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Parkinson Disease: HELP
Articles by David James Brooks
Based on 75 articles published since 2008
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Between 2008 and 2019, D. J. Brooks wrote the following 75 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial Can imaging separate multiple system atrophy from Parkinson's disease? 2012

Brooks, David J. · ·Mov Disord · Pubmed #22252889.

ABSTRACT: -- No abstract --

2 Editorial Resting tremor in Parkinson disease: is the pallidum to blame? 2011

Boecker, Henning / Brooks, David J. · ·Ann Neurol · Pubmed #21387365.

ABSTRACT: -- No abstract --

3 Review Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy. 2017

Obeso, J A / Stamelou, M / Goetz, C G / Poewe, W / Lang, A E / Weintraub, D / Burn, D / Halliday, G M / Bezard, E / Przedborski, S / Lehericy, S / Brooks, D J / Rothwell, J C / Hallett, M / DeLong, M R / Marras, C / Tanner, C M / Ross, G W / Langston, J W / Klein, C / Bonifati, V / Jankovic, J / Lozano, A M / Deuschl, G / Bergman, H / Tolosa, E / Rodriguez-Violante, M / Fahn, S / Postuma, R B / Berg, D / Marek, K / Standaert, D G / Surmeier, D J / Olanow, C W / Kordower, J H / Calabresi, P / Schapira, A H V / Stoessl, A J. ·HM CINAC, Hospital Universitario HM Puerta del Sur, Mostoles, Madrid, Spain. · Universidad CEU San Pablo, Madrid, Spain. · CIBERNED, Madrid, Spain. · Department of Neurology, Philipps University, Marburg, Germany. · Parkinson's Disease and Movement Disorders Department, HYGEIA Hospital and Attikon Hospital, University of Athens, Athens, Greece. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Canada. · Department of Medicine, University of Toronto, Toronto, Canada. · Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Parkinson's Disease and Mental Illness Research, Education and Clinical Centers (PADRECC and MIRECC), Corporal Michael J. Crescenz Veteran's Affairs Medical Center, Philadelphia, Pennsylvania, USA. · Medical Sciences, Newcastle University, Newcastle, UK. · Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, Australia. · School of Medical Sciences, University of New South Wales and Neuroscience Research Australia, Sydney, Australia. · Université de Bordeaux, Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, Institut des Maladies Neurodégénératives, Bordeaux, France. · China Academy of Medical Sciences, Institute of Lab Animal Sciences, Beijing, China. · Departments of Neurology, Pathology, and Cell Biology, the Center for Motor Neuron Biology and Disease, Columbia University, New York, New York, USA. · Columbia Translational Neuroscience Initiative, Columbia University, New York, New York, USA. · Institut du Cerveau et de la Moelle épinière - ICM, Centre de NeuroImagerie de Recherche - CENIR, Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Paris, France. · Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Clinical Sciences Department, Newcastle University, Newcastle, UK. · Department of Nuclear Medicine, Aarhus University, Aarhus, Denmark. · Human Neurophysiology, Sobell Department, UCL Institute of Neurology, London, UK. · Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. · Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA. · Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's disease, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Movement Disorders and Neuromodulation Center, Department of Neurology, University of California-San Francisco, San Francisco, California, USA. · Parkinson's Disease Research, Education and Clinical Center, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA. · Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii, USA. · Parkinson's Institute, Sunnyvale, California, USA. · Institute of Neurogenetics, University of Luebeck, Luebeck, Germany. · Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands. · Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA. · Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Department of Neurology, Universitätsklinikum Schleswig-Holstein, Christian Albrechts University Kiel, Kiel, Germany. · Department of Medical Neurobiology, Institute of Medical Research Israel-Canada, Jerusalem, Israel. · Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel. · Department of Neurosurgery, Hadassah University Hospital, Jerusalem, Israel. · Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, Barcelona, Spain. · Department of Medicine, Universitat de Barcelona, IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Barcelona, Spain. · Movement Disorders Clinic, Clinical Neurodegenerative Research Unit, Mexico City, Mexico. · Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico. · Department of Neurology, Columbia University Medical Center, New York, New York, USA. · Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada. · Klinik für Neurologie, UKSH, Campus Kiel, Christian-Albrechts-Universität, Kiel, Germany. · Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA. · Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, USA. · Research Center for Brain Repair, Rush University Medical Center, Chicago, Illinois, USA. · Neuroscience Graduate Program, Rush University Medical Center, Chicago, Illinois, USA. · Neurological Clinic, Department of Medicine, Hospital Santa Maria della Misericordia, University of Perugia, Perugia, Italy. · Laboratory of Neurophysiology, Santa Lucia Foundation, IRCCS, Rome, Italy. · University Department of Clinical Neurosciences, UCL Institute of Neurology, University College London, London, UK. · Pacific Parkinson's Research Centre, Division of Neurology & Djavadf Mowafaghian Centre for Brain Health, University of British Columbia, British Columbia, Canada. · Vancouver Coastal Health, Vancouver, British Columbia, Canada. ·Mov Disord · Pubmed #28887905.

