging markers of inflammation and neuronal dysfunction. Using C-PK11195 positron emission tomography (PET), we previously showed increased immune activation in the substantia nigra of iRBD patients, while F-DOPA PET detected reduced putaminal dopaminergic function. Here we describe that patients' blood monocytic cells showed increased expression of CD11b, while HLA-DR expression was decreased compared to healthy controls. The iRBD patients had increased classical monocytes and mature natural killer cells. Remarkably, the levels of expression of Toll-like receptor 4 (TLR4) on blood monocytes in iRBD patients were positively correlated with nigral immune activation measured by C-PK11195 PET and negatively correlated with putaminal F-DOPA uptake; the opposite was seen for the percentage of CD163 myeloid cells. This suggesting a deleterious role for TLR4 and, conversely, a protective one for the CD163 expression. We show an association between peripheral blood monocytes and brain immune and dopaminergic changes in a synucleinopathy-related disorder, thus suggesting a cross-talk among periphery and brain during the disease.
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http://dx.doi.org/10.1073/pnas.2020858118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958435PMC
March 2021

Microsleep disturbances are associated with noradrenergic dysfunction in Parkinson's disease.

Sleep 2021 Feb 20. Epub 2021 Feb 20.

Department of Neurology, University Hospital Cologne, Faculty of Medicine, University of Cologne, Köln, Germany.

Study Objectives: Parkinson's disease (PD) commonly involves degeneration of sleep-wake regulating brainstem nuclei; likewise, sleep-wake disturbances are highly prevalent in PD patients. As polysomnography macroparameters typically show only minor changes in PD, we investigated sleep microstructure, particularly cyclic alternating pattern (CAP), and its relation to alterations of the noradrenergic system in these patients.

Methods: We analysed 27 PD patients and 13 healthy control (HC) subjects who underwent over-night polysomnography and 11C-MeNER positron emission tomography for evaluation of noradrenaline transporter density. Sleep macroparameters as well as CAP metrics were evaluated according to the consensus statement from 2001. Statistical analysis comprised group comparisons and correlation analysis of CAP metrics with clinical characteristics of PD patients as well as noradrenaline transporter density.

Results: PD patients and HC subjects were comparable in demographic characteristics (age, sex, body mass index) and polysomnography macroparameters. CAP rate as well as A index differed significantly between groups, with PD patients having a lower CAP rate (46.7 ± 6.6% versus 38.0 ± 11.6%, p = 0.015) and lower A index (49.0 ± 8.7/hour versus 40.1 ± 15.4/hour, p = 0.042). In PD patients, both CAP metrics correlated significantly with diminished noradrenaline transporter density in arousal prompting brainstem nuclei (locus coeruleus, raphe nuclei) as well as arousal propagating brain structures like thalamus and bitemporal cortex.

Conclusions: Sleep microstructure is more severely altered than sleep macrostructure in PD patients and is associated with widespread dysfunction of the noradrenergic arousal system.
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http://dx.doi.org/10.1093/sleep/zsab040DOI Listing
February 2021

Gastrointestinal Dysfunction in Parkinson's Disease.

J Clin Med 2021 Jan 31;10(3). Epub 2021 Jan 31.

Department of Nuclear Medicine & PET, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, J220, 8200 Aarhus N, Denmark.

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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http://dx.doi.org/10.3390/jcm10030493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866791PMC
January 2021

Preserved noradrenergic function in Parkinson's disease patients with rest tremor.

Neurobiol Dis 2021 May 5;152:105295. Epub 2021 Feb 5.

Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, 8200 Aarhus N, Denmark; Department of Neurology, Restorative Parkinson Unit, Universitetssjukhuset, 22184 Lund, Sweden.

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 (PD) or without (PD) rest tremor had C-methylreboxetine(C-MeNER) positron emission tomography (PET) to test the hypothesis that noradrenaline terminal function was relatively preserved in PD compared to PD.

Methods: Sixty-five PD patients and 28 healthy controls (HC) were scanned with C-MeNER PET. Patients were categorized as PD if subscores in UPDRS-III item 3 or MDS-UPDRS-III item 17 was ≥2; remaining were categorized as PD. Simplified reference tissue model 2 distribution volume ratios (DVR) for C-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 C-MeNER DVR compared to PD in LC and thalamus. The PD mean LC DVR was similar to that of HC. PD mean C-MeNER DVRs were significantly lower than HC in the dorsal raphe while the PD group showed significantly lower mean C-MeNER DVR across all regions compared to HC.

