Citicoline in the treatment of cognitive impairment in first-degree relatives of AD patients: the influence of the ApoE genotype

Close metadata

OBJECTIVE

To study the effects of a three-month course of therapy with citicoline, aimed at preventing the progression of cognitive deficit in 1st-degree relatives of patients with Alzheimer’s disease (AD), depending on the carriage of the ApoE4(+) genotype.

MATERIAL AND METHODS

Study participants: 82 blood relatives of AD patients, 66 of them with signs of minimal cognitive dysfunction (group 1) objectively confirmed by clinical neuropsychological examination and 16 people with mild cognitive decline syndrome (group 2). Open comparative multidisciplinary study of the dynamics of cognitive status in relatives of AD patients who received a three-month course of citicoline therapy. The baseline indicators of the cognitive functioning of the relatives of the two groups were compared with the indicators at the end of the three-month course of therapy with citicoline in a daily dose of 1000 mg, depending on whether the treated persons had genotypes ApoE4(+) or ApoE4(–). Clinical-psychopathological, neuropsychological, psychometric, molecular-genetic, statistical.

RESULTS

An association of the ApoE4(–) genotype with a significantly more pronounced positive effect of the course therapy with citicoline was established according to the general clinical impression (CGI-I scale), indicators of cognitive functioning (MMSE and MoCA scales), as well as according to most psychometric tests (with the exception of the number repetition test in reverse order), as well as for almost all indicators of the neuropsychological «express method» (excluding the parameter of the volume of visual memory).

CONCLUSION

The results of course therapy with citicoline showed a negative effect of the carriage of the ε4 allele of the ApoE gene on the efficiency of treatment of blood relatives of AD patients who had signs of cognitive decline before the start of therapy, which did not reach the level of dementia. The obtained data can serve as the basis for the development of preventive therapeutic measures aimed at preventing the progression of cognitive deficit and the development of dementia in the group at high risk of developing dementia — in 1st degree relatives of AD patients, especially in carriers of the ApoE4(+) genotype.

Keywords:

1st-degree relatives of AD patients

minimal cognitive dysfunction

mild cognitive decline syndrome

ApoE genotype

prevention

citicolinine

Authors:

Selezneva N.D.

Mental Health Research Centre

Gavrilova S.I.

Mental Health Research Centre

SPIN RSCI: 6094-4303
Scopus AuthorID: 7004829216
ResearcherID: B-4548-2016
ORCID: 0000-0001-6683-0240

Roshchina I.F.

Mental Health Research Center;
Moscow State University of Psychology and Education

Ponomareva E.V.

Mental Health Research Center

Received:

18.07.2021

Accepted:

14.09.2021

List of references:

Rogaev EI, Korovajceva GI, Grigorenko AP, et al. Molecular basis of Alzheimer’s disease. In the book: Alzheimer’s disease and aging. Materials of the III Russian conference. Ed. Gavrilova S.I. M.: Pulse; 2003. (In Russ.).
Saunders AM, Strittmatter WJ, Schmechel D, George-Hyslop PH, Pericak-Vance MA, Joo SH, Rosi BL, Gusella JF, Crapper-Maclachlan DR, Alberts MJ, et al. Association of apolipiprotein E allele epsilon 4 with late onset familial and sporadic Alzheimer’s disease. Neurology. 1993;43:1467-1472.
Rebeck GW, Reiter JS, Strickland K, Hyman BT. Apolipiprotein E in sporadic Alzheimer’s disease: allelic variation and receptor interaction. Neuron. 1993;11:575-580. https://doi.org/10.1016/0896-6273(93)90070-8
Farrer LA. Genetics and the dementia patient. Neurologist. 1997;3:13-30.
Korovaytseva GI, Chipped TV, Selezneva ND, Gavrilova SI, Golimbet VE, Voskresenskaya NI, Rogayev EI. Genetic association between alleles of a gene of E (APOE) apolipoprotein and various forms of Alzheimer’s disease. Genetics. 2001;37(4):529-533. (In Russ.).
Roses AD. Apolipiprotein E genotyping in the differential diagnosis, not prediction, of Alzheimer’s disease. Ann Neurol. 1995;38:6-14. https://doi.org/10.1002/ana.410380105
Corbo RM, Scacchi R. Apolipiprotein E (APOE) allele distribution in the world. Is APOE*4 a «thrifly» allele? Ann Hum Genet. 1999;63:301-310.
St. George-Hislop PH. Molecular genetics of Alzheimer’s disease. Biol Psyhiatry. 2000;47:183-199.
Voevoda MI, Stepanov VA, Romashchenko AG, Maksimov V.N. Etogenetic features of susceptibility to atherosclerosis in ethnic groups of Siberia (on the example of the gene for apolipoprotein E). Bulletin of the SB RAMS. 2006;2(120):63-72. (In Russ.).
Caselli RJ, Reiman EM, Osborne D, Hentz JG, Baxter LC, Hernandez JL, Alexander GG. Longitudinal changes In cognition and behavior in asymptomatic carriers of the APOE e4 allele. Neurology. 2004;62:1990-1995. https://doi.org/10.1212/01.wnl.0000129533.26544.bf
Levy JA, Bergeson J, Putnam K, Rosen V. Context-specific memory and apolipoprotein E (APOE) epsilon 4: cognitive evidence from the NIMH prospective study of risk for Alzheimer’s disease. J Int Neuropsychol Soc. 2004;10:362-370. https://doi.org/10.1017/s1355617704103044
Sager MA, Hermann B, La Rue A. Middle-aged children of persons with Alzheimer’s disease: APOE genotypes and cognitive function in the Wisconsin Registry for Alzheimer’s Prevention. J Geriatr Psychiatry Neurol. 2005;18(4):245-249. https://doi.org/10.1177/0891988705281882
Velichkovskiy BM, Borinskaya SA, Vartanov AV, Velichkovskiy BB, Gavrilova SI, Prohorchuk EB, Rogaev EI, Roshchina IF, Selezneva ND. Neurocognitive features of apolipoprotein e (APOE) ε4 allele carriers. Theoretical and Experimental Psychology. 2009;2(4):25-37. (In Russ.).
Roshchina IF, Velichkovsky BB, Selezneva ND, Chudina YuA, Melikyan ZA. Plasticity of cognitive functions in carriers of the e4 allele of the alipoprotein E gene. Psychiatry. 2009;4(6):58-66. (In Russ.).
Roshchina IF, Velichkovsky BB, Selezneva ND, Gavrilova SI, Chudina YuA, Melikyan ZA. Cognitive control and memory in healthy APOE-e4 carriers with a family history of Alzheimer’s disease. Traditions and Innovations in Psychiatry WPA Regional Meeting Materials, June 10—12, 2010, St Petersburg, Russia. P. 103—104.
Rao AM, Hatcher JF, Dempsey RJ. Does CDP-choline modulate phospholipase activities after transient forebrain ischemia? Brain Res. 2001;893:268-272. https://doi.org/10.1016/S0006-8993(00)03280-7
Adibhatla RM, Hatcher JF. Citicoline decreases phospholipase A2 stimulation and hydroxyl radical generation in transient cerebral ischemia. J Neurosci Res. 2003;73:308-315. https://doi.org/10.1002/jnr.10672
Zhuravin IA, Nalivaeva NN, Kozlova DI, Kochkina EG, Fedorova YaB, Gavrilova SI. Plasma cholinesterase and neprilysin activity as potential biomarkers of mild cognitive decline syndrome and Alzheimer’s disease. Zhurnal Nevrologii i Psihiatrii im. S.S. Korsakova. 2015;115(12):110-117. (In Russ.). https://doi.org/10.17116/jnevro2015115112110-117
Gavrilova SI, Fedorova YaB, Gantman MV, Kalyn YaB, Kolykhalov IV. Ceraxon (Citicoline) in the treatment of mild cognitive decline syndrome. Zhurnal Nevrologii i Psihiatrii im. S.S. Korsakova. 2011;111(12):16-20. (In Russ.).
Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG., Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56:303-308. https://doi.org/10.1001/archneur.56.3.303
Korsakova NK, Balashova EYu, Roshchina IF. Express-method for assessing cognitive functions in normal aging. Zhurnal Nevrologii i Psihiatrii im. S.S. Korsakova. 2009;2:44-50. (In Russ.).
Lingjaerde O, Ahlfors UG, Bech P, Dencker SJ, Elgen K. The UKU Side Effect Rating Scale. Comprehensive Rating Scale for Psychotropic Drugs and a Cross-Sectional Study of Side Effects in Neuroleptic-Treated Patients. Acta Psychiatr Scand Suppl. 1987;334:1-100. https://doi.org/10.1111/j.1600-0447.1987.tb10566.x
Malashenkova IK, Krynskiy SA, Mamoshina MV, Didkovskiy NA. APOE gene polymorphism: the impact of APOE 4 allele on systemic inflammation and its role in the pathogenesis of Alzheimer’s disease. Medical Immunology (Russia). 2018;20(3):30-312. (In Russ.). https://doi.org/10.15789/1563-0625-2018-3-303-312
Selezneva ND, Gavrilova SI, Ponomareva EV. Efficacy and Safety of Citicoline to Prevent Cognitive Deficiency Progression in First-Degree Relatives of Patients with Alzheimer’s Disease: Prospective Study. Psychiatry. 2020;18(4):33-40. (In Russ.). https://doi.org/10.30629/2618-6667-2020-18-4-33-40

Close metadata