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      Neuropsychiatric symptoms and cognitive abilities over the initial quinquennium of Parkinson disease

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          Abstract

          Objective

          To determine the evolution of numerous neuropsychiatric symptoms and cognitive abilities in Parkinson disease from disease onset.

          Methods

          Prospectively collected, longitudinal (untreated, disease onset to year 5), observational data from Parkinson's Progression Markers Initiative annual visits was used to evaluate prevalence, correlates, and treatment of 10 neuropsychiatric symptoms and cognitive impairment in Parkinson disease participants and matched healthy controls.

          Results

          Of 423 Parkinson disease participants evaluated at baseline, 315 (74.5%) were assessed at year 5. Eight neuropsychiatric symptoms studied increased in absolute prevalence by 6.2–20.9% at year 5 relative to baseline, and cognitive impairment increased by 2.7–6.2%. In comparison, the frequency of neuropsychiatric symptoms in healthy controls remained stable or declined over time. Antidepressant and anxiolytic/hypnotic use in Parkinson disease were common at baseline and increased over time (18% to 27% for the former; 13% to 24% for the latter); antipsychotic and cognitive‐enhancing medication use was uncommon throughout (2% and 5% of patients at year 5); and potentially harmful anticholinergic medication use was common and increased over time. At year 5 the cross‐sectional prevalence for having three or more neuropsychiatric disorders/cognitive impairment was 56% for Parkinson disease participants versus 13% for healthy controls, and by then seven of the examined disorders had either occurred or been treated at some time point in the majority of Parkinson disease patients. Principal component analysis suggested an affective disorder subtype only.

          Interpretation

          Neuropsychiatric features in Parkinson disease are common from the onset, increase over time, are frequently comorbid, and fluctuate in severity.

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          Most cited references21

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          The MoCA: well-suited screen for cognitive impairment in Parkinson disease.

          To establish the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) when screening externally validated cognition in Parkinson disease (PD), by comparison with a PD-focused test (Scales for Outcomes in Parkinson disease-Cognition [SCOPA-COG]) and the standardized Mini-Mental State Examination (S-MMSE) as benchmarks. A convenience sample of 114 patients with idiopathic PD and 47 healthy controls was examined in a movement disorders center. The 21 patients with dementia (PD-D) were diagnosed using Movement Disorders Society criteria, externally validated by detailed independent functional and neuropsychological tests. The 21 patients with mild cognitive impairment (PD-MCI) scored 1.5 SD or more below normative data in at least 2 measures in 1 of 4 cognitive domains. Other patients had normal cognition (PD-N). Primary outcomes using receiver operating characteristic (ROC) curve analyses showed that all 3 mental status tests produced excellent discrimination of PD-D from patients without dementia (area under the curve [AUC], 87%-91%) and PD-MCI from PD-N patients (AUC, 78%-90%), but the MoCA was generally better suited across both assessments. The optimal MoCA screening cutoffs were <21/30 for PD-D (sensitivity 81%; specificity 95%; negative predictive value [NPV] 92%) and <26/30 for PD-MCI (sensitivity 90%; specificity 75%; NPV 95%). Further support that the MoCA is at least equivalent to the SCOPA-COG, and superior to the S-MMSE, came from the simultaneous classification of the 3 PD patient groups (volumes under a 3-dimensional ROC surface, chance = 17%: MoCA 79%, confidence interval [CI] 70%-89%; SCOPA-COG 74%, CI 62%-86%; MMSE-Sevens item 56%, CI 44%-68%; MMSE-World item 62%, CI 50%-73%). The MoCA is a suitably accurate, brief test when screening all levels of cognition in PD.
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            Update on treatments for nonmotor symptoms of Parkinson's disease—an evidence‐based medicine review

            ABSTRACT Objective To update evidence‐based medicine recommendations for treating nonmotor symptoms in Parkinson's disease (PD). Background The International Parkinson and Movement Disorder Society Evidence‐Based Medicine Committee's recommendations for treatments of PD were first published in 2002, updated in 2011, and now updated again through December 31, 2016. Methods Level I studies testing pharmacological, surgical, or nonpharmacological interventions for the treatment of nonmotor symptoms in PD were reviewed. Criteria for inclusion and quality scoring were as previously reported. The disorders covered were a range of neuropsychiatric symptoms, autonomic dysfunction, disorders of sleep and wakefulness, pain, fatigue, impaired olfaction, and ophthalmologic dysfunction. Clinical efficacy, implications for clinical practice, and safety conclusions are reported. Results A total of 37 new studies qualified for review. There were no randomized controlled trials that met inclusion criteria for the treatment of anxiety disorders, rapid eye movement sleep behavior disorder, excessive sweating, impaired olfaction, or ophthalmologic dysfunction. We identified clinically useful or possibly useful interventions for the treatment of depression, apathy, impulse control and related disorders, dementia, psychosis, insomnia, daytime sleepiness, drooling, orthostatic hypotension, gastrointestinal dysfunction, urinary dysfunction, erectile dysfunction, fatigue, and pain. There were no clinically useful interventions identified to treat non‐dementia‐level cognitive impairment. Conclusions The evidence base for treating a range of nonmotor symptoms in PD has grown substantially in recent years. However, treatment options overall remain limited given the high prevalence and adverse impact of these disorders, so the development and testing of new treatments for nonmotor symptoms in PD remains a top priority. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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              The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort.

