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Parkinson Disease: HELP
Articles by Flavia Niccolini
Based on 26 articles published since 2010
(Why 26 articles?)
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Between 2010 and 2020, F. Niccolini wrote the following 26 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Molecular Imaging of the Dopaminergic System in Idiopathic Parkinson's Disease. 2018

de Natale, Edoardo R / Niccolini, Flavia / Wilson, Heather / Politis, Marios. ·Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom. · Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom. Electronic address: marios.politis@kcl.ac.uk. ·Int Rev Neurobiol · Pubmed #30314595.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration of dopaminergic nigrostriatal connections which is recognized as the major pathophysiological event underlying the onset of motor symptoms. Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging allow the study of these connections in vivo at a molecular level. Several radiotracers have been developed targeting the synthesis and metabolism of dopamine and dopaminergic receptors to investigate the nigrostriatal pathway in vivo. Molecular imaging has greatly increased our knowledge on the progression and natural history of PD, as well as the development of motor and non-motor symptoms. PET molecular imaging could be a reliable biomarker to aid earlier diagnosis and for monitoring disease progression. Furthermore, PET imaging could be used as outcome measure in the design of clinical trials testing novel pharmacological compounds aiming to slow, and ultimately halt, disease progression.

2 Review The serotonergic system in Parkinson's patients with dyskinesia: evidence from imaging studies. 2018

Pagano, Gennaro / Niccolini, Flavia / Politis, Marios. ·Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, 125 Coldharbour Lane, Camberwell, London, SE5 9NU, UK. · Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, 125 Coldharbour Lane, Camberwell, London, SE5 9NU, UK. marios.politis@kcl.ac.uk. ·J Neural Transm (Vienna) · Pubmed #29264660.

ABSTRACT: The purpose of review is to review the current status of positron emission tomography (PET) molecular imaging of serotonergic system in Parkinson's patients who experience levodopa-induced (LIDs) and graft-induced dyskinesias (GIDs). PET imaging studies have shown that Parkinson's disease is characterized by progressive loss of dopaminergic and serotonergic neurons. Parkinson's patients who experienced LIDs and GIDs have an aberrant spreading of serotonergic terminals, which lead to an increased serotonergic/dopaminergic terminals ratio within the putamen. Serotonergic terminals convert exogenous levodopa into dopamine in a non-physiological manner and release an abnormal amount of dopamine without an auto-regulatory feedback. This results in higher swings in synaptic levels of dopamine, which leads to the development of LIDs and GIDs. The modulation of serotonergic terminals with 5-HT

3 Review Be vigilant for dementia in Parkinson’s disease. 2017

Niccolini, Flavia / Diamantopoulos, Konstantinos / Kiosses, Stelios / Politis, Marios. · ·Practitioner · Pubmed #29120562.

ABSTRACT: It is estimated that up to 80% of patients with Parkinson's disease will eventually develop cognitive impairment over the course of their illness. Even at the time of diagnosis, cognitive impairment has been reported in 20-25% of patients. Commonly affected cognitive domains are executive function, visuospatial ability and attention control. In addition, patients with Parkinson's disease dementia may present with deficits in language function and verbal memory. Psychosis may occur in approximately 40% of patients with Parkinson's disease, and is associated with an increased risk of developing cognitive impairment. Studies have shown that patients with Parkinson's disease with a history of visual hallucinations had an increased risk of developing dementia, four to eight years following diagnosis of the disease. Other clinical risk factors associated with cognitive decline in patients with Parkinson's disease include older age of onset, severe motor symptom burden and in particular akinetic-rigid subtype and olfactory dysfunction. Patients with Parkinson's disease who present with symptoms of cognitive decline, behavioural changes or psychotic symptoms should be referred for further investigation.

4 Review Imaging in Parkinson's Disease. 2017

Politis, Marios / Pagano, Gennaro / Niccolini, Flavia. ·Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom. Electronic address: marios.politis@kcl.ac.uk. · Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom. ·Int Rev Neurobiol · Pubmed #28554409.

ABSTRACT: Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by the loss of nigrostriatal dopaminergic neurons and aggregation of misfolded α-synuclein in Lewy bodies. The underlying mechanisms of neurodegeneration in PD are still unknown, and there are no disease-modifying treatments to slow the neurodegenerative processes. There is an urgent need to identify biomarkers that are able to monitor disease progression and assess the development and efficacy of novel disease-modifying drugs. Over the past years, neuroimaging techniques such as magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron emission tomography (PET) have provided important advances in our understanding of PD. MRI provides information about structural and functional organization of the brain, while SPECT and PET can detect molecular changes in the brain. Here, we review the current neuroimaging literature in sporadic and genetic PD, which have contributed to our understanding of the physiopathological mechanisms of the disease.

5 Review Serotonin transporter in Parkinson's disease: A meta-analysis of positron emission tomography studies. 2017

Pagano, Gennaro / Niccolini, Flavia / Fusar-Poli, Paolo / Politis, Marios. ·Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom. · Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom. ·Ann Neurol · Pubmed #28019672.

