Association between Cerebral Small Vessel Disease and Plasma Levels of LDL Cholesterol and Homocysteine: Implications for Cognitive Function

LDL, Homocysteine, Small Vessel Disease, Cognitive Function Link

  • Yan Cheng
  • Lichao Li
  • Yafei Lv
  • Long Zhang
  • Wenhua Chen
  • Gongda Xu Department of Neurology, Affiliated Hospital of Gansu Medical College
Keywords: low-density lipoprotein cholesterol, homocysteine, cerebral small-vessel disease, cognitive functions

Abstract


Background: Investigate the correlation between low-density lipoprotein (LDL) cholesterol, homocysteine and cognitive function in patients with cerebral small vessel disease (CSVD).

Methods: 240 patients with CSVD confirmed by head MRI in the Department of Neurology from January 2020 to December 2023 were retrospectively included in the study. All the patients had complete blood biochemical examination, and their cognitive function was evaluated by Montreal Cognitive Assessment Scale (MoCA), and after correcting for the factor of years of education, the patients were divided into a group of normal cognition (MoCA ≥26, 70 patients) and a group of cognitive function (MoCA ≥26, 70 patients) according to the scores. After correcting for the factor of years of education, the patients were divided into the normal cognitive function group (70 cases with MoCA ≥26) and the cognitive dysfunction group (170 cases with MoCA <26) according to their scores. The general information of the two groups and the patients' cognitive function characteristics, including visuospatial and executive ability, naming, attention and calculation, language, abstraction, delayed memory, and orientation, were compared, and the independent influences on the occurrence of cognitive dysfunction in patients with CSVD were analyzed by two-category multifactorial logistic regression.

Results: Compared with the group with normal cognitive function, the cognitive dysfunction group had lower years of education and higher homocysteine, and the differences were statistically significant (P < 0.05). Compared with the group with normal cognitive functioning, the cognitive dysfunction group had lower MoCA total scores, lower visuospatial and executive ability, naming, attention and calculation, language, abstraction, delayed memory, and orientation scores, and the differences were statistically significant (P < 0.05). Two-category multifactorial logistic regression analysis showed that low-density lipoprotein cholesterol (OR=2.756, 95% CI:0.673-0.938, P=0.012) and homocysteine (OR=1.859, 95% CI: 1.024-1.324, P=0.016) were the independent factors influencing cognitive dysfunction in CSVD patients. The lower the risk of cognitive impairment in CSVD patients, the higher the plasma LDL cholesterol and homocysteine levels, the higher the risk of cognitive impairment in CSVD patients.

Conclusion: Plasma LDL cholesterol and homocysteine levels are associated with and may be predictors of cognitive dysfunction in patients with CSVD.

