The Analysis of Related Factors of Cognitive Impairment after the Acute Ischemic Stroke and Construction of Nomogram Model
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摘要:
目的 探索急性缺血性脑卒中后认知障碍发生的相关因素并构建列线图临床预测模型。 方法 以175例急性缺血性脑卒中患者为研究对象,入院后使用简易精神状态量表、蒙特利尔认知评测量表进行认知功能评估,其中卒中后认知功能障碍(post-stroke cognitive impairment,PSCI)组81例,卒中后无认知障碍(post-stroke no cognitive impairment,PSNCI)组94例,收集2组患者基线资料、外周血及头颅磁共振结果,单因素及多因素分析探索急性缺血性卒中后认知障碍发生的影响因素,据此构建列线图预测模型,并对模型进行评价。 结果 多因素回归分析显示日常活动能力受损、HCY、脑梗死体积、脑萎缩是早期PSCI发生的独立危险因素(P < 0.05)。受教育年限、血红蛋白是PSCI发生的保护因素(P < 0.05)。据此构建列线图预测模型,ROC曲线分析列线图模型预测认知障碍的曲线下面积为0.830(95%CI:0.77~0.89),校准曲线内部验证结果显示偏倚校正曲线趋于理想曲线,模型区分度与准确度均较好。 结论 卒中后认知障碍早期往往容易被忽略,临床决策曲线显示模型能有较好的临床净获益。多因素联合构建临床预测模型有助于PSCI的早期识别和高危人群的筛查,对其防治有重要意义。 Abstract:Objective To explore the related factors of cognitive impairment after the acute ischemic stroke and develop a clinical nomogram model. Methods 175 patients with the acute ischemic stroke were selected as the study objects, and the cognitive function was assessed using the simple mental State Scale and the Montreal Cognitive Assessment Scale after the admission. There were 81 cases in post-stroke cognitive impairment (PSCI) group and 94 cases in post-stroke no cognitive impairment (PSNCI) group. The baseline data, peripheral blood and brain MRI results of the two groups were collected and the univariate and multivariate analysis were used to explore the influencing factors of the cognitive impairment after the acute ischemic stroke, and the prediction model was constructed based on the nomogram and evaluated. Results Multivariate regression analysis showed that several factors, including impaired daily activity, high levels of HCY, larger cerebral infarction volume, and cerebral atrophy, were independent risk factors for early PSCI. On the other hand, education and hemoglobin were identified as the protective factors against PSCI. A nomogram prediction model was created from this data. The ROC curve analysis predicted an area under the curve of 0.830 (95%CI: 0.77-0.89). The calibration curve indicated that the model had the good differentiation and prediction probability, with bias correction tending towards the ideal curve and consistent incidence in actual outcomes. The clinical decision curve showed that the model could provide a better net benefit for clinical use, making it a valuable tool for healthcare professionals. Conclusion The development of PSCI may be overlooked in its early stages. A clinical predictive model that considers multiple factors can aid in the early detection of PSCI and identification of high-risk individuals, which is crucial for the effective prevention and treatment. -
Key words:
- Stroke /
- Cognitive impairment /
- Influencing factors /
- Nomogram /
- Predictive model
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表 1 2组一般资料比较[n(%)/($\bar x \pm s $)/M(P25,P75)]
Table 1. Comparison of general data between 2 groups[n(%)/($\bar x \pm s $)/M(P25,P75)]
