Assessment of Four Serum Biochemical Markers in Elderly Patients with Vascular Dementia after Cerebral Infarction and Their Response to Donepezil and Idebenone

Abstract

Objective Our study aimed to explore four serum levels of biochemical markers, including brain-derived neurotrophic factor (BDNF), homocysteine (Hcy), nitric oxide (NO), and γ-interferon (IFN-γ), in elderly patients with vascular dementia (VD) after the cerebral infarction and to elucidate possible connections between them.

Method The elderly patients with VD after cerebral infarction admitted in our hospital, and the elderly persons for physical examination from November 2020 to December 2021 were included in this study. The serum levels of BDNF, Hcy, NO, and IFN-γ were compared between the study group and the control group.

Results In the study group, the serum levels of Hcy and IFN-γ were significantly higher than that in the control group, whereas significantly lower serum levels of BDNF and NO were found in the study group compared with the control group. After receiving the intervention of donepezil and/or idebenone, the serum levels of Hcy and IFN-γ in group B were significantly lower than that in group A, while the serum levels of BDNF and NO in group B were significantly higher than that in Group A.

Conclusion The results of our study showed abnormally expressed serum levels of Hcy, IFN-γ, BDNF, and NO in elderly patients with VD after cerebral infarction which might strongly reflect the severity of VD. Moreover, after intervention of donepezil alone or combined with idebenone, the changes of serum levels of Hcy, IFN-γ, BDNF, and NO may reflect the curative effect of the disease.

Keywords

brain-derived neurotrophic factor - homocysteine - nitric oxide - γ-interferon - vascular dementia - cerebral infarction - donepezil - idebenone

Ethics Approval and Consent to Participate

The study protocol was approved by the Ethics Committee of Hubei Third People's Hospital of Jianghan University. Informed consent was obtained from all the study subjects before enrollment.

Availability of Data and Materials

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Authors' Contributions

J.L. and Q.L. have made substantial contributions to conception and design of the study. T.P. was involved in acquisition of data, data entry and data cleaning. Q.Z. was involved in analysis and interpretation of data. B.H. and B.Z. have been involved in drafting the manuscript. J.L. and Q.L. were involved in revising manuscript critically for important intellectual content. All authors contributed substantially to its revision. All authors read and approved the final manuscript.

^* Jianlin Liu and Qin Li contributed equally to this paper.