References

1. Kim JS. Role of Blood Lipid Levels and Lipid-Lowering Therapy in Stroke Patients with Different Levels of Cerebral Artery Diseases: Reconsidering Recent Stroke Guidelines. J Stroke 2021; 23(2): 149-61.
2. Liu Y, Yuan C, Chen X, Fang X, Hao J, Zhou M, et al. Association of Plasma Lipids with White Matter Hyperintensities in Patients with Acute Ischemic Stroke. Int J Gen Med 2023; 16: 5405-15.
3. van Nieuwkerk AC, Delewi R, Wolters FJ, Muller M, Daemen M, Biessels GJ. Cognitive Impairment in Patients With Cardiac Disease: Implications for Clinical Practice. Stroke 2023; 54(8): 2181-91.
4. Chen Y, Hu M, Gong H. Correlation analysis between the LDL-C in serum and the onset of transient ischemic attack caused by CSVD. Exp Ther Med 2017; 14(2): 1119-25.
5. Li C, Bu X, Liu Y. Effect of folic acid combined with pravastatin on arteriosclerosis in elderly hypertensive patients with lacunar infarction. Medicine 2021; 100(28): e26540.
6. Amarenco P, Benavente O, Goldstein LB, Callahan AR, Sillesen H, Hennerici MG, et al. Results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial by stroke subtypes. Stroke 2009; 40(4): 1405-9.
7. Beltran RL, Vallejo-Vaz AJ, Muniz GO. Cerebrovascular Disease and Statins. Front Cardiovasc Med 2021; 8: 778740.
8. Todate Y, Uwano I, Yashiro S, Chida A, Hasegawa Y, Oda T, et al. High Prevalence of Cerebral Small Vessel Disease on 7T Magnetic Resonance Imaging in Familial Hypercholesterolemia. J Atheroscler Thromb 2019; 26(12): 1045-53.
9. Georgakis MK, Malik R, Anderson CD, Parhofer KG, Hopewell JC, Dichgans M. Genetic determinants of blood lipids and cerebral small vessel disease: role of high-density lipoprotein cholesterol. Brain 2020; 143(2): 597-610.
10. Zhang J, Liu N, Yang C. Effects of rosuvastatin in combination with nimodipine in patients with mild cognitive impairment caused by cerebral small vessel disease. Panminerva Med 2019; 61(4): 439-43.
11. Zhu S, Wei X, Yang X, Huang Z, Chang Z, Xie F, et al. Plasma Lipoprotein-associated Phospholipase A2 and Superoxide Dismutase are Independent Predicators of Cognitive Impairment in Cerebral Small Vessel Disease Patients: Diagnosis and Assessment. Aging Dis 2019; 10(4): 834-46.
12. Xin J, Huang X, Pan X, Lin L, Sun M, Liu C, et al. Risk Factors for Aphasia in Cerebral Small Vessel Diseases. Curr Neurovasc Res 2019; 16(2): 107-14.
13. Tang H, Wang Y, Cheng A, Wang A, Xu J, Zhang C, et al. Association between Low-Density Lipoprotein Cholesterol Levels and Proximal Single Subcortical Infarction in Comparison with Distal Single Subcortical Infarction. J Stroke Cerebrovasc 2020; 29(11): 105198.
14. Zhao Y, Zhou Y, Zhou H, Gong X, Luo Z, Li J, et al. Low-density lipoprotein cholesterol, statin therapy, and cerebral microbleeds: The CIRCLE study. Neuroimage-Clin 2023; 39: 103502.
15. Kang SH, Yoo H, Cheon BK, Park YH, Kim SJ, Ham H, et al. Distinct effects of cholesterol profile components on amyloid and vascular burdens. Alzheimers Res Ther 2023; 15(1): 197.
16. Wang R, Laveskog A, Laukka EJ, Kalpouzos G, Backman L, Fratiglioni L, et al. MRI load of cerebral microvascular lesions and neurodegeneration, cognitive decline, and dementia. Neurology 2018; 91(16): e1487-97.
17. Hilal S, Mok V, Youn YC, Wong A, Ikram MK, Chen CL. Prevalence, risk factors and consequences of cerebral small vessel diseases: data from three Asian countries. J Neurol Neurosur Ps 2017; 88(8): 669-74.
18. Wang T, Sun ZW, Shao LQ, Xu XB, Liu Y, Qin M, et al. Diagnostic Values of Serum Levels of Homocysteine and Uric Acid for Predicting Vascular Mild Cognitive Impairment in Patients with Cerebral Small Vessel Disease. Med Sci Monitor 2017; 23: 2217-25.
19. Wang CY, Chen ZW, Zhang T, Liu J, Chen SH, Liu SY, et al. Elevated plasma homocysteine level is associated with ischemic stroke in Chinese hypertensive patients. Eur J Intern Med 2014; 25(6): 538-44.
20. Lehmann M, Gottfries CG, Regland B. Identification of cognitive impairment in the elderly: homocysteine is an early marker. Dement Geriatr Cogn 1999; 10(1): 12-20.
21. Sachdev PS. Homocysteine and brain atrophy. Prog Neuro-Psychoph 2005; 29(7): 1152-61.
22. An XL, Li CL. Analysis of risk factors for vascular cognitive impairment in patients with cerebral infarction. Cell Biochem Biophys 2015; 71(2): 673-7.
23. Luo M, Ji H, Zhou X, Liang J, Zou T. Correlation of homocysteine metabolic enzymes gene polymorphism and mild cognitive impairment in the Xinjiang Uygur population. Med Sci Monitor 2015; 21: 326-32.
24. Feng C, Bai X, Xu Y, Hua T, Huang J, Liu XY. Hyperhomocysteinemia associates with small vessel disease more closely than large vessel disease. Int J Med Sci 2013; 10(4): 408-12.
25. Jakubowski H. Protein homocysteinylation: possible mechanism underlying pathological consequences of elevated homocysteine levels. Faseb J 1999; 13(15): 2277-83.
26. Perla-Kajan J, Twardowski T, Jakubowski H. Mechanisms of homocysteine toxicity in humans. Amino Acids 2007; 32(4): 561-72.
27. Imamura T, Doi Y, Arima H, Yonemoto K, Hata J, Kubo M, et al. LDL cholesterol and the development of stroke subtypes and coronary heart disease in a general Japanese population: the Hisayama study. Stroke 2009; 40(2): 382-8.
28. Skrobot OA, Black SE, Chen C, DeCarli C, Erkinjuntti T, Ford GA, et al. Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study. Alzheimers Dement 2018; 14(3): 280-92.
Published
2024/06/08
Section
Original paper