ABSTRACT: This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

4 Review Imaging Systemic Dysfunction in Parkinson's Disease. 2016

Borghammer, Per / Knudsen, Karoline / Brooks, David J. ·Department of Nuclear Medicine & PET Centre, Institute of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, building 10, DK-8000, Aarhus C, Denmark. perborgh@rm.dk. · Department of Nuclear Medicine & PET Centre, Institute of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, building 10, DK-8000, Aarhus C, Denmark. · Division of Neuroscience, Department of Medicine, Imperial College London, London, UK. · Division of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. ·Curr Neurol Neurosci Rep · Pubmed #27072951.

ABSTRACT: Parkinson's disease is now widely recognized to be a multisystem disorder affecting the brain and peripheral autonomic nerves. Extensive pathology is present in both the sympathetic and parasympathetic nervous system and the intrinsic gastrointestinal plexuses in patients. Autonomic pathology and symptoms such as constipation can predate the clinical diagnosis by years or decades. Imaging studies have contributed greatly to our understanding of Parkinson's disease but focused primarily on imaging cerebral pathology. However, given the importance of understanding the nature, chronology, and functional consequences of peripheral pathology, there has been renewed interest in imaging peripheral organs in Parkinson's disease. Suitable imaging tools can be divided into two types: radiotracer studies that directly estimate loss of sympathetic or parasympathetic nerve terminals, and imaging modalities to quantitate dysphagia, gastric emptying, esophageal and intestinal transit times, and anorectal dyssynergia. In this review, we summarize current knowledge about peripheral imaging in Parkinson's disease.

5 Review Imaging synucleinopathies. 2016

Brooks, David J / Tambasco, Nicola. ·Dept of Nuclear Medicine, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark. · Dept of Medicine, Imperial College London, London, United Kingdom. · Division of Neurology, Newcastle University, Newcastle, United Kingdom. · Dept of Neurology, Azienda Ospedaliera e Universitaria di Perugia, Perugia, Italy. ·Mov Disord · Pubmed #26879635.

ABSTRACT: In this review the structural and functional imaging changes associated with the synucleinopathies PD, MSA, and dementias associated with Lewy bodies are reviewed. The role of imaging for supporting differential diagnosis, detecting subclinical disease, and following disease progression is discussed and its potential use for monitoring disease progression is debated. © 2016 International Parkinson and Movement Disorder Society.

6 Review Molecular imaging of dopamine transporters. 2016

Brooks, David J. ·Dept. of Nuclear Medicine, Aarhus University, Denmark; Division of Neuroscience, Imperial College London, UK; Division of Neuroscience, Newcastle University, UK. Electronic address: dbrooks@clin.au.dk. ·Ageing Res Rev · Pubmed #26802555.

ABSTRACT: The dopamine transporter (DAT) is responsible for clearance of dopamine from the synaptic cleft after its release. Imaging DAT availability provides a measure of dopamine terminal function and a method for detecting the striatal dopamine terminal dysfunction present in idiopathic Parkinson's disease (PD) and atypical neurodegenerative parkinsonian disorders such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). DAT imaging with positron emission tomography (PET) or single photon emission computed tomography (SPECT) can be used to support or refute a diagnosis of dopamine deficient parkinsonism in cases where this is unclear and rationalise a trial of dopamine replacement agents as therapy. It can also detect subclinical dopaminergic dysfunction when present in subjects at risk for PD such as relatives of patients, susceptibility gene mutation carriers, and subjects with late onset hyposmia or sleep disorders. The presence of normal DAT availability on imaging can help categorise "subjects without evidence of dopamine deficiency" (SWEDDs) who on occasion mimic PD and include dystonic tremors, drug-induced and psychogenic parkinsonism in their ranks. Reduced levels of baseline striatal DAT availability on PET or SPECT scanning, however, should be regarded as supportive rather than diagnostic of dopamine deficient parkinsonism.

7 Review What can biomarkers tell us about cognition in Parkinson's disease? 2014

Mollenhauer, Brit / Rochester, Lynn / Chen-Plotkin, Alice / Brooks, David. ·Paracelsus-Elena-Klinik, Kassel and University Medical Center, Göttingen, Germany. ·Mov Disord · Pubmed #24757111.

ABSTRACT: Cognitive decline is common in Parkinson's disease (PD), even in the early motor stage, and this non-motor feature impacts quality of life and prognosis tremendously. In this article, we discuss marker candidates for cognitive decline in PD from different angles, including functional and structural imaging techniques, biological fluid markers in cerebrospinal fluid, and blood genetic predictors, as well as gait as a surrogate marker of cognitive decline. Specifically, imaging-based markers of cognitive impairment in PD include cortical atrophy, reduced cortical metabolism, loss of cortical cholinergic and frontal dopaminergic function, as well as an increased cortical amyloid load. Reduced β-amyloid(1-42) in cerebrospinal fluid and lower plasma levels of epidermal growth factor are predictors for cognitive decline in PD. In addition, genetic variation in the apolipoprotein E (APOE), catechol-O-methyltransferase (COMT), microtubule-associated protein tau (MAPT), and glucocerebrosidase (GBA) genes may confer risk for cognitive impairment in PD; and gait disturbance may also indicate an increased risk for dementia. Other marker candidates have been proposed and are discussed. All of the current studies are hampered by gaps in our knowledge about the molecular causes of cognitive decline, which will have to be considered in future biomarker studies.

