卒中后CIND危险因素与ACE I/D多态性的交互作用
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摘要
目的探讨缺血性脑卒中(IS)后CIND的危险因素及与ACE I/D的交互作用。方法以19～80岁盐亭县人民医院汉族初发IS患者作为研究对象,发病后3月采用简易智能量表(MMSE)和美国精神疾病统计和诊断手册第4版修订本(DSM-Ⅳ-R)进行认知测定,检测ACE I/D多态性,采用Logitic回归分析研究CIND患者的传统危险因素和易感基因以及交互作用;结果共纳入研究对象235例,212例完成3月随访和认知测试,其中27例诊断为痴呆被排除,42例诊断为CIND(22.7%)。分析发现,大面积和中等面积梗死(OR=4.687,P<0.05; OR=4.734,P<0.05)、糖尿病(OR=2.887,P<0.05)、DD基因型(OR=2.852,P<0.05)是IS后CIND的独立危险因素。然而,没有发现有统计学意义的交互作用;结论糖尿病、梗死大小、ACE DD基因型是IS后CIND的独立危险因素。
Objectives To determine the genetic and environmental risk factors in cognitive impairment no dementia(CIND) after ischemic stroke(IS), as well as whether there was evidence of gene-environment interactions. Methods The samples consisted the Han people with first-ever IS at the age of ranging from 19 to 80 years. The ACE I/D polymorphism was detected by polymerase chain reaction(PCR), and the possible risk factors involved in CIND were collected in detail. The cognitive function was evaluated at 3 months after IS according to the Chinese version of Mini-Mental State Examination(MMSE) and Diagnostic and Statistical Manual of Mental Disorders(DSM-Ⅳ-R). Univariate and logistic regression analysis was used for statistical analysis. Results 235 patients were entered into the study and 212 patients were evaluated at the post-IS 3 months. 185 were performed statistical analysis after exclusion of 27 patients with dementia, and 42 patients were diagnosed as CIND. Multivariate logistic regression suggested that the diabetes(OR=2.887, P<0.05), infarct volume(OR=4.734, P<0.05) and ACE DD genotype(OR=2.852, P<0.05)might be independent risk factors of CIND after IS, however, there was no evidence of interactions. Conclusion Diabetes, infarct volume and ACE DD genotype are associated independently with post-IS CIND.
Objectives To determine the genetic and environmental risk factors in cognitive impairment no dementia(CIND) after ischemic stroke(IS), as well as whether there was evidence of gene-environment interactions. Methods The samples consisted the Han people with first-ever IS at the age of ranging from 19 to 80 years. The ACE I/D polymorphism was detected by polymerase chain reaction(PCR), and the possible risk factors involved in CIND were collected in detail. The cognitive function was evaluated at 3 months after IS according to the Chinese version of Mini-Mental State Examination(MMSE) and Diagnostic and Statistical Manual of Mental Disorders(DSM-Ⅳ-R). Univariate and logistic regression analysis was used for statistical analysis. Results 235 patients were entered into the study and 212 patients were evaluated at the post-IS 3 months. 185 were performed statistical analysis after exclusion of 27 patients with dementia, and 42 patients were diagnosed as CIND. Multivariate logistic regression suggested that the diabetes(OR=2.887, P<0.05), infarct volume(OR=4.734, P<0.05) and ACE DD genotype(OR=2.852, P<0.05)might be independent risk factors of CIND after IS, however, there was no evidence of interactions. Conclusion Diabetes, infarct volume and ACE DD genotype are associated independently with post-IS CIND.
引文
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[2] Zhang Y,Shi Z,Liu M,et al.Prevalence of cognitive impairment no dementia in a rural area of Northern China[J].Neuroepidemiology,2014,42(4):197-203.
[3] Linden T,Skoog I,Fagerberg B,et al.Cognitive impairment and dementia 20 months after stroke[J].Neuroepidemiology,2004,23(1-2):45-52.