Conclusion: While both PD and PD groups showed a significant loss of noradrenaline terminal function compared to controls, noradrenergic neurons were relatively preserved in PD in LC and thalamus. The greater loss of noradrenergic transporters in PD in LC and thalamus compared with PD is in line with earlier in-vitro studies and could potentially contribute to their tremor negative phenotype.
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http://dx.doi.org/10.1016/j.nbd.2021.105295DOI Listing
May 2021

Cognitive impairment in Parkinson's disease is associated with Default Mode Network subsystem connectivity and cerebrospinal fluid Aβ.

Parkinsonism Relat Disord 2021 02 12;83:71-78. Epub 2021 Jan 12.

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA; Department of Neurosurgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA. Electronic address:

Introduction: To identify clinically implementable biomarkers of cognitive impairment in Parkinson's Disease (PD) derived from resting state-functional MRI (rs-fMRI) and CSF protein analysis.

Methods: In this single-center longitudinal cohort study, we analyzed rs-fMRI and CSF biomarkers from 50 PD patients (23 cognitively normal, 18 mild cognitive impairment, 9 dementia) and 19 controls, who completed comprehensive neuropsychological testing. A subgroup of participants returned for follow-up cognitive assessments three years later. From rs-fMRI, we studied the connectivity within two distinct Default Mode Network subsystems: left-to-right hippocampus (LHC-RHC) and medial prefrontal cortex-to-posterior cingulate cortex (mPFC-PCC). We used regression analyses to determine whether imaging (LHC-RHC, mPFC-PCC), clinical (CSF Aβ-42:40, disease duration), and demographic (age, sex, education) variables were associated with global and domain-specific cognitive impairments.

Results: LHC-RHC (F = 3.41,p=0.023) and CSF Aβ-42:40 (χ(3) = 8.77,p = 0.033) were reduced across more cognitively impaired PD groups. Notably, LHC-RHC connectivity was significantly associated with all global and domain-specific cognitive impairments (attention/executive, episodic memory, visuospatial, and language) at the baseline visit. In an exploratory longitudinal analysis, mPFC-PCC was associated with future global and episodic memory impairment.

Conclusion: We used biomarker techniques that are readily available in clinical and research facilities to shed light on the pathophysiologic basis of cognitive impairment in PD. Our findings suggest that there is a functionally distinct role of the hippocampal subsystem within the DMN resting state network, and that intrinsic connectivity between the hippocampi is critically related to a broad range of cognitive functions in PD.
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http://dx.doi.org/10.1016/j.parkreldis.2021.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940579PMC
February 2021

Cortical cholinergic dysfunction correlates with microglial activation in the substantia innominata in REM sleep behavior disorder.

Parkinsonism Relat Disord 2020 12 8;81:89-93. Epub 2020 Oct 8.

Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Denmark; Translational and Clinical Research Institute, Newcastle University, United Kingdom. Electronic address:

Introduction: In vivo PET studies in patients with isolated REM sleep behavior disorder (iRBD) have shown presence of neuroinflammation (microglial activation) in the substantia nigra, and reduced cortical acetylcholinesterase activity, suggestive of cholinergic dysfunction, that was more widespread in patients with poorer cognitive performances. This study aimed to explore whether reduced cortical acetylcholinesterase activity in iRBD is linked to microglial activation in the substantia innominata (SI), the major source of cholinergic input to the cortex.

Methods: We used C(R)-PK11195 and C-Donepezil PET to assess levels of activated microglia and cholinergic function, respectively, in 19 iRBD patients. C(R)-PK11195 binding potential (BP) and C-Donepezil distribution volume ratio (DVR) values were correlated using the Pearson statistic.

Results: We found that a lower cortical C-Donepezil DVR correlated with a higher C(R)-PK11195 BP in the SI (r = -0.48, p = 0.04). At a voxel level, the strongest negative correlations were found in the frontal and temporal lobes.