ABSTRACT: Positron emission tomography (PET) is a powerful analytical tool for in vivo molecular imaging of the human brain. Over the past years, a number of PET studies imaging the serotonin transporter (SERT) have been used and provided evidence for the key role of serotonergic pathology in patients with Parkinson's disease (PD). Here, we review the role of SERT in the development of motor and nonmotor complications in patients with PD, and we performed a meta-analysis to identify the patterns of SERT pathology and the relevance to symptoms. Consistent SERT pathology in raphe nuclei, striatum, thalamus, and hypothalamus and associations with aging, PD progression, development of dyskinesias, and cognitive decline were observed. Ann Neurol 2017;81:171-180.

6 Review Imaging in Parkinson's disease. 2016

Pagano, Gennaro / Niccolini, Flavia / Politis, Marios. ·Neurodegeneration Imaging Group, King's College London, London, UK. · Neurodegeneration Imaging Group, King's College London, London, UK marios.politis@kcl.ac.uk. ·Clin Med (Lond) · Pubmed #27481384.

ABSTRACT: The clinical presentation of Parkinson's disease (PD) is heterogeneous and overlaps with other conditions, including the parkinsonian variant of multiple system atrophy (MSA-P), progressive supranuclear palsy (PSP) and essential tremor. Imaging of the brain in patients with parkinsonism has the ability to increase the accuracy of differential diagnosis. Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET) allow brain imaging of structural, functional and molecular changes in vivo in patients with PD. Structural MRI is useful to differentiate PD from secondary and atypical forms of parkinsonism. 123I-ioflupane (DaTSCAN(TM)) SPECT is a valid tool in the differential diagnosis between PD and non-degenerative tremors, while cardiac 123I-metaiodobenzylguanidine SPECT and 18F-fluorodeoxyglucose PET are valid in the differential diagnosis between PD and atypical parkinsonism (MSA-P, PSP). However, despite significant evidence for the utility of neuroimaging in assessing parkinsonian patients, none of the neuroimaging techniques are specifically recommended for routine use in clinical practice. Hopefully, future larger trials will help to demonstrate additional evidence for the clinical utility of neuroimaging and will include an analysis of the financial benefits for the NHS in the longer term management of the patients.

7 Review A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism. 2016

Niccolini, Flavia / Politis, Marios. ·Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. · Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. marios.politis@kcl.ac.uk. ·Eur J Nucl Med Mol Imaging · Pubmed #27470326.

ABSTRACT: PURPOSE: To systematically review the previous studies and current status of positron emission tomography (PET) molecular imaging research in atypical parkinsonism. METHODS: MEDLINE, ISI Web of Science, Cochrane Library, and Scopus electronic databases were searched for articles published until 29th March 2016 and included brain PET studies in progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). Only articles published in English and in peer-reviewed journals were included in this review. Case-reports, reviews, and non-human studies were excluded. RESULTS: Seventy-seven PET studies investigating the dopaminergic system, glucose metabolism, microglial activation, hyperphosphorilated tau, opioid receptors, the cholinergic system, and GABA CONCLUSIONS: PET molecular imaging has provided valuable insight for understanding the mechanisms underlying atypical parkinsonism. Changes at a molecular level occur early in the course of these neurodegenerative diseases and PET imaging provides the means to aid differential diagnosis, monitor disease progression, identify of novel targets for pharmacotherapy, and monitor response to new treatments.

8 Review Parkinson's Disease, Diabetes and Cognitive Impairment. 2016

Ashraghi, Mohammad R / Pagano, Gennaro / Polychronis, Sotirios / Niccolini, Flavia / Politis, Marios. ·Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), 125 Coldharbour Lane, Camberwell, London, SE5 9NU; UK. marios.politis@kcl.ac.uk. ·Recent Pat Endocr Metab Immune Drug Discov · Pubmed #27396477.

ABSTRACT: BACKGROUND: Parkinson's disease is a chronic neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulinresistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment. OBJECTIVE: To review experimental and clinical evidence of underlying Parkinson's pathophysiology in common with diabetes and cognitive impairment. Anti-diabetic agents and recent patents for insulin-resistance that might be repositioned in the treatment of Parkinson's also have been included in this review. METHOD: A narrative review using MEDLINE database. RESULTS: Common antidiabetic treatments such as DPP4 inhibitors, GLP-1 agonists and metformin have shown promise in the treatment of Parkinson's disease and cognitive impairment in animals and humans. Study of the pathophysiology of neurodegeneration common between diabetes and Parkinson's disease has given rise to new treatment possibilities. Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments. CONCLUSION: Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.

9 Review Molecular imaging of levodopa-induced dyskinesias. 2015

Niccolini, Flavia / Rocchi, Lorenzo / Politis, Marios. ·Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, SE5 8AF, UK. ·Cell Mol Life Sci · Pubmed #25681866.

