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Parkinson Disease: HELP
Articles by Dag Aarsland
Based on 106 articles published since 2010
(Why 106 articles?)
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Between 2010 and 2020, D. Aarsland wrote the following 106 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Editorial Novel evidence associates higher plasma α-synuclein levels and cognitive impairment in Parkinson's disease. 2017

Aarsland, Dag / Rajkumar, Anto P / Hye, Abdul. ·Department of Old Age Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. · Mental Health of Older Adults and Dementia Clinical Academic Group, South London and Maudsley NHS Foundation Trust, London, UK. · NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation trust, London, UK. ·J Neurol Neurosurg Psychiatry · Pubmed #28607120.

ABSTRACT: -- No abstract --

2 Editorial Many roads lead to Parkinson's disease. 2013

Ravina, Bernard / Aarsland, Dag. · ·Mov Disord · Pubmed #23348828.

ABSTRACT: -- No abstract --

3 Editorial Using biomarkers to disentangle different causes of Parkinsonism. 2013

Aarsland, Dag / Svenningsson, Per. · ·J Neurol Neurosurg Psychiatry · Pubmed #22949480.

ABSTRACT: -- No abstract --

4 Editorial Developing predictive biomarkers for dementia of Parkinson's disease. 2011

Caviness, John N / Aarsland, Dag. · ·Expert Rev Neurother · Pubmed #22091589.

ABSTRACT: -- No abstract --

5 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.

6 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.

7 Review Risk factors for non-motor symptoms in Parkinson's disease. 2018

Marinus, Johan / Zhu, Kangdi / Marras, Connie / Aarsland, Dag / van Hilten, Jacobus J. ·Department of Neurology, Leiden University Medical Center, Leiden, Netherlands. Electronic address: j.marinus@lumc.nl. · Department of Neurology, Leiden University Medical Center, Leiden, Netherlands. · The Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's Research, University Health Network, University of Toronto, Toronto, ON, Canada. · Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Centre for Age-Related Medicine, Stavanger University, Stavanger, Norway. ·Lancet Neurol · Pubmed #29699914.

ABSTRACT: Non-motor symptoms (NMS) of Parkinson's disease can be predominant as the disease advances, thereby constituting a major source of disease burden for patients and caregivers. However, current understanding of NMS is incomplete, particularly as a result of the absence of standardisation of outcome definitions and the heterogeneity of the risk factors that are assessed. The best data on risk factors for NMS in Parkinson's disease come from longitudinal studies, with the strongest evidence identifying factors for cognitive impairment and dementia, hallucinations, depression, apathy, excessive daytime sleepiness, insomnia, and impulse-control disorders. Cognitive impairment, hallucinations, and depression have several common risk factors, and many other NMS share a few risk factors, showing the interdependence between NMS with advancing Parkinson's disease. Disease severity, sex, age, and antiparkinsonian medication might have roles in the development of different NMS, although only antiparkinsonian medication is potentially modifiable. Until disease-modifying therapies are developed, increased knowledge of risk factors could ameliorate early identification of patients who are at an increased risk of developing specific NMS and potentially allow improvement of symptom management or prevention of specific NMS.

8 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.

9 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.

10 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.

11 Review Glucocerebrosidase mutations and neuropsychiatric phenotypes in Parkinson's disease and Lewy body dementias: Review and meta-analyses. 2018

Creese, Byron / Bell, Emily / Johar, Iskandar / Francis, Paul / Ballard, Clive / Aarsland, Dag. ·University of Exeter Medical School, University of Exeter, Exeter, UK. · Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. · Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. ·Am J Med Genet B Neuropsychiatr Genet · Pubmed #28548708.

