Login Register Cart 0
Generic placeholder image

Reviews on Recent Clinical Trials

Editor-in-Chief

ISSN (Print): 1574-8871
ISSN (Online): 1876-1038

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Letter Article

An Overview of Combination Treatment with Citicoline in Dementia

Author(s): Pietro Gareri*, Nicola Veronese and Antonino Maria Cotroneo

Volume 17, Issue 1, 2022

Published on: 10 March, 2022

Page: [4 - 8] Pages: 5

DOI: 10.2174/1574887117666211221170344

Price: $65

conference banner
Abstract

Introduction: The present article reports an overview of the studies about combination treatment with citicoline of Alzheimer’s (AD) and mixed dementia (MD).

Methods: A Medline search was carried out by using the keywords Alzheimer’s dementia, mixed dementia, older people, treatment with citicoline, memantine, and acetylcholinesterase inhibitors (AchEIs).

Results: Six studies were found to match the combination treatment of citicoline with AcheIs and/or memantine. The CITIRIVAD and CITICHOLINAGE studies were the first to report the potential benefits of adding citicoline to acetylcholinesterase inhibitors (AchEIs). Then, we added citicoline to memantine in the CITIMEM study, and finally, we demonstrated benefits in terms of delay in cognitive worsening with the triple therapy (citicoline + AchEIs + memantine). Other authors also reinforced our hypothesis through two further studies.

Conclusion: Open, prospective studies are advised to confirm the utility of combination therapy with citicoline for the treatment of AD and MD.

Keywords: Citicoline, cognitive impairment, Alzheimer’s dementia, mixed dementia, older people, combination therapy.