ABSTRACT: Levodopa-induced dyskinesias (LIDs) occur in the majority of patients with Parkinson's disease (PD) following years of levodopa treatment. The pathophysiology underlying LIDs in PD is poorly understood, and current treatments generate only minor benefits for the patients. Studies with positron emission tomography (PET) molecular imaging have demonstrated that in advanced PD patients, levodopa administration induces sharp increases in striatal dopamine levels, which correlate with LIDs severity. Fluctuations in striatal dopamine levels could be the result of the attenuated buffering ability in the dopaminergically denervated striatum. Lines of evidence from PET studies indicate that serotonergic terminals could also be responsible for the development of LIDs in PD by aberrantly processing exogenous levodopa and by releasing dopamine in a dysregulated manner from the serotonergic terminals. Additionally, other downstream mechanisms involving glutamatergic, cannabinoid, opioid, cholinergic, adenosinergic, and noradrenergic systems may contribute in the development of LIDs. In this article, we review the findings from preclinical, clinical, and molecular imaging studies, which have contributed to our understanding the pathophysiology of LIDs in PD.

10 Review Serotonin in Parkinson's disease. 2015

Politis, Marios / Niccolini, Flavia. ·Neurodegeneration Imaging Group, Department of Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, United Kingdom; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom. ·Behav Brain Res · Pubmed #25086269.

ABSTRACT: Parkinson's disease is a chronic neurodegenerative disorder characterized by the motor symptoms of bradykinesia, tremor, rigidity and postural instability. However, non-motor symptoms such as chronic fatigue, depression, dementia and sleep disturbances are also frequent and play a significant role with negative consequences in the quality of life of patients with Parkinson's disease. Although the progressive dopaminergic denervation is the cardinal pathology in the brains of patients with Parkinson's disease, others systems such as the serotonergic are affected as well. Over the last decade, several lines of evidence suggest that a progressive and non-linear loss of serotonergic terminals takes place in Parkinson's disease, though this is at a slower pace compared to the dopaminergic loss. Several studies have indicated that serotonergic dysfunction in Parkinson's disease is associated with the development of motor and non-motor symptoms and complications. Here, we aim to review the current evidence with regards to the serotonergic pathology in Parkinson's disease and its relevance to the development of clinical symptoms. We are primarily revising in vivo human studies from research with positron emission tomography molecular imaging.

11 Review Dopamine receptor mapping with PET imaging in Parkinson's disease. 2014

Niccolini, Flavia / Su, Paul / Politis, Marios. ·Neurodegeneration Imaging Group, Department of Clinical Neuroscience, King's College London, London, SE5 8AF, UK. ·J Neurol · Pubmed #24627109.

ABSTRACT: Parkinson's disease (PD) is a chronic neurodegenerative disorder characterised pathologically by the loss of dopaminergic neurons in the substantia nigra pars compacta. These neurons project to the striatum, and their loss leads to alterations in the activity of the neural circuits that regulate movement. The striatal output of the circuit related to the control of movement is mediated by two pathways: the direct striatal pathway, which is mediated through facilitation of D1 receptors, and the indirect striatal pathway, mediated through D2 receptors. Positron emission tomography (PET) molecular imaging is a powerful in vivo technique in which using selective dopaminergic radioligands has been employed to investigate the dopaminergic system in humans. In this article we aim to review the role of PET imaging in understanding the postsynaptic dopaminergic mechanisms in PD. PET studies have allowed us to gain important insights into the functions of the dopaminergic system, the mechanisms of drug-induced motor and non-motor complications, and the placebo effect in PD.

12 Review Dyskinesias in Parkinson's disease: views from positron emission tomography studies. 2014

Niccolini, F / Loane, C / Politis, M. ·Department of Medicine, Hammersmith Hospital, Imperial College London, London, UK; Neurodegeneration Imaging Group, Department of Clinical Neuroscience, King's College London, London, UK. ·Eur J Neurol · Pubmed #24471508.

ABSTRACT: Levodopa-induced dyskinesias (LIDs) and graft-induced dyskinesias (GIDs) are serious and common complications of Parkinson's disease (PD) management following chronic treatment with levodopa or intrastriatal transplantation with dopamine-rich foetal ventral mesencephalic tissue, respectively. Positron emission tomography (PET) molecular imaging provides a powerful in vivo tool that has been employed over the past 20 years for the elucidation of mechanisms underlying the development of LIDs and GIDs in PD patients. PET used together with radioligands tagging molecular targets has allowed the functional investigation of several systems in the brain including the dopaminergic, serotonergic, glutamatergic, opioid, endocannabinoid, noradrenergic and cholinergic systems. In this article the role of PET imaging in unveiling pathophysiological mechanisms underlying the development of LIDs and GIDs in PD patients is reviewed.

13 Article Predict cognitive decline with clinical markers in Parkinson's disease (PRECODE-1). 2020

Wilson, Heather / Pagano, Gennaro / Yousaf, Tayyabah / Polychronis, Sotirios / De Micco, Rosa / Giordano, Beniamino / Niccolini, Flavia / Politis, Marios. ·Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, 125 Coldharbour Lane, Camberwell, London, SE5 9NU, UK. · Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, 125 Coldharbour Lane, Camberwell, London, SE5 9NU, UK. mariospolitis@gmail.com. ·J Neural Transm (Vienna) · Pubmed #31853652.