[4] Ingles J,Wentzel C,Fisk J,et al.Neuropsychological predictors of incident dementia in patients with vascular cognitive impairment without dementia[J].Stroke,2002,33(8):1999-2002.
[5] Liu M,Wu B,Wang WZ,et al.Stroke in China:epidemiology,prevention,and management Strategies.Lancet Neurol,2007,6(5):456–464.
[6] Sayed-Tabatabaei FA,Oostra BA,Isaacs A,et al.ACE Polymorphisms[J].Circ Res,2006,98(9):1123-1133.
[7] Lehmann DJ,Cortina-Borja M,Warden DR,et al.Large Meta-Analysis Establishes the ACE Insertion-Deletion Polymorphism as a Marker of Alzheimer’s Disease[J].Am J Epidemiol,2005,162(4):305-317.
[8] WHO Special Report.Stroke 1989:recommendations on stroke prevention,diagnosis,and therapy[J].Stroke,1989,20(10):1407-1431.
[9] 张明园,瞿光亚,金华,等.几种痴呆测试工具的比较[J].中华神经精神科杂志,1991,24(4):194-196
[10] American Psychiatric Association.DSM-Ⅳ:Diagnostic and statistical manual of mental disorders,4th ed[M].Washington:American Psychiatric Association,1994:92-94.
[11] Tang WK,Chan SS,Chiu HF,et al.Frequency and clinical determinants of poststroke cognitive impairment in nondemented stroke patients[J].J Geriatr Psychiatry Neurol,2006,19(2):65-71.
[12] Scandinavian Stroke Study Group.Multicenter trial of hemodilution in ischemic stroke--background and study protocol[J].Stroke,1985,16(5):885-890.
[13] Sulter G,Steen C,Keyser JD.Use of the Barthel index and modified Rankin scale in acute stroke trials[J].Stroke ,1999,30(8):1538-1541.
[14] North American Symptomatic Carotid Endarterectomy Trial Collaborators.Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade stenosis[J].N Engl J Med,1991,325(7):445-453.
[15] 黄茂盛,洪震,曾军,等.90年代上海社区脑卒中发病率、死亡率及其危险因素动态分析[J]。中华流行病学杂志,2001,22(3):198-201。
[16] Pullicino P,Nelson RF,Kendall BE,et al.Small deep infarcts diagnosed on computed tomography[J].Neurology,1980,30(10):1090-1096.
[17] De Ronchi D,Palmer K,Pioggiosi P,et al.The combined effect of age,education,and stroke on dementia and cognitive impairment no dementia in the elderly[J].Dement Geriatr Cogn Disord,2007,24(4):266-273.
[18] Cheng G,Huang C,Deng H,et al.Diabetes as a risk factor for dementia and mild cognitive impairment:a meta-analysis of longitudinal studies[J].Intern Med J,2012,42(5):484-491.
[19] Stebbins GT,Nyenhuis DL,Wang C,et al.Gray matter atrophy in patients with ischemic stroke with cognitive impairment[J].Stroke,2008,39(3):785-793.
[20] Leys D,Hénon H,Mackowiak-Cordoliani MA,et al.Poststroke dementia[J].Lancet Neurol,2005,4(11):752-759.
[21] Bowler JV.Vascular cognitive impairment[J].J Neurol Neurosurg Psychiatry,2005,76(Suppl V):v35-v44.
[22] Mark D’Esposito,editor,Neurological Foundations of Cognitive Neuroscience,A Bradford Book[M],The MIT Press,Cambridge,Massachusetts,London,England,2003.
[23] Bour AM,Rasquin SM,Baars L,et al.The effect of the APOE-epsilon4 allele and ACE-I/D polymorphism on cognition during a two-year follow-up in first-ever stroke patients[J].Dement Geriatr Cogn Disord,2010,29(6):534-542.
[24] Richard F,Fromentin-David I,Ricolfi F,et al.The angiotensin I converting enzyme gene as a susceptibility factor for dementia[J].Neurology,2001,56(11):1593-1595.