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Parkinson Disease: HELP
Articles from Stavanger Universitetssjukehus
Based on 120 articles published since 2010
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These are the 120 published articles about Parkinson Disease that originated from Stavanger Universitetssjukehus during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Review Cognitive Interventions in Parkinson's Disease: Where We Want to Go within 20 Years. 2018

Kalbe, Elke / Aarsland, Dag / Folkerts, Ann-Kristin. ·Medical Psychology | Neuropsychology and Gender Studies & Center for Neuropsychological Diagnostics and Intervention (CeNDI), University Hospital Cologne, Cologne, Germany. · Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. · Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway. ·J Parkinsons Dis · Pubmed #30584158.

ABSTRACT: Today, meta-analyses demonstrate that cognitive training is safe and effective to enhance vulnerable cognitive functions in patients with Parkinson's disease (PD), so that cognitive interventions can be regarded as a promising approach to treat or even prevent cognitive dysfunction in PD. However, many research gaps exist. Thus, this article aims to identify relevant research topics with regard to cognitive interventions in PD patients for the next 20 years. The most important to do's include the development of (non-digital and digital, maybe also artificial intelligence based) standardized cognitive interventions for PD patients in different cognitive stages and the conduct of large randomized controlled trials (RCTs) in these groups, also considering different patient profiles (e.g., motor subtypes) and the living setting (inpatient versus outpatient). The impact of cognitive and combined interventions in individuals with prodromal PD is of high relevance. Studies should elucidate underlying mechanisms of cognitive and neural plasticity induced by cognitive interventions and propose prediction models on which patients profit from which intervention. Health-economic analyses are also urgently needed. More generally, increasing the awareness of the concept of cognitive reserve and possibilities for the prevention of cognitive dysfunction is an important goal.

2 Review Detecting Mild Cognitive Deficits in Parkinson's Disease: Comparison of Neuropsychological Tests. 2018

Hoogland, Jeroen / van Wanrooij, Lennard L / Boel, Judith A / Goldman, Jennifer G / Stebbins, Glenn T / Dalrymple-Alford, John C / Marras, Connie / Adler, Charles H / Junque, Carme / Pedersen, Kenn F / Mollenhauer, Brit / Zabetian, Cyrus P / Eslinger, Paul J / Lewis, Simon J G / Wu, Ruey-Meei / Klein, Martin / Rodriguez-Oroz, Maria C / Cammisuli, Davide M / Barone, Paolo / Biundo, Roberta / de Bie, Rob M A / Schmand, Ben A / Tröster, Alexander I / Burn, David J / Litvan, Irene / Filoteo, J Vincent / Geurtsen, Gert J / Weintraub, Daniel / Anonymous5420961. ·Department of Neurology, Academic Medical Center Amsterdam, The Netherlands. · Department of Neurological Sciences, Section of Parkinson Disease and Movement Disorders, Rush University Medical Center, Chicago, Illinois, USA. · New Zealand Brain Research Institute, Brain Research New Zealand - Rangahau Roro Aotearoa, Christchurch, New Zealand. · Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J Safra Program in Parkinson's disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. · Arizona Parkinson's Disease Consortium, Mayo Clinic Arizona, Scottsdale, Arizona, USA and Banner Sun Health Research Institute, Sun City, Arizona, USA. · Department of Medicine, Faculty of Medicine, IDIBAPS, University of Barcelona, Barcelona, Spain. · The Norwegian Centre for Movement Disorders, Department of Neurology, and Memory Clinic, Stavanger University Hospital, Stavanger, Norway. · Paracelsus-Elena-Klinik, Kassel, Germany, and University Medical Center Goettingen, Department of Neurology, Goettingen, Germany. · VA Puget Sound Health Care System and Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA. · Department of Neurology, Penn State Hershey Medical Center, Hershey, Pennsylvania, USA. · Brain & Mind Centre, The University of Sydney, Sydney, Australia. · Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. · Department of Medical Psychology, section Medical Neuropsychology, VU University Medical Center, Amsterdam, The Netherlands. · Department of Neurology, Hospital Donostia, Donostia, San Sebastian and Ikerbasque, Basque Foundation for Science, Bilbao, Spain. · Fifth Local Sanitary Unit, Hospital Psychology, Pisa, Italy and Department of Surgical, Medical, Molecular, and Critical Area Pathology, Pisa University School of Medicine, Pisa, Italy. · Center for Neurodegenerative Diseases (CEMAND) Neuroscience Section, Department of Medicine University of Salerno, Salerno, Italy. · San Camillo Hospital IRCCS, Venice, Italy. · Department of Medical Psychology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Psychology, University of Amsterdam, The Netherlands. · Department of Clinical Neuropsychology and Center for Neuromodulation, Barrow Neurological Institute, Phoenix, Arizona, USA. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · Department of Neurosciences University of California San Diego, Parkinson and Other Movement Disorders Center, San Diego, California, USA. · Department of Psychiatry, University of California San Diego, and VA San Diego Healthcare System, San Diego, California, USA. · Departments of Psychiatry and Neurology, University of Pennsylvania School of Medicine, and Parkinson's Disease and Mental Illness Research, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA. ·Mov Disord · Pubmed #30216541.

ABSTRACT: BACKGROUND: Numerous neuropsychological tests and test versions are used in Parkinson's disease research, but their relative capacity to detect mild cognitive deficits and their comparability across studies are unknown. The objective of this study was to identify neuropsychological tests that consistently detect cognitive decline in PD across studies. METHODS: Data from 30 normed neuropsychological tests across 20 international studies in up to 2908 nondemented PD patients were analyzed. A subset of 17 tests was administered to up to 1247 healthy controls. A 2-step meta-analytic approach using standardized scores compared performance in PD with normative data. RESULTS: Pooled estimates of the differences between PD and site-specific healthy controls identified significant cognitive deficits in PD patients on 14 test scores across 5 commonly assessed cognitive domains (attention or working memory, executive, language, memory, and visuospatial abilities), but healthy control performance was statistically above average on 7 of these tests. Analyses based on published norms only, as opposed to direct assessment of healthy controls, showed high between-study variability that could not be accounted for and led to inconclusive results. CONCLUSIONS: Normed neuropsychological tests across multiple cognitive domains consistently detect cognitive deficits in PD when compared with site-specific healthy control performance, but relative PD performance was significantly affected by the inclusion and type of healthy controls versus the use of published norms only. Additional research is needed to identify a cognitive battery that can be administered in multisite international studies and that is sensitive to cognitive decline, responsive to therapeutic interventions, and superior to individual cognitive tests. © 2018 International Parkinson and Movement Disorder Society.