ABSTRACT: Over the course of the disease, about 80% of Parkinson's disease patients will develop cognitive impairment. However, predictive factors associated with cognitive decline are still under investigation. Here, we investigated which clinically available markers are predictive of cognitive impairment in a cohort of early drug-naïve Parkinson's disease patients. 294 drug-naïve Parkinson's disease patients, who were cognitively normal at baseline, were recruited from the Parkinson's Progression Markers Initiative. At 36-month follow-up, patients were diagnosed with cognitive impairment according to two levels: Level 1 diagnosis was defined as MoCA < 26 and Level 2 diagnosis was defined as MoCA < 26, alongside an impaired score on at least two neuropsychological tests. Predictive variables with a validated cut-off were divided into normal or abnormal measures, whilst others were divided into normal or abnormal measures based on the decile with the highest power of prediction. At 3 years' follow-up, 122/294 Parkinson's disease (41.5%) patients had cognitive decline. We found that age at Parkinson's disease onset, MDS-UPDRS Part-III, Hopkin's Learning Verbal Test-Revised Recall, Semantic Fluency Test and Symbol Digit Modalities Test were all predictors of cognitive decline. Specifically, age at Parkinson's disease onset, Semantic Fluency Test and symbol Digit Modalities Test were predictors of cognitive decline defined by Level 2. The combination of three abnormal tests, identified as the most significant predictors of cognitive decline, gave a 63.6-86.7% risk of developing cognitive impairment defined by Level 2 and Level 1 criteria, respectively, at 36-month follow-up. Our findings show that these clinically available measures encompass the ability to identify drug-naïve Parkinson's disease patients with the highest risk of developing cognitive impairment at the earliest stages. Therefore, by implementing this in a clinical setting, we can better monitor and manage patients who are at risk of cognitive decline.

14 Article Sleep disturbances and gastrointestinal dysfunction are associated with thalamic atrophy in Parkinson's disease. 2019

Niccolini, Flavia / Wilson, Heather / Giordano, Beniamino / Diamantopoulos, Konstantinos / Pagano, Gennaro / Chaudhuri, Kallol Ray / Politis, Marios. ·Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. · National Parkinson Foundation International Centre of Excellence, Department of Basic & Clinical Neuroscience, King's College London and Kings College Hospital, London, UK. · Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. marios.politis@kcl.ac.uk. ·BMC Neurosci · Pubmed #31640554.

ABSTRACT: BACKGROUND: Non-motor symptoms are common aspects of Parkinson's disease (PD) occurring even at the prodromal stage of the disease and greatly affecting the quality of life. Here, we investigated whether non-motor symptoms burden was associated with cortical thickness and subcortical nuclei volume in PD patients. METHODS: We studied 41 non-demented PD patients. Non-motor symptoms burden was assessed using the Non-Motor Symptoms Scale grading (NMSS). Cortical thickness and subcortical nuclei volume analyses were carried out using Free-Surfer. PD patients were divided into two groups according to the NMSS grading: mild to moderate (NMSS: 0-40) and severe (NMSS: ≥ 41) non-motor symptoms. RESULTS: Thalamic atrophy was associated with higher NMSQ and NMSS total scores. The non-motor symptoms that drove this correlation were sleep/fatigue and gastrointestinal tract dysfunction. We also found that PD patients with severe non-motor symptoms had significant thalamic atrophy compared to the group with mild to moderate non-motor symptoms. CONCLUSIONS: Our findings show that greater non-motor symptom burden is associated with thalamic atrophy in PD. Thalamus plays an important role in processing sensory information including visceral afferent from the gastrointestinal tract and in regulating states of sleep and wakefulness.

15 Article Comparison of phosphodiesterase 10A and dopamine transporter levels as markers of disease burden in early Parkinson's disease. 2019

Pagano, Gennaro / Niccolini, Flavia / Wilson, Heather / Yousaf, Tayyabah / Khan, Naheed L / Martino, Davide / Plisson, Christophe / Gunn, Roger N / Rabiner, Eugenii A / Piccini, Paola / Foltynie, Thomas / Politis, Marios. ·Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom. · Department of Neurology, Maidstone Hospital, Kent, United Kingdom. · Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. · Imanova Ltd, Centre for Imaging Sciences, Hammersmith Hospital, London, United Kingdom. · Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom. · Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kings College London, London, United Kingdom. · Neurology Imaging Unit, Centre of Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Hammersmith Campus, Imperial College London, London, United Kingdom. · Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, United Kingdom. ·Mov Disord · Pubmed #31158314.

ABSTRACT: BACKGROUND: Recent work has shown loss of phosphodiesterase 10A levels in middle-stage and advanced treated patients with PD, which was associated with motor symptom severity. OBJECTIVES: To assess phosphodiesterase 10A levels in early PD and compare with loss of dopamine transporter as markers of disease burden. METHODS: Seventy-eight subjects were included in this study (17 early de novo, 15 early l-dopa-treated, 24 moderate-advanced l-dopa-treated patients with PD, and 22 healthy controls). All participants underwent [ RESULTS: Early de novo PD patients showed loss of [ CONCLUSION: Our findings demonstrate loss of phosphodiesterase 10A levels very early in the course of PD and is associated with the gradual and progressive increase of motor symptoms. Phosphodiesterase 10A imaging shows similar potential with dopamine transporter imaging to follow disease progression. © 2019 International Parkinson and Movement Disorder Society.

