The relevance of creating a new combination drug for the treatment of cognitive disorders
DOI:
https://doi.org/10.14739/2409-2932.2025.2.316091Keywords:
cognitive functions, cognitive disorders, combination drug, sodium succinate, dimethylaminoethanolAbstract
Cognitive impairment is one of the most pressing problems of modern medicine, as its prevalence is steadily increasing worldwide. This trend is due to several global factors, including population aging, urbanization, the spread of chronic diseases, as well as the impact of the COVID-19 pandemic. Stress and social factors play a special role in the growth of cognitive disorders, which in recent years have significantly increased their impact on the population. In Ukraine, the problem of cognitive disorders has become even more acute due to socio-economic challenges and the consequences of the military aggression of the Russian Federation. Constant stress, loss of loved ones, forced displacement and a general sense of danger significantly affect cognitive functions, such as memory, concentration and planning ability. Understanding the basic mechanisms of the development of cognitive disorders is key to developing effective therapeutic approaches. Current research demonstrates that key pathogenetic factors include neurodegeneration, vascular disorders, metabolic dysfunction, and the effects of chronic stress. This emphasizes the need to develop new combination drugs that could comprehensively affect several pathogenetic links.
Aim. Analysis and systematization of current data on the mechanisms of development of cognitive disorders, as well as determination, based on the results of the analysis, of the most promising directions for the development of new drugs aimed at restoring and supporting cognitive functions.
Materials and methods. Data from sources of professional literature presented in international bibliographic databases (Web of Science, Scopus, PubMed, Chemical Abstracts) were used as the object of research. Methods of system analysis and information search were used. In the process of work, a bibliosemantic approach was used to analyze the relationship between key topics and research areas, as well as descriptive and generalized analysis methods to form conclusions about the current state and promising directions for the development of drugs for the treatment of cognitive disorders.
Results. Trend analysis showed a significant increase in cases of cognitive disorders both in the world and in Ukraine, which is associated with global factors of population aging, stress factors and neurodegenerative diseases. In Ukraine, this problem is exacerbated by socio-economic conditions and the consequences of armed aggression. Key mechanisms of cognitive disorders have been established, including neurodegeneration, vascular disorders and metabolic dysfunction. Based on these data, the prospects for the development of a new combined drug containing sodium succinate and dimethylaminoethanol for an effective impact on pathogenetic mechanisms, improving neuroprotection and supporting cognitive functions have been determined.
Conclusions. The review of current scientific literature devoted to the study of the causes of cognitive disorders reflects the current state of research in this area. A few scientific works emphasize the importance of finding more effective approaches to restoring cognitive functions, which emphasizes the high potential for the development of new therapeutic agents. This proves the promise of creating combination drugs that could affect several key mechanisms contributing to the development of cognitive disorders.
References
Ceban F, Ling S, Lui LM, Lee Y, Gill H, Teopiz KM, et al. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun. 2022;101:93-135. doi: https://doi.org/10.1016/j.bbi.2021.12.020
Tavares-Júnior JW, de Souza AC, Borges JW, Oliveira DN, Siqueira-Neto JI, Sobreira-Neto MA, et al. COVID-19 associated cognitive impairment: A systematic review. Cortex. 2022;152:77-97. doi: https://doi.org/10.1016/j.cortex.2022.04.006
Oros MM. [The effect of war on people. Psyche and character changes under war conditions]. Ukrainskyi medychnyi chasopys. 2023;0(2):3-7. Ukrainian. doi: https://doi.org/10.32471/umj.1680-3051.154.241952