« Previous
[1]
Jasielski P, Piędel F, Piwek M, Rocka A, Petit V, Rejdak K. Application of citicoline in neurological disorders: A Systematic Review. Nutrients 2020; 12(10): 1-20.
[http://dx.doi.org/10.3390/nu12103113] [PMID: 33053828]
[2]
Secades JJ. Citicoline in the treatment of cognitive impairment. J Neurol Exp Neurosci 2019; 5(1): 14-26.
[http://dx.doi.org/10.17756/jnen.2019-047]
[3]
Alvarez-Sabín J, Santamarina E, Maisterra O, Jacas C, Molina C, Quintana M. Long-Term treatment with citicoline prevents cognitive decline and predicts a better quality of life after a first ischemic stroke. Int J Mol Sci 2016; 17(3): 390.
[http://dx.doi.org/10.3390/ijms17030390] [PMID: 26999113]
[4]
Secades JJ, Lorenzo JL. Citicoline: pharmacological and clinical review, 2006 update. Methods Find Exp Clin Pharmacol 2006; 28(Suppl. B): 1-56.
[PMID: 17171187]
[5]
Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database Syst Rev 2005; 18(2): CD000269.
[http://dx.doi.org/10.1002/14651858.CD000269.pub3] [PMID: 15846601]
[6]
D’Orlando KJ, Sandage BW Jr. Citicoline (CDP-choline): Mechanisms of action and effects in ischemic brain injury. Neurol Res 1995; 17(4): 281-4.
[http://dx.doi.org/10.1080/01616412.1995.11740327] [PMID: 7477743]
[7]
Grieb P. Neuroprotective properties of citicoline: Facts, doubts and unresolved issues. CNS Drugs 2014; 28(3): 185-93.
[http://dx.doi.org/10.1007/s40263-014-0144-8] [PMID: 24504829]
[8]
Cotroneo AM, Castagna A, Putignano S, et al. Effectiveness and safety of citicoline in mild vascular cognitive impairment: The IDEALE study. Clin Interv Aging 2013; 8: 131-7.
[PMID: 23403474]
[9]
Castagna A, Cotroneo AM, Ruotolo G, Gareri P. The CITIRIVAD Study: CITIcoline plus RIVAstigmine in elderly patients affected with dementia study. Clin Drug Investig 2016; 36(12): 1059-65.
[http://dx.doi.org/10.1007/s40261-016-0454-3] [PMID: 27587069]
[10]
Gareri P, Castagna A, Cotroneo AM, et al. The Citicholinage study: Citicoline plus cholinesterase inhibitors in aged patients affected with Alzheimer’s disease Study. J Alzheimers Dis 2017; 56(2): 557-65.
[http://dx.doi.org/10.3233/JAD-160808] [PMID: 28035929]
[11]
Gareri P, Cotroneo AM, Orsitto G, Putignano S. The CITIMEM study: A pilot study. Optimizing pharmacological treatment in dementia. Arch Gerontol Geriatr 2020; 89: 104073.
[http://dx.doi.org/10.1016/j.archger.2020.104073] [PMID: 32447126]
[12]
Gareri P, Cotroneo AM, Orsitto G, Putignano S. The CITIDEMAGE study: Stressing the cholinergic hypothesis for the best outcomes in dementia patients. Alzheimer’s Dement 2020; 16(Suppl.9): e038178.
[http://dx.doi.org/10.1002/alz.038178]
[13]
Castagna A, Manzo C, Fabbo A, Lacava R, Ruberto C, Ruotolo G. Correction to: The CITIMERIVA study: CITIcoline plus MEmantine plus RIVAstigmine in older patients affected with Alzheimer’s disease. Clin Drug Investig 2021; 41(4): 413.
[http://dx.doi.org/10.1007/s40261-021-01015-8] [PMID: 33638864]
[14]
Castagna A, Fabbo A, Manzo C, Lacava R, Ruberto C, Ruotolo G. A retrospective study on the benefits of combined citicoline, memantine, and acetylcholinesterase inhibitor treatments in older patients affected with Alzheimer’s disease. J Alzheimers Dis 2021; 79(4): 1509-15.
[http://dx.doi.org/10.3233/JAD-201211] [PMID: 33459645]
[15]
Cacabelos R, Alvarez XA, Franco-Maside A, Fernández-Novoa L, Caamaño J. Effect of CDP-choline on cognition and immune function in Alzheimer’s disease and multi-infarct dementia. Ann N Y Acad Sci 1993; 695: 321-3.
[http://dx.doi.org/10.1111/j.1749-6632.1993.tb23076.x] [PMID: 8239305]
[16]
Cook S. The unique benefits of Citicoline: An emerging nootropic and brain health nutrient Natural Medicine Journal. IMPACT Health Media, Inc. 2018.
[17]
Secades JJ, Frontera G. CDP-choline: pharmacological and clinical review. Methods Find Exp Clin Pharmacol 1995; 17(Suppl. B): 1-54.
[PMID: 8709678]
[18]
Hurtado O, Lizasoain I, Moro MÁ. Neuroprotection and recovery: Recent data at the bench on citicoline. Stroke 2011; 42(1)(Suppl.): S33-5.
[http://dx.doi.org/10.1161/STROKEAHA.110.597435] [PMID: 21164125]
[19]
Hurtado O, Moro MA, Cárdenas A, et al. Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: Effects on glutamate transport. Neurobiol Dis 2005; 18(2): 336-45.
[http://dx.doi.org/10.1016/j.nbd.2004.10.006] [PMID: 15686962]
[20]
Cacabelos R, Caamaño J, Gómez MJ, Fernández-Novoa L, Franco-Maside A, Alvarez XA. Therapeutic effects of CDP-choline in Alzheimer’s disease. Cognition, brain mapping, cerebrovascular hemodynamics, and immune factors. Ann N Y Acad Sci 1996; 777: 399-403.
[http://dx.doi.org/10.1111/j.1749-6632.1996.tb34452.x] [PMID: 8624120]
[21]
