异氟醚与手术对大鼠学习记忆、氧化应激水平和海马AGEs/RAGE表达变化的影响
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摘要
背景与目的
老年患者麻醉与手术后患者常出现认知功能下降,主要表现为手术后谵妄(postoperative delirium,PD)与术后认知功能障碍(Postoperative Cognitive Dysfunction POCD)。PD与POCD可以发生在任何年龄患者,但更多见于老年人群,两者的关系及发病机制尚不清楚,但PD可能导致患者住院天数及花费增加、并可能导致患者术后6个月内死亡率增高,POCD同样可以增加患者死亡率、患者过早地失去劳动能力、并且增加社会及家庭负担。PD通常发生在术后1-3天,而POCD在术后一周发生率相对高,约为25%。尽管术后认知功能损害机制尚不明确,但无疑老龄是其重要的的危险因素之一。既往研究表明脑氧化应激损伤、高级糖基化终末产物(advanced glycosylation end product,AGEs)及其受体(receptor for advanced glycation end products RAGE)介导的神经功能损害与老年认知功能障碍疾病密切相关。本研究拟采用比色法、RT-PCR、免疫组化方法来观察异氟醚及手术对大鼠脑内氧化应激水平、AGEs与RAGE表达变化影响,同时应用Morris水迷宫检测麻醉与手术后大鼠学习及记忆功能,为术后认知损害的机制研究奠定一定基础。
材料与方法
选用健康雄性SD大鼠,老年大鼠20月龄,青年大鼠4月龄,随机分为6组:老年空白对照组(N1);老年异氟醚麻醉组(A1);老年手术组(B1);成年空白对照组(N2);成年异氟醚麻醉组(A2);成年手术组(B2);老年与成年异氟醚麻醉组分别吸入1.5%异氟醚麻醉2小时,老年与成年手术组在1.5%异氟醚麻醉过程中行剖腹探查术,持续时间2小时。空白对照组在麻醉吸入箱内吸入30%空氧混合气体2小时作为对照。处理结束后24小时60只大鼠行水迷宫试验,分别进行定位导航试验(Place navigation test)与空间探索实验(spatial probe test)以观察麻醉与手术对大鼠学习记忆功能的影响。48只大鼠于麻醉和手术后24小时处死,断脑取海马,部分海马及大脑皮质进行组织匀浆,采用比色法测定组织中丙二醛(Maleic Dialdehyde ,MDA)以及超氧化物歧化酶(Superoxide dismutase ,SOD)含量,以比较各组氧化应激水平差异。大鼠海马组织标本部分经多聚甲醛固定后石蜡切片,免疫组化染色观察AGEs、RAGE表达变化。部分海马组织提取总RNA后进行RT-PCR测定RAGE mRNA表达变化。
结果
1.水迷宫结果:A1、B1组第四、五天逃逸潜伏期较N1延长(P<0.05),而与A1比较,B1组延长更显著(P<0.05);A2组第四、五天逃逸潜伏期与对照组比较无统计学差异(P>0.05),B2组逃逸潜伏期与N1及A1组比较均延长(P<0.05)。A1、B1组穿越平台的次数与N1组比较明显减少(均P <0.01),而探索时间缩短(均P <0.05)。与N2组比较,A2组空间探索时间及穿越平台次数无显著差异,B2组穿越平台次数较N2及A2组减少(P <0.01),探索时间缩短(P <0.05)。
2.氧化应激指标:与N2组相比,N1组SOD值下降而MDA水平上升。异氟醚及手术处理后老年组大鼠SOD水平进一步降低,而MDA水平升高,且B1组改变最为明显,与N1及A1组比较差异显著(P<0.05)。与N2组比较,A2组氧化应激水平出现一定升高(P<0.05),而B2组SOD下降与MDA升高更为显著,与对照组及单纯异氟醚处理组比较均有显著差异(P<0.01)。
3. AGEs表达:N2组AGEs沉积最少,A2组与N2组比较未见差异,B2组出现明显升高,与N2及A2组比较均有统计学差异(P<0.05)。N1与N2组比较,AGEs基础值处与较高水平(P<0.05)。麻醉及手术后AGEs沉积量均有不同程度的升高,但B1组升高更为显著,与N1及A1比较均有明显差异(P<0.01)。
4. RAGE表达:mRNA结果比较,A1与B1组出现明显的RAGE表达上调(P<0.01),但B1组升高更为显著,与A1组比较有统计学差异(P<0.05)。A2组RAGE mRNA表达未见明显升高,而B2组表达上调,均高于N2与A2组。RAGE蛋白表达结果显示,A1组与B1组RAGE均呈现增高趋势,与N1比较有显著意义(P <0.05)。A2与N2组比较未见差异,B2组RAGE表达增多,与N2及B2比较均有显著差异(P<0.05)。
结论
1.1.5%异氟醚吸入麻醉后导致老年大鼠学习记忆能力下降,在此基础上手术导致了老年大鼠认知功能改变进一步加重;异氟醚麻醉未对成年大鼠学习记忆功能造成明显损害,但在此基础上手术处理导致了成年大鼠认知功能损害。
2.异氟醚与手术处理造成大鼠海马氧化应激水平增高,对老年大鼠影响更为明显,异氟醚麻醉及手术后均导致老年大鼠AGEs与RAGE表达升高,而成年大鼠仅表现为手术后表达升高。
3.由于异氟醚及手术导致的氧化应激增强及AGEs与RAGE表达变化可能是导致动物发生学习记忆能力下降的原因之一。
Implications and objective
Postoperative delirium and cognitive dysfunction (POCD) are topics of special importance in the geriatric surgical population. They are separate entities, whose relationship has yet to be fully elucidated. Although not limited to geriatric patients, the incidence and impact of both are more profound in geriatric patients. Delirium has been shown to be associated with longer and more costly hospital course and higher likelihood of death within six months or postoperative institutionalization. POCD has also been associated with increased mortality, risk of losing ability to work prematurely, and heavier burden on the society and families. Postoperative delirium tends to first be observed in one to three postoperative days, while up to twenty-five percent patients tend to experience a postoperative cognitive dysfunction in one postoperative week. To date, the etiology of PD and POCD remains unclear, but aging is considered as one of the riskiest factors. Previous studies show that cognitive dysfunction of the aged people is closely related to the brain injury induced by oxidative stress, and some geriatric neurological diseases were mediated by advanced glycation end products (AGEs) and the receptor for advanced glycation end products (RAGE). This study applies colorimetry, RT-PCR, immunohistochemical method to observe the impact of isoflurane and operation upon the oxidative stress in rat’s brain, the changes of AGEs and RAGE expression in hippocampus. At the same time, the author applies Morris water maze to test learning and memorizing ability of rats after operation and anesthesia, which lays a foundation for the study on mechanism of postoperative cognitive impairment.