Shydelko A. [Consequences of the combat stress influence on the serviceman psychological state]. Perspektyvy ta innovatsii nauky. 2022;0(1):476-86. Ukrainian. doi: https://doi.org/10.52058/2786-4952-2022-1(6)-476-486
Azam S, Haque ME, Balakrishnan R, Kim IS, Choi DK. The Ageing Brain: Molecular and Cellular Basis of Neurodegeneration. Front Cell Dev Biol. 2021;9:683459. doi: https://doi.org/10.3389/fcell.2021.683459
Poejo J, Salazar J, Mata AM, Gutierrez-Merino C. The Relevance of Amyloid β-Calmodulin Complexation in Neurons and Brain Degeneration in Alzheimer's Disease. Int J Mol Sci. 2021;22(9):4976. doi: https://doi.org/10.3390/ijms22094976
Tsering W, Prokop S. Neuritic Plaques - Gateways to Understanding Alzheimer's Disease. Mol Neurobiol. 2024;61(5):2808-21. doi: https://doi.org/10.1007/s12035-023-03736-7
Dronse J, Ohndorf A, Richter N, Bischof GN, Fassbender R, Behfar Q, et al. Serum cortisol is negatively related to hippocampal volume, brain structure, and memory performance in healthy aging and Alzheimer's disease. Front Aging Neurosci. 2023;15:1154112. doi: https://doi.org/10.3389/fnagi.2023.1154112
Song R, Xu H, Dintica CS, Pan KY, Qi X, Buchman AS, et al. Associations Between Cardiovascular Risk, Structural Brain Changes, and Cognitive Decline. J Am Coll Cardiol. 2020;75(20):2525-34. doi: https://doi.org/10.1016/j.jacc.2020.03.053
Zhang Y, Yang Y, Li H, Feng Q, Ge W, Xu X. Investigating the Potential Mechanisms and Therapeutic Targets of Inflammatory Cytokines in Post-stroke Depression. Mol Neurobiol. 2024;61(1):132-47. doi: https://doi.org/10.1007/s12035-023-03563-w
Zhang F, Ping Y, Jin X, Hou X, Song J. White matter hyperintensities and post-stroke depression: A systematic review and meta-analysis. J Affect Disord. 2023;320:370-80. doi: https://doi.org/10.1016/j.jad.2022.09.166
Sherlock L, Lee SF, Katsanos AH, Cukierman-Yaffe T, Canavan M, Joundi R, et al. Cognitive performance following stroke, transient ischaemic attack, myocardial infarction, and hospitalisation: an individual participant data meta-analysis of six randomised controlled trials. Lancet Healthy Longev. 2023;4(12):e665-e674. doi: https://doi.org/10.1016/S2666-7568(23)00207-6
Wu Y, Ke J, Ye S, Shan LL, Xu S, Guo SF, et al. 3D Visualization of Whole Brain Vessels and Quantification of Vascular Pathology in a Chronic Hypoperfusion Model Causing White Matter Damage. Transl Stroke Res. 2024;15(3):659-71. doi: https://doi.org/10.1007/s12975-023-01157-1
Iskusnykh IY, Zakharova AA, Pathak D. Glutathione in Brain Disorders and Aging. Molecules. 2022;27(1):324. doi: https://doi.org/10.3390/molecules27010324
Bai R, Guo J, Ye XY, Xie Y, Xie T. Oxidative stress: The core pathogenesis and mechanism of Alzheimer's disease. Ageing Res Rev. 2022;77:101619. doi: https://doi.org/10.1016/j.arr.2022.101619
Midlovets KK, Krasnenkov DS. [Oxidative stress in context etiology and pathogenesis of the disease Parkinson’s]. 2024;29(1):25-4. Ukrainian. Available from: https://pro-ageing.org.ua/index.php/journal/article/view/17
Sharma G, Parihar A, Talaiya T, Dubey K, Porwal B, Parihar MS. Cognitive impairments in type 2 diabetes, risk factors and preventive strategies. J Basic Clin Physiol Pharmacol. 2020;31(2):/j/jbcpp.2020.31.issue-2/jbcpp-2019-0105/jbcpp-2019-0105.xml. doi: https://doi.org/10.1515/jbcpp-2019-0105
Matthews K, Dawes P, Elliot R, Maharani A, Pendleton N, Tampubolon G. What Explains the Link Between Hearing and Vision Impairment and Cognitive Function? Analysis of Mediating Effects in the USA, England and Ireland. Int J Geriatr Psychiatry. 2024;39(9):e6149. doi: https://doi.org/10.1002/gps.6149
Slade K, Plack CJ, Nuttall HE. The Effects of Age-Related Hearing Loss on the Brain and Cognitive Function. Trends Neurosci. 2020;43(10):810-21. doi: https://doi.org/10.1016/j.tins.2020.07.005
Daroische R, Hemminghyth MS, Eilertsen TH, Breitve MH, Chwiszczuk LJ. Cognitive Impairment After COVID-19-A Review on Objective Test Data. Front Neurol. 2021;12:699582. doi: https://doi.org/10.3389/fneur.2021.699582