16 Article Speech difficulties in early de novo patients with Parkinson's disease. 2019

Polychronis, Sotirios / Niccolini, Flavia / Pagano, Gennaro / Yousaf, Tayyabah / Politis, Marios. ·Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom. · Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom. Electronic address: marios.politis@kcl.ac.uk. ·Parkinsonism Relat Disord · Pubmed #31078401.

ABSTRACT: INTRODUCTION: Speech difficulties are a common debilitating feature of Parkinson's disease and we aimed to investigate whether speech difficulties are associated with striatal dopaminergic deficits and faster disease progression. METHODS: Using the Parkinson's Progression Markers Initiative database, 143 early de novo Parkinson's disease patients with speech difficulties were identified and matched 1:1 with 143 Parkinson's disease patients without speech difficulties for age, disease duration and motor symptom severity. We investigated differences in clinical features and striatal [ RESULTS: Speech difficulties were more common in patients with an akinetic-rigid motor phenotype compared to those with a tremor-dominant phenotype. Parkinson's disease patients with speech difficulties had lower resting tremor (P = 0.027), higher autonomic dysfunction (P = 0.034), increased daytime sleepiness (ESS; P = 0.048), and a higher prevalence of REM sleep behaviour disorder (RBD) symptoms (P = 0.007) compared to those without speech difficulties. Parkinson's disease patients with speech difficulties had significantly lower [ CONCLUSION: Speech difficulties are associated with greater autonomic dysfunction, sleep disturbances and striatal dopaminergic deficit, and can serve as a predictor of faster cognitive decline in early Parkinson's disease.

17 Article The role of phosphodiesterase 4 in excessive daytime sleepiness in Parkinson's disease. 2019

Wilson, Heather / Pagano, Gennaro / Niccolini, Flavia / Muhlert, Nils / Mehta, Mitul A / Searle, Graham / Gunn, Roger N / Rabiner, Eugenii A / Foltynie, Thomas / Politis, Marios. ·Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, United Kingdom. · School of Psychology and Cardiff University Brain Research Imaging Centre, Cardiff University, United Kingdom; Division of Neuroscience & Experimental Psychology, University of Manchester, United Kingdom. · Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, United Kingdom. · Invicro London, Hammersmith Hospital, London, United Kingdom. · Invicro London, Hammersmith Hospital, London, United Kingdom; Division of Brain Sciences, Imperial College London, Hammersmith Hospital, London, United Kingdom. · Invicro London, Hammersmith Hospital, London, United Kingdom; Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, United Kingdom. · Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, United Kingdom. · Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, United Kingdom. Electronic address: marios.politis@kcl.ac.uk. ·Parkinsonism Relat Disord · Pubmed #30824285.

ABSTRACT: INTRODUCTION: Preclinical studies suggest a link between cAMP/PKA signalling, phosphodiesterase 4 (PDE4) expression and excessive daytime sleepiness (EDS). Here, we investigated in vivo the association between PDE4 expression and EDS in Parkinson's disease (PD) patients using [ METHODS: Eighteen participants, 12 PD and 6 healthy controls, underwent one [ RESULTS: PD patients with EDS showed significantly increased [ CONCLUSION: Our findings translate into humans preclinical data indicating that EDS is associated with elevated PDE4 in regions regulating sleep. The severity of EDS in PD was associated with elevated PDE4 expression; thus, suggesting a role of PDE4 in the pathophysiology of EDS in PD.

18 Article Predicting cognitive decline with non-clinical markers in Parkinson's disease (PRECODE-2). 2019

Yousaf, Tayyabah / Pagano, Gennaro / Niccolini, Flavia / Politis, Marios. ·Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Maurice Wohl Clinical Neuroscience Institute, King's College London, 125 Coldharbour Lane, Camberwell, London, SE5 9NU, UK. · Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Maurice Wohl Clinical Neuroscience Institute, King's College London, 125 Coldharbour Lane, Camberwell, London, SE5 9NU, UK. marios.politis@kcl.ac.uk. ·J Neurol · Pubmed #30820739.

ABSTRACT: OBJECTIVES: To investigate whether baseline [ METHODS: 262 de novo PD patients from the Parkinson's Progression Markers Initiative database were stratified into two CI groups at the 36-month follow-up: MoCA-defined diagnosis: PD patients who had a MoCA score < 26; neuropsychological test-defined diagnosis: PD patients with MoCA-defined diagnosis and at least two test scores (of six; irrespective of test domain) greater than 1.5 standard deviation below the mean score in healthy controls. Predictive variables of CI were divided into deciles, providing us with ideal cutoff values for each variable. RESULTS: At the 36-month follow-up, 108/262 (41.2%) PD patients had CI as defined by the MoCA, of which 40/108 (37.0%) had neuropsychological test-defined CI. Baseline CSF Aβ42 (hazard ratio [HR]: 0.996, confidence interval [CI]: 0.992-0.999, p = 0.025), CSF total tau ([HR]: 1.023, [CI]: 1.002-1.044, p = 0.031) and caudate [ CONCLUSION: We report a characteristic profile (reduced CSF Aβ42, increased CSF total tau and reduced caudate [