Materials and methods
Healthy male SD rats, rats of 20 months old, rats of 4 months old, were randomly divided into six groups: elderly control group (N1); elderly isoflurane anesthesia group (A1); elderly operation group (B1 ); adult control group (N2); adult isoflurane anesthesia group (A2); adult operation group (B2); In A1 and A2 groups rats were anesthetized with 1.5% isoflurane for 2 hours. In B1 and B2 groups rats underwent laparotomy in condition of 1.5% isoflurane anesthesia for 2 hours .As a comparison, rats in N1 and N2 groups breathe 30% oxygen and air mixed gas for 2 hours in Inhalation box. After 24 hours of anesthesia and operation, sixty rats were underwent Morris maze test, including place navigation test and spatial probe test, to observe the impacts of anesthesia and operation upon rat’s learning and memorizing ability. Fouty-eight rats were executed after 24 hours of anesthesia and operation. Part hippocampuses and cerebral cortex drawn from died rats’brain were homogenized in order to detect the amount of MDA and SOD in the tissue by means of colorimetry, which is applied to compare the discrepancy of oxidative stress in groups. Part of the sample of rats’hippocampus were prepared for RT-PCR and immunohistochemistry to observe the changes of AGEs and RAGE expression.
Results:
1. The result of water maze test: Escape latency in A1 and B1 were longer than that in N1 on the forth and fifth days (P<0.05), and escape latency in B1 was longer than that in A1(P<0.05); escape latency in A2 group had no statistics difference with the comparison group on the forth and fifth days (P>0.05); escape latency in B2 was longer than N2 and A2 groups(P<0.05). The times of acrossing the original platform in A1and B1 were obviously less than N1 (average P<0.01), while time consumption was shorter than N1 (P<0.05). Compared to N2, A2 was no obvious difference between the time consumption of staying the original platform quadrant and the times of acrossing the original platform. The times of acrossing the original platform in B1 group was less than N2 and A2(P<0.01), and time consumption was shorter (P<0.05).
2. Index of oxidative stress: Compared to N2, the level of SOD in N1 was lower but the level of MDA was higher. The level of SOD in old rats treated with isoflurane and operation declined and further with accelerated level of MDA. The change of B1 is most obvious, particularly compared to N1, A1 (P<0.05). Compared to N2, the oxidative stress in A2 appears higher (P<0.05). The level of SOD in B2 declined apparently,but MDA accelerated. There were sharp differences between B2 and the comparison & isoflurane groups(P<0.01).
3. AGEs expression: The level of AGEs in N2 was the merest, the same level in A2 and N2, but obvious elevation in B2 compared to N2 and A2 (P<0.05). In the elderly groups,the level of AGEs increased to some degree after anesthesia and operation, with B1 the most significant compared to N1 and A1 (P<0.01).
4. RAGE expression: Compared to the result of mRNA, there was an obvious elevation in terms of RAGE expression in A1 and B1 groups, with B1 the most (P<0.05). There was slight elevation in A2, but significantly in B2, higher than N2 and A2. According to the result of RAGE protein expression, the amount of RAGE in A1 and B1 had a tendency to increase, obvious when compared to N1 (P<0.05). The results in A2 and N2 were similar, and higher in B2 when compared to A2, N2 (P<0.05).
Conclusions:
1. The 1.5% isoflurane results in the declining ability to learn and memorize for old rats, but the impact is more significant when after operation; In this respect, under 1.5% isoflurane inhalation anesthesia ,there is no obviosly harm to adult rats. Operation result in cognitive impairment to adult rats.
2. Isoflurane and operation result in the elevation of oxidative stress in rat’s hippocampus and cerebral cortex, which appears more obvious in the old rats group. Isoflurane and operation both lead to the elevation of AGEs and RAGE expression in old rats, only operation do for adult rats.
3. The enhancement of oxidative stress caused by isoflurane and operation and the changes of AGEs and RAGE expression are likely to be one of the reasons of animals’declining ability to learn and memorize
老年患者麻醉与手术后患者常出现认知功能下降,主要表现为手术后谵妄(postoperative delirium,PD)与术后认知功能障碍(Postoperative Cognitive Dysfunction POCD)。PD与POCD可以发生在任何年龄患者,但更多见于老年人群,两者的关系及发病机制尚不清楚,但PD可能导致患者住院天数及花费增加、并可能导致患者术后6个月内死亡率增高,POCD同样可以增加患者死亡率、患者过早地失去劳动能力、并且增加社会及家庭负担。PD通常发生在术后1-3天,而POCD在术后一周发生率相对高,约为25%。尽管术后认知功能损害机制尚不明确,但无疑老龄是其重要的的危险因素之一。既往研究表明脑氧化应激损伤、高级糖基化终末产物(advanced glycosylation end product,AGEs)及其受体(receptor for advanced glycation end products RAGE)介导的神经功能损害与老年认知功能障碍疾病密切相关。本研究拟采用比色法、RT-PCR、免疫组化方法来观察异氟醚及手术对大鼠脑内氧化应激水平、AGEs与RAGE表达变化影响,同时应用Morris水迷宫检测麻醉与手术后大鼠学习及记忆功能,为术后认知损害的机制研究奠定一定基础。
材料与方法
选用健康雄性SD大鼠,老年大鼠20月龄,青年大鼠4月龄,随机分为6组:老年空白对照组(N1);老年异氟醚麻醉组(A1);老年手术组(B1);成年空白对照组(N2);成年异氟醚麻醉组(A2);成年手术组(B2);老年与成年异氟醚麻醉组分别吸入1.5%异氟醚麻醉2小时,老年与成年手术组在1.5%异氟醚麻醉过程中行剖腹探查术,持续时间2小时。空白对照组在麻醉吸入箱内吸入30%空氧混合气体2小时作为对照。处理结束后24小时60只大鼠行水迷宫试验,分别进行定位导航试验(Place navigation test)与空间探索实验(spatial probe test)以观察麻醉与手术对大鼠学习记忆功能的影响。48只大鼠于麻醉和手术后24小时处死,断脑取海马,部分海马及大脑皮质进行组织匀浆,采用比色法测定组织中丙二醛(Maleic Dialdehyde ,MDA)以及超氧化物歧化酶(Superoxide dismutase ,SOD)含量,以比较各组氧化应激水平差异。大鼠海马组织标本部分经多聚甲醛固定后石蜡切片,免疫组化染色观察AGEs、RAGE表达变化。部分海马组织提取总RNA后进行RT-PCR测定RAGE mRNA表达变化。
结果
1.水迷宫结果:A1、B1组第四、五天逃逸潜伏期较N1延长(P<0.05),而与A1比较,B1组延长更显著(P<0.05);A2组第四、五天逃逸潜伏期与对照组比较无统计学差异(P>0.05),B2组逃逸潜伏期与N1及A1组比较均延长(P<0.05)。A1、B1组穿越平台的次数与N1组比较明显减少(均P <0.01),而探索时间缩短(均P <0.05)。与N2组比较,A2组空间探索时间及穿越平台次数无显著差异,B2组穿越平台次数较N2及A2组减少(P <0.01),探索时间缩短(P <0.05)。