Gutiérrez-Fernández M, Rodríguez-Frutos B, Fuentes B, et al. CDP-choline treatment induces brain plasticity markers expression in experimental animal stroke. Neurochem Int 2012; 60(3): 310-7.
[http://dx.doi.org/10.1016/j.neuint.2011.12.015] [PMID: 22226841]
[22]
García-Cobos R, Frank-García A, Gutiérrez-Fernández M, EDíez-Tejedor E. Citicoline, use in cognitive decline: Vascular and degenerative. J Neurol Sci 2010; 15, 299(1-2): 188-92.
[http://dx.doi.org/10.1016/j.jns.2010.08.027] [PMID: 20875651]
[23]
Krupinski J, Abudawood M, Matou-Nasri S, et al. Citicoline induces angiogenesis improving survival of vascular/human brain microvessel endothelial cells through pathways involving ERK1/2 and insulin receptor substrate-1. Vasc Cell 2012; 4(1): 20.
[http://dx.doi.org/10.1186/2045-824X-4-20] [PMID: 23227823]
[24]
Krupinski J, Slevin M, Badimon L. Citicoline inhibits MAP kinase signalling pathways after focal cerebral ischaemia. Neurochem Res 2005; 30(8): 1067-73.
[http://dx.doi.org/10.1007/s11064-005-7201-0] [PMID: 16258856]
[25]
Zafonte RD, Bagiella E, Ansel BM, et al. Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT). JAMA 2012; 308(19): 1993-2000.
[http://dx.doi.org/10.1001/jama.2012.13256] [PMID: 23168823]
[26]
Secades JJ. Role of Citicoline in the management of traumatic brain injury. Pharmaceuticals (Basel) 2021; 14(5): 410.
[http://dx.doi.org/10.3390/ph14050410] [PMID: 33926011]
[27]
Putignano S, Gareri P, Castagna A, et al. Retrospective and observational study to assess the efficacy of citicoline in elderly patients suffering from stupor related to complex geriatric syndrome. Clin Interv Aging 2012; 7: 113-8.
[http://dx.doi.org/10.2147/CIA.S29366] [PMID: 22654511]
[28]
Alvarez-Sabín J, Román GC. Citicoline in vascular cognitive impairment and vascular dementia after stroke. Stroke 2011; 42(1 Suppl.): S40-3.
[http://dx.doi.org/10.1161/STROKEAHA.110.606509] [PMID: 21164117]
[29]
Alvarez-Sabín J, Ortega G, Jacas C, et al. Long-term treatment with citicoline may improve poststroke vascular cognitive impairment. Cerebrovasc Dis 2013; 35(2): 146-54.
[http://dx.doi.org/10.1159/000346602] [PMID: 23406981]
[30]
Lozano Fernández R. Efficacy and safety of oral CDP-choline. Drug surveillance study in 2817 cases. Arzneimittelforschung 1983; 33(7A): 1073-80.
[PMID: 6684470]
[31]
Zhang F, Wang S, Gan L, et al. Protective effects and mechanisms of sirtuins in the nervous system. Prog Neurobiol 2011; 95(3): 373-95.
[http://dx.doi.org/10.1016/j.pneurobio.2011.09.001] [PMID: 21930182]
[32]
Donmez G. The neurobiology of sirtuins and their role in neurodegeneration. Trends Pharmacol Sci 2012; 33(9): 494-501.
[http://dx.doi.org/10.1016/j.tips.2012.05.007] [PMID: 22749331]
[33]
Donmez G, Arun A, Chung CY, McLean PJ, Lindquist S, Guarente L. SIRT1 protects against α-synuclein aggregation by activating molecular chaperones. J Neurosci 2012; 32(1): 124-32.
[http://dx.doi.org/10.1523/JNEUROSCI.3442-11.2012] [PMID: 22219275]
[34]
Donmez G, Wang D, Cohen DE, Guarente L. SIRT1 suppresses beta-amyloid production by activating the alpha-secretase gene ADAM10. Cell 2010; 142(2): 320-32.
[http://dx.doi.org/10.1016/j.cell.2010.06.020] [PMID: 20655472]
[35]
Adibhatla RM, Hatcher JF, Dempsey RJ. Effects of citicoline on phospholipid and glutathione levels in transient cerebral ischemia. Stroke 2001; 32(10): 2376-81.
[http://dx.doi.org/10.1161/hs1001.096010] [PMID: 11588329]
[36]
Gareri P, Castagna A, Cotroneo AM, Putignano S, De Sarro G, Bruni AC. The role of citicoline in cognitive impairment: Pharmacological characteristics, possible advantages, and doubts for an old drug with new perspectives. Clin Interv Aging 2015; 10: 1421-9.
[http://dx.doi.org/10.2147/CIA.S87886] [PMID: 26366063]
[37]
Synoradzki K, Grieb P. Citicoline: A superior form of choline? Nutrients 2019; 11(7): 1569.
[http://dx.doi.org/10.3390/nu11071569] [PMID: 31336819]
[38]
Zhuravin IA, Nalivaeva NN, Kozlova DI, et al. The activity of blood serum cholinesterases and neprilysin as potential biomarkers of mild-cognitive impairment and Alzheimer’s disease. Zh Nevrol Psikhiatr 2015; 11: 77-85.
[http://dx.doi.org/10.17116/jnevro2015115112110-117]
[39]
Alvarez XA, Mouzo R, Pichel V, et al. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer’s disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. Methods Find Exp Clin Pharmacol 1999; 21(9): 633-44.
[PMID: 10669911]
[40]
Pardossi-Piquard R, Dunys J, Yu G, St George-Hyslop P, Alves da Costa C, Checler F. Neprilysin activity and expression are controlled by nicastrin. J Neurochem 2006; 97(4): 1052-6.
[http://dx.doi.org/10.1111/j.1471-4159.2006.03822.x] [PMID: 16606360]

Rights & Permissions Print Cite
Article Metrics
41
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy