Background: To investigate the effect of creatine and coenzyme Q10 (CoQ10) combination therapy on mild cognitive impairment (MCI) in Parkinson's disease (PD; PD-MCI) and its influences on plasma phospholipid (PL) levels in PD-MCI. Methods: The demographic data of 75 PD-MCI patients who enrolled in this collaborative PD study were collected. These patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) III and the Montreal Cognitive Assessment (MoCA). These 75 PD-MCI patients were randomly treated with creatine monohydrate 5 g b.i.d. and CoQ10 100 mg t.i.d. orally or placebo. MoCA evaluation and PL level measurements were performed after 12 and 18 months of treatment. Results: After 12 and 18 months of treatment, the differences in the MoCA scores of the combination therapy and control groups were statistically significant (p < 0.05 at 12 months and p < 0.01 at 18 months), and the plasma PL levels of the combination therapy group were significantly lower than those of the control group (p < 0.01 at 12 months and p < 0.001 at 18 months). Conclusions: Combination therapy with creatine and CoQ10 could delay the decline of cognitive function in PD-MCI patients and could lower their plasma PL levels; therefore, this combination therapy may have a neuroprotective function.

Kones R: Mitochondrial therapy for Parkinson's disease: neuroprotective pharmaconutrition may be disease-modifying. Clin Pharmacol 2010;2:185-198.
Yang L, Calingasan NY, Wille EJ, Cormier K, Smith K, Ferrante RJ, Beal MF: Combination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson's and Huntington's diseases. J Neurochem 2009;109:1427-1439.
Litvan I, Goldman JG, Tröster AI, et al: Diagnostic criteria for mild cognitive impairment in Parkinson's disease: movement disorder society task force guidelines. Mov Disord 2012;27:349-356.
Parashos SA, Luo S, Biglan KM, Bodis-Wollner I, He B, Liang GS, Ross GW, Tilley BC, Shulman LM: Measuring disease progression in early Parkinson disease: the national institutes of health exploratory trials in Parkinson disease (NET-PD) experience. JAMA Neurol 2014;71:710-716.
Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H: The montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005;53:695-699.
Memória CM, Yassuda MS, Nakano EY, Forlenza OV: Brief screening for mild cognitive impairment: validation of the Brazilian version of the montreal cognitive assessment. Int J Geriatr Psychiatry 2013;28:34-40.
Hu MT, Szewczyk-Królikowski K, Tomlinson P, Nithi K, Rolinski M, Murray C, Talbot K, Ebmeier KP, Mackay CE, Ben-Shlomo Y: Predictors of cognitive impairment in an early stage Parkinson's disease cohort. Mov Disord 2014;29:351-359.
Ng A, Chew I, Narasimhalu K, Kandiah N: Effectiveness of montreal cognitive assessment for the diagnosis of mild cognitive impairment and mild Alzheimer's disease in Singapore. Singapore Med J 2013;54:616-619.
Zhou S, Zhu J, Zhang N, Wang B, Li T, Lv X, Ng TP, Yu X, Wang H: The influence of education on Chinese version of montreal cognitive assessment in detecting amnesic mild cognitive impairment among older people in a Beijing rural community. ScientificWorldJournal 2014;2014:689456.
Goldman JG, Litvan I: Mild cognitive impairment in Parkinson's disease. Minerva Med 2011;102:441-459.
Jellinger K: Heterogenous mechanisms of mild cognitive impairment in Parkinson's disease. J Neural Transm 2012;119:381-382.
Dolder M, Walzel B, Speer O, Schlattner U, Wallimann T: Inhibition of the mitochondrial permeability transition by creatine kinase substrates. Requirement for microcompartmentation. J Biol Chem 2003;278:17760-17766.
Beal MF: Neuroprotective effects of creatine. Amino Acids 2011;40:1305-1313.
Prass K, Royl G, Lindauer U, Freyer D, Megow D, Dirnagl U, Stockler-Ipsiroglu G, Wallimann T, Priller J: Improved reperfusion and neuroprotection by creatine in a mouse model of stroke. J Cereb Blood Flow Metab 2007;27:452-459.
Couzin J: Clinical research. Testing a novel strategy against Parkinson's disease. Science 2007;315:1778.
Matthews RT, Ferrante RJ, Klivenyi P, Yang L, Klein AM, Mueller G, Kaddurah-Daouk R, Beal MF: Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol 1999;157:142-149.
Bender A, Koch W, Elstner M, Schombacher Y, Bender J, Moeschl M, Gekeler F, Müller-Myhsok B, Gasser T, Tatsch K, Klopstock T: Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial. Neurology 2006;67:1262-1264.
NINDS NET-PD Investigators: A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology 2006;66:664-671.
Elm JJ; NINDS NET-PD Investigators: Design innovations and baseline findings in a long-term Parkinson's trial: the national institute of neurological disorders and stroke exploratory trials in Parkinson's disease long-term study-1. Mov Disord 2012;27:1513-1521.
Lewis SJ, Shine JM, Duffy S, Halliday G, Naismith SL: Anterior cingulate integrity: executive and neuropsychiatric features in Parkinson's disease. Mov Disord 2012;27:1262-1267.
Levin BE, Katzen HL, Maudsley A, Post J, Myerson C, Govind V, Nahab F, Scanlon B, Mittel A: Whole-brain proton MR spectroscopic imaging in Parkinson's disease. J Neuroimaging 2014;24:39-44.
Turunen M, Olsson J, Dallner G: Metabolism and function of coenzyme Q. Biochim Biophys Acta 2004;1660:171-199.
Sutachan JJ, Casas Z, Albarracin SL, Stab BR 2nd, Samudio I, Gonzalez J, Morales L, Barreto GE: Cellular and molecular mechanisms of antioxidants in Parkinson's disease. Nutr Neurosci 2012;15:120-126.
Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M; Parkinson Study Group: Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 2002;59:1541-1550.
Snow BJ, Rolfe FL, Lockhart MM, Frampton CM, O'Sullivan JD, Fung V, Smith RA, Murphy MP, Taylor KM; Protect Study Group: A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease. Mov Disord 2010;25:1670-1674.
Effects of Coenzyme Q10 (CoQ) in Parkinson Disease (QE3).
Parkinson Study Group QE3 Investigators, Beal MF, et al: A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol 2014;71:543-552.
Kosicek M, Hecimovic S: Phospholipids and Alzheimer's disease: alterations, mechanisms and potential biomarkers. Int J Mol Sci 2013;14:1310-1322.
Orsucci D, Mancuso M, Ienco EC, LoGerfo A, Siciliano G: Targeting mitochondrial dysfunction and neurodegeneration by means of coenzyme Q10 and its analogues. Curr Med Chem 2011;18:4053-4064.
Cleren C, Yang L, Lorenzo B, Calingasan NY, Schomer A, Sireci A, Wille EJ, Beal MF: Therapeutic effects of coenzyme Q10 (CoQ10) and reduced CoQ10 in the MPTP model of Parkinsonism. J Neurochem 2008;104:1613-1621.
Seidl SE, Potashkin JA: The promise of neuroprotective agents in Parkinson's disease. Front Neurol 2011;2:68.
Kones R: Parkinson's disease: mitochondrial molecular pathology, inflammation, statins, and therapeutic neuroprotective nutrition. Nutr Clin Pract 2010;25:371-389.
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.