8 Review Parkinson's disease--the debate on the clinical phenomenology, aetiology, pathology and pathogenesis. 2013

Jenner, Peter / Morris, Huw R / Robbins, Trevor W / Goedert, Michel / Hardy, John / Ben-Shlomo, Yoav / Bolam, Paul / Burn, David / Hindle, John V / Brooks, David. ·Neurodegenerative Diseases Research Group, Institute of Pharmaceutical Sciences, School of Biomedical Sciences, King's College, London, UK. peter.jenner@kcl.ac.uk ·J Parkinsons Dis · Pubmed #23938306.

ABSTRACT: The definition of Parkinson's disease (PD) is changing with the expansion of clinical phenomenology and improved understanding of environmental and genetic influences that impact on the pathogenesis of the disease at the cellular and molecular level. This had led to debate and discussion with as yet, no general acceptance of the direction that change should take either at the level of diagnosis or of what should and should not be sheltered under an umbrella of PD. This article is one contribution to this on-going discussion. There are two different themes running through the article--widening the definition of PD/LBD/synucleinopathies and the heterogeneity that exists within PD itself from a clinical, pathological and genetic perspective. The conclusion reached is that in the future, further diagnostic categories will need to be recognized. These are likely to include--Parkinson's syndrome, Parkinson's syndrome likely to be Lewy body PD, clinical PD (defined by QSBB criteria), Lewy body disease (PD, LBD, REM SBD) and synucleinopathies (including LBD, MSA).

9 Review Parkinson's disease: diagnosis. 2012

Brooks, David J. ·Centre for Neuroscience, Department of Medicine, Imperial College London, UK. ·Parkinsonism Relat Disord · Pubmed #22166447.

ABSTRACT: In established PD the Queen Square Brain Bank criteria applied by experts show 90% sensitivity and specificity for the presence of midbrain Lewy bodies. However, in early disease clinical diagnosis is less straightforward. PD diagnosis made in the community by non-experts is associated with a 25% error rate. Nigral abnormalities can now be detected in vivo with 7 tesla MRI and diffusion tensor MRI. Magnetisation transfer can demonstrate melanin loss in the substantia nigra. Transcranial sonography (TCS) detects midbrain hyperechogenicity in both sporadic and genetic PD. PET and SPECT ligands can demonstrate the presence of dopamine terminal dysfunction in early and preclinical disease and an abnormal covariance pattern between levels of resting brain blood flow metabolism in cortical and subcortical regions. In the atypical parkinsonian syndrome multiple system atrophy (MSA) T2-weighted MRI can reveal characteristic changes including reduced putmen signal due to iron deposition and the pontine 'hot cross bun' sign as transverse fibres become visible. Progressive supranuclear palsy (PSP) is associated with midbrain atrophy and 3(rd) ventricular widening. In both these conditions diffusion weighted MRI shows increased striatal water diffusivity but the middle cerebellar peduncle is targeted in MSA and the superior peduncle in PSP. In this review the role of structural and functional imaging for supporting the differential diagnosis of the various degenerative parkinsonian syndromes will be discussed.

10 Review Imaging biomarkers in Parkinson's disease. 2011

Brooks, David J / Pavese, Nicola. ·Centre for Neuroscience, Department of Medicine, Imperial College London, UK. davidjbrooks@sky.com ·Prog Neurobiol · Pubmed #21896306.

ABSTRACT: Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons associated with intracellular Lewy inclusion bodies. The result is poverty of movement, increased muscle rigidity, and tremor at rest and on posture. Midbrain/nigral structural abnormalities can be demonstrated in vivo with both transcranial sonography (TCS) and diffusion tensor magnetic resonance imaging (DTI) while positron emission tomography (PET) and single photon emission computed tomography (SPECT) ligands exist to demonstrate dopamine terminal dysfunction. These radiotracers are markers of dopamine storage capacity, vesicular monoamine and dopamine transporter availability. While loss of putamen dopaminergic function leads to motor disability, Lewy bodies not only target dopamine neurons but have also been observed in serotoninergic, noradrenergic, and cholinergic neurons. As a consequence, non-dopaminergic neurotransmission is also impaired resulting in non-motor symptoms including sleep disturbance, fatigue, depression, dementia, and autonomic dysfunction. PET and SPECT ligands exist to interrogate the function of monoaminergic and cholinergic neurons. Cortical and limbic Lewy body disease is seen in more advanced PD and this can be detected with FDG PET as abnormal covariance between levels of resting brain metabolism in these regions. Additionally, widespread microglial activation can be detected in PD with PET. This review discusses the role of structural and functional imaging for understanding parkinsonian syndromes and aiding in their diagnosis and management.

