轻度认知障碍调查与诊断研究
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摘要
目的:轻度认知障碍(mild cognitive impairment,MCI)是介于正常衰老与痴呆之间的认知功能缺损状态,以获得性认知功能障碍,但不伴有显著的日常生活能力下降为特征。MCI患者每年约有一定比例转化为老年性痴呆,是老年性痴呆的高危人群。如果能在MCI阶段给予治疗干预,有可能降低老年性痴呆发病率。因此如何早期诊断MCI成为近年来老年病学和神经病学的研究[1]热点。MCI的诊断目前国内外研究没有固定标准,其危险因素也有很大争议,需要对其进行更多的研究工作。本研究旨在明确轻度认知障碍的影响因素,明确控制危险因素对轻度认知障碍的防治作用,以及分析灵敏的轻度认知障碍神经心理评估量表。
方法:(1)调查对象为2007年12月~2009年12月期间,在秦皇岛市社区选取65岁及以上老年人,包括城市人口和农村人口。最终入选本研究1011例,男410例,女601例。采用统一的调查表和标准化调查用语,按名单入户调查,详细记录调查资料。对符合入选标准的受试者进行认知功能评估,记录受试者的人口学资料(表1)、生活习惯(表2)、既往病史(表3)、神经心理评估结果(表4-8)。最后完成诊断(包括认知水平和其他疾病诊断)。不能完成评估或不能配合进行认知评估者,依据临床信息进行诊断。
结果:(1)轻度认知障碍人数67例,痴呆人数45例,正常人数899例,MCI的发生率为6.63%,痴呆发生率4.45%;
(2)人口学资料中年龄(趋势χ2=120.106,P≤0.000)、长期居住地(χ2=4.758,P=0.029)与MCI的发生率存在显著的统计学差异,其中随着年龄增长,MCI发生率随之增长趋势明显;性别(χ2=1.773,P=0.183)、受教育情况(χ2=0.702,P=0.402)、体重指数(T=0.876,P=0.386)、职业(χ2=10.030,P=0.123)未见明显统计学差异。(3)生活习惯中吸烟史(趋势χ2=5.097,P=0.024)、是否饮酒(χ2=7.251,P=0.007),运动状态(趋势χ2=43.729,P≤0.000)与MCI的发生率存在显著的统计学差异,其中随着吸烟史增长,MCI发生率随之增长趋势明显,运动状态持续时间增长,MCI发生率随之降低趋势明显;是否喝茶(χ2=0.171,P=0.679)未见明显统计学差异。(4)患病史中脑血管疾病(χ2=8.760,P=0.003)、心脏疾病(χ2=8.767,P=0.003)、内分泌代谢疾病(χ2=4.018,P=0.045)、癫痫(χ2=21.558,P≤0.000)、抑郁症(χ2=5.026,P=0.060)、脑外伤史(χ2=39.447,P≤0.000)、家族史(χ2=11.630,P=0.001)与MCI的发生率存在显著的统计学差异。高血压(χ2=1.068,P=0.301)未见明显差异。5 MMSE、MoCA、FAQ识别MCI的效果:MMSE识别MCI的灵敏度(%)为59.70,特异度(%)为89.21,准确度(%)为87.16,假阳性率(%)为10.79,假阴性率(%)为40.30;MoCA识别MCI的灵敏度(%)为89.55,特异度(%)为97.66,准确度(%)为97.10,假阳性率(%)为23.36,假阴性率(%)10.45;FAQ识别MCI的灵敏度(%)为58.20,特异度(%)为89.43,准确度(%)为87.27,假阳性率(%)为10.57,假阴性率(%)41.79;
结论:1 MCI的发生率为6.63%,痴呆发生率4.45%。2人口学资料中年龄、长期居住地与MCI的发生率存在显著的统计学差异,其中随着年龄增长,MCI发生率随之增长趋势明显;长期居住地中城市、农村,其中农村的MCI的发生率明显高于城市。性别、受教育情况、体重指数、职业未见明显统计学差异。3生活习惯中吸烟史、是否饮酒、运动状态、与MCI的发生率存在显著的统计学差异,其中随着吸烟史增长,MCI发生率随之增长趋势明显,运动状态持续时间增长,MCI发生率随之降低趋势明显,饮酒人群MCI患病率明显高于非饮酒人群。是否喝茶未见明显统计学差异。4患病史中脑血管疾病、心脏疾病、内分泌代谢疾病、癫痫、抑郁症、脑外伤史、家族史与MCI的发生率存在显著的统计学差异。高血压未见明显差异。5 MMSE、MoCA、FAQ识别MCI的效果比较,MoCA的灵敏度、特异度、准确度均高于MMSE、FAQ,可以发现MMSE、FAQ区分不了的MCI和被错误区分的MCI; MMSE与FAQ灵敏度、特异度、准确度相差不大。
Objective: Mild cognitive impairment (mild cognitive impairment, MCI) is the state between normal aging and dementia, for cognitive dysfunction, but not accompanied by a significant decline in activities of daily living characterized. Each year about a certain percentage of patients with MCI gets into dementia, and MCI is a high risk population of dementia. If treatment can be given in the MCI stage , may reduce the incidence of dementia. So how early diagnosis of MCI is being as the research Hot of geriatrics and neurology in recent years. The standard in diagnosis of MCI at home and abroad is no fixed , and its risk factors are also highly controversial, so we need to be more research. This study was designed to clear the impact factors of mild cognitive impairment , the explicit control of risk factors to prevention and treatment of mild cognitive impairment, sensitive neuropsychological assessment scales of mild cognitive impairment.