19 Article Cortical thinning across Parkinson's disease stages and clinical correlates. 2019

Wilson, Heather / Niccolini, Flavia / Pellicano, Clelia / Politis, Marios. ·Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. · Department of Neuroscience, Mental Health and Secnsory Organs-(NESMOS), Sapienza University, Rome, Italy. · Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Electronic address: marios.politis@kcl.ac.uk. ·J Neurol Sci · Pubmed #30682518.

ABSTRACT: BACKGROUND: Imaging studies have revealed cortical thinning and subcortical atrophy occurring in Parkinson's disease (PD); however, the topographical distribution and clinical associations related to advancing stages of PD remains unclear. OBJECTIVE: We aimed to investigate the topographical distribution of cortical and subcortical morphometric changes, and their clinical associations, related to increasing disease severity. METHODS: In this cross-sectional imaging study, T1-weighted structural magnetic resonance imaging data for 80 non-demented PD patients and 30 age-matched healthy controls were analysed using FreeSurfer software suite to derive morphometric changes using whole-brain vertex-wise analysis, and surface-based (cortical) and volume-based (subcortical) parcellation maps. PD patients were divided into three groups of mild (n = 27), moderate (n = 27), and severe (n = 26) PD based disease duration and Hoehn and Yahr and Unified Parkinson's Disease Rating Scale Part-III motor severity scores. RESULTS: Whole-brain vertex-wise analysis revealed cortical thinning in the orbitofrontal cortex in early PD (P = .011), and in the superior frontal (P = .002), caudal middle frontal gyrus (P = .001) and inferior parietal cortex (P = .006) in moderate PD. Severe PD patients showed additional cortical thinning in temporal and occipital cortices (P < .005). Subcortical volume loss was detected in the thalamus (P = .012) and hippocampus (P = .032) in moderate PD, which extended to the caudate (P = .012), putamen (P = .042) and amygdala (P = .008) in severe PD. Increasing disease duration and motor severity scores, correlated with cortical thinning in frontal, temporal, parietal and occipital cortices, and subcortical volumetric loss in the thalamus, caudate, putamen, amygdala and hippocampus. Lower global cognitive status, measured with MMSE, correlated with cortical thinning in temporal, parietal, frontal and cingulate cortices, and with volumetric loss in the hippocampus (r = 0.31; P = .009); suggesting subclinical pathogenic changes occur prior to the onset of cognitive impairment. CONCLUSION: In conclusion, in more severe disease stages PD patients exhibit progressive cortical thinning and subcortical volume loss which could have relevance to the development of cognitive impairment.

20 Article Diabetes mellitus and Parkinson disease. 2018

Pagano, Gennaro / Polychronis, Sotirios / Wilson, Heather / Giordano, Beniamino / Ferrara, Nicola / Niccolini, Flavia / Politis, Marios. ·From the Neurodegeneration Imaging Group (G.P., S.P., H.W., B.G., F.N., M.P.), Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK · and Division of Geriatrics (B.G., N.F.), Department of Translational Medical Sciences, University of Naples Federico II, Italy. ·Neurology · Pubmed #29626177.

ABSTRACT: OBJECTIVE: To investigate whether diabetes mellitus is associated with Parkinson-like pathology in people without Parkinson disease and to evaluate the effect of diabetes mellitus on markers of Parkinson pathology and clinical progression in drug-naive patients with early-stage Parkinson disease. METHODS: We compared 25 patients with Parkinson disease and diabetes mellitus to 25 without diabetes mellitus, and 14 patients with diabetes mellitus and no Parkinson disease to 14 healthy controls (people with no diabetes mellitus or Parkinson disease). The clinical diagnosis of diabetes mellitus was confirmed by 2 consecutive fasting measurements of serum glucose levels >126 mL/dL. Over a 36-month follow-up period, we then investigated in the population with Parkinson disease whether the presence of diabetes mellitus was associated with faster motor progression or cognitive decline. RESULTS: The presence of diabetes mellitus was associated with higher motor scores ( CONCLUSIONS: Diabetes mellitus may predispose toward a Parkinson-like pathology, and when present in patients with Parkinson disease, can induce a more aggressive phenotype.

21 Article Excessive daytime sleepiness may be associated with caudate denervation in Parkinson disease. 2018

Yousaf, Tayyabah / Pagano, Gennaro / Niccolini, Flavia / Politis, Marios. ·Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. Electronic address: tayyabah.yousaf@kcl.ac.uk. · Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. Electronic address: gennaro.pagano@kcl.ac.uk. · Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. Electronic address: flavia.niccolini@kcl.ac.uk. · Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. Electronic address: marios.politis@kcl.ac.uk. ·J Neurol Sci · Pubmed #29571867.