11 Review Imaging dopamine transporters in Parkinson's disease. 2010

Brooks, David J. ·Department of Medicine, Imperial College London, Cyclotron Building, Hammersmith Hospital, Du Cane Road, W12 0NN, UK. david.brooks@imperial.ac.uk ·Biomark Med · Pubmed #20945978.

ABSTRACT: The dopamine transporter (DAT) is responsible for clearance of dopamine from the synaptic cleft after its release. Imaging DAT availability provides a measure of dopamine terminal function and a method for detecting striatal dopamine deficiency states present in idiopathic Parkinson's disease and atypical neurodegenerative Parkinsonian disorders such as multiple system atrophy and progressive supranuclear palsy. DAT imaging with PET or single photon emission computed tomography can be used to support a diagnosis of dopamine-deficient parkinsonism in cases where this is suspected and rationalize the use of dopaminergic agents as therapy. It can also detect subclinical dopaminergic dysfunction when present in subjects at risk of Parkinson's disease, such as relatives of patients, susceptibility gene mutation carriers, and subjects with late-onset hyposmia or sleep disorders. Finally, the presence of normal DAT availability on imaging can help exclude nondopamine-deficient syndromes, such as dystonic and severe essential tremors, drug-induced and psychogenic parkinsonism that, on occasion, mimic Parkinson's disease.

12 Review Imaging non-motor aspects of Parkinson's disease. 2010

Brooks, David J / Pavese, Nicola. ·Division of Experimental Medicine, Imperial College London, Hammersmith Hospital, London, UK. david.brooks@csc.mrc.ac.uk ·Prog Brain Res · Pubmed #20887877.

ABSTRACT: In this chapter the imaging changes associated with non-motor aspects of Parkinson's disease (PD) are reviewed. The relationship between reduced monoaminergic and cholinergic function and cognitive difficulties, depression, fatigue, sleep disorders, and dysautonomia is discussed and the relevance of Alzheimer pathology to PD dementia debated. Finally the discordance between the development of functional changes in PD and Braak staging is highlighted.

13 Review Imaging approaches to Parkinson disease. 2010

Brooks, David J. ·MRC Clinical Sciences Centre and Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom. david.brooks@csc.mrc.ac.uk ·J Nucl Med · Pubmed #20351351.

ABSTRACT: Parkinson disease (PD) is associated with nigral degeneration and striatal dopamine deficiency. Demonstrating midbrain structural abnormalities with transcranial sonography or diffusion-weighted MRI or showing striatal dopamine terminal dysfunction with PET or SPECT supports the diagnosis and rationalizes the use of dopaminergic medications. In atypical PD variants, transcranial sonography can detect striatal hyperechogenicity, and diffusion-weighted imaging can detect increased putamen water diffusion, whereas (18)F-FDG PET reveals reduced lentiform nucleus glucose metabolism. PET and SPECT can detect changes in striatal dopamine levels after levodopa administration and relate these to motor responses. Loss of cortical dopaminergic and cholinergic function is present in demented PD and, on occasion, amyloid deposits can be detected. Loss of cardiac sympathetic innervation can be sensitively detected in PD with (18)F-dopamine PET or (123)I-metaiodobenzylguanidine SPECT. Finally, PET can detect widespread brain inflammation in PD. This review discusses the role of structural and functional imaging for diagnosing and managing different parkinsonian syndromes.

14 Review Imaging amyloid in Parkinson's disease dementia and dementia with Lewy bodies with positron emission tomography. 2009

Brooks, David J. ·MRC Clinical Sciences Centre and Division of Neuroscience, Imperial College, London, United Kingdom. david.brooks@csc.mrc.ac.uk ·Mov Disord · Pubmed #19877240.

ABSTRACT: Although Parkinson's disease with later dementia (PDD) and dementia with Lewy bodies (DLB) are pathologically characterized by the presence of intraneuronal Lewy inclusion bodies, amyloid deposition is also associated to varying degrees with both these disorders. Fibrillar amyloid load can now be quantitated in vivo with positron emission tomography (PET) using imaging biomarkers. Here the reported findings of 11C-PIB PET studies concerning the amyloid load associated with PD and its influence on dementia are reviewed. It is concluded that the presence of amyloid acts to accelerate the dementia process in Lewy body disorders, though has little influence on its nature. Anti-amyloid strategies could be a relevant approach for slowing dementia in a number of DLB and PDD cases.

15 Review Imaging neurodegeneration in Parkinson's disease. 2009

Pavese, Nicola / Brooks, David J. ·MRC Clinical Sciences Centre and Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, UK. ·Biochim Biophys Acta · Pubmed #18992326.