3 Review Assessment and Management of Neuropsychiatric Symptoms in Parkinson's Disease. 2018

Mueller, Christoph / Rajkumar, Anto P / Wan, Yi Min / Velayudhan, Latha / Ffytche, Dominic / Chaudhuri, Kallol Ray / Aarsland, Dag. ·Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, De Crespigny Park, London, SE5 8AF, UK. christoph.mueller@kcl.ac.uk. · South London and Maudsley NHS Foundation Trust, London, UK. christoph.mueller@kcl.ac.uk. · Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, De Crespigny Park, London, SE5 8AF, UK. · South London and Maudsley NHS Foundation Trust, London, UK. · Ng Teng Fong General Hospital, Singapore, Singapore. · National Parkinson Foundation International Centre of Excellence, King's College Hospital, London, UK. · Stavanger University Hospital, Stavanger, Norway. ·CNS Drugs · Pubmed #30027401.

ABSTRACT: Neuropsychiatric symptoms are highly prevalent in Parkinson's disease and associated with decreased quality of life and adverse health outcomes. In this review, the assessment and management of common neuropsychiatric symptoms are discussed: depression, anxiety, psychosis, cognitive impairment, dementia and apathy. Validated assessment scales are now available for the majority of symptoms. Balancing dopaminergic therapy plays an important role in their management as increasing doses of dopaminergic agents might address depression and anxiety related to 'off' phases, non-motor fluctuations and apathy, while dose reduction might alleviate psychotic symptoms. More targeted treatment is possible through medications utilising different pathways. Although efficacy profiles of individual agents require further exploration, antidepressants as a drug class have shown utility in depression and anxiety in Parkinson's disease. Psychological therapies, especially cognitive behavioural approaches, are effective. Pimavanserin allows the treatment of psychosis in Parkinson's disease without directly affecting the dopaminergic and cholinergic system. The cholinergic system is currently the only target in Parkinson's disease dementia, and antagonists of this system, as are many psychotropic drugs, need to be used with caution. Management of apathy largely relies on non-pharmacological strategies adapted from dementia care, with antidepressants being ineffective and the role of stimulant therapy needing further evaluation.

4 Review Biomarkers for cognitive impairment in Lewy body disorders: Status and relevance for clinical trials. 2018

Siderowf, Andrew / Aarsland, Dag / Mollenhauer, Brit / Goldman, Jennifer G / Ravina, Bernard. ·Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Philadelphia, USA. · Department of Old Age Psychiatry, Kings College, London, United Kingdom. · Centre for Age-Related Diseases, Stavanger University Hospital, Stavanger, Norway. · Paracelsus-Elena-Klinik, Kassel, Klinikstrasse 16, 34128 Kassel and University Medical Center, Department of Neurology, Göttingen, Germany. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois. · Voyager Therapeutics, Cambridge, Massachusetts, USA. ·Mov Disord · Pubmed #29624752.

ABSTRACT: Biomarkers have the potential to improve diagnosis and prognosis, and guide clinical treatment decisions. In research, biomarkers can be used for patient selection and as outcome measures in clinical trials. A range of biochemical and imaging biomarkers are relevant to patients with Lewy body disorders, including PD, PD dementia, and dementia with Lewy bodies. Dopaminergic imaging is used for differential diagnosis of parkinsonian disorders versus tremor disorders without dopamingeric deficits, and also to differentiate dementia with Lewy bodies from Alzheimer's disease. Markers of underlying Alzheimer's disease pathology have been applied to PD patients experiencing cognitive decline to determine the extent of mixed pathology in these cases. Assessment of alpha-synuclein species in spinal fluid is possible, and more specific assays attempt to identify alpha-synuclein aggregates or phosphorylated alpha-synuclein. While alpha-synuclein markers are intended to measure the pathology most central to PD dementia and dementia with Lewy bodies, convincing evidence of robust reliability and validity from multiple laboratories is lacking. Similarly, alpha-synuclein imaging by PET or single-photon emission computed tomography, while an important research goal, is not yet available. In addition to their uses in the clinic, biomarkers have natural uses in therapeutic trials that target cognitive and neuropsychiatric features of Lewy body disorders. The biomarkers most likely to be incorporated into trials are dopaminergic and amyloid imaging for the purpose of accurate patient selection, and possibly to demonstrate the utility of antiamyloid treatments in Lewy body disorders patients with mixed pathology. © 2018 International Parkinson and Movement Disorder Society.

5 Review Strengths and challenges in conducting clinical trials in Parkinson's disease mild cognitive impairment. 2018

Litvan, Irene / Kieburtz, Karl / Tröster, Alexander I / Aarsland, Dag. ·University of California San Diego, Department of Neurosciences, Parkinson and Other Movement Disorders Center, San Diego, California, USA. · Center for Health & Technology, University of Rochester Medical Center, Rochester, New York, USA. · Clintrex LLC, Sarasota, Florida. · Barrow Neurological Institute, Department of Clinical Neuropsychology and Barrow Center for Neuromodulation, Phoenix, Arizona, USA. · King's College, Institute of Psychiatry, Psychology and Neuroscience, London, UK; Centre for Age-Related Diseases, Stavanger. · Centre for Age-Related Diseases, Stavanger University Hospital, Stavanger, Norway. ·Mov Disord · Pubmed #29573469.

ABSTRACT: Treatments to slow the progression of cognitive dysfunction to dementia and improve the quality of life of persons with Parkinson's disease (PD) are desperately needed. Because PD mild cognitive impairment is considered a transitional stage before dementia, it opens a window to timely intervention. This article critically reviews the strengths and challenges of pharmacologic and nonpharmacologic clinical therapeutic trials in PD mild cognitive impairment conducted during the past 5 years, including ongoing trials. Relatively few high-quality trials have been conducted, and some important factors in designing future clinical trials are discussed. © 2018 International Parkinson and Movement Disorder Society.

6 Review New Tracers and New Perspectives for Molecular Imaging in Lewy Body Diseases. 2018

Bauckneht, Matteo / Arnaldi, Dario / Nobili, Flavio / Aarsland, Dag / Morbelli, Silvia. ·Nuclear Medicine Unit, Department of Health Sciences, Policlinic San Martino Hospital, 16132 Genoa, Italy. · Clinical Neurology Unit, Department of Neuroscience (DINOGMI) University of Genoa and Policlinic San Martino Hospital, 16132 Genoa, Italy. · King`s College of London, London, United Kingdom. · Center for Age-Related Diseases, Stavanger University Hospital, Stavanger, Norway. ·Curr Med Chem · Pubmed #28595550.

ABSTRACT: The term Lewy body diseases (LBDs) refers to a subset of neurodegenerative disorders that share the accumulation of the so-called Lewy bodies (LB) including: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and PD later characterized by the occurrence of dementia (PDD). Moreover, multiple system atrophy (MSA) and idiopatic Rem Sleeping behaviour disorders (RBD) complete the group of synucleinopathies and have also common symptoms with respect to LBDs. The clinical diagnosis of LBDs can be challenging for physicians, particularly in the early stages of disease. Given the growing number of individuals affected by these neurodegenerative disorders, early and accurate diagnosis can lead to improved clinical management of patients. For this reason, information obtained from molecular imaging biomarkers is playing an increasingly important role in this framework. The present narrative review discusses both established milestones and new evidence on the use of molecular imaging tracers already part of the clinical practice as well as available evidence on new molecular imaging approaches in PD, PDD and DLB.