2.氧化应激指标:与N2组相比,N1组SOD值下降而MDA水平上升。异氟醚及手术处理后老年组大鼠SOD水平进一步降低,而MDA水平升高,且B1组改变最为明显,与N1及A1组比较差异显著(P<0.05)。与N2组比较,A2组氧化应激水平出现一定升高(P<0.05),而B2组SOD下降与MDA升高更为显著,与对照组及单纯异氟醚处理组比较均有显著差异(P<0.01)。
3. AGEs表达:N2组AGEs沉积最少,A2组与N2组比较未见差异,B2组出现明显升高,与N2及A2组比较均有统计学差异(P<0.05)。N1与N2组比较,AGEs基础值处与较高水平(P<0.05)。麻醉及手术后AGEs沉积量均有不同程度的升高,但B1组升高更为显著,与N1及A1比较均有明显差异(P<0.01)。
4. RAGE表达:mRNA结果比较,A1与B1组出现明显的RAGE表达上调(P<0.01),但B1组升高更为显著,与A1组比较有统计学差异(P<0.05)。A2组RAGE mRNA表达未见明显升高,而B2组表达上调,均高于N2与A2组。RAGE蛋白表达结果显示,A1组与B1组RAGE均呈现增高趋势,与N1比较有显著意义(P <0.05)。A2与N2组比较未见差异,B2组RAGE表达增多,与N2及B2比较均有显著差异(P<0.05)。
结论
1.1.5%异氟醚吸入麻醉后导致老年大鼠学习记忆能力下降,在此基础上手术导致了老年大鼠认知功能改变进一步加重;异氟醚麻醉未对成年大鼠学习记忆功能造成明显损害,但在此基础上手术处理导致了成年大鼠认知功能损害。
2.异氟醚与手术处理造成大鼠海马氧化应激水平增高,对老年大鼠影响更为明显,异氟醚麻醉及手术后均导致老年大鼠AGEs与RAGE表达升高,而成年大鼠仅表现为手术后表达升高。
3.由于异氟醚及手术导致的氧化应激增强及AGEs与RAGE表达变化可能是导致动物发生学习记忆能力下降的原因之一。
Implications and objective
Postoperative delirium and cognitive dysfunction (POCD) are topics of special importance in the geriatric surgical population. They are separate entities, whose relationship has yet to be fully elucidated. Although not limited to geriatric patients, the incidence and impact of both are more profound in geriatric patients. Delirium has been shown to be associated with longer and more costly hospital course and higher likelihood of death within six months or postoperative institutionalization. POCD has also been associated with increased mortality, risk of losing ability to work prematurely, and heavier burden on the society and families. Postoperative delirium tends to first be observed in one to three postoperative days, while up to twenty-five percent patients tend to experience a postoperative cognitive dysfunction in one postoperative week. To date, the etiology of PD and POCD remains unclear, but aging is considered as one of the riskiest factors. Previous studies show that cognitive dysfunction of the aged people is closely related to the brain injury induced by oxidative stress, and some geriatric neurological diseases were mediated by advanced glycation end products (AGEs) and the receptor for advanced glycation end products (RAGE). This study applies colorimetry, RT-PCR, immunohistochemical method to observe the impact of isoflurane and operation upon the oxidative stress in rat’s brain, the changes of AGEs and RAGE expression in hippocampus. At the same time, the author applies Morris water maze to test learning and memorizing ability of rats after operation and anesthesia, which lays a foundation for the study on mechanism of postoperative cognitive impairment.
Materials and methods
Healthy male SD rats, rats of 20 months old, rats of 4 months old, were randomly divided into six groups: elderly control group (N1); elderly isoflurane anesthesia group (A1); elderly operation group (B1 ); adult control group (N2); adult isoflurane anesthesia group (A2); adult operation group (B2); In A1 and A2 groups rats were anesthetized with 1.5% isoflurane for 2 hours. In B1 and B2 groups rats underwent laparotomy in condition of 1.5% isoflurane anesthesia for 2 hours .As a comparison, rats in N1 and N2 groups breathe 30% oxygen and air mixed gas for 2 hours in Inhalation box. After 24 hours of anesthesia and operation, sixty rats were underwent Morris maze test, including place navigation test and spatial probe test, to observe the impacts of anesthesia and operation upon rat’s learning and memorizing ability. Fouty-eight rats were executed after 24 hours of anesthesia and operation. Part hippocampuses and cerebral cortex drawn from died rats’brain were homogenized in order to detect the amount of MDA and SOD in the tissue by means of colorimetry, which is applied to compare the discrepancy of oxidative stress in groups. Part of the sample of rats’hippocampus were prepared for RT-PCR and immunohistochemistry to observe the changes of AGEs and RAGE expression.
Results:
1. The result of water maze test: Escape latency in A1 and B1 were longer than that in N1 on the forth and fifth days (P<0.05), and escape latency in B1 was longer than that in A1(P<0.05); escape latency in A2 group had no statistics difference with the comparison group on the forth and fifth days (P>0.05); escape latency in B2 was longer than N2 and A2 groups(P<0.05). The times of acrossing the original platform in A1and B1 were obviously less than N1 (average P<0.01), while time consumption was shorter than N1 (P<0.05). Compared to N2, A2 was no obvious difference between the time consumption of staying the original platform quadrant and the times of acrossing the original platform. The times of acrossing the original platform in B1 group was less than N2 and A2(P<0.01), and time consumption was shorter (P<0.05).
2. Index of oxidative stress: Compared to N2, the level of SOD in N1 was lower but the level of MDA was higher. The level of SOD in old rats treated with isoflurane and operation declined and further with accelerated level of MDA. The change of B1 is most obvious, particularly compared to N1, A1 (P<0.05). Compared to N2, the oxidative stress in A2 appears higher (P<0.05). The level of SOD in B2 declined apparently,but MDA accelerated. There were sharp differences between B2 and the comparison & isoflurane groups(P<0.01).
3. AGEs expression: The level of AGEs in N2 was the merest, the same level in A2 and N2, but obvious elevation in B2 compared to N2 and A2 (P<0.05). In the elderly groups,the level of AGEs increased to some degree after anesthesia and operation, with B1 the most significant compared to N1 and A1 (P<0.01).