ABSTRACT: Neuroimaging techniques have evolved over the past several years giving us unprecedented information about the degenerative process in Parkinson's disease (PD) and other movement disorders. Functional imaging approaches such as positron emission tomography (PET) and single photon emission computerised tomography (SPECT) have been successfully employed to detect dopaminergic dysfunction in PD, even while at a preclinical stage, and to demonstrate the effects of therapies on function of intact dopaminergic neurons within the affected striatum. PET and SPECT can also monitor PD progression as reflected by changes in brain levodopa and glucose metabolism and dopamine transporter binding. Structural imaging approaches include magnetic resonance imaging (MRI) and transcranial sonography (TCS). Recent advances in voxel-based morphometry and diffusion-weighted MRI have provided exciting potential applications for the differential diagnosis of parkinsonian syndromes. Substantia nigra hyperechogenicity, detected with TCS, may provide a marker of susceptibility to PD, probably reflecting disturbances of iron metabolism, but does not appear to correlate well with disease severity or change with disease progression. In the future novel radiotracers may help us assess the involvement of non-dopaminergic brain pathways in the pathology of both motor and non-motor complications in PD.

16 Review The role of structural and functional imaging in parkinsonian states with a description of PET technology. 2008

Brooks, David J. ·Division of Neuroscience and Medical Research Council Clinical Sciences Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London, United Kingdom. david.brooks@csc.mrc.ac.uk ·Semin Neurol · Pubmed #18843572.

ABSTRACT: In this article, after providing a description of the technique of brain positron emission tomography (PET), the review focuses on the application of PET and other recent advances of neuroimaging in understanding the structural, pathophysiological, and pharmacological changes associated with Parkinson's disease (PD). In early cases of PD, demonstration of the presence of nigral structural abnormalities with transcranial sonography and striatal dopaminergic dysfunction with functional imaging provides a rationale for the use of dopaminergic medications. The presence of altered striatal signal with diffusion-weighted magnetic resonance imaging (DWI) or reduced lentiform nucleus glucose metabolism with fluorodeoxyglucose PET suggests the presence of an atypical PD variant. Finally, the value of functional imaging as a biomarker for following the progression of PD and for understanding mechanisms of dementia when present is debated.

17 Review Technology insight: imaging neurodegeneration in Parkinson's disease. 2008

Brooks, David J. ·Faculty of Medicine at Imperial College, London, UK. david.brooks@csc.mrc.ac.uk ·Nat Clin Pract Neurol · Pubmed #18382437.

ABSTRACT: Currently, the clinical diagnosis of Parkinson's disease (PD) can be problematic, particularly at the early stages of the disease when the full spectrum of symptoms and signs might not yet be manifest. In addition, the mechanisms that underlie the nonmotor complications of PD, such as dementia and depression, are poorly understood, despite the fact that these symptoms largely determine the patient's quality of life at the end stage of the disease. This article reviews the latest advances in structural and functional imaging that have provided important insights into the structural, pathophysiological and pharmacological changes associated with PD. The contribution of inflammatory processes to the pathology of PD is discussed, as are the various possible mechanisms that lead to coexistent dementia and depression.

18 Clinical Trial Age at onset and Parkinson disease phenotype. 2016

Pagano, Gennaro / Ferrara, Nicola / Brooks, David J / Pavese, Nicola. ·From the Department of Medicine (G.P., D.J.B., N.P.), Neurology Imaging Unit, Imperial College London, Hammersmith Hospital, London, UK · Department of Translational Medical Sciences (G.P., N.F.), Federico II University of Naples · Salvatore Maugeri Foundation (N.F.), IRCCS, Scientific Institute of Telese, Telese Terme (BN), Italy · and Department of Clinical Medicine-Center for Functionally Integrative Neuroscience (D.J.B., N.P.), Aarhus University, Denmark. ·Neurology · Pubmed #26865518.

ABSTRACT: OBJECTIVE: To explore clinical phenotype and characteristics of Parkinson disease (PD) at different ages at onset in recently diagnosed patients with untreated PD. METHODS: We have analyzed baseline data from the Parkinson's Progression Markers Initiative database. Four hundred twenty-two patients with a diagnosis of PD confirmed by DaTSCAN imaging were divided into 4 groups according to age at onset (onset younger than 50 years, 50-59 years, 60-69 years, and 70 years or older) and investigated for differences in side, type and localization of symptoms, occurrence/severity of motor and nonmotor features, nigrostriatal function, and CSF biomarkers. RESULTS: Older age at onset was associated with a more severe motor and nonmotor phenotype, a greater dopaminergic dysfunction on DaTSCAN, and reduction of CSF α-synuclein and total tau. The most common presentation was the combination of 2 or 3 motor symptoms (bradykinesia, resting tremor, and rigidity) with rigidity being more common in the young-onset group. In about 80% of the patients with localized onset, the arm was the most affected part of the body, with no difference across subgroups. CONCLUSIONS: Although the presentation of PD symptoms is similar across age subgroups, the severity of motor and nonmotor features, the impairment of striatal binding, and the levels of CSF biomarkers increase with age at onset. The variability of imaging and nonimaging biomarkers in patients with PD at different ages could hamper the results of future clinical trials.