比较指标 PSCI(n=81) PSNCI(n=94) t/χ2/z P 性别 男 49(60.49) 66(70.21) 1.824 0.177 女 32(39.51) 28(29.79) 年龄(岁) 66.420±10.42 60.030±11.74 −3.780 <0.001* 受教育年限(a) 6.457±4.60 9.154±3.88 −4.205 <0.001* 吸烟史 34(42.00) 42(44.70) 0.13 0.719 饮酒史 10(12.35) 17(18.09) 1.098 0.295 高血压 51(62.96) 70(74.47) 2.699 0.100 糖尿病 21(25.93) 28(29.79) 0.322 0.571 冠心病 5(6.17) 9(9.57) 0.684 0.408 房颤 6(7.41) 7(7.45) 0.868 1.000 卒中史 22(27.16) 16(17.02) 2.631 0.105 TOAST分型 LAA 59(72.84) 65(69.15) 1.608 0.658 CE 7(8.64) 8(8.51) SAO 8(9.88) 15(15.96) UND&ODC 7(8.64) 6(6.38) MMSE评分(分) 22(17.5~24) 28(27~29) −10.197 <0.001* MoCA评分(分) 16(11.5~20) 25(24~27) −11.284 <0.001* NIHSS评分(分) 3(2~6) 3.5(1~5) −0.768 0.443 ADL评分(分) 80(65~100) 100(80~100) −3.937 <0.001* 就医时间间隔(d) 1.0(1.0~3.0) 1.0(0.58~3.25) −0.387 0.699 *P < 0.05。 表 2 2组颅内病变情况比较[n(%)/M(P25,P75)]
Table 2. Comparison of intracranial lesions between 2 groups[n(%)/M(P25,P75)]
组别 PSCI(n=81) PSNCI(n=94) Z/χ2 P 脑梗死半球 左侧 37(45.7) 49(52.1) 3.462 0.177 右侧 36(44.4) 42(44.4) 双侧 8(9.9) 3(3.2) 脑白质病变 46(56.8) 38(40.4) 4.668 0.031* 腔隙性梗死 55(67.9) 67(71.3) 0.235 0.628 脑萎缩 49(60.5) 34(36.2) 10.324 0.001* 脑梗死体积(mL) 1.76(0.33~9.00) 0.72(0.28~1.33) −2.782 0.005* 脑梗死部位 脑叶 7(8.6) 9(9.6) 0.046 0.831 基底节 20(24.7) 30(31.9) 1.112 0.292 脑干 6(7.4) 19(20.2) 5.826 0.016* 小脑 2(2.5) 6(6.4) − 0.289 丘脑 3(3.7) 4(4.3) − 1.00 胼胝体 2(2.5) 1(1.1) − 0.337 多发 41(50.6) 25(26.6) 10.688 0.001* *P < 0.05。 表 3 外周血液学指标的比较[($\bar x \pm s $)/M(P25,P75)]
Table 3. Comparison of peripheral hematological indicators[($\bar x \pm s $)/M(P25,P75)]
指标 PSCI(n=81) PSNCI(n=94) t/Z P 白细胞(×109/L) 6.918±1.904 6.968±1.786 −0.180 0.857 中性粒细胞(×109/L) 4.363±1.632 4.287±1.522 0.318 0.751 淋巴细胞(×109/L) 1.826±0.651 1.954±0.723 −1.223 0.223 单核细胞(×109/L) 0.575±0.184 0.567±0.174 0.313 0.756 红细胞(×1012/L) 4.575±0.533 4.789±0.573 −2.548 0.012* 红细胞平均体积(fl) 90.457±11.331 91.367±4.965 −0.705 0.482 平均红细胞血红蛋白量(pg) 30.526±2.135 30.754±1.853 −0.758 0.45 平均红细胞血红蛋白浓度(g/L) 333.02±10.882 336.63±10.208 −2.258 0.025* 血红蛋白(g/L) 139.56±18.599 147.37±20.423 −2.631 0.009* 血小板(×109/L) 241.51±98.521 219.38±55.636 1.860 0.065 总蛋白(g/L) 64.059±5.260 65.934±5.578 −2.276 0.024* 白蛋白(g/L) 38.016±3.385 39.829±3.565 −3.433 0.001* 谷草转氨酶(U/L) 21.310±7.576 24.970±31.197 −1.029 0.305 谷丙转氨酶(U/L) 17.690±9.608 21.830±12.975 −2.365 0.019* 血肌酐(μmol/L) 76.203±23.765 79.200±22.120 −0.855 0.394 尿素(mmol/L) 5.130±1.684 4.932±1.659 0.780 0.436 总胆汁酸(μmol/L) 3.3(2.0~5.1) 2.9(1.9~4.8) −1.331 0.183 前白蛋白(mg/L) 209.190±52.015 227.340±45.259 −2.469 0.015* 胆碱酯酶(U/L) 6661.310±1693.373 7091.160±1608.846 −1.720 0.087 尿酸(μmol/L) 311.510±107.031 349.500±96.974 −2.463 0.015* 随机血糖(mmol/L) 5.54(4.805~6.385) 5.52(5.075~6.765) −1.122 0.262 总胆固醇(mmol/L) 4.41(3.775~5.235) 4.415(3.733~5.003) −0.432 0.665 甘油三酯(mmol/L) 1.41(1.010~1.985) 1.49(1.145~2.043) −1.094 0.274 HDL-C(mmol/L) 1.06(0.88~1.30) 0.955(0.858~1.14) −1.739 0.082 LDL-C(mmol/L) 2.7(2.13~3. 47) 2.8(2.20~3.30) −0.186 0.853 HCY(μmol/L) 13.7(11.5~17.8) 13.0(10.0~16.2) −1.730 0.084 *P < 0.05。 表 4 PSCI发生的相关影响因素
Table 4. Related influencing factors of PSCI
指标 B 标准误差 Wald P OR(95%CI) 受教育年限(a) −0.153 0.045 11.408 0.001* 0.858(0.785~0.938) 脑梗死体积(mL) 0.123 0.038 10.597 0.001* 1.131(1.050~1.217) 脑萎缩 0.901 0.391 5.299 0.021* 2.462(1.143~5.300) ADL受损 1.089 0.377 8.349 0.004* 2.971(1.420~6.220) HGB(g/L) −0.021 0.010 4.128 0.042* 0.980(0.960~0.999) HCY(μmol/L) 0.038 0.016 5.316 0.021* 1.038(1.006~1.072) 常量 1.851 1.439 1.655 0.198* 6.367 *P < 0.05。 表 5 不同指标及预测模型对PSCI发生的预测价值