Becker JH, Lin JJ, Doernberg M, Stone K, Navis A, Festa JR, et al. Assessment of Cognitive Function in Patients After COVID-19 Infection. JAMA Netw Open. 2021;4(10):e2130645. doi: https://doi.org/10.1001/jamanetworkopen.2021.30645
Oros MM. [Cognitive impairment as a result of the direct impact of COVID-19 on the nervous system]. Medicine of Ukraine. 2023;(3):33-5. Ukrainian. doi: https://doi.org/10.37987/1997-9894.2023.3(269).281701
Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021;93(1):250-6. doi: https://doi.org/10.1002/jmv.26232
Fara A, Mitrev Z, Rosalia RA, Assas BM. Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines. Open Biol. 2020;10(9):200160. doi: https://doi.org/10.1098/rsob.200160
Wang X, Cui L, Ji X. Cognitive impairment caused by hypoxia: from clinical evidences to molecular mechanisms. Metab Brain Dis. 2022;37(1):51-66. doi: https://doi.org/10.1007/s11011-021-00796-3
Snyder B, Simone SM, Giovannetti T, Floyd TF. Cerebral Hypoxia: Its Role in Age-Related Chronic and Acute Cognitive Dysfunction. Anesth Analg. 2021;132(6):1502-13. doi: https://doi.org/10.1213/ANE.0000000000005525
Haidar MA, Shakkour Z, Reslan MA, Al-Haj N, Chamoun P, Habashy K, et al. SARS-CoV-2 involvement in central nervous system tissue damage. Neural Regen Res. 2022;17(6):1228-39. doi: https://doi.org/10.4103/1673-5374.327323
Elyaspour Z, Zibaeenezhad MJ, Razmkhah M, Razeghian-Jahromi I. Is It All About Endothelial Dysfunction and Thrombosis Formation? The Secret of COVID-19. Clin Appl Thromb Hemost. 2021;27:10760296211042940. doi: https://doi.org/10.1177/10760296211042940
Turna J, Zhang J, Lamberti N, Patterson B, Simpson W, Francisco AP, et al. Anxiety, depression and stress during the COVID-19 pandemic: Results from a cross-sectional survey. J Psychiatr Res. 2021;137:96-103. doi: https://doi.org/10.1016/j.jpsychires.2021.02.059
Cooke JE, Eirich R, Racine N, Madigan S. Prevalence of posttraumatic and general psychological stress during COVID-19: A rapid review and meta-analysis. Psychiatry Res. 2020;292:113347. doi: https://doi.org/10.1016/j.psychres.2020.113347
Weisskopf MG, Kioumourtzoglou MA, Roberts AL. Air Pollution and Autism Spectrum Disorders: Causal or Confounded? Curr Environ Health Rep. 2015;2(4):430-9. doi: https://doi.org/10.1007/s40572-015-0073-9
Sun S, Stewart JD, Eliot MN, Yanosky JD, Liao D, Tinker LF, et al. Short-term exposure to air pollution and incidence of stroke in the Women's Health Initiative. Environ Int. 2019;132:105065. doi: https://doi.org/10.1016/j.envint.2019.105065
Schikowski T, Altuğ H. The role of air pollution in cognitive impairment and decline. Neurochem Int. 2020;136:104708. doi: https://doi.org/10.1016/j.neuint.2020.104708
Delgado-Saborit JM, Guercio V, Gowers AM, Shaddick G, Fox NC, Love S. A critical review of the epidemiological evidence of effects of air pollution on dementia, cognitive function and cognitive decline in adult population. Sci Total Environ. 2021;757:143734. doi: https://doi.org/10.1016/j.scitotenv.2020.143734
Peeples L. News Feature: How air pollution threatens brain health. Proc Natl Acad Sci U S A. 2020;117(25):13856-60. doi: https://doi.org/10.1073/pnas.2008940117
Gangwar RS, Bevan GH, Palanivel R, Das L, Rajagopalan S. Oxidative stress pathways of air pollution mediated toxicity: Recent insights. Redox Biol. 2020;34:101545. doi: https://doi.org/10.1016/j.redox.2020.101545
Moroz FM, Markina O, Markin M. Systema monitorynhu povitria vid vybukhiv boieprypasiv. In: Information society: technological, economic and technical aspects of formation. Proceedings of the International scientific internet conference [Internet]; 2023 Jun 8-9; Ternopil, Ukraine: FOP Shpak VB; 2023 [cited 2024 Dec 21]. p. 66-8. Ukrainian. Available from: http://www.konferenciaonline.org.ua/us/article/id-1172/
Kvasnii L, Mural V, Balanda N. [Impact of war on the physical and mental health of the population]. Society and National Interests. 2024;5(5):27-35. Ukrainian. doi: https://doi.org/10.52058/3041-1572-2024-5(5)-27-35
Dolynskyi Р, Napryeyenko О. [Cognitive impairment in victims of Russian aggression associated with post-traumatic stress disorder (PTSD)]. Psykhosomatychna medytsyna ta zahalna praktyka. 2024;9(3):e0903531. Ukrainian. Available from: https://e-medjournal.com/index.php/psp/article/view/531