ABSTRACT: Heterozygous mutations in glucocerebrosidase gene (GBA) are a major genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recently, there has been a considerable focus on the relationship between GBA mutations and emergence of cognitive impairment and neuropsychiatric symptoms in these diseases. Here, we review the literature in this area, with a particular focus, including meta-analysis, on the key neuropsychiatric symptoms of cognitive impairment, psychosis, and depression in Parkinson's disease. Our meta-analysis demonstrated that GBA mutations are associated with a 2.4-fold increased risk of cognitive impairment. In addition, our novel meta-analyses of psychosis and depression showed a 1.8- and 2.2-fold increased risk respectively associated with GBA mutations, although due to possible bias and heterogeneity the depression findings should be interpreted with caution. While the precise mechanisms which increase susceptibility to neurodegeneration in GBA carriers are not known, evidence of greater cortical Lewy body pathology, reduced patterns of cortical activation, and hippocampal pathology in animal models are all consistent with a direct effect of GBA mutations on these symptoms. Extension of this work in DLB and individuals without neurodegeneration will be important in further characterizing how GBA mutations increase risk for PD and DLB and influence disease course.

12 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.

13 Review New Therapeutic Strategies for Lewy Body Dementias. 2017

Velayudhan, Latha / Ffytche, Dominic / Ballard, Clive / Aarsland, Dag. ·Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neurosciences, Kings College London, Box PO 70, De Crespigny Park, London, SE5 8AF, UK. · University of Exeter Medical School, Exeter, UK. · Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neurosciences, Kings College London, Box PO 70, De Crespigny Park, London, SE5 8AF, UK. Dag.Aarsland@kcl.ac.uk. ·Curr Neurol Neurosci Rep · Pubmed #28741230.

ABSTRACT: This article reviews current treatment strategies and recent advances for the Lewy body dementias (LBDs). Current available symptom treatment strategies are based on monoaminergic, cholinergic and glutaminergic neurotransmitter systems. Relatively robust evidence exists for cholinesterase inhibitors for cognitive impairment in LBD and in Parkinson's disease for antidepressants, clozapine and recently pimavanserin for psychosis. interpidine (RVT 101) and nelotanserin are currently under investigation. Non-pharmacological interventions, such as cognitive stimulation, physical exercises and neuromodulation strategies, may be useful in Parkinson's disease but have not yet been tested in dementias. Disease-modifying approaches are aimed at preventing, slowing or ameliorating the production, aggregation and deposition of pathological proteins, including immunotherapy targeting α-synuclein and an ongoing trial using ambroxol which increases glucocerebrosidase activity to lower the levels of the protein alpha-synuclein. Other disease-modifying clinical trials are using agents to augment insulin signalling, stem cell therapy, reducing amyloid pathology and gene therapy.

14 Review Cerebrospinal Fluid Biomarkers of Cognitive Decline in Parkinson's Disease. 2017

Johar, Iskandar / Mollenhauer, Brit / Aarsland, Dag. ·Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. · Paracelsus-Elena-Klinik, Kassel, Germany; University Medical Center, Göttingen, Germany. · Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. Electronic address: dag.aarsland@kcl.ac.uk. ·Int Rev Neurobiol · Pubmed #28554411.

ABSTRACT: Among the nonmotor symptoms in Parkinson's disease (PD), cognitive impairment is one of the most common and devastating. Over recent years, mild cognitive impairment (MCI) has become a recognized feature of PD (PD-MCI). The underlying mechanisms which influence onset, rate of decline, and conversion to dementia (PDD) are largely unknown. Adding to this uncertainty is the heterogeneity of cognitive domains affected. Currently there are no disease-modifying treatments that can slow or reverse this process. Identification of biomarkers that can predict rate and risk of cognitive decline is therefore an unmet need. Cerebrospinal fluid (CSF) is an ideal biomarker candidate as its constituents reflect the metabolic processes underlying the functioning of brain parenchyma. The pathological hallmark of PD is the presence of aggregated α-synuclein (α-Syn) in intracellular Lewy inclusions. In addition, there is concomitant Alzheimer's disease (AD) pathology. In AD, decreased CSF β-amyloid 1-42 (Aβ42) and increased CSF tau levels are predictive of future cognitive decline, setting a precedent for such studies to be carried out in PD. CSF studies in PD have focused on the classical AD biomarkers and α-Syn. Longitudinal studies indicate that low levels of CSF Aβ42 are predictive of cognitive decline; however, results for tau and α-Syn were not consistent. This chapter summarizes recent findings of CSF biomarker studies and cognitive dysfunction in PD.

