The predictive value of lipoprotein associated-phospholipase A2 and homocysteine combined with white matter hyperintensities on cognitive impairment in patients with cerebral small vessel disease

doi:10.11958/20251084

Abstract

Abstract:

Objective To investigate the predictive value of serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and homocysteine (Hcy) combined with white matter hyperintensities (WMH) for cognitive impairment in patients with cerebral small vessel disease (CSVD). Methods A total of 240 patients with CSVD were selected. According to the Montreal Cognitive Assessment (MoCA) scale, all subjects were divided into the non-cognitive impairment group (MoCA≥26 points, 120 cases) and the cognitive impairment group (MoCA<26 points, 120 cases). Paraventricular white matter high signal (PWMHs) and deep white matter high signal (DWMHs) were scored by Fazekas scale. The sum of the two parts was the total score, and the severity of DWMHs was graded by the score. The basic information, serum Lp-PLA2, Hcy level and severity of WMH were compared between the two groups. Logistic regression was applied to analyze influencing factors of cognitive impairment in CSVD patients.The predictive value of serum level of Lp-PLA2 and Hcy and WMH for cognitive impairment in CSVD patients was analyzed by receiver operating characteristic (ROC) curve. Results Compared with the non-cognitive impairment group, patients of the cognitive impairment group were older, had higher serum levels of Lp-PLA2 and Hcy, and had more severe of WMH (P<0.05). Results of Logistic regression analysis showed that serum Lp-PLA2, Hcy levels and severity of WMH were influencing factors for cognitive impairment of patients with CSVD (P<0.05). The results of ROC curve analysis showed that the area under the curve of serum Lp-PLA2, Hcy level combined with severity of WMH predicting cognitive impairment in patents with CSVD was 0.812, the sensitivity was 81.7% and the specificity was 71.7% (P<0.05). Conclusion Patients with cognitive impairment caused by CSVD have higher serum levels of Lp-PLA2 and Hcy, and more severe WMH. The combination of the three has a relatively high predictive value for cognitive impairment in patents with CSVD.

Key words: cerebral small vessel diseases, 1-Alkyl-2-acetylglycerophosphocholine esterase, cognitive impairment, homocysteine, ROC curve, white matter hyperintensities

CLC Number:

R743

Figures/Tables 5

References 22

[1]	张晓倩, 有慧, 冯逢. MRI脑小血管病总负荷评分的临床应用进展[J]. 国际医学放射学杂志, 2023, 46(2):163-167.
	ZHANG X Q, YOU H, FENG F. Clinical application progress of total MRI burden score in cerebral small vessel disease[J]. Int J Med Radiol, 2023, 46(2):163-167. doi:10.19300/j.2023.Z20032.
[2]	NYÚL-TÓTH Á, PATAI R, CSISZAR A, et al. Linking peripheral atherosclerosis to blood-brain barrier disruption: elucidating its role as a manifestation of cerebral small vessel disease in vascular cognitive impairment[J]. Geroscience, 2024, 46(6):6511-6536. doi:10.1007/s11357-024-01194-0.
[3]	JANSMA A, DE BRESSER J, SCHOONES J W, et al. Sporadic cerebral small vessel disease and cognitive decline in healthy older adults:A systematic review and meta-analysis[J]. J Cereb Blood Flow Metab, 2024, 44(5):660-679. doi:10.1177/0271678X241235494.
[4]	黎莹, 田庆华, 姜亦欣, 等. 脑小血管病与血管储备及认知障碍相关性研究进展[J]. 中风与神经疾病杂志, 2024, 41(10): 945-949.
	LI Y, TIAN Q H, JIANG Y X, et al. Advances in the study of the correlation between cerebral small vessel disease and vascular reserve and cognitive impairment[J]. Stroke and Neurological Diseases, 2024, 41(10):945-949. doi:10.19845/j.cnki.zfysjjbzz.2024.0180.
[5]	中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组, 黄一宁, 等. 中国脑小血管病诊治指南2020[J]. 中华神经科杂志, 2022, 55(8):807-818.
	Chinese Medical Association Neurology Branch, Chinese Medical Association Neurology Branch Cerebrovascular Disease Group, HHANG Y N, et al. Guidelines for the diagnosis and treatment of small vessel diseases in China 2020[J]. Chinese Journal of Neurology, 2022, 55(8):807-818. doi:10.3760/cma.j.cn113694-20220321-00220.
[6]	XIAO Y, TENG Z, XU J, et al. Systemic immune-inflammation index is associated with cerebral small vessel disease burden and cognitive impairment[J]. Neuropsychiatr Dis Treat, 2023, 19:403-413. doi:10.2147/ndt.S401098.
[7]	DUPRÉ N, DRIEU A, JOUTEL A. Pathophysiology of cerebral small vessel disease:a journey through recent discoveries[J]. J Clin Invest, 2024, 134(10):e172841. doi:10.1172/JCI172841.
[8]	SEKI M, YOSHIZAWA H, HOSOYA M, et al. Neuropsychological profile of early cognitive impairment in cerebral small vessel disease[J]. Cerebrovasc Dis, 2022, 51(5):600-607. doi:10.1159/000522438.
[9]	ZULIANI G, MARSILLACH J, TRENTINI A, et al. Lipoprotein-associated phospholipase A2 activity as potential biomarker of vascular dementia[J]. Antioxidants (Basel), 2023, 12(3):597. doi:10.3390/antiox12030597.
[10]	QIAO S, LI H, GUO F, et al. Research progress on cognitive impairment and the expression of serum inflammatory markers in patients with white matter hyperintensities:a narrative review[J]. Ann Transl Med, 2022, 10(7):421. doi:10.21037/atm-22-1016.
[11]	CAO Y, ZHU X, SHANG J, et al. Correlation between lipoprotein-associated phospholipase A2 and poststroke mild cognitive impairment[J]. Expert Rev Mol Diagn, 2024, 24(6):541-547. doi:10.1080/14737159.2024.2370410.
[12]	HAINSWORTH A H, MARKUS H S, SCHNEIDER J A. Cerebral small vessel disease,hypertension,and vascular contributions to cognitive impairment and dementia[J]. Hypertension, 2024, 81(1):75-86. doi:10.1161/hypertensionaha.123.19943.
[13]	WU D F, YIN R X, DENG J L. Homocysteine, hyperhomocysteinemia,and H-type hypertension[J]. Eur J Prev Cardiol, 2024, 31(9):1092-1103. doi:10.1093/eurjpc/zwae022.
[14]	JAKUBOWSKI H. Homocysteine thiolactone detoxifying enzymes and Alzheimer's disease[J]. Int J Mol Sci, 2024, 25(15):8095. doi:10.3390/ijms25158095.
[15]	郑月, 马运婷, 赵晓莹, 等. 高血压患者同型半胱氨酸与左心室心肌纤维化的相关性[J]. 天津医药, 2023, 51(4):395-399.
	ZHENG Y, MA Y T, ZHAO X Y, et al. Correlation between homocysteine and left ventricular myocardial fibrosis in patients with hypertension[J]. Tianjin Med J, 2023, 51(4):395-399. doi:10.11958/20221111.
[16]	LIAO L, HUANG W, MA R, et al. Potential biomarkers for cerebral small vessel disease with cognitive impairment: a systematic review and meta-analysis[J]. Front Aging Neurosci, 2024,16:1475571. doi:10.3389/fnagi.2024.1475571.
[17]	LIN W Z, YU D, XIONG L Y, et al. Homocysteine, neurodegenerative biomarkers, and APOE ε4 in neurodegenerative diseases[J]. Alzheimers Dement, 2025, 21(1):e14376. doi:10.1002/alz.14376.
[18]	PATEL Y, SHIN J, SLIZ E, et al. Genetic risk factors underlying white matter hyperintensities and cortical atrophy[J]. Nat Commun, 2024, 15(1):9517. doi:10.1038/s41467-024-53689-1.
[19]	ZHANG J, CHEN H, WANG J, et al. Linking white matter hyperintensities to regional cortical thinning, amyloid deposition, and synaptic density loss in Alzheimer's disease[J]. Alzheimers Dement, 2024, 20(6):3931-3942. doi:10.1002/alz.13845.
[20]	丁娜, 崔凌, 白金娟, 等. 脑白质损伤程度及脑血流灌注对老年脑小血管病患者认知功能的影响[J]. 中国老年学杂志, 2024, 44(17):4106-4109.
	DING N, CUI L, BAI J J, et al. The impact of white matter injury and cerebral blood flow on cognitive function in elderly patients with small vessel disease[J]. Chinese Journal of Gerontology, 2024, 44(17):4106-4109. doi:10.3969/j.issn.1005-9202.2024.17.003.
[21]	HUANG W Q, LIN Q, TZENG C M. Leukoaraiosis:epidemiology,imaging,risk factors,and management of age-related cerebral white matter hyperintensities[J]. J Stroke, 2024, 26(2):131-163. doi:10.5853/jos.2023.02719.
[22]	JIANG J, GAO Y, ZHANG R, et al. Differential effects of serum lipoprotein-associated phospholipase A2 on periventricular and deep subcortical white matter hyperintensity in brain[J]. Front Neurol, 2021,12:605372. doi:10.3389/fneur.2021.605372.