Publikationsverlauf

Eingereicht: 02. März 2022

Angenommen: 03. August 2022

Artikel online veröffentlicht:
01. November 2022

• References

• 1 Jiao C, Wei S, Liu T. et al. The prevalence of vascular dementia in China: a systematic review and meta-analysis from 2009-2019. Iran J Public Health 2021; 50 (01) 11-23
• 2 Wang XX, Zhang B, Xia R, Jia QY. Inflammation, apoptosis and autophagy as critical players in vascular dementia. Eur Rev Med Pharmacol Sci 2020; 24 (18) 9601-9614
• 3 Emrani S, Lamar M, Price CC. et al. Alzheimer's/vascular spectrum dementia: classification in addition to diagnosis. J Alzheimers Dis 2020; 73 (01) 63-71
• 4 O'Brien JT, Thomas A. Vascular dementia. Lancet 2015; 386 (10004): 1698-1706
• 5 Jian W-X, Zhang Z, Zhan J-H. et al. Donepezil attenuates vascular dementia in rats through increasing BDNF induced by reducing HDAC6 nuclear translocation. Acta Pharmacol Sin 2020; 41 (05) 588-598
• 6 Ma Y, Sun W. Effects of Dengzhan Shengmai Capsule combined with butylphthalide soft capsule on oxidative stress indexes and serum Hcy and CRP levels in patients with vascular dementia. Cell Mol Biol 2020; 66 (06) 8-14
• 7 Sun R, Yin G, Liang M. et al. Pathophysiological mechanism of vascular cognitive impairment. Int J Cerebrovasc Dis 2021; 29 (08) 613-618
• 8 Zhang Y, Li X, Wang B. Effect and mechanism of idebenone combined with donepezil in the treatment of mild to moderate vascular dementia in older patients. Int J Geriatr 2020; 41 (04) 205-208
• 9 Govind N. Donepezil for dementia due to Alzheimer's disease. Br J Community Nurs 2020; 25 (03) 148-149
• 10 Chatzikonstantinou S, McKenna J, Karantali E, Petridis F, Kazis D, Mavroudis I. Electroencephalogram in dementia with Lewy bodies: a systematic review. Aging Clin Exp Res 2021; 33 (05) 1197-1208
• 11 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed.. Philadelphia, PA: American Psychiatric Association; 2013
• 12 Tsoi KKF, Chan JYC, Hirai HW, Wong SY, Kwok TC. Cognitive tests to detect dementia: a systematic review and meta-analysis. JAMA Intern Med 2015; 175 (09) 1450-1458
• 13 Birks JS, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev 2018; 6 (06) CD001190
• 14 Klopstock T, Yu-Wai-Man P, Dimitriadis K. et al. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy. Brain 2011; 134 (Pt 9): 2677-2686
• 15 Rass V, Helbok R. How to diagnose delayed cerebral ischaemia and symptomatic vasospasm and prevent cerebral infarction in patients with subarachnoid haemorrhage. Curr Opin Crit Care 2021; 27 (02) 103-114
• 16 Roebuck-Spencer TM, Glen T, Puente AE. et al. Cognitive screening tests versus comprehensive neuropsychological test batteries: a national academy of neuropsychology education paper†. Arch Clin Neuropsychol 2017; 32 (04) 491-498
• 17 Stillman J, Martin A, Miguez M-J. et al. Relationship between brain-derived neurotrophic factor and immune function during dietary supplement treatment of elderly with Alzheimer's dementia. J Clin Transl Res 2020; 5 (02) 68-75
• 18 Chen H, Lombès M, Le Menuet D. Glucocorticoid receptor represses brain-derived neurotrophic factor expression in neuron-like cells. Mol Brain 2017; 10 (01) 12
• 19 Fang Y-C, Chan L, Liou J-P. et al. HDAC inhibitor protects chronic cerebral hypoperfusion and oxygen-glucose deprivation injuries via H3K14 and H4K5 acetylation-mediated BDNF expression. J Cell Mol Med 2020; 24 (12) 6966-6977
• 20 Meng S, Fu J, Huo Q. et al. Relation between serum homocysteine, high-sensitivity C-reactive protein, D-dimer, brain-derived neurotrophic factor and basic fibroblast growth factor levels and their clinical significance in patients with vascular dementia. Guangxi Medical Journal 2020; 42 (02) 134-137
• 21 Zhou Y, Li T, Fan C. et al. The effects of donepezil hydrochloride and nimodipine on serum Lp-PLA2, BDNF and Ang1–7 in elderly patients with vascular dementia after cerebral infarction. Pract J Clin Med 2021; 18 (05) 119-122
• 22 Gao X, Qi S, Xu H. Fasudil combined with atorvastatin on the changes of serum SOD,MDA,Hcy and IFN-γ expression in patients with senile vascular dementia. J Clin Experiment Med 2021; 20 (06) 621-624
• 23 Lianbiao D, Wei W, Wang S, Yingqi Z. Effect on inflammation, vascular endothelial function and inflammation in patients with cerebral infarction complicated with vascular dementia by u-sing rosuvastatin calcium tablets combined with donepezil. J North Sichuan Med Coll 2020; 35 (01) 122-125
• 24 Zhang L, Li B. Effect of nimodipine combined with donepezil in treating elderly patients with vascular dementia. J Clin Experiment Med 2020; 24 (17) 41-44
• 25 Kawakami M, Itoh T. Effects of idebenone on monoamine metabolites in cerebrospinal fluid of patients with cerebrovascular dementia. Arch Gerontol Geriatr 1989; 8 (03) 343-353
• 26 Wang X, Chen X, Li Z. et al. Effectiveness of rehabilitation training combined with idebenone on cognitive function and plasma neurotransmitter for elderly patients with vascular dementia. J Apoplexy Nerv Dis 2018; 35 (07) 632-634