Conclusion: Our results suggest that reduced cortical acetylcholinesterase activity observed in our iRBD patients could be linked to the occurrence of neuroinflammation in the SI. Early modulation of microglial activation might therefore preserve cortical cholinergic functions in these patients.
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http://dx.doi.org/10.1016/j.parkreldis.2020.10.014DOI Listing
December 2020

Brain-first versus body-first Parkinson's disease: a multimodal imaging case-control study.

Brain 2020 10;143(10):3077-3088

Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark.

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.
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http://dx.doi.org/10.1093/brain/awaa238DOI Listing
October 2020

Absent 18F-FDG Uptake in the Brain-Unsuspected Brain Death.

Clin Nucl Med 2020 Oct;45(10):e433-e434

From the Department of Nuclear Medicine & PET Centre, Aarhus University Hospital.

Brain death is the complete, irreversible cessation of brain function, including the capacity for brainstem, respiratory, and vegetative activities. It is a clinical diagnosis that can be supplemented with brain perfusion imaging. Absent cerebral blood flow can be visualized with CT angiography or perfusion scintigraphy. F-FDG PET/CT, visualizing glucose uptake, is another approach that has been shown to indicate brain death in small case series. We here present a case with unsuspected absent F-FDG uptake and thus no metabolic activity, in the brain. The patient was declared brain dead later the same day.
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http://dx.doi.org/10.1097/RLU.0000000000003237DOI Listing
October 2020

Skin Temperature in Parkinson's Disease Measured by Infrared Thermography.

Parkinsons Dis 2020 25;2020:2349469. Epub 2020 Jul 25.

Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark.

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%,  = 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 3 and 5 phalanx and body mass index (BMI) ( = 0.661,  = 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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http://dx.doi.org/10.1155/2020/2349469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397449PMC
July 2020

Colonic motility in patients with type 1 diabetes and gastrointestinal symptoms.

Neurogastroenterol Motil 2020 12 20;32(12):e13948. Epub 2020 Jul 20.

Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

Background: Gastrointestinal (GI) symptoms are common in patients with diabetes mellitus (DM). The electromagnetic 3D-Transit system allows assessment of regional transit times and motility patterns throughout the GI tract. We aimed to compare GI transit times and detailed motility patterns of the colon in patients with DM and GI symptoms to those of healthy controls (HC). We further aimed to determine whether any abnormalities in motility were reversible by cholinergic stimulation.

Methods: We compared 18 patients with DM with 20 HC by means of the 3D-Transit system. Patients were studied before and during oral administration of 60 mg pyridostigmine.

Key Results: Compared to HC, patients had prolonged gastric emptying (DM: 3.3 hours (interquartile range (IQR) 2.6-4.6); HC: 2.3 hours (IQR 1.7-2.7) (P < .01)), colonic transit time (DM: 52.6 hours (IQR 23.3-83.0); HC: 22.4 hours (IQR 18.9-43.6) (P = .02)), and whole gut transit time (DM: 69.4 hours (IQR 32.9-103.6); HC: 30.3 hours (IQR 25.2-49.9) (P < .01)). In addition, compared to HC, patients had prolonged transit time in the ascending colon (DM: 20.5 hours (IQR 11.0-44.0); HC: 8.0 hours (IQR 3.8-21.0) (P < .05)) and more slow retrograde movements in the colon (DM: 2 movements (IQR 1-4); HC: 1 movement (IQR 0-1) (P = .01)). In patients, pyridostigmine increased the number of bowel movements (P < .01) and reduced small intestine transit times (P < .05).

Conclusions: Patients with DM and GI symptoms have longer than normal GI transit times. This is only partly reversible by pyridostigmine. The increased number of retrograde colonic movements in patients could potentially explain the abnormally long transit time in proximal colon.
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http://dx.doi.org/10.1111/nmo.13948DOI Listing
December 2020

Altered sensorimotor cortex noradrenergic function in idiopathic REM sleep behaviour disorder - A PET study.

Parkinsonism Relat Disord 2020 06 19;75:63-69. Epub 2020 May 19.

Aarhus University Hospital, Department of Nuclear Medicine and PET Centre, Aarhus, Denmark.