              Cognitive abnormalities are common in Parkinson's disease, with important social and economic implications. Factors influencing their evolution remain unclear but are crucial to the development of targeted therapeutic strategies. We have investigated the development of cognitive impairment and dementia in Parkinson's disease using a longitudinal approach in a population-representative incident cohort (CamPaIGN study, n = 126) and here present the 5-year follow-up data from this study. Our previous work has implicated two genetic factors in the development of cognitive dysfunction in Parkinson's disease, namely the genes for catechol-O-methyltransferase (COMT Val(158)Met) and microtubule-associated protein tau (MAPT) H1/H2. Here, we have explored the influence of these genes in our incident cohort and an additional cross-sectional prevalent cohort (n = 386), and investigated the effect of MAPT H1/H2 haplotypes on tau transcription in post-mortem brain samples from patients with Lewy body disease and controls. Seventeen percent of incident patients developed dementia over 5 years [incidence 38.7 (23.9-59.3) per 1000 person-years]. We have demonstrated that three baseline measures, namely, age >or=72 years, semantic fluency less than 20 words in 90 s and inability to copy an intersecting pentagons figure, are significant predictors of dementia risk, thus validating our previous findings. In combination, these factors had an odds ratio of 88 for dementia within the first 5 years from diagnosis and may reflect the syndrome of mild cognitive impairment of Parkinson's disease. Phonemic fluency and other frontally based tasks were not associated with dementia risk. MAPT H1/H1 genotype was an independent predictor of dementia risk (odds ratio = 12.1) and the H1 versus H2 haplotype was associated with a 20% increase in transcription of 4-repeat tau in Lewy body disease brains. In contrast, COMT genotype had no effect on dementia, but a significant impact on Tower of London performance, a frontostriatally based executive task, which was dynamic, such that the ability to solve this task changed with disease progression. Hence, we have identified three highly informative predictors of dementia in Parkinson's disease, which can be easily translated into the clinic, and established that MAPT H1/H1 genotype is an important risk factor with functional effects on tau transcription. Our work suggests that the dementing process in Parkinson's disease is predictable and related to tau while frontal-executive dysfunction evolves independently with a more dopaminergic basis and better prognosis.
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                Author and article information

                Contributors
                daniel.weintraub@pennmedicine.upenn.edu
                Journal
                Ann Clin Transl Neurol
                Ann Clin Transl Neurol
                10.1002/(ISSN)2328-9503
                ACN3
                Annals of Clinical and Translational Neurology
                John Wiley and Sons Inc. (Hoboken )
                2328-9503
                13 April 2020
                April 2020
                : 7
                : 4 ( doiID: 10.1002/acn3.v7.4 )
                : 449-461
                Affiliations
                [ 1 ] Department of Psychiatry Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania
                [ 2 ] Department of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania
                [ 3 ] Parkinson’s Disease Research, Education and Clinical Center Philadelphia Veterans Affairs Medical Center Philadelphia Pennsylvania
                [ 4 ] Department of Biostatistics College of Public Health University of Iowa Iowa City Iowa
                [ 5 ] Feinberg School of Medicine Northwestern University Chicago Illinois
                [ 6 ] Institute of Psychiatry, Psychology and Neuroscience King’s College London London England
                [ 7 ] Department of Neurology Columbia University Vagelos College of Physicians and Surgeons New York New York
                [ 8 ] Department of Neurology Virginia Commonwealth University Richmond Virginia
                [ 9 ] Department of Neurology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania
                [ 10 ] Michael J. Fox Foundation for Parkinson’s Research New York New York
                [ 11 ] Department of Neurology University of Cincinnati Academic Health Center Cincinnati Ohio
                [ 12 ] Department of Psychiatry Yale School of Medicine New Haven Connecticut
                [ 13 ] Lou Ruvo Center for Brain Health Cleveland Clinic Cleveland Ohio
                [ 14 ] UCSD Movement Disorder Center Department of Neurosciences University of California San Diego San Diego California
                [ 15 ] Departments of Neurology and Psychiatry School of Medicine and Dentistry University of Rochester Rochester New York
                [ 16 ] Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland
                [ 17 ] Departments of Neurology and Psychiatry & Behavioral Sciences Baylor College of Medicine Houston Texas
                Author notes
                [*] [* ] Correspondence

                Daniel Weintraub, Perelman School of Medicine at the University of Pennsylvania, 3615 Chestnut St., #330, Philadelphia, PA 19014. Tel: +1 (215) 349‐8207; Fax: +1 (215) 349‐8389; E‐mail: daniel.weintraub@ 123456pennmedicine.upenn.edu

                [*]

                See PPMI author list at http://www.ppmi-info.org/authorslist/

                Author information
                https://orcid.org/0000-0003-0633-7168
                https://orcid.org/0000-0002-5717-4875
                Article
                ACN351022
                10.1002/acn3.51022
                7187707
                32285645
                31699b2d-f40e-47b1-8b50-2336e49a5e45
                © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 31 January 2020
                : 21 February 2020
                : 24 February 2020
                Page count
                Figures: 3, Tables: 5, Pages: 13, Words: 8121
                Funding
                Funded by: Michael J. Fox Foundation for Parkinson's Research , open-funder-registry 10.13039/100000864;
                This work was funded by Michael J. Fox Foundation for Parkinson's Research , open-funder-registry 10.13039/100000864; grant .
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                April 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.1 mode:remove_FC converted:28.04.2020

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