Harnett NG, Goodman AM, Knight DC. PTSD-related neuroimaging abnormalities in brain function, structure, and biochemistry. Exp Neurol. 2020;330:113331. doi: https://doi.org/10.1016/j.expneurol.2020.113331
Haris EM, Bryant RA, Williamson T, Korgaonkar MS. Functional connectivity of amygdala subnuclei in PTSD: a narrative review. Mol Psychiatry. 2023;28(9):3581-94. doi: https://doi.org/10.1038/s41380-023-02291-w
Lupien SJ, Juster RP, Raymond C, Marin MF. The effects of chronic stress on the human brain: From neurotoxicity, to vulnerability, to opportunity. Front Neuroendocrinol. 2018;49:91-105. doi: https://doi.org/10.1016/j.yfrne.2018.02.001
Zbytkovskyi MI, Telehina HV. Problema kontuzii holovnoho mozku u medykosotsialnomu, psykholohichnomu i prohnostychnomu dyskursi [The problem of brain contusion in the medico-social, psychological and prognostic discourse]. In: Okhorona pratsi: osvita i praktyka. Problemy ta perspektyvy rozvytku okhorony pratsi. Proceedings of the 3rd All-Ukrainian scientific and practical conference [Internet]; Lviv, Ukraine; 2023 [cited 2024 Dec 21]. p. 133-4. Ukrainian. Available from: https://sci.ldubgd.edu.ua/jspui/bitstream/123456789/11900/1/%D0%97%D0%B1%D1%96%D1%80%D0%BD%D0%B8%D0%BA%20%D0%9A%D0%BE%D0%BD%D1%84%D0%B5%D1%80%D0%B5%D0%BD%D1%86%D1%96%D1%8F%20%D0%9E%D0%9F%202023_29.05.pdf#page=133
Yuryk OE. [Nature of neurological damages of the fighters of the armed forces of Ukraine which fight on Donbass]. Zbirnyk naukovykh prats spivrobitnykiv NMAPO im. P.L. Shupyka. 2019;34:87-93. Ukrainian. Available from: http://nbuv.gov.ua/UJRN/Znpsnmapo_2019_34_11
Maliar L, Pyroh H. Vplyv cherepno-mozkovykh travm na kohnityvni ta psykhichni funktsii viiskovosluzhbovtsiv. Aktualni problemy psykhichnoho zdorovia. In: The impact of traumatic brain injuries on the cognitive and mental functions of military personnel. Proceedings of the All-Ukrainian student-teacher scientific and practical internet conference [Internet]; 2024 May 21; Zhytomyr, Ukraine: Vydavnytstvo ZhDU imeni Ivana Franka; 2024 [cited 2024 Dec 21]. p. 50-2. Ukrainian. Available from: http://eprints.zu.edu.ua/40899/1/Zbirnyk_2024.pdf#page=49
Surhund N, Kapustina V. Experimental study of negative emotional states in the period of war. Psychology Travelogs. 2023;(1):87-96. Ukrainian. doi: https://doi.org/10.31891/PT-2023-1-9
Semkovska M, Quinlivan L, O'Grady T, Johnson R, Collins A, O'Connor J, et al. Cognitive function following a major depressive episode: a systematic review and meta-analysis. Lancet Psychiatry. 2019;6(10):851-861. doi: https://doi.org/10.1016/S2215-0366(19)30291-3
Volkov I, Katelevska N. Doslidzhennia porushen snu pid chas viiny [Study of sleep disorders during war]. In: Technologies and strategies for the implementation of scientific achievements. Proceedings of the 1st International Scientific and Theoretical Conference [Internet]; 2022 May 27. Stockholm, Sweden: Collection of Scientific Papers "SCIENTIA; 2022 [cited 2024 Dec 21]. p. 54-5. Ukrainian. Available from: https://previous.scientia.report/index.php/archive/article/view/73
Neha K, Haider MR, Pathak A, Yar MS. Medicinal prospects of antioxidants: A review. Eur J Med Chem. 2019;178:687-704. doi: https://doi.org/10.1016/j.ejmech.2019.06.010
Franzoni F, Scarfò G, Guidotti S, Fusi J, Asomov M, Pruneti C. Oxidative Stress and Cognitive Decline: The Neuroprotective Role of Natural Antioxidants. Front Neurosci. 2021;15:729757. doi: https://doi.org/10.3389/fnins.2021.729757
Palchevska TA, Lysenko YS, Hula LD, Razhyk AV. Zastosuvannia burshtynovoi kysloty ta natriiu suktsynatu u farmatsii. In: Science, society, education: topical issues and development prospects. Abstracts of 5th International scientific and practical conference [Internet]; 2020 Apr 12-14. Kharkiv, Ukraine; 2020 [cited 2024 Dec 21]. p. 160-6. Ukrainian. Available from: https://er.knutd.edu.ua/handle/123456789/19673
Malanga G, Aguiar MB, Martinez HD, Puntarulo S. New insights on dimethylaminoethanol (DMAE) features as a free radical scavenger. Drug Metab Lett. 2012;6(1):54-9. doi: https://doi.org/10.2174/187231212800229282
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