ABSTRACT: Excessive daytime sleepiness (EDS) is one of the earliest and most common non-motor symptoms of PD, substantially impacting on patient's quality of life. Using the Parkinson's Progression Markers Initiative database, we performed a case-control study to investigate whether dopaminergic deficit is associated with the development of EDS using dopaminergic specific single photon emission computed tomography (SPECT) molecular imaging of dopamine transporters (DAT). We enrolled 84 early de novo PD patients with EDS and 84 without EDS, who were matched for age, gender, age of diagnosis, years of education and disease duration. We assessed and compared semi-quantified [

22 Article Constipation is not associated with dopamine transporter pathology in early drug-naïve patients with Parkinson's disease. 2018

Pagano, G / Yousaf, T / Wilson, H / Niccolini, F / Polychronis, S / Chaudhuri, K R / Politis, M. ·Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. · National Parkinson Foundation International Centre of Excellence, Department of Basic & Clinical Neuroscience, King's College London and Kings College Hospital, London, UK. ·Eur J Neurol · Pubmed #29078029.

ABSTRACT: BACKGROUND AND PURPOSE: Constipation is a common non-motor symptom of Parkinson's disease (PD). Deposition of α-synuclein inclusions that spread from the gut to the substantia nigra through the vagus nerve has recently been speculated to be a pre-motor and early stage of PD. The aim of the study was to investigate whether constipation is associated with dopaminergic pathology on dopamine transporter (DAT) single-photon emission computed tomography in early drug-naïve patients with PD. Our hypothesis was that constipation is associated with other signs of pre-motor PD and is independent of DAT pathology. We then investigated for associations with motor and non-motor symptoms, and with cerebrospinal fluid biomarkers of PD pathology. METHODS: Using the Parkinson's Progression Markers Initiative database, we investigated the prevalence of constipation and the association between constipation and clinical features, striatal [ RESULTS: One third (132/398) of de-novo patients with PD had constipation. Higher severity of constipation correlated with older age (r = 0.728, P < 0.001), higher MDS-UPDRS total score (r = 0.285, P < 0.001), worse postural instability (r = 0.190, P = 0.012), rapid eye movement sleep behaviour disorder (r = 0.228, P < 0.0001) and depression (r = 0.187, P = 0.024). No correlation was found with cerebrospinal fluid, serum and imaging markers of PD pathology. CONCLUSIONS: Constipation was not associated with DAT pathology but with rapid eye movement sleep behaviour disorder and depression, which are speculated to be pre-motor symptoms of PD. This confirms the hypothesis that constipation may be a pre-motor sign of PD due to an impairment of non-dopaminergic pathways.

23 Article Loss of phosphodiesterase 4 in Parkinson disease: Relevance to cognitive deficits. 2017

Niccolini, Flavia / Wilson, Heather / Pagano, Gennaro / Coello, Christopher / Mehta, Mitul A / Searle, Graham E / Gunn, Roger N / Rabiner, Eugenii A / Foltynie, Thomas / Politis, Marios. ·From the Neurodegeneration Imaging Group (F.N., H.W., G.P., M.P.) and Department of Neuroimaging (M.A.M., E.A.R.), Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London · Imanova Ltd., Centre for Imaging Sciences (C.C., G.E.S., R.N.G., E.A.R.), and Division of Brain Sciences, Imperial College London (R.N.G), Hammersmith Hospital · and Sobell Department of Motor Neuroscience (T.F.), UCL Institute of Neurology, London, UK. ·Neurology · Pubmed #28701494.

ABSTRACT: OBJECTIVE: To assess in vivo the expression of phosphodiesterase 4 (PDE4) and its relevance to cognitive symptoms in patients with Parkinson disease (PD) using [ METHODS: We studied 12 levodopa-treated patients with PD with no concurrent diagnosis of mild cognitive impairment or dementia. Their data were compared with those from 12 healthy controls. All participants underwent neuropsychiatric and cognitive assessment using the Cambridge Neuropsychological Test Automated Battery. Parametric images of [ RESULTS: Patients with PD performed worse than healthy controls in cognitive examinations assessing psychomotor speed, episodic memory, and spatial working memory and executive function. Patients with PD showed reductions in [ CONCLUSIONS: Our findings demonstrate loss of PDE4 expression in the striato-thalamo-cortical circuit, which is associated with deficits of spatial working memory in patients with PD.

24 Article Morphometric changes in the reward system of Parkinson's disease patients with impulse control disorders. 2015

Pellicano, Clelia / Niccolini, Flavia / Wu, Kit / O'Sullivan, Sean S / Lawrence, Andrew D / Lees, Andrew J / Piccini, Paola / Politis, Marios. ·Division of Brain Sciences, Neurology Imaging Unit, Centre of Neuroinflammation and Neurodegeneration, Hammersmith Campus, Imperial College London, London, UK. · Department of Neuroscience, Mental Health and Sensory Organs-(NESMOS), Sapienza University, Rome, Italy. · Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, 1 Windsor Walk, London, SE5 8AF, UK. · Reta Lila Weston Institute of Neurological Studies, University College London, London, UK. · Cardiff University Brain Research Imaging Centre (CUBRIC) and School of Psychology, Cardiff University, Cardiff, UK. · Division of Brain Sciences, Neurology Imaging Unit, Centre of Neuroinflammation and Neurodegeneration, Hammersmith Campus, Imperial College London, London, UK. marios.politis@kcl.ac.uk. · Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, 1 Windsor Walk, London, SE5 8AF, UK. marios.politis@kcl.ac.uk. ·J Neurol · Pubmed #26410743.