4. RAGE expression: Compared to the result of mRNA, there was an obvious elevation in terms of RAGE expression in A1 and B1 groups, with B1 the most (P<0.05). There was slight elevation in A2, but significantly in B2, higher than N2 and A2. According to the result of RAGE protein expression, the amount of RAGE in A1 and B1 had a tendency to increase, obvious when compared to N1 (P<0.05). The results in A2 and N2 were similar, and higher in B2 when compared to A2, N2 (P<0.05).
Conclusions:
1. The 1.5% isoflurane results in the declining ability to learn and memorize for old rats, but the impact is more significant when after operation; In this respect, under 1.5% isoflurane inhalation anesthesia ,there is no obviosly harm to adult rats. Operation result in cognitive impairment to adult rats.
2. Isoflurane and operation result in the elevation of oxidative stress in rat’s hippocampus and cerebral cortex, which appears more obvious in the old rats group. Isoflurane and operation both lead to the elevation of AGEs and RAGE expression in old rats, only operation do for adult rats.
3. The enhancement of oxidative stress caused by isoflurane and operation and the changes of AGEs and RAGE expression are likely to be one of the reasons of animals’declining ability to learn and memorize
引文
1. Deiner S, Silverstein JH, Postoperative delirium and cognitive dysfunction. Br J Anaesth. 2009,103(1):41-46.
2. Rasmussen LS, Siersma VD. Postoperative cognitive dysfunction: true deterioration versus random variation.Acta Anaesthesiol. Scand.2004, (48):1137–1143.
3. Lewis MC, Nevo I, Paniagua MA, Ben-Ari A, Pretto E, Eisdorfer S,Davidson E,Matot I, Eisdorfer C.Uncomplicated general anesthesia in the elderly results in cognitive decline: does cognitive decline predict morbidity and mortality?Med. Hypotheses,2007, (68):484–492.
4. Jevtovic-Todorovic V,Hartman RE, Izumi Y,et al.Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits Neurosci,2003,23(3):876-882.
5. Pratico C,Quattrone D,Lueanto T,et a1.Drugs of anesthesia acting on central cholinergic system may cause postoperative cognitive dysfunction and delirium.Med Hypotheses,2005,65(5):972-982.
6. Culley DJ,BaxterMG, Yukhananov R, et al. Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats.Anesthesiology,2004,100(2):309-314.
7.谭嵘.丙泊酚和异氟烷对老年患者术中应激反应和术后认知功能恢复的影响.南方医科大学学报,2009,29(6):1247-1248.
8.张雪蓉,伍湘伊.异氟烷与七氟烷对老年病人术后早期认知功能的影响.新疆医科大学学报,2009,32(9):1331-1334.
9.段开明,常业恬,欧阳文等.异氟醚与七氟醚麻醉对老年患者术后认知功能的影响.实用预防医学,2006,13(3):501-502.
10. Wu CL, Hsu W, Richman JM,et al. Postoperative cognitive function as an outcome of regional anesthesia and analgesia. Reg Anesth Pain Med,2004,29:257–268.
11. Muller SV, Krause N, Schmidt M, et al.Cognitive dysfunction after abdominal surgery in elderly patients.Z Gerontol Geriatr,2004,37(6):475-485.
12. Canet J, Raeder J, Rasmussen LS,et al.Congnitive dysfunction after minor surgery in the elderly.Acta Anesthesiol Scand,2003,47(10):1204-1210.
13. Kharb S,Ghalaut VS.PLasma lipoperoxides:a preliminary reference range.Indian J Med Sci,2003,57(3):105-107.
14. Hsieh CC,Roswnblatt JI,Papaconstantinou J.Age associated changes in SAPK/JNKand p38 MAPK signaling in response to the generation of ROS by 3-nitrop ropionic acid.Mech Ageing Dev,2003,124(6):733-746.
15. Xie Z,Dong Y,Maeda U,et al The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta protein levels.Anesthesiology,2006,104:988-994.
16. Much G,Schinzel R,Loske C,et al.Alzheimer's disease--synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts.J Neural Transm,1998,105(4-5):439-461.
17.王培昌赵琪彦张建.北京健康人群AGEs水平测定及其增龄性变化的研究[J]中国老年学杂志,2006,6(26):725-726.
18. Gasic-Milenkovic J, Loske C, Münch G.Advanced glycation endproducts cause lipid peroxidation in the human neural cell line SH-SY5Y.Alzheimers Disease,2003, 5(1):25～30
19. Wong CH,Liu TZ,Chye SM,et al.Sevoflurane-induced oxidative stress and cellularinjury in human peripheral polymorphonuclear neutrophils.Food Chem Toxicol,2006,44(8):1399-1407.
20. Culley DJ,Baxter M,Yukhananov R,et al.The memory effects of general anesthesiapersit for weeks in young and aged rats.Anesth Analg,2003,96(4):1004.
21.夏月峰.异氟烷对老龄大鼠认知功能及海马CA3去突触界面结构的影响.中国优秀硕士学位论文全文数据库,2007.
22.邓娟周,华东,李敬诚,等.吸烟对AD大鼠认知功能和tau蛋白异常磷酸化的影响.中国行为医学科学,2007,16:591-593.
23. Orliaguet G,Vivien B,Langeron O,et al.Minimum alveolar concentration of volatile anesthetics in rats during postnatal maturation. Anesthesiology,2001,95:734-739.
24.王毅,孙波.腹腔手术后患者认知障碍发生的影响因素及护理需求.护理学报,2007,14(3):9-12.
25.耿德勤,王红梅,王志萍等.老龄大鼠麻醉术后认知障碍动物模型的建立及评价.实用临床医药杂志,2005,9(1):9-12.
26.黎涌,招伟贤,杨阳等.腹部手术对不同年龄患者氧化应激的影响.广东医药,2009,30(5):734-736.
27. Haripriya D, Sangeetha P,Kanchana A,et al. Modulation of age-associated oxidative DNA damage in rat brain cerebral cortex,striatum and hippocampus by L-carnitine.Exp Gerontol,2005,40(3):129-135.
28. Farr SA,Poon HF,Dogrukol-Ak D.The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and oxidative stress in aged SAMP8 mice.J Neurochem,2003,84(5):1173-1183.
29. Fukui K,Onodera K,Shinkai T,et al.Impairment of learing and memory in rats caused by oxidative stress and aging,and changes in antioxidatibe defense syestems.Ann N Y Acad Sci,2001,928:168-175.