Table 5. The predictive value of different indexes and prediction models for PSCI
影响因素 最佳截断值 AUC 敏感性(%) 特异性(%) 95%CI P 受教育年限(a) 6.5 0.66 60.5 70.2 0.578~0.741 <0.001* ADL (分) 97.5 0.664 69.1 60.6 0.582~0.745 <0.001* 脑梗死体积(mL) 1.522 0.622 51.9 78.7 0.536~0.708 0.005* 脑萎缩 − 0.622 60.5 63.83 0.538~0.705 0.006* HCY (μmol/L) 11.45 0.576 79 37.2 0.491~0.661 0.084 HGB (g/L) 144.5 0.621 64.2 57.4 0.538~0.705 0.006* 模型预测值 0.529 0.830 69.1 83 0.77~0.89 <0.001* *P < 0.05。 -
[1] 中国脑卒中防治报告2019 编写组. 中国脑卒中防治报告2019 概要[J]. 中国脑血管病杂志,2020,17(5):272-281. [2] 中国卒中学会血管性认知障碍分会. 卒中后认知障碍管理专家共识2021[J]. 中国卒中杂志,2021,16(4):376-389. [3] Bejot Y,Daubail B,Giroud M. Epidemiology of stroke and transient ischemic attacks: Current knowledge and perspectives[J]. Rev Neurol (Paris),2016,172(1):59-68. doi: 10.1016/j.neurol.2015.07.013 [4] Wang Y J,Li Z X,Gu H Q,et al. China stroke statistics 2019: A report from the national center for healthcare quality management in neurological diseases,China national clinical research center for neurological diseases,the Chinese stroke association,national center for chronic and non-communicable disease control and prevention,Chinese center for disease control and prevention and institute for global neuroscience and stroke collaborations[J]. Stroke Vasc Neurol,2020,5(3):211-239. doi: 10.1136/svn-2020-000457 [5] 贾建平,陈生弟. 神经病学[M]. 第8版. 北京: 人民卫生出版社,2018: 231-235. [6] 中国卒中学会卒中后认知障碍研究圆桌会议专家组. 中国卒中后认知障碍防治研究专家共识[J]. 中国卒中杂志,2020,15(2):158-166. [7] Sun J H,Tan L,Yu J T. Post-stroke cognitive impairment: Epidemiology,mechanisms and management[J]. Ann Transl Med,2014,2(8):80. [8] Pendlebury S T,Rothwell P M. Prevalence,incidence,and factors associated with pre-stroke and post-stroke dementia: A systematic review and meta-analysis[J]. Lancet Neurol,2009,8(11):1006-1018. doi: 10.1016/S1474-4422(09)70236-4 [9] 中国医师协会神经内科分会认知障碍专业委员会, 中国血管性认知障碍诊治指南编写组. 2019年中国血管性认知障碍诊治指南[J]. 中华医学杂志,2019,99(35):2737-2744. [10] 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. 中国急性缺血性脑卒中诊治指南2018[J]. 中华神经科杂志,2018,51(9):666-682. [11] 邱晓雪,陈红霞,李世文,等. 卒中后认知障碍的危险因素分析[J]. 中国卒中杂志,2021,16(3):272-277. [12] Meng X,Wen R,Li X. Values of serum LDL and PCT levels in evaluating the condition and prognosis of acute cerebral infarction[J]. Exp Ther Med,2018,16(4):3065-3069. [13] 曲艳吉,卓琳,詹思延. 中国脑卒中后认知障碍流行病学特征的系统评价[J]. 中华老年心脑血管病杂志,2013,15(12):1294-1301. [14] Rost N S,Brodtmann A,Pase M P,et al. Post-stroke cognitive impairment and dementia[J]. Circ Res,2022,130(8):1252-1271. doi: 10.1161/CIRCRESAHA.122.319951 [15] Akinyemi R O,Firbank M,Ogbole G I,et al. Medial temporal lobe atrophy,white matter hyperintensities and cognitive impairment among Nigerian African stroke survivors[J]. BMC Res Notes,2015,8(1):625. doi: 10.1186/s13104-015-1552-7 [16] Zhu Y,Zhao S,Fan Z,et al. Evaluation of the mini-mental state examination and the montreal cognitive assessment for predicting post-stroke cognitive impairment during the acute phase in Chinese minor stroke patients[J]. Front Aging Neurosci,2020,12(2020):236. [17] Boutros C F,Khazaal W,Taliani M,et al. Factors associated with cognitive impairment at 3,6,and 12 months after the first stroke among Lebanese survivors[J]. Brain Behav,2023,13(1):e2837. doi: 10.1002/brb3.2837 [18] Srithumsuk W,Kabayama M,Gondo Y,et al. The importance of stroke as a risk factor of cognitive decline in community dwelling older and oldest peoples: The SONIC study[J]. BMC Geriatr,2020,20(1):24. doi: 10.1186/s12877-020-1423-5 [19] Wolters F J,Zonneveld H I,Licher S,et al. Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI[J]. Neurology,2019,93(9):e917-e926. [20] Gu Y,Wang F,Gong L,et al. A nomogram incorporating red blood cell indices to predict post-stroke cognitive impairment in the intracerebral hemorrhage population[J]. Front Aging Neurosci,2022,14(2022):985386. [21] Dlugaj M,Winkler A,Weimar C,et al. Anemia and mild cognitive impairment in the German general population[J]. J Alzheimers Dis,2016,49(4):1031-1042. doi: 10.3233/JAD-150434 [22] 张小丽,邢凤梅. 脑卒中患者认知障碍与人口学及临床特征的关系[J]. 中国老年学杂志,2011,31(16):3146-3147. [23] Galle S A,Deijen J B,Milders M V,et al. The effects of a moderate physical activity intervention on physical fitness and cognition in healthy elderly with low levels of physical activity: A randomized controlled trial[J]. Alzheimers Res Ther,2023,15(1):12. doi: 10.1186/s13195-022-01123-3 [24] Cumming T B,Tyedin K,Churilov L,et al. The effect of physical activity on cognitive function after stroke: A systematic review[J]. Int Psychogeriatr,2012,24(4):557-567. doi: 10.1017/S1041610211001980 [25] Di Raimondo D,Rizzo G,Musiari G,et al. Role of Regular physical activity in neuroprotection against acute ischemia[J]. Int J Mol Sci,2020,21(23):9086. [26] Gorelick P B,Furie K L,Iadecola C,et al. Defining optimal brain health in adults: A presidential advisory from the American Heart Association/American Stroke Association[J]. Stroke,2017,48(10):e284-e303. [27] 方靖. MRI病灶体积和BDNF在缺血性脑卒中病情及预后评估中的价值[J]. 临床放射学杂志,2016,35(12):1800-1803. [28] Prodjohardjono A,Vidyanti A N,Susianti N A,et al. Higher level of acute serum VEGF and larger infarct volume are more frequently associated with post-stroke cognitive impairment[J]. PLoS One,2020,15(10):e0239370. doi: 10.1371/journal.pone.0239370 [29] Jaillard A,Grand S,Le Bas J F,et al. Predicting cognitive dysfunctioning in nondemented patients early after stroke[J]. Cerebrovasc Dis,2010,29(5):415-423. doi: 10.1159/000289344 [30] 韩燕,印旭阳,曹鑫,等. 脑小血管病头颅磁共振成像特征与认知损害的研究新进展[J]. 中国临床神经科学,2022,30(4):451-459. [31] Ding M Y,Xu Y,Wang Y Z,et al. Predictors of cognitive impairment after stroke: A prospective stroke cohort study[J]. J Alzheimers Dis,2019,71(4):1139-1151. doi: 10.3233/JAD-190382 [32] Casolla B,Caparros F,Cordonnier C,et al. Biological and imaging predictors of cognitive impairment after stroke: A systematic review[J]. J Neurol,2019,266(11):2593-2604. doi: 10.1007/s00415-018-9089-z [33] Pendlebury S T,Rothwell P M,Oxford Vascular S. Incidence and prevalence of dementia associated with transient ischaemic attack and stroke: analysis of the population-based Oxford Vascular Study[J]. Lancet Neurol,2019,18(3):248-258. doi: 10.1016/S1474-4422(18)30442-3 [34] 陆珍辉. H型高血压与脑白质疏松及卒中后认知障碍的关系研究[D],苏州: 苏州大学,2020. [35] 王维维,申致远,李凡,等. 血浆低密度脂蛋白胆固醇和同型半胱氨酸与脑小血管病患者认知功能的相关性研究[J]. 中国脑血管病杂志,2021,18(12):836-842. [36] Smith A D,Refsum H,Bottiglieri T,et al. Homocysteine and dementia: An international consensus statement[J]. J Alzheimers Dis,2018,62(2):561-570. doi: 10.3233/JAD-171042