Method: (1) The survey was conducted in December 2007 ~ December 2009 period, in Qinhuangdao city community 65 years and older selected, including urban and rural populations. Eventually enrolled in the study 1011 cases, 410 cases of male and female 601 cases. Adopt a unified and standardized survey questionnaire language, according to the list of household, and detailed record survey data. Subjects who meet inclusion criteria are given cognitive function assessment, and recorded demographic data (Table 1), habits (Table 2), past medical history (Table 3), neuropsychological assessment (Table 4-6 ). Finalized diagnosis (including diagnosis of cognitive level and other diseases).The subjects who can not complete the assessment or who can not meet the cognitive assessment are based on clinical information for diagnosis.
Results: (1) 67 cases with mild cognitive impairment, 45 cases with dementia , 899 cases of normal, MCI's rate was 6.63%, 4.45% incidence of dementia; (2)Between age (trendχ2 = 120.106, P≤0.000), long-term residence (χ2 = 4.758, P = 0.029) and incidence of MCI, there are significant statistical differences, which increase with age, MCI followed the trend rate of growth significantly; Gender (χ2 = 1.773, P = 0.183), educational situation (χ2 = 0.702, P = 0.402), body mass index (T = 0.876, P = 0.386), occupational (χ2 = 10.030, P = 0.123) are no significant statistical school different. (3)Between smoking habits in the history (trendχ2 = 5.097, P = 0.024), whether drinking (χ2 = 7.251, P = 0.007), exercise status (trendχ2 = 43.729, P≤0.000) and the incidence of MCI, there are significant statistical differences, which increase with the smoking history, MCI has significantly the incidence of subsequent growth trends, and with exercise duration increased state, MCI has significantly the incidence of subsequent growth trends; Wheater tea (χ2 = 0.171, P = 0.679) is no significant statistical different. (4)Between cerebrovascular disease (χ2 = 8.760, P = 0.003), heart disease (χ2 = 8.767, P = 0.003), endocrine and metabolic diseases (χ2 = 4.018, P = 0.045), epilepsy (χ2 = 21.558, P≤0.000), depression (χ2 = 5.026, P = 0.060), history of brain trauma (χ2 = 39.447, P≤0.000), family history (χ2 = 11.630, P = 0.001) and incidence of MCI, there are significant statistical school differences. Hypertension (χ2 = 1.068, P = 0.301) has no significant difference. 5 MMSE, MoCA, FAQ recognize the effect of MCI: MMSE MCI recognition sensitivity (%) were 59.70, specificity (%) were 89.21, accuracy (%) were 87.16, the false positive rate (%) were 10.79, false negative rate (%) were 40.30; MoCA MCI recognition sensitivity (%) were 89.55, specificity (%) were 97.66, accuracy (%) were 97.10, the false positive rate (%) were 23.36, the false negative rate (%) were 10.45; FAQ MCI recognition sensitivity (%) were 58.20, specificity (%) were 89.43, accuracy (%) were 87.27, false positive rate (%) were 10.57, false negative rate (%) were 41.79;
Conclusion: 1 MCI's rate was 6.63%, 4.45% was incidence of dementia. 2 Between age, long-term residence and incidence of MCI, there are significant statistical differences, which increase with age, MCI has significantly the incidence of subsequent growth trends; Between city and rural, rural areas where the incidence of MCI was significantly higher than the city. Gender, educational background, body mass index, occupation have no significant statistical difference. 3 Between habits of smoking, drinking motion state, and the incidence of MCI, there are significant statistical differences, which increase with the smoking history, MCI growth rate followed the trend apparently, with the duration of growth of motion state, MCI followed the trend rate of growth significantly, the prevalence of drinking among MCI was significantly higher than non-drinkers. whether tea has no significant statistical difference. 4 Between cerebrovascular disease, heart disease, endocrine and metabolic diseases, epilepsy, depression, brain trauma history, family history and the incidence of MCI, there are significant statistical difference. No significant difference in blood pressure. 5 MMSE, MoCA, FAQ recognize the effect of MCI compared: MoCA's sensitivity, specificity and accuracy were higher than MMSE, FAQ, which can find the case that MMSE, FAQ can not distinguish between MCI and wrongly differentiated MCI; MMSE and FAQ sensitivity, specificity and accuracy were the same.
方法:(1)调查对象为2007年12月~2009年12月期间,在秦皇岛市社区选取65岁及以上老年人,包括城市人口和农村人口。最终入选本研究1011例,男410例,女601例。采用统一的调查表和标准化调查用语,按名单入户调查,详细记录调查资料。对符合入选标准的受试者进行认知功能评估,记录受试者的人口学资料(表1)、生活习惯(表2)、既往病史(表3)、神经心理评估结果(表4-8)。最后完成诊断(包括认知水平和其他疾病诊断)。不能完成评估或不能配合进行认知评估者,依据临床信息进行诊断。
结果:(1)轻度认知障碍人数67例,痴呆人数45例,正常人数899例,MCI的发生率为6.63%,痴呆发生率4.45%;