30. Zhang Y,Dong Y,Wu X,et al.The mitochondrial pathway of anesthetic isoflurane-induced apoptosis.J Biol Chem,2010,285(6):4025-4037.
31. Miyata T, Fu MX,Kurokawa K,et al.Autoxidation products of both carbohydrates and lipid are increased in uremic plasma:Is there oxidative stress in uremia?.Kidney Int,1998,54(4):1290-1295.
32. Miyata T, Van Y,Kurokawa K,et al.Alterations in nonenzymatic biochemistry in uremia:Origin and significance of“carbonyl stress”in long-term uremic complications. Kidney Int,1999,55(2):389-399.
33. Wang Z,Li DD,Liang YY,et al.Activation of astrocytes by advanced glycation end products:cytokines induction and nitric oxide release.Acta Pharmacol Sin,2002,23(11):974-980.
34. Woltier RL,Maezawal,Ou JJ,et al.Advanced glycation endproduct precursor alters intracellular amyloid-beta/A beta PP carboxy-terminal fragment aggregation and cytotoxicity.J Alzheimers Dis,2003,5(6):467-476.
35. Takeuchi M,Bucala R,Suzuki T et al.Intraneuronal advanced glycation endproducts for cultures cortical neurons.J Neuropathol Exp Neurol,200,59(12):1094-1105.
36. Wantier MP,Chappey O,Corda S,et al.Activation of NADPH oxidase by AGE links oxidant stress to alter gene expression via RAGE.Am J Physiol.Endocrinol Metab,2001,280(5):E685-694.
37. Rasmussen LS,Johnson T,Kuipers HM,et al.Does anaesthesia cause postoperative cognitive dysfunction?A randomized study of regional versus general annaesthesia in
438 elderly patients.Acta Anaesthesiol Scan,2003,47(3):260-266.
38. Savic MM,Obradovic DI,Ugresic ND,et al.Bidirectional effects of benzodiazepine binding site ligands on active avoidance acquisition and retention: differential antagonism by flumazenil and beta-CCt.Psychopharmacology (Berl),2005,180(3): 455-465.
39. Pain L,Angst MJ,LeGourrier L,et al.Effect of a nonsedative does of p ropofol on memory for aversively loaded information in rats.Anesthesiology,2002,97(2) : 447– 453.
40. Komatsu H,Nogaya J,Anabuki D,et al.Memory facilitation by posttraining exposure to halothane, enflurane, and isoflurane in ddN mice.Anesth Analg,1993,76(3):609-612.
41. Canet J, Raeder J, Rasmussen LS, et al.Congnitive dysfunction afterminor surgery in the elderly[J].Acta Anesthesiol Scand, 2003,47(10):1204-1210.
42.郭蓉,曹云鹏.雌激素在阿尔茨海默病中的作用研究进展.国外医学.老年医学分册,2007,28(3):97-100.
43. Edwards H,Rose EA,Schorow M,et al.Postoperative deterioration in psychomotor function.JAMA,1981,245(13):1342-1343.
44. Grichnik KP,Ijsselmniden AJ,D’Amico TA,et al.Cognitive dicline after major nacardiac operations:a preliningary prospective study.Ann Thorac Surg,1999,68(5):1786-1791.
45. Rohan D,BuggyDJ, Crowley S, et a1.Increased incidence of postoperative cognitive dysfunction 24 hr after minor surgery in the elderly.CanAnaesth,2005;52(2):137-142.
46. Koksal,G.M.,Sayilgan,C,Aydin,S,et al.The effects of sevoflurane and desflurane on lipid peroxidation during laparoscopic cholecystectomy.Eur J Anaesthesiol,2004,21(3): 217–220.
1. Cole MG. Delirium in elderly patients. Am J Geriatr Psychiatry,2004,2:7–21.
2. Inouye SK. Delirium in older persons. N Engl J Med,2006,354:1157–1165.
3. Kain ZN, Caldwell-Andrews AA,Maranets I,et al. Preoperative anxiety and emergence delirium and postoperativemaladaptive behaviors. Anesth Analg,2004,99:1648–1654.
4. Marcantonio ER, Flacker JM, Wright RJ,et al. Reducing delirium after hip fracture:A randomized trial. J Am Geriatr Soc,2001,49:516–522.
5. Brauer C, Morrison RS, Silberzweig SB, et al. The cause of delirium in patients with hip fracture. Arch Intern Med,2000,160:1856–1860.
6. Pandharipande P, Jackson J, Ely EW.Delirium: acute cognitive dysfunction in the critically ill. Curr Opin Crit Care,2005,11:360–368
7. Inouye SK, van Dyck CH, Alessi CA,et al.Clarifying confusion: The confusion assessment method: A new method for detection of delirium. Ann Intern Med,1990,113:941–948.
8. Ely EW, Inouye SK, Bernard GR,et al.Delirium in mechanically ventilated patients: Validity and reliability of the Confusion Assessment Method for the intensive care unit (CAM-ICU). JAMA,2001,286:2703–2710.
9. Bekker AY, Weeks EJ. Cognitive function after anaesthesia in the elderly.Best Pract Res Clin Anaesthesiol,2003,17:259–272.
10. Bitsch M, Foss N, Kristensen B, et al.Pathogenesis of and management strategies for postoperative delirium after hip fracture: A review. Acta Orthop Scand 2004,75: 378–389.
11. Litaker D, Locala J, Franco K,et al. Preoperative risk factors for postoperative delirium. Gen Hosp Psychiatry,2001,23:84–89.
12. Leung JM, Sands LP, Mullen EA,et al. Are preoperative depressive symptoms associated with postoperative delirium in geriatric surgical patients? J Gerontol A Biol Sci Med Sci,2005,60:1563–1568.
13. Marcantonio ER, Goldman L, Orav EJ,et al. The association of intraoperative factorswith the development of postoperative delirium. Am J Med,1998,105:380–384.
14. Fong HK, Sands LP, Leung JM. The role of postoperative analgesia in delirium and cognitive decline in elderly patients: A systematic review. Anesth Analg,2006, 102:1255–1266.
15. Pandharipande P, Shintani A, Peterson J, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. ANESTHESIOLOGY, 2006,104:21–26.
16. Papaioannou A, Fraidakis O, Michaloudis D, et al. The impact of the type of anaesthesia on cognitive status and delirium during the first postoperative days in elderly patients. Eur J Anaesthesiol,2005,22:492–499.
17. Bryson GL, Wyand A. Evidence-based clinical update: General anesthesiaand the risk of delirium and postoperative cognitive dysfunction. Can J Anaesth,2006,53:669–677.
18. Tune LE. Serum anticholinergic activity levels and delirium in the elderly.Semin Clin Neuropsychiatry,2000,5:149–153.