ABSTRACT: Impulse control disorders (ICDs) occur in a subset of patients with Parkinson's disease (PD) who are receiving dopamine replacement therapy. In this study, we aimed to investigate structural abnormalities within the mesocortical and limbic cortices and subcortical structures in PD patients with ICDs. We studied 18 PD patients with ICDs, 18 PD patients without ICDs and a group of 24 age and sex-matched healthy controls. Cortical thickness (CTh) and subcortical nuclei volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.3.0). We found significant differences in MRI measures between the three groups. There was volume loss in the nucleus accumbens of both PD patients with ICDs and without ICDs compared to the control group. In addition, PD patients with ICDs showed significant atrophy in caudate, hippocampus and amygdala compared to the group of healthy controls. PD patients with ICDs had significant increased cortical thickness in rostral anterior cingulate cortex and frontal pole compared to PD patients without ICDs. Cortical thickness in rostral anterior cingulate and frontal pole was increased in PD patients with ICDs compared to the control group, but the differences failed to reach corrected levels of statistical significance. PD patients with ICDs showed increased cortical thickness in medial prefrontal regions. We speculate that these findings reflect either a pre-existing neural trait vulnerability to impulsivity or the expression of a maladaptive synaptic plasticity under non-physiological dopaminergic stimulation.

25 Article Loss of phosphodiesterase 10A expression is associated with progression and severity in Parkinson's disease. 2015

Niccolini, Flavia / Foltynie, Thomas / Reis Marques, Tiago / Muhlert, Nils / Tziortzi, Andri C / Searle, Graham E / Natesan, Sridhar / Kapur, Shitij / Rabiner, Eugenii A / Gunn, Roger N / Piccini, Paola / Politis, Marios. ·1 Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK 2 Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK. · 3 Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, UK. · 4 Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. · 5 School of Psychology and Cardiff University Brain Research Imaging Centre, Cardiff University, UK 6 School of Psychological Sciences, University of Manchester, Manchester, UK. · 7 Imanova Ltd., Centre for Imaging Sciences, Hammersmith Hospital, London, UK. · 7 Imanova Ltd., Centre for Imaging Sciences, Hammersmith Hospital, London, UK 8 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. · 2 Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK 2 Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK. · 2 Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK. · 1 Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK 2 Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK marios.politis@kcl.ac.uk. ·Brain · Pubmed #26210536.

ABSTRACT: The mechanisms underlying neurodegeneration and loss of dopaminergic signalling in Parkinson's disease are still only partially understood. Phosphodiesterase 10A (PDE10A) is a basal ganglia expressed dual substrate enzyme, which regulates cAMP and cGMP signalling cascades, thus having a key role in the regulation of dopaminergic signalling in striatal pathways, and in promoting neuronal survival. This study aimed to assess in vivo the availability of PDE10A in patients with Parkinson's disease using positron emission tomography molecular imaging with (11)C-IMA107, a highly selective PDE10A radioligand. We studied 24 patients with levodopa-treated, moderate to advanced Parkinson's disease. Their positron emission tomography imaging data were compared to those from a group of 12 healthy controls. Parametric images of (11)C-IMA107 binding potential relative to non-displaceable binding (BPND) were generated from the dynamic (11)C-IMA107 scans using the simplified reference tissue model with the cerebellum as the reference tissue. Corresponding region of interest analysis showed lower mean (11)C-IMA107 BPND in the caudate (P < 0.001), putamen (P < 0.001) and globus pallidus (P = 0.025) in patients with Parkinson's disease compared to healthy controls, which was confirmed with voxel-based analysis. Longer Parkinson's duration correlated with lower (11)C-IMA107 BPND in the caudate (r = -0.65; P = 0.005), putamen (r = -0.51; P = 0.025), and globus pallidus (r = -0.47; P = 0.030). Higher Unified Parkinson's Disease Rating Scale part-III motor scores correlated with lower (11)C-IMA107 BPND in the caudate (r = -0.54; P = 0.011), putamen (r = -0.48; P = 0.022), and globus pallidus (r = -0.70; P < 0.001). Higher Unified Dyskinesia Rating Scale scores in those Parkinson's disease with levodopa-induced dyskinesias (n = 12), correlated with lower (11)C-IMA107 BPND in the caudate (r = -0.73; P = 0.031) and putamen (r = -0.74; P = 0.031). Our findings demonstrate striatal and pallidal loss of PDE10A expression, which is associated with Parkinson's duration and severity of motor symptoms and complications. PDE10A is an enzyme that could be targeted with novel pharmacotherapy, and this may help improve dopaminergic signalling and striatal output, and therefore alleviate symptoms and complications of Parkinson's disease.

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