7 Review Psychosis in Parkinson's Disease. 2017

Ffytche, Dominic H / Aarsland, Dag. ·Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom. Electronic address: dominic.ffytche@kcl.ac.uk. · Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Centre of Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway. ·Int Rev Neurobiol · Pubmed #28802934.

ABSTRACT: Although illusions, hallucinations and delusions did not play a prominent role in James Parkinson's original clinical descriptions, the longitudinal view of disease progression he advocated has important lessons for the study of such symptoms today. A focus on longitudinal progression rather than individual symptoms led to the concept of PD psychosis-a spectrum of positive symptoms in Parkinson's disease. The publication of criteria for PD psychosis in 2007 helped unify the disparate set of symptoms, raising their profile and resulting in a rapid expansion of literature focussing on clinical aspects, mechanisms, and treatment. Here we review this literature and the evolving view of PD psychosis. Adding to previous evidence of a prospective risk for dementia and the move to supervised care, key recent developments include: recognition of prevalence increase with disease duration; a broadening of symptoms included in PD psychosis; better characterization of higher visual and cognitive dysfunction risk factors; structural, functional, and neurotransmitter imaging biomarker evidence; and approval of pimavanserin in the United States for the treatment of PD psychosis. The accumulating evidence raises novel questions and directions for future research that promise a better understanding of the clinical management of PD psychosis and its role as a biomarker for PD stage and progression.

8 Review Prodromal Markers in Parkinson's Disease: Limitations in Longitudinal Studies and Lessons Learned. 2016

Heinzel, Sebastian / Roeben, Benjamin / Ben-Shlomo, Yoav / Lerche, Stefanie / Alves, Guido / Barone, Paolo / Behnke, Stefanie / Berendse, Henk W / Bloem, Bastiaan R / Burn, David / Dodel, Richard / Grosset, Donald G / Hu, Michele / Kasten, Meike / Krüger, Rejko / Moccia, Marcello / Mollenhauer, Brit / Oertel, Wolfgang / Suenkel, Ulrike / Walter, Uwe / Wirdefeldt, Karin / Liepelt-Scarfone, Inga / Maetzler, Walter / Berg, Daniela. ·Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of TübingenTübingen, Germany; German Center for Neurodegenerative Diseases, University of TübingenTübingen, Germany. · School of Social and Community Medicine, University of Bristol Bristol, UK. · Norwegian Centre for Movement Disorders and Department of Neurology, Stavanger University Hospital Stavanger, Norway. · Center for Neurodegenerative Diseases (CEMAND), Neuroscience Section, Department of Medicine, University of Salerno Salerno, Italy. · Department of Neurology, University of Homburg Homburg, Germany. · Department of Neurology and Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, Netherlands. · Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Department of Neurology Nijmegen, Netherlands. · Institute of Neuroscience, Newcastle University Newcastle Upon Tyne, UK. · Department of Neurology, Philipps-University Marburg Marburg, Germany. · Institute of Neurological Sciences, Queen Elizabeth University Hospital Glasgow, UK. · Oxford Parkinson's Disease Centre and Nuffield Department of Clinical Neurosciences, University of Oxford Oxford, UK. · Institute of Neurogenetics, University of Lübeck Lübeck, Germany. · Clinical and Experimental Neuroscience, Luxembourg Center for Systems Biomedicine Belva, Luxembourg. · Paracelsus-Elena-KlinikKassel, Germany; Department of Neuropathology, University Medical CenterGöttingen, Germany. · Department of Neurology, University of Rostock Rostock, Germany. · Department of Medical Epidemiology and Biostatistics and Department of Clinical Neuroscience, Karolinska Institutet Stockholm, Sweden. · Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of TübingenTübingen, Germany; German Center for Neurodegenerative Diseases, University of TübingenTübingen, Germany; Department of Neurology, Christian-Albrechts-UniversityKiel, Germany. ·Front Aging Neurosci · Pubmed #27445791.

ABSTRACT: A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson's disease (PD). Studies have identified several different prodromal markers that may have the potential to predict the conversion from healthy to clinical PD but use considerably different approaches. We systematically reviewed 35 longitudinal studies reporting prodromal PD features and evaluated the methodological quality across 10 different predefined domains. We found limitations in the following domains: PD diagnosis (57% of studies), prodromal marker assessments (51%), temporal information on prodromal markers or PD diagnosis (34%), generalizability of results (17%), statistical methods (accounting for at least age as confounder; 17%), study design (14%), and sample size (9%). However, no limitations regarding drop-out (or bias investigation), or report of inclusion/exclusion criteria or prodromal marker associations were revealed. Lessons learned from these limitations and additional aspects of current prodromal marker studies in PD are discussed to provide a basis for the evaluation of findings and the improvement of future research in prodromal PD. The observed heterogeneity of studies, limitations and analyses might be addressed in future longitudinal studies using a, yet to be established, modular minimal set of assessments improving comparability of findings and enabling data sharing and combined analyses across studies.

9 Review Biological confounders for the values of cerebrospinal fluid proteins in Parkinson's disease and related disorders. 2016

Mollenhauer, Brit / Parnetti, Lucilla / Rektorova, Irena / Kramberger, Milica G / Pikkarainen, Maria / Schulz-Schaeffer, Walter J / Aarsland, Dag / Svenningsson, Per / Farotti, Lucia / Verbeek, Marcel M / Schlossmacher, Michael G. ·Paracelsus-Elena-Klinik, Kassel, Germany. brit.mollenhauer@paracelsus-kliniken.de. · University Medical Center (Department of Neuropathology), Georg-August University Goettingen, Goettingen, Germany. brit.mollenhauer@paracelsus-kliniken.de. · Centro Disturbi della Memoria- Unità Valutativa Alzheimer, Clinica Neurologica, Università di Perugia, Perugia, Italy. · Applied Neuroscience Group, CEITEC MU, Masaryk University, Brno, Czech Republic. · Department of Neurology, University Medical Center Ljubljana, Ljubljana, Slovenia. · Division for Neurogeriatrics, Department of NVS, Karolinska Institutet, Center for Alzheimer Research, Stockholm, Sweden. · Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway. · Institute of Clinical Medicine / Neurology, University of Eastern Finland, Kuopio, Finland. · University Medical Center (Department of Neuropathology), Georg-August University Goettingen, Goettingen, Germany. · Department for Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. · Department of Neurology, Department of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands. · Program in Neuroscience and Division of Neurology, The Ottawa Hospital, University of Ottawa Brain & Mind Research Institute, Ottawa, Ontario, Canada. ·J Neurochem · Pubmed #26452984.