19. Franco K, Litaker D, Locala J,et al. The cost of delirium in the surgical patient. Psychosomatics,2001,42:68–73.
20. Inouye SK, Bogardus ST Jr, Charpentier PA,et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med,1999,340:669–676.
21. Marcantonio ER, Flacker JM, Wright RJ, et al. Reducing deliriumafter hip fracture: A randomized trial. J Am Geriatr,Soc 2001,49:516–522.
22. Battaglia J. Pharmacological management of aacute agitation. Drugs,2005,65: 1207–1222.
23. Lezak MD, Howieson DB, Loring DW. Neuropsychological Assessment,4th edition. New York, Oxford University Press, 2004.
24. Jorm AF, Christensen H, Korten AE,et al. Do cognitive complaints either predict future cognitive decline or reflect past cognitive decline? A longitudinal study of an elderly community sample. Psychol Med,1997,27:91–98.
25. Rasmussen LS. Defining postoperative cognitive dysfunction. Eur J Anaesthesiol, 1998,15:761–764.
26. Lewis MS, Maruff P, Silbert BS, et al. The influence ofdifferent error estimates in the detection of post-operative cognitive dysfunction using reliable change indices with correction for practice effects. Arch Clin Neuropsychol,2006,21:421–427.
27. Moller JT, Cluitmans P, Rasmussen LS,et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. Lancet,1998,351:857–861.
28. Dodds C, Allison J. Postoperative cognitive deficit in the elderly surgicalpatient. Br J Anaesth,1998,81:449–462.
29. Abildstrom H, Rasmussen LS, Rentowl P,et al. Cognitive dysfunction 1-2 years after non-cardiac surgery in the elderly. ISPOCD group. International Study of Post-Operative Cognitive Dysfunction. Acta Anaesthesiol Scand,2000,1246–1251.
30. Rasmussen LS, Siersma VD. Postoperative cognitive dysfunction: True deterioration versus random variation. Acta Anaesthesiol Scand,2004,48:1137–1143.
31. Johnson T, Monk T, Rasmussen LS, et al. Postoperative cognitive dysfunction in middle-aged patients. ANESTHESIOLOGY,2002,96:1351–1357.
32. Canet J, Raeder J, Rasmussen LS,et al. Cognitive dysfunction after minor surgery in the elderly. Acta Anaesthesiol Scand,2003,47:1204–1210.
33. Heyer EJ, Sharma R, Winfree CJ,et al. Severe pain confounds neuropsychological test performance. J Clin Exp Neuropsychol,2000,22:633–639.
34. Wu CL, Hsu W, Richman JM,et al. Postoperative cognitive function as an outcome of regional anesthesia and analgesia. Reg Anesth Pain Med,2004,29:257–268.
35. Culley DJ, Baxter MG, Crosby CA,et al. Impaired acquisition of spatial memory 2 weeks after isoflurane and isoflurane-nitrous oxide anesthesia in aged rats. Anesth Analg,2004,99:1393–1397.
36. Eckenhoff RG, Johansson JS, Wei H,et al. Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. ANESTHESIOLOGY,2004; 101:703–709.
37. Harwood DG,BarkerWW,Ownby RL, et al.Apolipop rotein E polymorphism and age of onset for Alzheimer’s disease in a biethnic sample.Int Psychiatry,2004,16(3):317-326.
38. Abildstrom H, Christiansen M, Siersma VD,et al. Apolipoprotein E genotype and cognitive dysfunction after noncardiac surgery. ANESTHESIOLOGY,2004, 101:855–861.
39. Rasmussen LS, Christiansen M, Eliasen K,et al. Biochemical markers for brain damage after cardiac surgery: Time profile and correlation with cognitive dysfunction. Acta Anaesthesiol Scand,2002,46:547–551.
40. Williams-Russo P, Sharrock NE, Mattis S,et al.Cognitive effects after epidural versus general anesthesia in older adults: A randomized trial. JAMA,1995,274:44–50.
41. Jackson JC, Gordon SM, Hart RP,et al. The associationbetween delirium and cognitive decline: A review of the empirical literature.Neuropsychol Rev,2004,14:87–1498.
2. Rasmussen LS, Siersma VD. Postoperative cognitive dysfunction: true deterioration versus random variation.Acta Anaesthesiol. Scand.2004, (48):1137–1143.
3. Lewis MC, Nevo I, Paniagua MA, Ben-Ari A, Pretto E, Eisdorfer S,Davidson E,Matot I, Eisdorfer C.Uncomplicated general anesthesia in the elderly results in cognitive decline: does cognitive decline predict morbidity and mortality?Med. Hypotheses,2007, (68):484–492.
4. Jevtovic-Todorovic V,Hartman RE, Izumi Y,et al.Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits Neurosci,2003,23(3):876-882.
5. Pratico C,Quattrone D,Lueanto T,et a1.Drugs of anesthesia acting on central cholinergic system may cause postoperative cognitive dysfunction and delirium.Med Hypotheses,2005,65(5):972-982.
6. Culley DJ,BaxterMG, Yukhananov R, et al. Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats.Anesthesiology,2004,100(2):309-314.
7.谭嵘.丙泊酚和异氟烷对老年患者术中应激反应和术后认知功能恢复的影响.南方医科大学学报,2009,29(6):1247-1248.
8.张雪蓉,伍湘伊.异氟烷与七氟烷对老年病人术后早期认知功能的影响.新疆医科大学学报,2009,32(9):1331-1334.
9.段开明,常业恬,欧阳文等.异氟醚与七氟醚麻醉对老年患者术后认知功能的影响.实用预防医学,2006,13(3):501-502.
10. Wu CL, Hsu W, Richman JM,et al. Postoperative cognitive function as an outcome of regional anesthesia and analgesia. Reg Anesth Pain Med,2004,29:257–268.
11. Muller SV, Krause N, Schmidt M, et al.Cognitive dysfunction after abdominal surgery in elderly patients.Z Gerontol Geriatr,2004,37(6):475-485.
12. Canet J, Raeder J, Rasmussen LS,et al.Congnitive dysfunction after minor surgery in the elderly.Acta Anesthesiol Scand,2003,47(10):1204-1210.
13. Kharb S,Ghalaut VS.PLasma lipoperoxides:a preliminary reference range.Indian J Med Sci,2003,57(3):105-107.
14. Hsieh CC,Roswnblatt JI,Papaconstantinou J.Age associated changes in SAPK/JNKand p38 MAPK signaling in response to the generation of ROS by 3-nitrop ropionic acid.Mech Ageing Dev,2003,124(6):733-746.
15. Xie Z,Dong Y,Maeda U,et al The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta protein levels.Anesthesiology,2006,104:988-994.