(2)人口学资料中年龄(趋势χ2=120.106,P≤0.000)、长期居住地(χ2=4.758,P=0.029)与MCI的发生率存在显著的统计学差异,其中随着年龄增长,MCI发生率随之增长趋势明显;性别(χ2=1.773,P=0.183)、受教育情况(χ2=0.702,P=0.402)、体重指数(T=0.876,P=0.386)、职业(χ2=10.030,P=0.123)未见明显统计学差异。(3)生活习惯中吸烟史(趋势χ2=5.097,P=0.024)、是否饮酒(χ2=7.251,P=0.007),运动状态(趋势χ2=43.729,P≤0.000)与MCI的发生率存在显著的统计学差异,其中随着吸烟史增长,MCI发生率随之增长趋势明显,运动状态持续时间增长,MCI发生率随之降低趋势明显;是否喝茶(χ2=0.171,P=0.679)未见明显统计学差异。(4)患病史中脑血管疾病(χ2=8.760,P=0.003)、心脏疾病(χ2=8.767,P=0.003)、内分泌代谢疾病(χ2=4.018,P=0.045)、癫痫(χ2=21.558,P≤0.000)、抑郁症(χ2=5.026,P=0.060)、脑外伤史(χ2=39.447,P≤0.000)、家族史(χ2=11.630,P=0.001)与MCI的发生率存在显著的统计学差异。高血压(χ2=1.068,P=0.301)未见明显差异。5 MMSE、MoCA、FAQ识别MCI的效果:MMSE识别MCI的灵敏度(%)为59.70,特异度(%)为89.21,准确度(%)为87.16,假阳性率(%)为10.79,假阴性率(%)为40.30;MoCA识别MCI的灵敏度(%)为89.55,特异度(%)为97.66,准确度(%)为97.10,假阳性率(%)为23.36,假阴性率(%)10.45;FAQ识别MCI的灵敏度(%)为58.20,特异度(%)为89.43,准确度(%)为87.27,假阳性率(%)为10.57,假阴性率(%)41.79;
结论:1 MCI的发生率为6.63%,痴呆发生率4.45%。2人口学资料中年龄、长期居住地与MCI的发生率存在显著的统计学差异,其中随着年龄增长,MCI发生率随之增长趋势明显;长期居住地中城市、农村,其中农村的MCI的发生率明显高于城市。性别、受教育情况、体重指数、职业未见明显统计学差异。3生活习惯中吸烟史、是否饮酒、运动状态、与MCI的发生率存在显著的统计学差异,其中随着吸烟史增长,MCI发生率随之增长趋势明显,运动状态持续时间增长,MCI发生率随之降低趋势明显,饮酒人群MCI患病率明显高于非饮酒人群。是否喝茶未见明显统计学差异。4患病史中脑血管疾病、心脏疾病、内分泌代谢疾病、癫痫、抑郁症、脑外伤史、家族史与MCI的发生率存在显著的统计学差异。高血压未见明显差异。5 MMSE、MoCA、FAQ识别MCI的效果比较,MoCA的灵敏度、特异度、准确度均高于MMSE、FAQ,可以发现MMSE、FAQ区分不了的MCI和被错误区分的MCI; MMSE与FAQ灵敏度、特异度、准确度相差不大。
Objective: Mild cognitive impairment (mild cognitive impairment, MCI) is the state between normal aging and dementia, for cognitive dysfunction, but not accompanied by a significant decline in activities of daily living characterized. Each year about a certain percentage of patients with MCI gets into dementia, and MCI is a high risk population of dementia. If treatment can be given in the MCI stage , may reduce the incidence of dementia. So how early diagnosis of MCI is being as the research Hot of geriatrics and neurology in recent years. The standard in diagnosis of MCI at home and abroad is no fixed , and its risk factors are also highly controversial, so we need to be more research. This study was designed to clear the impact factors of mild cognitive impairment , the explicit control of risk factors to prevention and treatment of mild cognitive impairment, sensitive neuropsychological assessment scales of mild cognitive impairment.
Method: (1) The survey was conducted in December 2007 ~ December 2009 period, in Qinhuangdao city community 65 years and older selected, including urban and rural populations. Eventually enrolled in the study 1011 cases, 410 cases of male and female 601 cases. Adopt a unified and standardized survey questionnaire language, according to the list of household, and detailed record survey data. Subjects who meet inclusion criteria are given cognitive function assessment, and recorded demographic data (Table 1), habits (Table 2), past medical history (Table 3), neuropsychological assessment (Table 4-6 ). Finalized diagnosis (including diagnosis of cognitive level and other diseases).The subjects who can not complete the assessment or who can not meet the cognitive assessment are based on clinical information for diagnosis.