19 Article In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control study. 2018

Knudsen, Karoline / Fedorova, Tatyana D / Hansen, Allan K / Sommerauer, Michael / Otto, Marit / Svendsen, Kristina B / Nahimi, Adjmal / Stokholm, Morten G / Pavese, Nicola / Beier, Christoph P / Brooks, David J / Borghammer, Per. ·Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark. · Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark; Department of Neurology, University Hospital Cologne, Cologne, Germany. · Department of Clinical Neurophysiology, Aarhus University Hospital, Aarhus, Denmark; Department of Neurology, Aarhus University Hospital, Aarhus, Denmark. · Department of Neurology, Aarhus University Hospital, Aarhus, Denmark. · Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark; Division of Neuroscience, Department of Medicine, Imperial College London, London, UK; Division of Neuroscience, Newcastle University, Newcastle, UK. · Southern University of Denmark, Department of Neurology, Odense, Denmark. · Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark. Electronic address: perborgh@rm.dk. ·Lancet Neurol · Pubmed #29866443.

ABSTRACT: BACKGROUND: Accumulating evidence suggests that α-synuclein aggregates-a defining pathology of Parkinson's disease-display cell-to-cell transmission. α-synuclein aggregation is hypothesised to start in autonomic nerve terminals years before the appearance of motor symptoms, and subsequently spread via autonomic nerves to the spinal cord and brainstem. To assess this hypothesis, we investigated sympathetic, parasympathetic, noradrenergic, and dopaminergic innervation in patients with idiopathic rapid eye movement (REM) sleep behaviour disorder, a prodromal phenotype of Parkinson's disease. METHODS: In this prospective, case-control study, we recruited patients with idiopathic REM sleep behaviour disorder, confirmed by polysomnography, without clinical signs of parkinsonism or dementia, via advertisement and through sleep clinics in Denmark. We used FINDINGS: Between June 3, 2016, and Dec 19, 2017, we recruited 22 consecutive patients with idiopathic REM sleep behaviour disorder to the study. Compared with controls, patients with idiopathic REM sleep behaviour disorder had decreased colonic INTERPRETATION: Patients with idiopathic REM sleep behaviour disorder had fully developed pathology in the peripheral autonomic nervous system and the locus coeruleus, equal to that in diagnosed Parkinson's disease. These patients also showed noradrenergic thalamic denervation, but most had normal putaminal dopaminergic storage capacity. This caudorostral gradient of dysfunction supports the hypothesis that α-synuclein pathology in Parkinson's disease initially targets peripheral autonomic nerves and then spreads rostrally to the brainstem. FUNDING: Lundbeck Foundation, Jascha Foundation, and the Swiss National Foundation.

20 Article Longitudinal diffusion tensor imaging changes in early Parkinson's disease: ICICLE-PD study. 2018

Minett, Thais / Su, Li / Mak, Elijah / Williams, Guy / Firbank, Michael / Lawson, Rachael A / Yarnall, Alison J / Duncan, Gordon W / Owen, Adrian M / Khoo, Tien K / Brooks, David J / Rowe, James B / Barker, Roger A / Burn, David / O'Brien, John T. ·Department of Radiology, University of Cambridge, Cambridge, UK. thaisminett@hotmail.com. · Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Cambridge Biomedical Campus, Cambridge, CB2 0SR, UK. thaisminett@hotmail.com. · Department of Psychiatry, University of Cambridge, Cambridge, UK. · China-UK Centre for Cognition and Ageing Research, Southwest University, Chongqing, China. · Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK. · Brain and Mind Institute, University of Western Ontario, London, Canada. · Department of Psychology, University of Western Ontario, London, Canada. · School of Medicine, University of Wollongong, Wollongong, NSW, Australia. · Division of Neuroscience, Imperial College London, London, UK. · Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark. · Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. · Medical Research Council, Cognition and Brain Sciences Unit, Cambridge, UK. · Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK. · John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK. · Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. ·J Neurol · Pubmed #29696499.

ABSTRACT: OBJECTIVE: To investigate whether white matter microstructural changes can be used as a predictor of worsening of motor features or cognitive decline in patients with Parkinson's disease and verify whether white matter microstructural longitudinal changes differ between patients with Parkinson's disease with normal cognition and those with mild cognitive impairment. METHODS: We enrolled 120 newly diagnosed patients with early stage Parkinson's disease (27 with mild cognitive impairment and 93 with normal cognition) along with 48 controls. Participants were part of the incidence of cognitive impairment in cohorts with longitudinal evaluation in Parkinson's disease study and were assessed at baseline and 18 months later with cognitive, motor tests and diffusion tensor imaging. The relationships between fractional anisotropy and mean diffusivity with disease status, cognitive and motor function were investigated. RESULTS: At baseline, patients with early stage Parkinson's disease had significantly higher widespread mean diffusivity relative to controls, regardless of cognitive status. In patients with Parkinson's disease/mild cognitive impairment, higher mean diffusivity was significantly correlated with lower attention and executive function scores. At follow-up frontal mean diffusivity increased significantly when comparing patients with Parkinson's disease/mild cognitive impairment with those with normal cognition. Baseline mean diffusivity was a significant predictor of worsening of motor features in Parkinson's disease. CONCLUSIONS: Mean diffusivity represents an important correlate of cognitive function and predictor of motor impairment in Parkinson's disease: DTI is potentially a useful tool in stratification of patients into clinical trials and to monitor the impact of treatment on motor function.