ABSTRACT: Cerebrospinal fluid (CSF) has been extensively studied to explore biochemical alterations in subjects with neurodegenerative disorders. In Alzheimer's disease, levels of increased CSF tau protein and decreased levels of β-amyloid 1-42 (Aβ42) have been shown to correlate with brain plaque formation and tangle pathology. Intracellular Lewy inclusions containing aggregated α-synuclein (α-syn) represent a pathological hallmark of Parkinson's disease (PD). In most - but not all - studies published to date total CSF α-syn concentrations have been found to be decreased in disorders related to α-syn pathology, that is, PD, dementia with Lewy bodies and multiple system atrophy. However, these reports show extensive signal overlap among tested individuals, thereby diminishing its potential for routine use in clinical practice. To investigate potential biological (i.e., non-technical) confounders of reported CSF levels for α-syn, Aβ42, and tau in PD and related disorders, we carried out a methodical review of known factors that underlie signal variability and speculate on those that have not yet been tested. We discuss several biological factors, such as neuropathology, demographics, clinical phenotype, progression and duration of disease, concomitant illnesses and, last but not least, pharmacotherapy, which in isolation or combination can substantially alter values for CSF proteins of interest. Enhanced implementation of standardized clinical protocols, streamlined operating procedures, and further progress in the development of validated assays for CSF proteins have the potential to (i) inform us as to the pathogenesis of disease, (ii) support the laboratory-based diagnosis for symptomatic subjects in the future, and (iii) facilitate breakthrough therapies to alter the course of neurodegenerative disorders, such as PD and Alzheimer's disease. Cerebrospinal fluid (CSF) has been extensively studied to explore biochemical alterations in subjects with neurodegenerative disorders. To investigate potential biological confounders of reported CSF levels for α-synuclein (α-Syn), amyloid-β 1-42(Aβ42) and tau protein in Parkinson's disease and related disorders, we reviewed the current literature for known factors that underlie signal variability and speculate on those that have not yet been tested. This article is part of a special issue on Parkinson disease.

10 Review Cognitive impairment in Parkinson's disease and dementia with Lewy bodies. 2016

Aarsland, Dag. ·Karolinska Institutet, Dept NVS, Center for Alzheimer Research, Division for Neurogeriatrics, 141 57 Huddinge, Sweden; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway. Electronic address: daarsland@gmail.com. ·Parkinsonism Relat Disord · Pubmed #26411499.

ABSTRACT: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share clinical and pathological similarities. The defining features are motor parkinsonism and cognitive impairment, often accompanied by visual hallucinations, fluctuating consciousness, autonomic and sleep disturbances, and a number of other non-motor symptoms. Mild cognitive impairment (MCI) can be identified in 15% of PD patients at time of diagnosis, and may even precede motor symptoms. MCI usually progresses further, and dementia is a common endpoint. Cognitive impairment is usually the initial symptom of DLB, and the disease course is severe. A variety of biomarkers can assist in the diagnosis and prognosis of PD and DLB, including structural and functional imaging, cerebrospinal fluid, and EEG. Compared to the many treatments available for motor symptoms, relatively few systematic studies exist to guide the treatment of cognitive impairment in PD, and even less in DLB. However, there is good evidence for cholinesterase inhibitors in both DLB and PD with dementia, and some indications that memantine is helpful. Emerging evidence suggest that physical exercise and cognitive training are also effective, as are some reports of various brain stimulation techniques. Disease-modifying agents that delay the rate of cognitive decline in PD and DLB are urgently needed.

11 Review Lewy body dementias. 2015

Walker, Zuzana / Possin, Katherine L / Boeve, Bradley F / Aarsland, Dag. ·Division of Psychiatry, University College London, London, UK; North Essex Partnership University NHS Foundation Trust, Epping, UK. Electronic address: z.walker@ucl.ac.uk. · University of California, San Francisco School of Medicine, San Francisco, CA, USA. · Division of Behavioral Neurology, Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA; Division of Movement Disorders, Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA; Center for Sleep Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA. · Centre for Age-Related Diseases, Stavanger University Hospital, Stavanger, Norway; Department of Geriatric Psychiatry, Akershus University Hospital, Oslo, Norway; Department of Neurobiology, Care Sciences and Society, Division of Alzheimer's Disease Research Centre, Karolinska Institute, Stockholm, Sweden. ·Lancet · Pubmed #26595642.

ABSTRACT: The broad importance of dementia is undisputed, with Alzheimer's disease justifiably getting the most attention. However, dementia with Lewy bodies and Parkinson's disease dementia, now called Lewy body dementias, are the second most common type of degenerative dementia in patients older than 65 years. Despite this, Lewy body dementias receive little attention and patients are often misdiagnosed, leading to less than ideal management. Over the past 10 years, considerable effort has gone into improving diagnostic accuracy by refining diagnostic criteria and using imaging and other biomarkers. Dementia with Lewy bodies and Parkinson's disease dementia share the same pathophysiology, and effective treatments will depend not only on successful treatment of symptoms but also on targeting the pathological mechanisms of disease, ideally before symptoms and clinical signs develop. We summarise the most pertinent progress from the past 10 years, outlining some of the challenges for the future, which will require refinement of diagnosis and clarification of the pathogenesis, leading to disease-modifying treatments.

12 Review Neuropsychiatric Symptoms in Parkinson's Disease. 2015

Aarsland, Dag / Kramberger, Milica Gregoric. ·Karolinska Institute, Department of Neurobiology, Care Sciences and Society (NVS), H1, Division of Neurogeriatrics, Huddinge, Sweden. · Stavanger University Hospital, Stavanger, Norway. · Department of Neurology, University Medical Center Ljubljana, Slovenia. ·J Parkinsons Dis · Pubmed #26406147.

ABSTRACT: Parkinson's disease (PD) is characterized by motor symptoms, but focused and extensive research in the last years has provided new knowledge in the field of non-motor symptoms. Non-motor symptoms include neuropsychiatric symptoms such as depression, anxiety, psychosis, apathy, impulse control disorders, and occur in the majority of patients with PD. They are associated with impaired quality of life for patients and relatives, additional deterioration of function and increased use of health resources. Medical and surgical therapies commonly used for treatment of PD can induce or worsen such symptoms. This paper discusses the epidemiology, clinical features and treatment approaches for neuropsychiatric symptoms (NPS) in PD in the perspective of clinical practice and management. The prevalence rates of various NPS are high, various demographic, clinical and treatment related variables have shown to be associated with higher risk of NPS. Randomized controlled trials of pharmacological and non-pharmacological treatments of NPS in PD are sparse. Current evidence supports tricyclic antidepressants as efficacious treatment of depression in PD and antipsychotic clozapine as efficacious choice for psychosis. Further studies to evaluate various other management strategies of NPS in PD are required. Neuropsychiatric symptoms in PD should be considered an integral part of the disease; hence a multidisciplinary approach is essential to improve the overall outcome of PD also through raised awareness and enriched knowledge on NPS.