Results: (1) 67 cases with mild cognitive impairment, 45 cases with dementia , 899 cases of normal, MCI's rate was 6.63%, 4.45% incidence of dementia; (2)Between age (trendχ2 = 120.106, P≤0.000), long-term residence (χ2 = 4.758, P = 0.029) and incidence of MCI, there are significant statistical differences, which increase with age, MCI followed the trend rate of growth significantly; Gender (χ2 = 1.773, P = 0.183), educational situation (χ2 = 0.702, P = 0.402), body mass index (T = 0.876, P = 0.386), occupational (χ2 = 10.030, P = 0.123) are no significant statistical school different. (3)Between smoking habits in the history (trendχ2 = 5.097, P = 0.024), whether drinking (χ2 = 7.251, P = 0.007), exercise status (trendχ2 = 43.729, P≤0.000) and the incidence of MCI, there are significant statistical differences, which increase with the smoking history, MCI has significantly the incidence of subsequent growth trends, and with exercise duration increased state, MCI has significantly the incidence of subsequent growth trends; Wheater tea (χ2 = 0.171, P = 0.679) is no significant statistical different. (4)Between cerebrovascular disease (χ2 = 8.760, P = 0.003), heart disease (χ2 = 8.767, P = 0.003), endocrine and metabolic diseases (χ2 = 4.018, P = 0.045), epilepsy (χ2 = 21.558, P≤0.000), depression (χ2 = 5.026, P = 0.060), history of brain trauma (χ2 = 39.447, P≤0.000), family history (χ2 = 11.630, P = 0.001) and incidence of MCI, there are significant statistical school differences. Hypertension (χ2 = 1.068, P = 0.301) has no significant difference. 5 MMSE, MoCA, FAQ recognize the effect of MCI: MMSE MCI recognition sensitivity (%) were 59.70, specificity (%) were 89.21, accuracy (%) were 87.16, the false positive rate (%) were 10.79, false negative rate (%) were 40.30; MoCA MCI recognition sensitivity (%) were 89.55, specificity (%) were 97.66, accuracy (%) were 97.10, the false positive rate (%) were 23.36, the false negative rate (%) were 10.45; FAQ MCI recognition sensitivity (%) were 58.20, specificity (%) were 89.43, accuracy (%) were 87.27, false positive rate (%) were 10.57, false negative rate (%) were 41.79;
Conclusion: 1 MCI's rate was 6.63%, 4.45% was incidence of dementia. 2 Between age, long-term residence and incidence of MCI, there are significant statistical differences, which increase with age, MCI has significantly the incidence of subsequent growth trends; Between city and rural, rural areas where the incidence of MCI was significantly higher than the city. Gender, educational background, body mass index, occupation have no significant statistical difference. 3 Between habits of smoking, drinking motion state, and the incidence of MCI, there are significant statistical differences, which increase with the smoking history, MCI growth rate followed the trend apparently, with the duration of growth of motion state, MCI followed the trend rate of growth significantly, the prevalence of drinking among MCI was significantly higher than non-drinkers. whether tea has no significant statistical difference. 4 Between cerebrovascular disease, heart disease, endocrine and metabolic diseases, epilepsy, depression, brain trauma history, family history and the incidence of MCI, there are significant statistical difference. No significant difference in blood pressure. 5 MMSE, MoCA, FAQ recognize the effect of MCI compared: MoCA's sensitivity, specificity and accuracy were higher than MMSE, FAQ, which can find the case that MMSE, FAQ can not distinguish between MCI and wrongly differentiated MCI; MMSE and FAQ sensitivity, specificity and accuracy were the same.
引文
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1 Petersen RC.Mild cognitive impairment:transition between agingand Alzheimer’S disease[J].Neurologia,2000,l5(3):93-l01