21 Article Evaluation of the noradrenergic system in Parkinson's disease: an 11C-MeNER PET and neuromelanin MRI study. 2018

Sommerauer, Michael / Fedorova, Tatyana D / Hansen, Allan K / Knudsen, Karoline / Otto, Marit / Jeppesen, Jesper / Frederiksen, Yoon / Blicher, Jakob U / Geday, Jacob / Nahimi, Adjmal / Damholdt, Malene F / Brooks, David J / Borghammer, Per. ·Aarhus University Hospital, Department of Nuclear Medicine and PET Centre, Aarhus, Denmark. · Department of Neurology, University Hospital Cologne, Cologne, Germany. · Aarhus University Hospital, Department of Clinical Neurophysiology, Aarhus, Denmark. · Aarhus University, Department of Clinical Medicine and Department of Psychology, Aarhus, Denmark. · Center of Functionally Integrative Neuroscience, Aarhus University, Denmark. · Aarhus University Hospital, Department of Neurology, Aarhus, Denmark. · Division of Neuroscience, Department of Medicine, Imperial College London, London, UK. · Division of Neuroscience, Newcastle University, Newcastle, UK. ·Brain · Pubmed #29272343.

ABSTRACT: Pathological involvement of the noradrenergic locus coeruleus occurs early in Parkinson's disease, and widespread noradrenaline reductions are found at post-mortem. Rapid eye movement sleep behaviour disorder (RBD) accompanies Parkinson's disease and its presence predicts an unfavourable disease course with a higher propensity to cognitive impairment and orthostatic hypotension. MRI can detect neuromelanin in the locus coeruleus while 11C-MeNER PET is a marker of noradrenaline transporter availability. Here, we use both imaging modalities to study the association of RBD, cognition and autonomic dysfunction in Parkinson's disease with loss of noradrenergic function. Thirty non-demented Parkinson's disease patients [16 patients with RBD and 14 without RBD, comparable across age (66.6 ± 6.7 years), sex (22 males), and disease stage (Hoehn and Yahr, 2.3 ± 0.5)], had imaging of the locus coeruleus with neuromelanin sensitive MRI and brain noradrenaline transporter availability with 11C-MeNER PET. RBD was confirmed with polysomnography; cognitive function was assessed with a neuropsychological test battery, and blood pressure changes on tilting were documented; results were compared to 12 matched control subjects. We found that Parkinson's disease patients with RBD showed decreased locus coeruleus neuromelanin signal on MRI (P < 0.001) and widespread reduced binding of 11C-MeNER (P < 0.001), which correlated with amount of REM sleep without atonia. Parkinson's disease with RBD was also associated with a higher incidence of cognitive impairment, slowed EEG activity, and orthostatic hypotension. Reduced 11C-MeNER binding correlated with EEG slowing, cognitive performance, and orthostatic hypotension. In conclusion, reduced noradrenergic function in Parkinson's disease was linked to the presence of RBD and associated with cognitive deterioration and orthostatic hypotension. Noradrenergic impairment may contribute to the high prevalence of these non-motor symptoms in Parkinson's disease, and may be of relevance when treating these conditions in Parkinson's disease.

22 Article Chronic exposure to dopamine agonists affects the integrity of striatal D 2017

Politis, Marios / Wilson, Heather / Wu, Kit / Brooks, David J / Piccini, Paola. ·Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. · Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK. · Positron Emission Tomography Center, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark. ·Neuroimage Clin · Pubmed #28879087.

ABSTRACT: We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (D

23 Article Longitudinal whole-brain atrophy and ventricular enlargement in nondemented Parkinson's disease. 2017

Mak, Elijah / Su, Li / Williams, Guy B / Firbank, Michael J / Lawson, Rachael A / Yarnall, Alison J / Duncan, Gordon W / Mollenhauer, Brit / Owen, Adrian M / Khoo, Tien K / Brooks, David J / Rowe, James B / Barker, Roger A / Burn, David J / O'Brien, John T. ·Department of Psychiatry, University of Cambridge, Cambridgeshire, UK. · Wolfson Brain Imaging Centre, University of Cambridge, Cambridgeshire, UK. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · Medicine of the Elderly, Western General Hospital, Edinburgh, UK. · Paracelsus-Elena-Klinik, Kassel, Germany; University Medical Center Goettingen, Institute of Neuropathology, Goettingen, Germany. · Brain and Mind Institute, University of Western Ontario, London, Canada; Department of Psychology, University of Western Ontario, London, Canada. · Menzies Health Institute, Queensland and School of Medicine, Griffith University, Gold Coast, Australia. · Division of Neuroscience, Imperial College London, London, UK; Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark. · Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; Medical Research Council, Cognition and Brain Sciences Unit, Cambridge, UK; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK. · John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK. · Department of Psychiatry, University of Cambridge, Cambridgeshire, UK. Electronic address: John.obrien@medschl.cam.ac.uk. ·Neurobiol Aging · Pubmed #28431288.