15 Review Cognitive decline in Parkinson disease. 2017

Aarsland, Dag / Creese, Byron / Politis, Marios / Chaudhuri, K Ray / Ffytche, Dominic H / Weintraub, Daniel / Ballard, Clive. ·KCL-PARCOG group, Institute of Psychiatry, Psychology &Neuroscience, King's College London, De Crespigny Park, London SE5 8AF, UK. · Department of Old Age Psychiatry, Institute of Psychiatry, Psychology &Neuroscience, King's College London, De Crespigny Park, London SE5 8AF, UK. · University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK. · Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology &Neuroscience, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK. · Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, National Parkinson Foundation Centre of Excellence, King's College London/Kings College Hospital, 5 Cutcombe Road, London SE5 9RT, UK. · Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania 3615 Chestnut Street, #330, Philadelphia, Pennsylvania 19104, USA. · Parkinson's Disease and Mental Illness Research, Education and Clinical Centres (PADRECC and MIRECC), Philadelphia Veterans Affairs Medical Centre 3900 Woodland Avenue, Philadelphia, Pennsylvania 19104, USA. ·Nat Rev Neurol · Pubmed #28257128.

ABSTRACT: Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition - or even reversal to normal cognition - is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β

16 Review The psychosis spectrum in Parkinson disease. 2017

Ffytche, Dominic H / Creese, Byron / Politis, Marios / Chaudhuri, K Ray / Weintraub, Daniel / Ballard, Clive / Aarsland, Dag. ·KCL-PARCOG group, Institute of Psychiatry, Psychology &Neuroscience, King's College London, De Crespigny Park, London SE5 8AF, UK. · Department of Old Age Psychiatry, Institute of Psychiatry, Psychology &Neuroscience, King's College London, UK. De Crespigny Park, London SE5 8AF, UK. · University of Exeter Medical School, University of Exeter, EX1 2LU, UK. · Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology &Neuroscience, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK. · Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, National Parkinson Foundation Centre of Excellence, King's College London/Kings College Hospital, 5 Cutcombe Road, London SE5 9RT, UK. · Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania 3615 Chestnut Street, #330, Philadelphia, Pennsylvania 19104, USA. · Parkinson's Disease and Mental Illness Research, Education and Clinical Centres (PADRECC and MIRECC), Philadelphia Veterans Affairs Medical Centre 3900 Woodland Avenue, Philadelphia, Pennsylvania 19104, USA. ·Nat Rev Neurol · Pubmed #28106066.

ABSTRACT: In 2007, the clinical and research profile of illusions, hallucinations, delusions and related symptoms in Parkinson disease (PD) was raised with the publication of a consensus definition of PD psychosis. Symptoms that were previously deemed benign and clinically insignificant were incorporated into a continuum of severity, leading to the rapid expansion of literature focusing on clinical aspects, mechanisms and treatment. Here, we review this literature and the evolving view of PD psychosis. Key topics include the prospective risk of dementia in individuals with PD psychosis, and the causal and modifying effects of PD medication. We discuss recent developments, including recognition of an increase in the prevalence of psychosis with disease duration, addition of new visual symptoms to the psychosis continuum, and identification of frontal executive, visual perceptual and memory dysfunction at different disease stages. In addition, we highlight novel risk factors - for example, autonomic dysfunction - that have emerged from prospective studies, structural MRI evidence of frontal, parietal, occipital and hippocampal involvement, and approval of pimavanserin for the treatment of PD psychosis. The accumulating evidence raises novel questions and directions for future research to explore the clinical management and biomarker potential of PD psychosis.

17 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.

18 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.

19 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.

20 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.

21 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.

22 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.

23 Review Neuropsychiatric symptoms in patients with dementias associated with cortical Lewy bodies: pathophysiology, clinical features, and pharmacological management. 2013

Ballard, Clive / Aarsland, Dag / Francis, Paul / Corbett, Anne. ·Wolfson Centre for Age-Related Diseases, King's College London, Wolfson Building, Guy's Campus, London, SE1 1UL, UK. clive.ballard@kcl.ac.uk ·Drugs Aging · Pubmed #23681401.