2 Petersen RC,Smith GE,Waring SC,et al.Mild cognitive impairm- ent. Clinical characterization and outcome[J].ArchNeurol,1999, 56:303-308
3 Barbeau E,Didic M,Tramoni E,et a1.Evaluation of visual recog- nition memory in MCI patients[J].Neurology,2004,62:13l7-1322
4 Ostberg P,Fernaeus SE,Hellstrom K,et a1.Impaired verb fluency: a sign of mild cognitive impairment[J].Brain lang,2005,95:273-279
5 Feldman H,Scheltens P,Scarpini E,et a1.Behavioral symptoms in mild cognitive impairment[J].Neurology,2004,62:ll99-1201
6 Petersen RC, Steven JC, Ganguli M, et a1. Practice parameter: early detection of dementia:mild cognitive impairment(an evide- nce-based review).Report of the Quality Standards subcommittee of the American Academy of Neurology[J].Neurology,200l,56:l133- l142
7 Andreasen N,Minthon L,Vanmechelen E,et a1.Cere-brospinal fluid tau and Abeta42 as predictors of developmentof Alzheimer’s disease in patients with mild cognitive impairment[J].Neurosci Lett, 1999,273(1):5-8
8 Riemenschneider M,Lautenschlager N,Wagenpfeil S,et al.Cere- brospinal fluid tau and beta-amyloid 42 proteins identify Alzh-eimer disease in subjects with mild cognitive impairment [J].Arch Neurol, 2002, 59(11): 1729-1734
9 Andreasen N,Vanmechelen E,Vanderstichele H,et a1. Cerebros- pinal fluid levels of total-tau,phosphor-tau and A beta 42 pre- dicts development ofAlzheimer's disease in patients with mild cognitive impairm ent[J].Acta Neurol Scand Suppl,2003, 179:47-51
10 Buerger K,Teipel SJ,Zinkowski R,et a1.CSF tau protein phos- phorylated at threonine 231 correlates with cognitive decline in MCI subjects[J]. Neurology,2002,59(4):627-629
11 Jensen M,Schroder J,Blomberg M,et a1.Cerebrospinal fluid A beta42 is increased early in sporadic Alzheimer’s disease and declines with disease progression[J].Ann Neurol,1999,45(4): 504 -511
12 Andreasen N,Mintl1on L,Davidsson P,et a1.Evaluation of CSF tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice[J].Arch Neurol,2001,58(3):373-379
13 Fukuyama R,Mizuno T,Moil S,et a1.Age dependent change in tl1e levels of Abeta40 and Abeta42 in cere-brospinal fluid from control subjects,and a decrease in tl1e ratio of Abeta42 to Abeta40 level in cerebrospinal fluid from Alzheimer’s disease patients[J].Eur Neurol,2000,43(3):155-160
14 Assini A,Cammarata S,Vitali A,et a1.Plasma levels of amyloid be ta.protein 42 are increased in women with mild cognitive impairment[J]. Neurology,2004,63(5):828-831
15 Padovani A,Borroni B,Colciaghi F,et a1.Abnorm alities in the pattern of platelet amyloid precursor protein forms in patients with mild cognitive impairm ent and Alzheimer disease[J]. Arch Neurol,2002,59(1):71-75
16 Borroni B, Colciaghi F, Cahagirone C, et a1. Platelet amyloid precursor protein abnorm alities in mild cogn itive impairm ent predict conversion to dementia of Alzheimer type:a 2-year follow-up study[J].Arch Neurol, 2003,60(12):1740-1744
17 Ikonomovic MD,Mufson EJ,Wuu J,et a1.Cholinergic plasticity in hippocampus of individuals with mild cognitive impairment: correlation with Alzheimer's neuropathology[J].J Alzheimers Dis,2003,5(1):39-48
18 Dickerson BC.Functional magnetic resonance imaging of chol- inergic modulation in mild cognitive impairm ent[J].Cur Opin Psychiatry, 2006, 19(3):299-306
19 Ravaglia G,Forti P,Maioli F,et a1.Plasma amino acid concent- rations in healthy and cognitively impaired oldest old individuals:associations with anthropometric parameters of body composition and functional disability[J]. Br J Nutr, 2002,88 (5):563-572
20 Weaver JD,Huang MH,Albert M,et a1.Interleukin.6 and risk of cognitive decline:MacArthur studies of successful aging [J]. Neurology, 2002, 59(3): 371-378