13 Review Cerebrospinal fluid biomarkers in trials for Alzheimer and Parkinson diseases. 2015

Lleó, Alberto / Cavedo, Enrica / Parnetti, Lucilla / Vanderstichele, Hugo / Herukka, Sanna Kaisa / Andreasen, Niels / Ghidoni, Roberta / Lewczuk, Piotr / Jeromin, Andreas / Winblad, Bengt / Tsolaki, Magda / Mroczko, Barbara / Visser, Pieter Jelle / Santana, Isabel / Svenningsson, Per / Blennow, Kaj / Aarsland, Dag / Molinuevo, José Luis / Zetterberg, Henrik / Mollenhauer, Brit. ·Department of Neurology, Institut d'Investigacions Biomèdiques, Hospital de Sant Pau, Sant Antoni Maria, Claret 167, Barcelona 08025, Spain. · IRCCS Istituto Centro San Giovanni di Dio-Fatebenefratelli, Italy. · Ospedale Santa Maria della Misericordia, Università di Perugia, Italy. · ADxNeurosciences, Belgium. · University of Eastern Finland and Kuopio University Hospital, Finland. · Karolinska Institute, Sweden. · Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany. · Quanterix, USA. · Aristotle University of Thessaloniki, Greece. · Medical University of Białystok, Poland. · Maastricht University, Netherlands. · University of Coimbra, Portugal. · The Sahlgrenska Academy at University of Gothenburg, Sweden. · Stavanger University Hospital, Norway. · ICN Hospital Clinic i Universitari, IDIBAPS, Spain. · Paracelsus-Elena-Klinik, Germany. ·Nat Rev Neurol · Pubmed #25511894.

ABSTRACT: Alzheimer disease (AD) and Parkinson disease (PD) are the most common neurodegenerative disorders. For both diseases, early intervention is thought to be essential to the success of disease-modifying treatments. Cerebrospinal fluid (CSF) can reflect some of the pathophysiological changes that occur in the brain, and the number of CSF biomarkers under investigation in neurodegenerative conditions has grown rapidly in the past 20 years. In AD, CSF biomarkers are increasingly being used in clinical practice, and have been incorporated into the majority of clinical trials to demonstrate target engagement, to enrich or stratify patient groups, and to find evidence of disease modification. In PD, CSF biomarkers have not yet reached the clinic, but are being studied in patients with parkinsonism, and are being used in clinical trials either to monitor progression or to demonstrate target engagement and downstream effects of drugs. CSF biomarkers might also serve as surrogate markers of clinical benefit after a specific therapeutic intervention, although additional data are required. It is anticipated that CSF biomarkers will have an important role in trials aimed at disease modification in the near future. In this Review, we provide an overview of CSF biomarkers in AD and PD, and discuss their role in clinical trials.

14 Review Parkinson's disease and age: The obvious but largely unexplored link. 2015

Abdullah, Rashed / Basak, Indranil / Patil, Ketan S / Alves, Guido / Larsen, Jan Petter / Møller, Simon Geir. ·Department of Biological Sciences, St John's University, New York, NY, USA. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · Department of Biological Sciences, St John's University, New York, NY, USA; The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. Electronic address: mollers@stjohns.edu. ·Exp Gerontol · Pubmed #25261764.

ABSTRACT: Parkinson's disease is a chronic, progressive neurodegenerative disorder with increased prevalence in the aging population. It is estimated that approximately 1.5 million individuals in the US alone suffer from Parkinson's disease and with the extension of life expectancy this number is expected to rise dramatically within the next twenty-five years. The majority of Parkinson's disease cases are sporadic. But mutations in genes such as α-synuclein, Parkin, PINK1, DJ-1 and LRRK2, have been conclusively associated with both early- and late-onset of the disease. Although the genetics of Parkinson's disease is starting to become unraveled, the interplay between genetic and environmental factors is largely unknown as are the underlying mechanisms that trigger the disease as the brain ages. The risk of Parkinson's disease increases dramatically in individuals over the age of 60 and it is estimated that more than 1% of all seniors have some form of the condition. In this review, we will highlight some of the central proteins associated with Parkinson's disease and how they may be linked to processes and factors associated with age.

15 Review Psychiatric issues in cognitive impairment. 2014

Aarsland, Dag / Taylor, John-Paul / Weintraub, Daniel. ·Alzheimer's Disease Research Centre, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway; Department of Geriatric Psychiatry, Akershus University Hospital, Oslo, Norway. ·Mov Disord · Pubmed #24757113.

ABSTRACT: Neuropsychiatric symptoms (NPS) such as depression, hallucinations and apathy commonly occur in Parkinson's disease (PD) and have major clinical consequences including a negative impact on quality of life. This review discusses the epidemiology, clinical features, diagnostic procedures and treatment issues of NPS in PD and related disorders in the perspective of cognitive impairment, focusing on depression, anxiety, visual hallucinations, apathy, sleep disturbances, impulse control disorder and non-motor fluctuations. The majority of NPS are more common in PD patients with dementia, possibly related to shared underlying pathologies. Recent studies also suggest that NPS are associated with mild cognitive impairment in PD, in particular with the amnestic type. Accurate diagnosis of NPS is important but can be difficult, due to overlapping symptoms and similar appearance of symptoms of motor symptoms of parkinsonism, cognitive impairment, mood disorders and apathy. There are few systematic studies focusing on the management of NPS in PD with cognitive impairment.

16 Review Mild cognitive impairment in Parkinson's disease. 2011

Aarsland, Dag / Brønnick, Kolbjørn / Fladby, Tormod. ·Centre for Age-Related Diseases, Division of Psychiatry, Stavanger University Hospital, Stavanger, Norway. daarsland@gmail.com ·Curr Neurol Neurosci Rep · Pubmed #21487730.

ABSTRACT: Prospective studies conducted during the last decade have shown that the majority of patients with Parkinson's disease (PD) develop dementia. In addition, using a variety of definitions and methods, more recent research suggests that approximately a quarter of PD patients without dementia have mild cognitive impairment (PD-MCI). Furthermore, several studies have shown that approximately 20% have MCI even at time of diagnosis of PD. The typical cognitive deficits include visuospatial, attentional, and executive deficits, but memory deficits have also been shown. The etiology of PD-MCI is not known, but it is likely that mechanisms known to contribute to dementia in PD (ie, limbic and cortical Lewy bodies, amyloid plaques, and cholinergic deficits) play a role, in addition to dysfunction of dopaminergic frontostriatal circuits. PD-MCI predicts a shorter time to dementia, and preliminary evidence suggests that this is particularly true for posterior cognitive deficits. There are currently no systematic clinical trials in PD-MCI.

17 Review The epidemiology of dementia associated with Parkinson's disease. 2010

Aarsland, Dag / Kurz, Martin Wilhelm. ·Department of Psychiatry, Stavanger University Hospital, Postboks 8100, 4068 Stavanger, Norway. daarsland@gmail.com ·Brain Pathol · Pubmed #20522088.

ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative illness after Alzheimer's disease (AD). Cognitive impairment and dementia are common features in PD and characterized by a wide range of cognitive deficits distinct from those seen in AD. Mild cognitive impairment occurs even early in PD and is associated with shorter time to dementia. The purpose of this review is to present recent findings on clinical aspects of dementia in PD and to elucidate underlying clinical and neurobiological risk factors.

18 Clinical Trial Combined Diffusion Tensor Imaging and Arterial Spin Labeling as Markers of Early Parkinson's disease. 2016

Wei, Xiaobo / Yan, Ronghua / Chen, Zhaoyu / Weng, Ruihui / Liu, Xu / Gao, Huimin / Xu, Xiaofeng / Kang, Zhuang / Liu, Zhexing / Guo, Yan / Liu, Zhenhua / Larsen, Jan Petter / Wang, Jin / Tang, Beisha / Hallett, Mark / Wang, Qing. ·Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Tianhe Road 600, Guangzhou, Guangdong 510630, China. · Department of Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Tianhe Road 600, Guangzhou, Guangdong 510630, China. · School of biomedical Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China. · Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, #74 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China. · Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Box 8100, N-4068 Stavanger, Norway. · Department of Neurology and The State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078 China. · Human Motor Control Section, NINDS, NIH, Bethesda, MD 20892-1428 Stavanger, USA. ·Sci Rep · Pubmed #27646647.

ABSTRACT: This study aimed to identify a PD-specific MRI pattern using combined diffusion tensor imaging (DTI) and arterial spin labeling (ASL) to discriminate patients with early PD from healthy subjects and evaluate disease status. Twenty-one early and 22 mid-late PD patients, and 22 healthy, age/gender-matched controls underwent 3-T MRI with apparent diffusion coefficient (ADC), fractional anisotropy (FA), fiber number (FN) and cerebral blood flow (CBF) measurements. We found that compared with healthy subjects, there was a profound reduction in FN passing through the SN in PD. FA in the SN and CBF in the caudate nucleus were inversely correlated with motor dysfunction. A negative correlation was observed between FA in the hippocampus (Hip) and the NMSS-Mood score, whereas CBF in the Hip and the prefrontal cortex(PFC) correlated with declined cognition. Stratified five-fold cross-validation identified FA in the SN(FA-SNAv), CBF in the PFC(CBF-PFCAv) and FA in the parietal white matter(FA-PWMAv), and the combination of these measurements offered relatively high accuracy (AUC 0.975, 90% sensitivity and 100% specificity) in distinguishing those with early PD from healthy subjects. We demonstrate that the decreased FNs through SN in combination with changes in FA-SNAv, CBF-PFCAv and FA-PWMAv values might serve as potential markers of early-stage PD.

19 Clinical Trial Motor symptoms after deep brain stimulation of the subthalamic nucleus. 2015

Lilleeng, B / Gjerstad, M / Baardsen, R / Dalen, I / Larsen, J P. ·The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. ·Acta Neurol Scand · Pubmed #25346142.

ABSTRACT: OBJECTIVES: Stimulation of the subthalamic nucleus (STN-DBS) is an established treatment with long-term beneficial effects on motor symptoms in patients with Parkinson's disease (PD). The efficacy of STN-DBS on non-dopaminergic motor symptoms remains less elucidated. In this study, we have examined short- and long-term impacts of STN-DBS on the development of the postural instability and gait difficulties (PIGD) phenotype, freezing of gait (FOG), and falls. MATERIALS AND METHODS: We collected data from a prospectively followed cohort of patients that had been operated with STN-DBS 6-9 years before final examination and compared our findings to the longitudinal development of the same symptoms in a non-operated, historical reference population. RESULTS: During short-term follow-up after surgery, we observed a marked improvement in mean UPDRS-motor score from 27 to 18. We also found clear improvements in tremor, bradykinesia, rigidity, and PIGD scores. However, 6-9 years after surgery, all patients had a dominating PIGD pattern of parkinsonism and 50% of the patients had developed FOG and/or had become recurrent fallers. The disease development in a group of patients with PD from the presurgery period had a similar trajectory as among the operated patients. In addition, mean annual change of both bradykinesia and PIGD scores was nearly identical in both study groups while tremor and rigidity had a significant better development in the operated patients. CONCLUSIONS: We found that STN-DBS induces an acute improvement of PIGD symptoms. The following long-term development was however characterized by a marked progression of non-dopaminergic symptoms.

20 Article Evolution of impulsive-compulsive behaviors and cognition in Parkinson's disease. 2020

Erga, Aleksander H / Alves, Guido / Tysnes, Ole Bjørn / Pedersen, Kenn Freddy. ·The Norwegian Centre for Movement Disorders, Stavanger University Hospital, P.O. Box 8100, 4068, Stavanger, Norway. alkn@sus.no. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, P.O. Box 8100, 4068, Stavanger, Norway. · Department of Neurology, Stavanger University Hospital, Stavanger, Norway. · Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway. · Department of Clinical Medicine, University of Bergen, Bergen, Norway. · Department of Neurology, Haukeland University Hospital, Bergen, Norway. ·J Neurol · Pubmed #31628533.

ABSTRACT: The longitudinal course of ICBs in patients with Parkinson's disease (PwP) relative to controls has not been explored as of yet. The aim of this study is to determine the frequency, evolution and associated cognitive and clinical features of impulsive and compulsive behaviors (ICBs) over 4 years of prospective follow-up in a population-based cohort with early Parkinson's disease (PD). We recruited 124 cognitively intact participants with early PD and 156 matched controls from the Norwegian ParkWest study. ICBs were assessed using the self-report short form version of the Questionnaire for Impulsive-Compulsive Disorders in PD. Cognitive changes were examined in PwP with and without ICBs who completed the 4-year follow-up. Generalized linear mixed modelling and mixed linear regression were used to analyze clinical factors and cognitive changes associated with ICBs in PwP over time. ICBs were more common in PwP than controls at all visits, with an age-adjusted odds ratio (OR) varying between 2.5 (95% CI 1.1-5.6; p = 0.022) and 5.1 (95% CI 2.4-11.0; p < 0.001). The 4-year cumulative frequency of ICBs in PwP was 46.8% and 23.3% developed incident ICBs during the study period, but the presence of ICBs was non-persistent in nearly 30%. ICBs were independently associated with younger age (OR 0.95, 95% CI 0.91-0.99: p = 0.008) and use of dopamine agonist (OR 4.1, 95% CI 1.56-10.69). Cognitive changes over time did not differ between patients with and without ICBs. In conclusion, ICBs are common in PwP, but are often non-persistent and not associated with greater cognitive impairment over time.

21 Article Orthostatic hypotension in Parkinson disease: A 7-year prospective population-based study. 2019

Hiorth, Ylva Hivand / Pedersen, Kenn Freddy / Dalen, Ingvild / Tysnes, Ole-Bjørn / Alves, Guido. ·From the Department of Physical Medicine and Rehabilitation (Y.H.H.), The Norwegian Centre for Movement Disorders (Y.H.H., K.F.P., G.A.), Department of Neurology (K.F.P., G.A.), and Department of Research, Section of Biostatistics (I.D.), Stavanger University Hospital · Department of Clinical Medicine (O.-B.T.), University of Bergen · Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen · and Department of Chemistry, Bioscience and Environmental Engineering (G.A.), University of Stavanger, Norway. ·Neurology · Pubmed #31527282.

