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A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial for Efficacy of Acetyl-L-carnitine in Patients with Dementia Associated with Cerebrovascular Disease

  • Yang, YoungSoon (Department of Neurology, Veteran Health Service Medical Center) ;
  • Choi, Hojin (Department of Neurology, Hanyang University Guri Hospital) ;
  • Lee, Chan-Nyoung (Department of Neurology, Korea University College of Medicine) ;
  • Kim, Yong Bum (Department of Neurology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Kwak, Yong Tae (Department of Neurology, Hyoja Geriatric Hospital)
  • Received : 2018.03.10
  • Accepted : 2018.03.15
  • Published : 2018.03.31

Abstract

Background and Purpose: Acetyl-L-carnitine (ALC) is a widely used drug for various neurodegenerative diseases including dementia. The aim of the present study was to elucidate the efficacy of ALC in dementia patients with cerebrovascular disease (vascular cognitive impairment; VCI). Methods: Fifty-six patients were randomized to treatment with 500 mg ter in die ALC, or placebo in this 28-week, double-blind, placebo-controlled trial. The primary outcome measure was the Korean version of Montreal Cognitive Assessment (MoCA-K). Results: Following treatment with ALC, the cognitive function measured by the MoCA-K was significantly improved in the ALC-treated groups. However, other secondary outcomes were not statistically significant between ALC- and placebo-treated groups. In MoCA-K analysis, attention and language sub-items significantly favored the ALC-treated group. Conclusions: Compared with placebo, treatment with ALC 1,500 mg/day produced significant changes in MoCA-K in dementia patients with VCI. ALC was well tolerated in this population. Despite the study limitations, the findings suggested the potential benefits associated with the use of ALC in dementia patients with VCI.

Keywords

Acknowledgement

Supported by : Hanmi Pharmaceutical Co., Ltd.

References

  1. O'Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, et al. Vascular cognitive impairment. Lancet Neurol 2003;2:89-98. https://doi.org/10.1016/S1474-4422(03)00305-3
  2. Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:2672-2713. https://doi.org/10.1161/STR.0b013e3182299496
  3. Barker WW, Luis CA, Kashuba A, Luis M, Harwood DG, Loewenstein D, et al. Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank. Alzheimer Dis Assoc Disord 2002;16:203-212. https://doi.org/10.1097/00002093-200210000-00001
  4. Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 2007;69:2197-2204. https://doi.org/10.1212/01.wnl.0000271090.28148.24
  5. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study(MRC CFAS). Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Lancet 2001;357:169-175. https://doi.org/10.1016/S0140-6736(00)03589-3
  6. Skoog I, Kalaria RN, Breteler MM. Vascular factors and Alzheimer disease. Alzheimer Dis Assoc Disord 1999;13 Suppl 3:S106-S114.
  7. Kalaria RN, Ballard C. Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord 1999;13 Suppl 3:S115-S123.
  8. Jellinger KA. The pathology of "vascular dementia": a critical update. J Alzheimers Dis 2008;14:107-123. https://doi.org/10.3233/JAD-2008-14110
  9. Kavirajan H, Schneider LS. Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials. Lancet Neurol 2007;6:782-792. https://doi.org/10.1016/S1474-4422(07)70195-3
  10. Kumaran D, Udayabanu M, Kumar M, Aneja R, Katyal A. Involvement of angiotensin converting enzyme in cerebral hypoperfusion induced anterograde memory impairment and cholinergic dysfunction in rats. Neuroscience 2008;155:626-639. https://doi.org/10.1016/j.neuroscience.2008.06.023
  11. Pettegrew JW, Levine J, McClure RJ. Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression. Mol Psychiatry 2000;5:616-632. https://doi.org/10.1038/sj.mp.4000805
  12. Ghelardini C, Galeotti N, Bartolini A. Amitriptyline and clomipramine activate Gi-protein signaling pathway in the induction of analgesia. Naunyn Schmiedebergs Arch Pharmacol 2002;365:1-7.
  13. Imperato A, Ramacci MT, Angelucci L. Acetyl-L-carnitine enhances acetylcholine release in the striatum and hippocampus of awake freely moving rats. Neurosci Lett 1989;107:251-255. https://doi.org/10.1016/0304-3940(89)90826-4
  14. Moghaddas A, Dashti-Khavidaki S. L-carnitine and potential protective effects against ischemiareperfusion injury in noncardiac organs: from experimental data to potential clinical applications. J Diet Suppl 2017:1-17.
  15. Sano M, Bell K, Cote L, Dooneief G, Lawton A, Legler L, et al. Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease. Arch Neurol 1992;49:1137-1141. https://doi.org/10.1001/archneur.1992.00530350051019
  16. Hudson S, Tabet N. Acetyl-L-carnitine for dementia. Cochrane Database Syst Rev 2003:CD003158.
  17. World Medical Association declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997;277:925-926. https://doi.org/10.1001/jama.1997.03540350075038
  18. Lee JY, Lee DW, Cho SJ, Na DL, Jeon HJ, Kim SK, et al. Brief screening for mild cognitive impairment in elderly outpatient clinic: validation of the Korean version of the Montreal Cognitive Assessment. J Geriatr Psychiatry Neurol 2008;21:104-110. https://doi.org/10.1177/0891988708316855
  19. Onofrj M. Evaluation of efficacy of chronic administration (6 months) of acetyl-l-carnitine in patients suffering from Senile Dementia Alzheimer Type (SDAT) and Alzheimer Disease (AD) statistical report, study protocol no.: ST20032189 (DRN4-021), on file Sigma-Tau (unpublished data). Pomezia: Sigma-Tau; 1992.
  20. Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomised controlled clinical trials acetyl-lcarnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Int Clin Psychopharmacol 2003;18:61-71. https://doi.org/10.1097/00004850-200303000-00001
  21. Puca FM, Genco S, Specchio LM, Brancasi B, D'Ursi R, Prudenzano A, et al. Clinical pharmacodynamics of acetyl-L-carnitine in patients with Parkinson's disease. Int J Clin Pharmacol Res 1990;10:139-143.
  22. Malaguarnera M. Acetyl-L-carnitine in hepatic encephalopathy. Metab Brain Dis 2013;28:193-199. https://doi.org/10.1007/s11011-013-9376-4
  23. Koski L. Validity and applications of the Montreal cognitive assessment for the assessment of vascular cognitive impairment. Cerebrovasc Dis 2013;36:6-18. https://doi.org/10.1159/000352051
  24. Gill DP, Hubbard RA, Koepsell TD, Borrie MJ, Petrella RJ, Knopman DS, et al. Differences in rate of functional decline across three dementia types. Alzheimers Dement 2013;9:S63-S71. https://doi.org/10.1016/j.jalz.2012.10.010
  25. Scacchi R, Gambina G, Broggio E, Corbo RM. Sex and ESR1 genotype may influence the response to treatment with donepezil and rivastigmine in patients with Alzheimer's disease. Int J Geriatr Psychiatry 2014;29:610-615. https://doi.org/10.1002/gps.4043

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