Introduction: Noradrenergic denervation is thought to aggravate motor dysfunction in Parkinson's disease (PD). In a previous PET study with the norepinephrine transporter (NART) ligand C-MeNER, we detected reduced NART binding in primary sensorimotor cortex (M1S1) of PD patients. Idiopathic rapid-eye-movement sleep behaviour disorder (iRBD) is a phenotype of prodromal PD. Using C-MeNER PET, we investigated whether iRBD patients showed similar NART binding reductions in M1S1 cortex as PD patients. Additionally, we investigated whether C-MeNER binding and loss of nigrostriatal dopamine storage capacity measured with F-DOPA PET were correlated.

Methods: 17 iRBD patients, 16 PD patients with (PD) and 14 without RBD (PD), and 25 control subjects underwent C-MeNER PET. iRBD patients also had F-DOPA PET. Volume-of-interest analyses and voxel-level statistical parametric mapping were performed.

Results: Partial-volume corrected C-MeNER binding potential (BP) values in M1S1 differed across the groups (P = 0.022) with the iRBD and PD groups showing significant reductions (controls vs. iRBD P = 0.007; control vs. PDP = 0.008). Voxel-wise comparisons confirmed reductions of M1S1 C-MeNER binding in PD and iRBD patients. Significant correlation was seen between putaminal F-DOPA uptake and thalamic C-MeNER binding in iRBD patients (r = 0.343, P = 0.013).

Conclusions: This study found altered noradrenergic neurotransmission in the M1S1 cortex of iRBD patients. The observed reduction of M1S1 C-MeNER binding in iRBD may represent noradrenergic terminal degeneration or physiological down-regulation of NARTs in this prodromal phenotype of PD. The correlation between thalamic C-MeNER binding and putaminal F-DOPA binding suggests that these neurotransmitter systems degenerate in parallel in the iRBD phenotype of prodromal PD.
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http://dx.doi.org/10.1016/j.parkreldis.2020.05.013DOI Listing
June 2020

A Screening-Based Method for Identifying Patients with REM Sleep Behaviour Disorder in a Danish Community Setting.

J Parkinsons Dis 2020 ;10(3):1249-1253

Aarhus University Hospital, Department of Nuclear Medicine and PET Centre, Aarhus, Denmark.

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.
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http://dx.doi.org/10.3233/JPD-202020DOI Listing
January 2020

Imaging dopamine function and microglia in asymptomatic LRRK2 mutation carriers.

J Neurol 2020 Aug 21;267(8):2296-2300. Epub 2020 Apr 21.

Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Noerrebrogade 44, bldg. 10G, 8000, Aarhus C, Denmark.

Neuroinflammation (microglial activation) and subclinical nigrostriatal dysfunction have been reported in subjects at risk of Parkinsonism. Eight non-manifesting carriers (NMCs) of LRRK2 G2019S mutation had C-PK11195 and F-DOPA PET to assess microglial activation and striatal dopamine system integrity, respectively. Comparisons were made with healthy controls. Five LRRK2-NMCs had subclinical reductions of putaminal F-DOPA uptake. Three of them had significantly raised nigral C-PK11195 binding bilaterally. These findings indicate that nigrostriatal dysfunction and neuroinflammation occur in LRRK2-NMCs. Studies in larger cohorts with appropriate follow-up are needed to elucidate the significance of neuroinflammation in the premotor phase of LRRK2-PD.
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http://dx.doi.org/10.1007/s00415-020-09830-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359140PMC
August 2020

Applied strategy in the Iowa Gambling Task: Comparison of individuals with Parkinson's disease to healthy controls.

J Clin Exp Neuropsychol 2020 07 14;42(5):425-435. Epub 2020 Apr 14.

Department of Psychology and Behavioural Sciences, Aarhus University , Aarhus, Denmark.

Introduction: Decision-making impairments in Parkinson's disease (PD) have frequently been measured using the Iowa Gambling Task (IGT), though results have been inconsistent. At present, task performance has primarily been evaluated based on the total IGT score, and there is a need for further analysis of the strategy of older individuals with PD and healthy control (HC) participants in IGT.

Objective: The present study aims to explore possible impairments in IGT performance in individuals with PD compared to healthy controls using strategy analysis, extending previous results on this subject, and to discuss potential effects of medication on task performance.

Methods: 67 individuals with PD and 29 HC participants completed the IGT. Results were analyzed to evaluate impairments, applied strategies, presence of subgroups, and potential effects of medication on performance.