ABSTRACT: OBJECTIVE: To determine the frequency, evolution, and associated features of orthostatic hypotension (OH) over 7 years of prospective follow-up in a population-based, initially drug-naive Parkinson disease (PD) cohort. METHODS: We performed repeated lying and standing blood pressure measurements in 185 patients with newly diagnosed PD and 172 matched normal controls to determine the occurrence of (1) OH using consensus-based criteria and (2) clinically significant OH (mean arterial pressure in standing position ≤75 mm Hg). We applied generalized estimating equations models for correlated data to investigate associated features of these 2 outcomes in patients with PD. RESULTS: OH was more common in patients with PD than controls at all visits, with the relative risk increasing from 3.0 (95% confidence interval [CI] 1.6-5.8; CONCLUSIONS: In this population-based study, we found OH to be a very frequent but undertreated complication in early PD, with associations to both disease-specific symptoms and drug treatment. Our findings suggest that clinicians should more actively assess and manage OH abnormalities in PD.

22 Article Genomewide association study of Parkinson's disease clinical biomarkers in 12 longitudinal patients' cohorts. 2019

Iwaki, Hirotaka / Blauwendraat, Cornelis / Leonard, Hampton L / Kim, Jonggeol J / Liu, Ganqiang / Maple-Grødem, Jodi / Corvol, Jean-Christophe / Pihlstrøm, Lasse / van Nimwegen, Marlies / Hutten, Samantha J / Nguyen, Khanh-Dung H / Rick, Jacqueline / Eberly, Shirley / Faghri, Faraz / Auinger, Peggy / Scott, Kirsten M / Wijeyekoon, Ruwani / Van Deerlin, Vivianna M / Hernandez, Dena G / Gibbs, J Raphael / Anonymous20211124 / Chitrala, Kumaraswamy Naidu / Day-Williams, Aaron G / Brice, Alexis / Alves, Guido / Noyce, Alastair J / Tysnes, Ole-Bjørn / Evans, Jonathan R / Breen, David P / Estrada, Karol / Wegel, Claire E / Danjou, Fabrice / Simon, David K / Andreassen, Ole / Ravina, Bernard / Toft, Mathias / Heutink, Peter / Bloem, Bastiaan R / Weintraub, Daniel / Barker, Roger A / Williams-Gray, Caroline H / van de Warrenburg, Bart P / Van Hilten, Jacobus J / Scherzer, Clemens R / Singleton, Andrew B / Nalls, Mike A. ·Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA. · Data Tecnica International, Glen Echo, Maryland, USA. · School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China. · Advanced Center for Parkinson's Disease Research, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Precision Neurology Program, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · Department of Chemistry, Bioscience and Environmental Engineering, University in Stavanger, Stavanger, Norway. · Assistance-Publique Hôpitaux de Paris, ICM, INSERM UMRS 1127, CNRS 7225, ICM, Department of Neurology and CIC Neurosciences, Pitié-Salpêtrière Hospital, Paris, France. · Department of Neurology, Oslo University Hospital, Oslo, Norway. · Radboud University Medical Centre, Donders Institute for Brain, Cognition, and Behaviour; Department of Neurology, Nijmegen, The Netherlands. · The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA. · Translational Genome Sciences, Biogen, Cambridge, Massachusetts, USA. · Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York, USA. · Department of Computer Science, University of Illinois Urbana-Champaign, Champaign, Illinois, USA. · Department of Neurology, Center for Health + Technology, University of Rochester, Rochester, New York, USA. · Department of Clinical Neurosciences, University of Cambridge, John van Geest Centre for Brain Repair, Cambridge, United Kingdom. · Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Parelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA. · Flagship Labs 60 Inc, Cambridge, Massachusetts, USA. · Statistical Genetics, Biogen, Cambridge, Massachusetts, USA. · Institut du cerveau et de la moelle épinière ICM, Paris, France. · Sorbonne Université SU, Paris, France. · INSERM UMR1127, Paris, France. · Department of Neurology, Stavanger University Hospital, Stavanger, Norway. · Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom. · Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, United Kingdom. · Department of Neurology, Haukeland University Hospital, Bergen, Norway. · University of Bergen, Bergen, Norway. · Department of Neurology, Nottingham University NHS Trust, Nottingham, United Kingdom. · Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, Scotland. · Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, Scotland. · Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland. · Department of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana, USA. · Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. · Harvard Medical School, Boston, Massachusetts, USA. · NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway, Norway. · Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway, Norway. · Voyager Therapeutics, Cambridge, Massachusetts, USA. · Department of Neurology, University of Rochester School of Medicine, Rochester, New York, USA. · Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · German Center for Neurodegenerative Diseases-Tubingen, Tuebingen, Germany. · HIH Tuebingen, Tubingen, Tuebingen, Germany. · Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. · Department of Veterans Affairs, Philadelphia, Pennsylvania, USA. · Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom. · Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. ·Mov Disord · Pubmed #31505070.

ABSTRACT: BACKGROUND: Several reports have identified different patterns of Parkinson's disease progression in individuals carrying missense variants in GBA or LRRK2 genes. The overall contribution of genetic factors to the severity and progression of Parkinson's disease, however, has not been well studied. OBJECTIVES: To test the association between genetic variants and the clinical features of Parkinson's disease on a genomewide scale. METHODS: We accumulated individual data from 12 longitudinal cohorts in a total of 4093 patients with 22,307 observations for a median of 3.81 years. Genomewide associations were evaluated for 25 cross-sectional and longitudinal phenotypes. Specific variants of interest, including 90 recently identified disease-risk variants, were also investigated post hoc for candidate associations with these phenotypes. RESULTS: Two variants were genomewide significant. Rs382940(T>A), within the intron of SLC44A1, was associated with reaching Hoehn and Yahr stage 3 or higher faster (hazard ratio 2.04 [1.58-2.62]; P value = 3.46E-8). Rs61863020(G>A), an intergenic variant and expression quantitative trait loci for α-2A adrenergic receptor, was associated with a lower prevalence of insomnia at baseline (odds ratio 0.63 [0.52-0.75]; P value = 4.74E-8). In the targeted analysis, we found 9 associations between known Parkinson's risk variants and more severe motor/cognitive symptoms. Also, we replicated previous reports of GBA coding variants (rs2230288: p.E365K; rs75548401: p.T408M) being associated with greater motor and cognitive decline over time, and an APOE E4 tagging variant (rs429358) being associated with greater cognitive deficits in patients. CONCLUSIONS: We identified novel genetic factors associated with heterogeneity of Parkinson's disease. The results can be used for validation or hypothesis tests regarding Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.