ABSTRACT: We investigated whole-brain atrophy and ventricular enlargement over 18 months in nondemented Parkinson's disease (PD) and examined their associations with clinical measures and baseline CSF markers. PD subjects (n = 100) were classified at baseline into those with mild cognitive impairment (MCI; PD-MCI, n = 36) and no cognitive impairment (PD-NC, n = 64). Percentage of whole-brain volume change (PBVC) and ventricular expansion over 18 months were assessed with FSL-SIENA and ventricular enlargement (VIENA) respectively. PD-MCI showed increased global atrophy (-1.1% ± 0.8%) and ventricular enlargement (6.9 % ± 5.2%) compared with both PD-NC (PBVC: -0.4 ± 0.5, p < 0.01; VIENA: 2.1% ± 4.3%, p < 0.01) and healthy controls. In a subset of 35 PD subjects, CSF levels of tau, and Aβ42/Aβ40 ratio were correlated with PBVC and ventricular enlargement respectively. The sample size required to demonstrate a 20% reduction in PBVC and VIENA was approximately 1/15th of that required to detect equivalent changes in cognitive decline. These findings suggest that longitudinal MRI measurements have potential to serve as surrogate markers to complement clinical assessments for future disease-modifying trials in PD.

24 Article Cerebral glucose metabolism and cognition in newly diagnosed Parkinson's disease: ICICLE-PD study. 2017

Firbank, M J / Yarnall, A J / Lawson, R A / Duncan, G W / Khoo, T K / Petrides, G S / O'Brien, J T / Barker, R A / Maxwell, R J / Brooks, D J / Burn, D J. ·Institute of Neuroscience and Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK. · Department of Geriatric Medicine, University of Edinburgh, Edinburgh, UK. · School of Medicine & Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. · Department of Nuclear Medicine, Freeman Hospital, Newcastle upon Tyne, UK. · Department of Psychiatry, University of Cambridge, Cambridge, UK. · John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK. · Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK. · Division of Neuroscience, Imperial College London, London, UK. · Institute of Clinical Medicine, Aarhus University, Denmark. ·J Neurol Neurosurg Psychiatry · Pubmed #28315844.

ABSTRACT: OBJECTIVE: To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline. METHODS: FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA. RESULTS: PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (β=0.38, p=0.001) and MoCA (β=0.3, p=0.002) at 18 months controlling for baseline score. CONCLUSIONS: Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia.

25 Article In Vivo cortical tau in Parkinson's disease using 18F-AV-1451 positron emission tomography. 2017

Hansen, Allan K / Damholdt, Malene Flensborg / Fedorova, Tatyana D / Knudsen, Karoline / Parbo, Peter / Ismail, Rola / Østergaard, Karen / Brooks, David J / Borghammer, Per. ·Dept of Nuclear Medicine & PET Centre, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark. · Unit of Psychooncology and Health psychology, Dept of Psychology and Behavioral Sciences, Aarhus University, Aarhus, Denmark. · Dept of Neurology, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark. · Division of Neuroscience, Dept of Medicine, Imperial College London, United Kingdom. · Division of Neuroscience, Newcastle University, United Kingdom. ·Mov Disord · Pubmed #28256006.

ABSTRACT: BACKGROUND: Alzheimer's disease copathology is common in PD at autopsy. In non-PD subjects with mild cognitive impairment, tau depositions can be detected using 18F-AV-1451 PET. We hypothesized that 18F-AV-1451 PET would show tau aggregation in PD with mild cognitive impairment and correlate with cognitive dysfunction. OBJECTIVES: To describe tau aggregation in PD patients. METHODS: Twenty-six PD patients and 23 controls had 18F-AV-1451 PET and neuropsychological assessment to detect mild cognitive impairment. RESULTS: Nine PD patients (35%) were identified with mild cognitive impairment. Regional analyses showed no significant differences between groups. Voxel-wise analyses showed no correlation with cognitive domain z-scores within patients. One patient with mild cognitive impairment was estimated Braak tau stage 5; all other patients were stage 0. CONCLUSION: Our results indicate that tau pathology, as detected by 18F-AV-1451, is uncommon in PD with mild cognitive impairment and shows no significant correlation with cognitive dysfunction at this stage. © 2017 International Parkinson and Movement Disorder Society.

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