Results: Both groups obtained a low overall IGT score and individuals with PD had significantly lower total IGT scores compared to HC participants. Regression analysis showed a small, but significant relationship between levodopa and dopamine agonist dosage and total IGT score, indicating that medication level could be a marker of level of executive functions. Subgroups of advantageous and disadvantageous choosers differed significantly in deck preferences for both groups.

Conclusion: Individuals with PD were significantly impaired in IGT performance, both in overall scores and in detailed analyses, and they utilized an inefficient strategy during task performance. However, HC participants also presented with a suboptimal strategy and results suggest the presence of subgroups in both individuals with PD and HC participants, which may reflect age-related changes. These results are in line with previous research on performance of older individuals and alternative deck preferences in the IGT and underline the importance of considering the applied strategy in the evaluation of IGT performance.
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http://dx.doi.org/10.1080/13803395.2020.1749237DOI Listing
July 2020

Normative values for gastric motility assessed with the 3D-transit electromagnetic tracking system.

Neurogastroenterol Motil 2020 06 10;32(6):e13829. Epub 2020 Mar 10.

Neurogastroenterology Unit, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

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.
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http://dx.doi.org/10.1111/nmo.13829DOI Listing
June 2020

PET Visualized Stimulation of the Vestibular Organ in Menière's Disease.

Front Neurol 2020 28;11:11. Epub 2020 Jan 28.

Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

The cortical metabolic activity in patients with Menière's disease has not been investigated. The aim of this study was to investigate the F-FDG cerebral uptake in Menière's patients compared to healthy controls. 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 F-FDG-based PET examinations of the brain. Participants were seated in a self-propelled chair, injected with F-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 F-FDG while seated without movement. Analyses of baseline scans revealed decreased F-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 F-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 F-FDG uptake in the medial part of Heschl's gyrus in the right hemisphere and also bilaterally in the posterior insula. In addition, decreased F-FDG uptake was seen in the thalamus during vestibular stimulation. 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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http://dx.doi.org/10.3389/fneur.2020.00011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997538PMC
January 2020

Tau Tangles in Parkinson's Disease: A 2-Year Follow-Up Flortaucipir PET Study.

J Parkinsons Dis 2020 ;10(1):161-171

Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark.

Background: Flortaucipir PET, a marker of tau tangles, has shown lower than expected cortical uptake in Parkinson's disease (PD), than would be predicted from neuropathologic estimates of Alzheimer's disease co-pathology. Instead, the most characteristic finding of flortaucipir imaging in PD is decreased uptake in the substantia nigra, reflecting reduction in its "off-target" binding to neuromelanin. We have previously reported these observations in cross-sectional studies.

Objective: Here, we present two-year follow-up data of cortical and nigral flortaucipir uptake in PD patients.

Methods: Seventeen PD patients received repeat flortaucipir PET two years after baseline. We interrogated vertex-based group-wise cortical tracer binding (SUVRs) with a cerebellar reference using the general linear model while mean substantia nigra SUVRs were compared with volumes of interest group comparisons and voxel-wise group analyses using ANOVA. Finally, we performed linear regressions of tau load with changes in MoCA and UPDRS motor scores.

Results: We found no significant changes in substantia nigra or cortex flortaucipir uptake in Parkinson's disease patients over two years and no association with changes in cognitive symptoms. Signal reduction in the medial substantia nigra trended towards an association with worsening of motor symptoms.

Conclusion: No significant increase in tau tangles occurred after a two-year follow-up of Parkinson's disease patients using flortaucipir PET.
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http://dx.doi.org/10.3233/JPD-191774DOI Listing
April 2021

In vivo positron emission tomography imaging of decreased parasympathetic innervation in the gut of vagotomized patients.

Neurogastroenterol Motil 2020 03 12;32(3):e13759. Epub 2019 Nov 12.

Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Aarhus, Denmark.

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 C-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 C-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 C-donepezil signal in the intestine of vagotomized patients, supporting that C-donepezil PET is a valid measure of intestinal parasympathetic denervation.
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http://dx.doi.org/10.1111/nmo.13759DOI Listing
March 2020

Enteric cholinergic neuropathy in patients with diabetes: Non-invasive assessment with positron emission tomography.

