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      Rivastigmine in the Treatment of Dementia Associated with Parkinson’s Disease: Effects on Activities of Daily Living

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          Abstract

          Aims: To investigate the effects of rivastigmine capsule 3–12 mg/day over 24 weeks on activities of daily living (ADLs) in patients with dementia associated with Parkinson’s disease (PDD). Methods: Post hocanalysis of a prospective, multicenter, randomized, double-blind, placebo-controlled trial in patients with PDD (≧50 years) randomized to rivastigmine 3–12 mg/day (capsules bid) or placebo over 24 weeks. This analysis was carried out with three subscales derived from a factor analysis of the 23 items in the Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) scale. These subscales were basic ADLs (10 items), high-level function ADLs (eight items) and autonomy ADLs (five items). Results: 541 patients were randomized (362 to rivastigmine, 179 to placebo) and 410 (75.8%) completed the study. Rivastigmine was associated with significantly better outcomes in basic ADLs (–0.5 ± 6.19 vs. –1.7 ± 5.46; p = 0.025; effect size 22.1%) and high-level function ADLs (0.1 ± 4.95 vs. –1.0 ± 4.49; p = 0.017; effect size 22.9%) compared with placebo, at week 24. Conclusion: In patients with PDD, treatment with rivastigmine may show beneficial effects on overall ADLs, as well as modest, statistically significant improvements in basic ADLs and high-level function ADLs.

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          Stages in the development of Parkinson's disease-related pathology.

          The synucleinopathy, idiopathic Parkinson's disease, is a multisystem disorder that involves only a few predisposed nerve cell types in specific regions of the human nervous system. The intracerebral formation of abnormal proteinaceous Lewy bodies and Lewy neurites begins at defined induction sites and advances in a topographically predictable sequence. As the disease progresses, components of the autonomic, limbic, and somatomotor systems become particularly badly damaged. During presymptomatic stages 1-2, inclusion body pathology is confined to the medulla oblongata/pontine tegmentum and olfactory bulb/anterior olfactory nucleus. In stages 3-4, the substantia nigra and other nuclear grays of the midbrain and forebrain become the focus of initially slight and, then, severe pathological changes. At this point, most individuals probably cross the threshold to the symptomatic phase of the illness. In the end-stages 5-6, the process enters the mature neocortex, and the disease manifests itself in all of its clinical dimensions.
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            Prevalence and Characteristics of Dementia in Parkinson Disease

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              Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study.

              Pathology reports have shown that cholinergic forebrain neuronal losses in parkinsonian dementia (PDem) are equal to or greater than those in Alzheimer disease (AD). We hypothesized that patients with PDem would have cholinergic deficits that were similar to or greater than those of patients with AD. To determine in vivo cortical acetylcholinesterase (AChE) activity in healthy control subjects and in patients with mild AD, PDem, and Parkinson disease without dementia using AChE positron emission tomography. University and Veterans' Administration medical center. Design and Patients Group comparison design of patients with AD (n = 12), PDem (n = 14), and Parkinson disease without dementia (n = 11), and controls (n = 10) who underwent AChE imaging between July 1, 2000, and January 31, 2003. Patients with AD and PDem had approximately equal dementia severity. Cerebral AChE activity. Compared with controls, mean cortical AChE activity was lowest in patients with PDem (-20.0%), followed by patients with Parkinson disease without dementia (-12.9%; P<.001). Mean cortical AChE activity was relatively preserved in patients with AD (-9.1%), except for regionally selective involvement of the lateral temporal cortex (-15%; P<.001). Reduced cortical AChE activity is more characteristic of patients with PDem than of patients with mild AD.
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                Author and article information

                Journal
                DEM
                Dement Geriatr Cogn Disord
                10.1159/issn.1420-8008
                Dementia and Geriatric Cognitive Disorders
                S. Karger AG
                1420-8008
                1421-9824
                2010
                July 2010
                05 June 2010
                : 29
                : 6
                : 510-515
                Affiliations
                aNovartis Pharmaceuticals Corporation, East Hanover, N.J., USA; bStavanger University Hospital, Stavanger, Norway
                Author notes
                *Dag Aarsland, Stavanger University Hospital, Arm Hansen, NO–4068 Stavanger (Norway), Tel. +47 51 51 50 62, Fax +47 51 51 55 15, E-Mail daarsland@gmail.com
                Article
                305100 Dement Geriatr Cogn Disord 2010;29:510–515
                10.1159/000305100
                20523050
                302cf00f-5d15-4051-95bd-a703511fb118
                © 2010 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 19 March 2010
                Page count
                Figures: 1, Tables: 1, References: 32, Pages: 6
                Categories
                Original Research Article

                Geriatric medicine,Neurology,Cardiovascular Medicine,Neurosciences,Clinical Psychology & Psychiatry,Public health
                Parkinson’s disease,Rivastigmine,Activities of daily living

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