16. Much G,Schinzel R,Loske C,et al.Alzheimer's disease--synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts.J Neural Transm,1998,105(4-5):439-461.
17.王培昌赵琪彦张建.北京健康人群AGEs水平测定及其增龄性变化的研究[J]中国老年学杂志,2006,6(26):725-726.
18. Gasic-Milenkovic J, Loske C, Münch G.Advanced glycation endproducts cause lipid peroxidation in the human neural cell line SH-SY5Y.Alzheimers Disease,2003, 5(1):25～30
19. Wong CH,Liu TZ,Chye SM,et al.Sevoflurane-induced oxidative stress and cellularinjury in human peripheral polymorphonuclear neutrophils.Food Chem Toxicol,2006,44(8):1399-1407.
20. Culley DJ,Baxter M,Yukhananov R,et al.The memory effects of general anesthesiapersit for weeks in young and aged rats.Anesth Analg,2003,96(4):1004.
21.夏月峰.异氟烷对老龄大鼠认知功能及海马CA3去突触界面结构的影响.中国优秀硕士学位论文全文数据库,2007.
22.邓娟周,华东,李敬诚,等.吸烟对AD大鼠认知功能和tau蛋白异常磷酸化的影响.中国行为医学科学,2007,16:591-593.
23. Orliaguet G,Vivien B,Langeron O,et al.Minimum alveolar concentration of volatile anesthetics in rats during postnatal maturation. Anesthesiology,2001,95:734-739.
24.王毅,孙波.腹腔手术后患者认知障碍发生的影响因素及护理需求.护理学报,2007,14(3):9-12.
25.耿德勤,王红梅,王志萍等.老龄大鼠麻醉术后认知障碍动物模型的建立及评价.实用临床医药杂志,2005,9(1):9-12.
26.黎涌,招伟贤,杨阳等.腹部手术对不同年龄患者氧化应激的影响.广东医药,2009,30(5):734-736.
27. Haripriya D, Sangeetha P,Kanchana A,et al. Modulation of age-associated oxidative DNA damage in rat brain cerebral cortex,striatum and hippocampus by L-carnitine.Exp Gerontol,2005,40(3):129-135.
28. Farr SA,Poon HF,Dogrukol-Ak D.The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and oxidative stress in aged SAMP8 mice.J Neurochem,2003,84(5):1173-1183.
29. Fukui K,Onodera K,Shinkai T,et al.Impairment of learing and memory in rats caused by oxidative stress and aging,and changes in antioxidatibe defense syestems.Ann N Y Acad Sci,2001,928:168-175.
30. Zhang Y,Dong Y,Wu X,et al.The mitochondrial pathway of anesthetic isoflurane-induced apoptosis.J Biol Chem,2010,285(6):4025-4037.
31. Miyata T, Fu MX,Kurokawa K,et al.Autoxidation products of both carbohydrates and lipid are increased in uremic plasma:Is there oxidative stress in uremia?.Kidney Int,1998,54(4):1290-1295.
32. Miyata T, Van Y,Kurokawa K,et al.Alterations in nonenzymatic biochemistry in uremia:Origin and significance of“carbonyl stress”in long-term uremic complications. Kidney Int,1999,55(2):389-399.
33. Wang Z,Li DD,Liang YY,et al.Activation of astrocytes by advanced glycation end products:cytokines induction and nitric oxide release.Acta Pharmacol Sin,2002,23(11):974-980.
34. Woltier RL,Maezawal,Ou JJ,et al.Advanced glycation endproduct precursor alters intracellular amyloid-beta/A beta PP carboxy-terminal fragment aggregation and cytotoxicity.J Alzheimers Dis,2003,5(6):467-476.
35. Takeuchi M,Bucala R,Suzuki T et al.Intraneuronal advanced glycation endproducts for cultures cortical neurons.J Neuropathol Exp Neurol,200,59(12):1094-1105.
36. Wantier MP,Chappey O,Corda S,et al.Activation of NADPH oxidase by AGE links oxidant stress to alter gene expression via RAGE.Am J Physiol.Endocrinol Metab,2001,280(5):E685-694.
37. Rasmussen LS,Johnson T,Kuipers HM,et al.Does anaesthesia cause postoperative cognitive dysfunction?A randomized study of regional versus general annaesthesia in
438 elderly patients.Acta Anaesthesiol Scan,2003,47(3):260-266.
38. Savic MM,Obradovic DI,Ugresic ND,et al.Bidirectional effects of benzodiazepine binding site ligands on active avoidance acquisition and retention: differential antagonism by flumazenil and beta-CCt.Psychopharmacology (Berl),2005,180(3): 455-465.
39. Pain L,Angst MJ,LeGourrier L,et al.Effect of a nonsedative does of p ropofol on memory for aversively loaded information in rats.Anesthesiology,2002,97(2) : 447– 453.
40. Komatsu H,Nogaya J,Anabuki D,et al.Memory facilitation by posttraining exposure to halothane, enflurane, and isoflurane in ddN mice.Anesth Analg,1993,76(3):609-612.
41. Canet J, Raeder J, Rasmussen LS, et al.Congnitive dysfunction afterminor surgery in the elderly[J].Acta Anesthesiol Scand, 2003,47(10):1204-1210.
42.郭蓉,曹云鹏.雌激素在阿尔茨海默病中的作用研究进展.国外医学.老年医学分册,2007,28(3):97-100.
43. Edwards H,Rose EA,Schorow M,et al.Postoperative deterioration in psychomotor function.JAMA,1981,245(13):1342-1343.
44. Grichnik KP,Ijsselmniden AJ,D’Amico TA,et al.Cognitive dicline after major nacardiac operations:a preliningary prospective study.Ann Thorac Surg,1999,68(5):1786-1791.
45. Rohan D,BuggyDJ, Crowley S, et a1.Increased incidence of postoperative cognitive dysfunction 24 hr after minor surgery in the elderly.CanAnaesth,2005;52(2):137-142.
46. Koksal,G.M.,Sayilgan,C,Aydin,S,et al.The effects of sevoflurane and desflurane on lipid peroxidation during laparoscopic cholecystectomy.Eur J Anaesthesiol,2004,21(3): 217–220.
1. Cole MG. Delirium in elderly patients. Am J Geriatr Psychiatry,2004,2:7–21.
2. Inouye SK. Delirium in older persons. N Engl J Med,2006,354:1157–1165.
3. Kain ZN, Caldwell-Andrews AA,Maranets I,et al. Preoperative anxiety and emergence delirium and postoperativemaladaptive behaviors. Anesth Analg,2004,99:1648–1654.
4. Marcantonio ER, Flacker JM, Wright RJ,et al. Reducing delirium after hip fracture:A randomized trial. J Am Geriatr Soc,2001,49:516–522.