23 Article Combinatory microRNA serum signatures as classifiers of Parkinson's disease. 2019

Patil, Ketan S / Basak, Indranil / Dalen, Ingvild / Hoedt, Esthelle / Lange, Johannes / Lunde, Kristin A / Liu, Ying / Tysnes, Ole-Bjørn / Forsgren, Lars / Aarsland, Dag / Neubert, Thomas A / Larsen, Jan Petter / Alves, Guido / Møller, Simon Geir. ·Department of Biological Sciences, St. John's University, New York, NY, USA
. · Norwegian Center for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · Kimmel Center for Biology and Medicine at the Skirball Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA. · Norwegian Center for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Norway. · Department of Computer Science, Mathematics and Science, St. John's University, New York, NY, USA. · Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Neurology, Haukeland University Hospital, Bergen, Norway. · Department of Pharmacology and Clinical Neuroscience, University of Umeå, Umeå, Sweden. · Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, UK; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway. · Network for Medical Sciences, University of Stavanger, Stavanger, Norway. · Department of Biological Sciences, St. John's University, New York, NY, USA
. Electronic address: mollers@stjohns.edu. ·Parkinsonism Relat Disord · Pubmed #31003905.

ABSTRACT: INTRODUCTION: As current clinical diagnostic protocols for Parkinson's disease (PD) may be prone to inaccuracies there is a need to identify and validate molecular biomarkers, such as circulating microRNAs, which will complement current practices and increase diagnostic accuracy. This study identifies, verifies and validates combinatory serum microRNA signatures as diagnostic classifiers of PD across different patient cohorts. METHODS: 370 PD (drug naïve) and control serum samples from the Norwegian ParkWest study were used for identification and verification of differential microRNA levels in PD which were validated in a blind study using 64 NY Parkinsonism in UMeå (NYPUM) study serum samples and tested for specificity in 48 Dementia Study of Western Norway (DemWest) study Alzheimer's disease (AD) serum samples using miRNA-microarrays, and quantitative (q) RT-PCR. Proteomic approaches identified potential molecular targets for these microRNAs. RESULTS: Using Affymetrix GeneChip CONCLUSIONS: Our study has identified and validated unique miRNA serum signatures that represent PD classifiers, which may complement and increase the accuracy of current diagnostic protocols.

24 Article Risk of Parkinson's disease dementia related to level I MDS PD-MCI. 2019

Hoogland, Jeroen / Boel, Judith A / de Bie, Rob M A / Schmand, Ben A / Geskus, Ronald B / Dalrymple-Alford, John C / Marras, Connie / Adler, Charles H / Weintraub, Daniel / Junque, Carmen / Pedersen, Kenn F / Mollenhauer, Brit / Goldman, Jennifer G / Tröster, Alexander I / Burn, David J / Litvan, Irene / Geurtsen, Gert J / Anonymous841024. ·Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands. · Department of Medical Psychology, Academic Medical Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. · Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam. · New Zealand Brain Research Institute, Brain Research New Zealand - Rangahau Roro Aotearoa, Christchurch, New Zealand. · Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Ontario, Canada. · Arizona Parkinson's Disease Consortium, Mayo Clinic Arizona, Scottsdale, Arizona, USA, and Banner Sun Health Research Institute, Sun City, Arizona, USA. · Departments of Psychiatry and Neurology, University of Pennsylvania School of Medicine, and Parkinson's Disease and Mental Illness Research, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA. · Department of Medicine, Faculty of Medicine, IDIBAPS, University of Barcelona, Barcelona, Spain. · The Norwegian Centre for Movement Disorders, Department of Neurology, and Memory Clinic, Stavanger University Hospital, Stavanger, Norway. · Department of Neurosurgery and Institute of Neuropathology, Paracelsus-Elena-Klinik, Kassel, Germany, and University Medical Center Goettingen, Goettingen, Germany. · Department of Neurological Sciences, Section of Parkinson Disease and Movement Disorders, Rush University Medical Center, Chicago, Illinois, USA. · Department of Clinical Neuropsychology and Center for Neuromodulation, Barrow Neurological Institute, Phoenix, Arizona, USA. · Institute of Neuroscience, Newcastle University, Upon Tyne, Newcastle, UK. · Department of Neurosciences University of California San Diego, Parkinson and Other Movement Disorder Center, San Diego, California, USA. ·Mov Disord · Pubmed #30653248.

ABSTRACT: BACKGROUND: The International Parkinson and Movement Disorders Society criteria for mild cognitive impairment in PD need validation. The objectives of this present study were to evaluate prognostic validity of level I (abbreviated) International Parkinson and Movement Disorders Society mild cognitive impairment in PD criteria for development of PD dementia and compared them with level II (comprehensive) criteria. METHODS: We analyzed data from 8 international studies (1045 patients) from our consortium that included baseline data on demographics, motor signs, depression, detailed neuropsychological testing, and longitudinal follow-up for conversion to Parkinson's disease dementia. Survival analysis evaluated their contribution to the hazard of Parkinson's disease dementia. RESULTS: Level I mild cognitive impairment in PD, increasing age, male sex, and severity of PD motor signs independently increased the hazard of Parkinson's disease dementia. Level I and level II mild cognitive impairment in PD classification had similar discriminative ability with respect to the time to Parkinson's disease dementia. CONCLUSIONS: Level I mild cognitive impairment in PD classification independently contributes to the hazard of Parkinson's disease dementia. This finding supports the prognostic validity of the abbreviated mild cognitive impairment in PD criteria. © 2019 International Parkinson and Movement Disorder Society.

25 Article Excessive Daytime Sleepiness and REM Sleep Behavior Disorders in Parkinson's Disease: A Narrative Review on Early Intervention With Implications to Neuroprotection. 2018

Gjerstad, Michaela D / Alves, Guido / Maple-Grødem, Jodi. ·The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway. · Department of Neurology, Stavanger University Hospital, Stavanger, Norway. ·Front Neurol · Pubmed #30487775.

ABSTRACT: Sleep contributes to the consolidation of our memory and facilitates learning. Short term sleep deprivation temporarily reduces mnestic capacity, whereas long lasting sleep deprivation is associated with structural changes in the hippocampus and cortical areas. However, it is unknown whether early intervention and treatment of sleep disorders could have a neuroprotective effect. In neurodegenerative diseases sleep disorders can occur at preclinical stages and are frequently observed in patients with established Parkinson's disease (PD) and other α-synucleinopathies. REM sleep behavior disorder (RBD) is recognized as a hallmark for the development of α-synucleinopathies and may predict early cognitive decline, while excessive daytime sleepiness (EDS) is present in 12% of patients with PD before treatment initiation and increases continuously over time, causing substantial restrictions for the patients' social life. In more advanced disease, EDS is associated with dementia. Even though well recognized, limited attention has been given to genetics or the treatment of RBD and EDS in early PD. Systematic screening and early intervention can be expected to increase the patients' quality of life, but it remains unclear if this will also impact disease progression. Intervention studies in preclinical and early stages of α-synucleinopathies are needed to increase our understanding of the underlying pathomechanisms and may also provide important inroads to help clarify whether sleep disturbances are secondary to the neurodegenerative process or also contribute to disease exacerbation.

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