Neurogastroenterol Motil 2020 01 8;32(1):e13731. Epub 2019 Oct 8.

Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

Background: C-Donepezil positron emission tomography (PET) allows non-invasive assessment of cholinergic innervation of visceral organs. We aimed to compare cholinergic innervation in the gut in patients with diabetes mellitus (DM) and in healthy controls (HC).

Methods: C-Donepezil PET and computed tomography (CT) were performed in 19 patients with type 1 DM and gastrointestinal symptoms and in 19 age- and sex-matched HC in a cross-sectional design.

Key Results: All patients had severe gastrointestinal symptoms when assessed by standard questionnaires. DM patients had significantly increased volume of the small intestinal wall (DM: median 557 cm [interquartile range [IQR] 446-697] vs HC median: 448 cm [IQR; 341-518; P < .01]), and the C Donepezil PET uptake was reduced in patients (DM: median 7.08 standardized uptake value [SUV] [IQR; 5.94-8.43] vs HC: median 9.18 SUV [IQR; 8.57-10.11; P < .01]). A similar pattern was found in colon (DM: median volume 1064 cm [IQR; 882-1312] vs HC: median 939 cm [IQR; 785-1081; P = .13] and DM: median 1.22 SUV (IQR; 1.08-1.36) vs HC: median 1.42 SUV (IQR; 1.32-1.53; P = .03). Furthermore, patients had significantly reduced pancreatic volume (DM: median 53 cm [IQR; 41-69] vs HC: median 98 cm [IQR;82-110; P < .01]) and reduced PET uptake of the pancreas (DM: median 13.14 SUV [IQR;9.58-15.82] vs HC: median 21.46 SUV [IQR;18.97-24.06; P < .01]) as well as the adrenal gland (DM: median 7.62 SUV [IQR;7.61;15.82] vs HC: median 15.51 SUV [IQR;12.22;19.49; P = .03]).

Conclusion And Inferences: Assessed with C-Donepezil PET/CT, patients with DM and severe bowel symptoms have reduced cholinergic innervation of the gut indicative of parasympathetic denervation.
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http://dx.doi.org/10.1111/nmo.13731DOI Listing
January 2020

Normative values for region-specific colonic and gastrointestinal transit times in 111 healthy volunteers using the 3D-Transit electromagnet tracking system: Influence of age, gender, and body mass index.

Neurogastroenterol Motil 2020 02 29;32(2):e13734. Epub 2019 Sep 29.

GI Physiology Unit, Barts and the London School of Medicine and Dentistry, The Blizard Institute, Queen Mary University of London, London, UK.

Background: The 3D-Transit electromagnet tracking system (Motilis Medica, SA, Lausanne, Switzerland) is an emerging tool for the ambulatory assessment of gastrointestinal (GI) transit and motility. Using this tool, we aimed to derive normative values for region-specific colonic and GI transit times and to assess the influence of age, gender, and body mass index (BMI).

Methods: Regional and total colonic transit times (CTT), gastric emptying (GET), small intestinal (SITT), and whole gut (WGTT) transit times were extracted from 111 healthy volunteers from the United Kingdom and Denmark (58 female; median age: 40 years [range: 21-88]). The effects of age, gender, and BMI were assessed using standard statistical methods.

Key Results: The ascending, transverse, descending, and rectosigmoid colon transit times accounted for 32%, 34%, 17%, and 17% of total CTT in females, and 33%, 25%, 14%, and 28% of total CTT in males. CTT and WGTT were seen to cluster at intervals separated by approximately 24 hours, providing further evidence of the non-continuous nature of these measurements. Increasing age was associated with longer CTT (P = .021), WGTT (P < .001) ascending (P = .004), transverse (P < .001), and total right (P < .001) colon transit times, but shorter rectosigmoid (P = .004) transit time. Female gender was significantly associated with longer transverse (P = .049) and descending (P < .001) colon transit times, but shorter rectosigmoid (P < .001) transit time. Increasing BMI was significantly associated with shorter WGTT (P = .012).

Conclusions And Inferences: For the first time, normative reference values for region-specific colonic transit have been presented. Age, gender, and BMI were seen to have an effect on transit times.
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http://dx.doi.org/10.1111/nmo.13734DOI Listing
February 2020