5. Brauer C, Morrison RS, Silberzweig SB, et al. The cause of delirium in patients with hip fracture. Arch Intern Med,2000,160:1856–1860.
6. Pandharipande P, Jackson J, Ely EW.Delirium: acute cognitive dysfunction in the critically ill. Curr Opin Crit Care,2005,11:360–368
7. Inouye SK, van Dyck CH, Alessi CA,et al.Clarifying confusion: The confusion assessment method: A new method for detection of delirium. Ann Intern Med,1990,113:941–948.
8. Ely EW, Inouye SK, Bernard GR,et al.Delirium in mechanically ventilated patients: Validity and reliability of the Confusion Assessment Method for the intensive care unit (CAM-ICU). JAMA,2001,286:2703–2710.
9. Bekker AY, Weeks EJ. Cognitive function after anaesthesia in the elderly.Best Pract Res Clin Anaesthesiol,2003,17:259–272.
10. Bitsch M, Foss N, Kristensen B, et al.Pathogenesis of and management strategies for postoperative delirium after hip fracture: A review. Acta Orthop Scand 2004,75: 378–389.
11. Litaker D, Locala J, Franco K,et al. Preoperative risk factors for postoperative delirium. Gen Hosp Psychiatry,2001,23:84–89.
12. Leung JM, Sands LP, Mullen EA,et al. Are preoperative depressive symptoms associated with postoperative delirium in geriatric surgical patients? J Gerontol A Biol Sci Med Sci,2005,60:1563–1568.
13. Marcantonio ER, Goldman L, Orav EJ,et al. The association of intraoperative factorswith the development of postoperative delirium. Am J Med,1998,105:380–384.
14. Fong HK, Sands LP, Leung JM. The role of postoperative analgesia in delirium and cognitive decline in elderly patients: A systematic review. Anesth Analg,2006, 102:1255–1266.
15. Pandharipande P, Shintani A, Peterson J, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. ANESTHESIOLOGY, 2006,104:21–26.
16. Papaioannou A, Fraidakis O, Michaloudis D, et al. The impact of the type of anaesthesia on cognitive status and delirium during the first postoperative days in elderly patients. Eur J Anaesthesiol,2005,22:492–499.
17. Bryson GL, Wyand A. Evidence-based clinical update: General anesthesiaand the risk of delirium and postoperative cognitive dysfunction. Can J Anaesth,2006,53:669–677.
18. Tune LE. Serum anticholinergic activity levels and delirium in the elderly.Semin Clin Neuropsychiatry,2000,5:149–153.
19. Franco K, Litaker D, Locala J,et al. The cost of delirium in the surgical patient. Psychosomatics,2001,42:68–73.
20. Inouye SK, Bogardus ST Jr, Charpentier PA,et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med,1999,340:669–676.
21. Marcantonio ER, Flacker JM, Wright RJ, et al. Reducing deliriumafter hip fracture: A randomized trial. J Am Geriatr,Soc 2001,49:516–522.
22. Battaglia J. Pharmacological management of aacute agitation. Drugs,2005,65: 1207–1222.
23. Lezak MD, Howieson DB, Loring DW. Neuropsychological Assessment,4th edition. New York, Oxford University Press, 2004.
24. Jorm AF, Christensen H, Korten AE,et al. Do cognitive complaints either predict future cognitive decline or reflect past cognitive decline? A longitudinal study of an elderly community sample. Psychol Med,1997,27:91–98.
25. Rasmussen LS. Defining postoperative cognitive dysfunction. Eur J Anaesthesiol, 1998,15:761–764.
26. Lewis MS, Maruff P, Silbert BS, et al. The influence ofdifferent error estimates in the detection of post-operative cognitive dysfunction using reliable change indices with correction for practice effects. Arch Clin Neuropsychol,2006,21:421–427.
27. Moller JT, Cluitmans P, Rasmussen LS,et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. Lancet,1998,351:857–861.
28. Dodds C, Allison J. Postoperative cognitive deficit in the elderly surgicalpatient. Br J Anaesth,1998,81:449–462.
29. Abildstrom H, Rasmussen LS, Rentowl P,et al. Cognitive dysfunction 1-2 years after non-cardiac surgery in the elderly. ISPOCD group. International Study of Post-Operative Cognitive Dysfunction. Acta Anaesthesiol Scand,2000,1246–1251.
30. Rasmussen LS, Siersma VD. Postoperative cognitive dysfunction: True deterioration versus random variation. Acta Anaesthesiol Scand,2004,48:1137–1143.
31. Johnson T, Monk T, Rasmussen LS, et al. Postoperative cognitive dysfunction in middle-aged patients. ANESTHESIOLOGY,2002,96:1351–1357.
32. Canet J, Raeder J, Rasmussen LS,et al. Cognitive dysfunction after minor surgery in the elderly. Acta Anaesthesiol Scand,2003,47:1204–1210.
33. Heyer EJ, Sharma R, Winfree CJ,et al. Severe pain confounds neuropsychological test performance. J Clin Exp Neuropsychol,2000,22:633–639.
34. Wu CL, Hsu W, Richman JM,et al. Postoperative cognitive function as an outcome of regional anesthesia and analgesia. Reg Anesth Pain Med,2004,29:257–268.
35. Culley DJ, Baxter MG, Crosby CA,et al. Impaired acquisition of spatial memory 2 weeks after isoflurane and isoflurane-nitrous oxide anesthesia in aged rats. Anesth Analg,2004,99:1393–1397.
36. Eckenhoff RG, Johansson JS, Wei H,et al. Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. ANESTHESIOLOGY,2004; 101:703–709.
37. Harwood DG,BarkerWW,Ownby RL, et al.Apolipop rotein E polymorphism and age of onset for Alzheimer’s disease in a biethnic sample.Int Psychiatry,2004,16(3):317-326.
38. Abildstrom H, Christiansen M, Siersma VD,et al. Apolipoprotein E genotype and cognitive dysfunction after noncardiac surgery. ANESTHESIOLOGY,2004, 101:855–861.
39. Rasmussen LS, Christiansen M, Eliasen K,et al. Biochemical markers for brain damage after cardiac surgery: Time profile and correlation with cognitive dysfunction. Acta Anaesthesiol Scand,2002,46:547–551.
40. Williams-Russo P, Sharrock NE, Mattis S,et al.Cognitive effects after epidural versus general anesthesia in older adults: A randomized trial. JAMA,1995,274:44–50.
41. Jackson JC, Gordon SM, Hart RP,et al. The associationbetween delirium and cognitive decline: A review of the empirical literature.Neuropsychol Rev,2004,14:87–1498.