ABSTRACT: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are synucleinopathies that lead to neurodegeneration and dementia. Although they result in symptoms common to Alzheimer's disease, they are associated with early emergence of parkinsonism and high frequency of neuropsychiatric symptoms, most commonly hallucinations and delusions. This review summarizes the current understanding of the underlying biology of neuropsychiatric symptoms in DLB and PDD and the evidence base for treatment to address them. Disruption to cholinergic and serotonergic neurotransmission and synapse activity are highlighted as primary pathological factors in neuropsychiatric symptoms, particularly loss of key neurotransmitter functions, alterations to neuronal receptors in the serotonergic pathway, and regionally specific structural changes that are linked to specific symptoms. Review of options for pharmacological treatment of neuropsychiatric symptoms suggests that the best evidence for the value of treatment is for cholinesterase inhibitors, with an indication that people with visual hallucinations are particularly likely to benefit. Evidence for the benefits of antipsychotics other than clozapine is limited, and there are serious safety concerns about the use of antipsychotics in these patients. Evidence to support other pharmacological interventions is very preliminary. Nonpharmacological approaches based on person-centered care and cholinesterase inhibitors should be considered as the first-line treatment for neuropsychiatric symptoms except in extreme cases.

24 Review Cognitive impairment in patients with Parkinson's disease: diagnosis, biomarkers, and treatment. 2012

Svenningsson, Per / Westman, Eric / Ballard, Clive / Aarsland, Dag. ·Centre for Molecular Medicine, Department of Neurology and Clinical Neuroscience, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. ·Lancet Neurol · Pubmed #22814541.

ABSTRACT: Dementia is one of the most common and important aspects of Parkinson's disease and has consequences for patients and caregivers, and has health-related costs. Mild cognitive impairment is also common and frequently progresses to dementia. The underlying mechanisms of dementia associated with Parkinson's disease are only partly known and no mechanism-based treatments are available. Both dysmetabolism of α-synuclein and amyloid-protein and cholinergic deficits contribute to cognitive impairment in Parkinson's disease, and preliminary findings show that imaging and neurophysiological and peripheral biomarkers could be useful in diagnosis and prognosis. Rivastigmine is the only licensed treatment for dementia in Parkinson's disease, but emerging evidence suggests that memantine might also be useful. Whether these or other treatments can delay the progression from mild cognitive impairment to dementia in Parkinson's disease is a key research question.

25 Review Identifying prodromal Parkinson's disease: pre-motor disorders in Parkinson's disease. 2012

Postuma, Ronald B / Aarsland, Dag / Barone, Paolo / Burn, David J / Hawkes, Christopher H / Oertel, Wolfgang / Ziemssen, Tjalf. ·Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada. ronald.postuma@mcgill.ca ·Mov Disord · Pubmed #22508280.

ABSTRACT: Increasing recognition that Parkinson's disease (PD) may start outside of the substantia nigra has led to a rapidly expanding effort to define prodromal stages of PD, before motor signs permit classical diagnosis. Many of these efforts center around the identification of clinical non-motor symptoms and signs of disease. There is now direct evidence that olfaction, rapid eye movement (REM) sleep behavior disorder (RBD), constipation, and depression can be present in prodromal PD. In addition, there is suggestive evidence that visual changes, other autonomic symptoms, and subtle cognitive changes may also be present at prodromal stages. A critical issue in utility of these prodromal markers will be assessment of sensitivity, specificity, and positive and negative predictive values. Although these have yet to be fully defined, olfactory deficits, some visual changes, and autonomic symptoms occur in the majority of PD patients at diagnosis, suggesting good potential sensitivity. However, with the exception of RBD and perhaps some specific autonomic measures, specificity, and positive predictive value of these markers may be insufficient to be used alone as identifiers of prodromal disease. The evidence for the utility of olfaction, RBD, autonomic markers, visual changes, mood disorders, and cognitive loss as markers of prodromal PD and the potential sensitivity and specificity of these markers are summarized.

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