组别		性别（男/女）	年龄/ 岁		TG/ （mmol/L）		TC/ （mmol/L）
无认知障碍组		62/58	66.0（60.0，71.0）		1.56（1.10，1.80）		4.27±1.06
认知障碍组		61/59	68.5（65.0，76.0）		1.46（1.14，1.97）		4.31±1.18
χ²、Z或t		0.897	3.087^＊		0.474		0.273
组别	HDL-C/ （mmol/L）			LDL-C/ （mmol/L）		IL-6/ （mmol/L）
无认知障碍组	1.25（0.99，2.80）			2.40（1.80，3.00）		10.35（5.76，14.02）
认知障碍组	1.27（1.04，2.70）			2.45（1.70，2.90）		11.40（7.33，14.44）
Z	0.073			0.004		1.484

组别		性别（男/女）	年龄/ 岁		TG/ （mmol/L）		TC/ （mmol/L）
无认知障碍组		62/58	66.0（60.0，71.0）		1.56（1.10，1.80）		4.27±1.06
认知障碍组		61/59	68.5（65.0，76.0）		1.46（1.14，1.97）		4.31±1.18
χ²、Z或t		0.897	3.087^＊		0.474		0.273
组别	HDL-C/ （mmol/L）			LDL-C/ （mmol/L）		IL-6/ （mmol/L）
无认知障碍组	1.25（0.99，2.80）			2.40（1.80，3.00）		10.35（5.76，14.02）
认知障碍组	1.27（1.04，2.70）			2.45（1.70，2.90）		11.40（7.33，14.44）
Z	0.073			0.004		1.484

组别	Hcy/（μmol/L）			Lp-PLA2/（μg/L）
无认知障碍组	13.30（11.70，16.68）			170.30（135.00，234.68）
认知障碍组	16.75（12.70，20.23）			237.20（167.40，330.75）
Z	3.787^＊			4.791^＊
组别		WMH
组别		无	轻度		中度	重度
无认知障碍组		10（8.3）	62（51.7）		33（27.5）	15（12.5）
认知障碍组		6（5.0）	14（11.7）		37（30.8）	63（52.5）
Z或χ²		61.083^＊

组别	Hcy/（μmol/L）			Lp-PLA2/（μg/L）
无认知障碍组	13.30（11.70，16.68）			170.30（135.00，234.68）
认知障碍组	16.75（12.70，20.23）			237.20（167.40，330.75）
Z	3.787^＊			4.791^＊
组别		WMH
组别		无	轻度		中度	重度
无认知障碍组		10（8.3）	62（51.7）		33（27.5）	15（12.5）
认知障碍组		6（5.0）	14（11.7）		37（30.8）	63（52.5）
Z或χ²		61.083^＊

变量	β	SE	Wald χ²	P	OR（95%CI）
Lp-PLA2	0.004	0.002	6.731	0.009	1.004（1.001~1.007）
Hcy	0.082	0.027	9.087	0.003	1.086（1.029~1.146）
WMH			44.801	<0.001
轻度	-0.998	0.631	2.504	0.114	0.368（0.107~1.269）
中度	0.580	0.604	0.921	0.337	1.786（0.547~5.836）
重度	1.877	0.624	9.058	0.003	6.537（1.925~22.201）
常数项	-0.823	0.592	1.931	0.165	0.439