21 Magaki S, Mueller C, Dickson C, et a1. Increased production of inflammatory cytokines in mild cognitive impairment[J]. Exp Gerontol, 2007, 42(3):233-240
22 Schmidt R, Schmidt H, Curb JD, et a1. Early inflammation and dementia:a 25-year follow-uD of the Honolulu.Asia AgingStudy [J].Ann Neurol, 2002, 52(2):168-174
23 Galimberti D,Fenoglio C,Lovati C,et a1.Serum MCP 1 levels are increased in mild cogn itive impairm ent and mild Alzheimer's disease[J].Neurobiol Aging,2006,27(12):1763-1768
24 Pratico D,Clark CM,Liun,et a1.Increase of brain oxidative stress in mild cognitive impairm ent:a possible predictor of Alzheimer disease[J].Arch Neurol,2002,59(6):972-976
25 Butterfield DA,Reed T,Perluigi M,et a1.Elevated protein- bound levels of the lipid peroxidation product,4-hydroxy- 2-nonenal,in brain from persons with mild cogn itive impairm- ent[J].Neurosci Lett,2006,397(3):170-173
26 Schipper HM,Bennett DA,Liberman A,et a1.Gliheme oxygenase-1 expression in Alzheimer disease and mild cognitive impairment [J]. Neurobiol Aging,2006,27(2):252-261
27 Yao Y,Clark CM,Trojanowski JQ,et a1.Elevation of 12/15 lipoxygenase products in AD and mild cognitive impairment[J].Ann Neurol,2005, 58(4):623-626
28 Butterfield DA,Poon HF,St Clair D,et a1.Redox proteom ics identification of oxidatively modified hippocampal proteins in mild cognitive impairment:insights into the development of Alzhe- imer’s disease[J].Neurobiol Dis,2006,22(2):223-232
29 Seshadri S,Beiser A,Selhub J, et a1.Plasma homocysteine as,a risk factor for dementia and Alzheimer’s disease[J].NEnsl J Med, 2002, 346(7): 476-483
30 Religa D,Styczynska M,Peplonska B,et a1.Homocysteine,apol-ipo proteine E and methylenetetrahydrofolate reductase in Alzh- eimer’s disease and mild cognitive impairment[J].Dement Geriatr Cogn Disord, 2003, 16(2):64-70
31 Annerbo S,Wahlund LO,Lokk J.The relation between homoeysteine levels and development of Alzheimer’s disease in mild cognitive impairment patients[J].Dement Geriatr Cogn Disord,2005,20(4): 209-214
32 Papassotiropoulos A,LuOohann D,Bagli M,et a1.24S-hydroxycho- lesterol in cerebrospinal fluid is elevated in early stages of dementia[J].J Psychiatr Res,2002,36(1):27-32
33 Lovell MA,Smith JL,Xiong S,et a1.Alterations in zinc trans- porter protein-1(ZnT-1)in the brain of subjects with mild cogn- itive impairm ent,early,and late-stage Alzheimer’s disease [J]. Neurotox Res, 2005, 7(4):265-271
34 Odetti P,Piccini A,Giliberto L,et a1.Plasma levels of insulin and amyloid beta 42 are correlated in patients with amnestic Mild Cognitive Impairment[J].J Alzheimers Dis,2005,8(3):243-245
35 Yafe K,Blackwell T,Whitmer RA,et a1.Glycosylated hemoglobin level and development of mild cogn itive impairment or dementia in older women [J].J Nutr Health Aging,2006,10(4):293-295
36 Valla J,Schneider L,Niedzielko T,et a1.Impaired platelet mitochondrial activity in Alzheimer's disease and mild cognitive impairm ent [J]. Mitochondrion,2006,6(6):323-330
37 Luis CA,Loewenstein DA,Acevedo A,et a1.Mild cognitive impairm ent:directions for future research[J].Neurology,2003,61(4): 438 -444
38 Petersen RC, Wafing SC, Smith GE, et a1. Predictive value of APOE genotyping in incipient Alzheimer’s disease[J]. Ann N Y Acad sci, 1996,802(1):58-69
39 Chiappelli M,Borroni B,Archetti S,et a1.VEGF gene and phenol- type relation with Alzheimer's disease and mild cognitive impairm ent[J]. Rejuvenation Res,2006,9(4):485-493
40 Babiloni C,Benussi L,Binetti G,et a1.Genotype(cystatin C) and EEG phenotype in Alzheimer disease and mild cognitive impairment : a muhicentric study[J].Neuroimage,2006,29(3):948-964
41 Jack CR Jr,Petersen RC,Xu Y,et al.Rates of hippocampal atrophy correlate with change in clinical status in aging and AD[J].Neuroloy,2000, 55(4): 484-489
42 Tabert MH, Albert SM, Borukhova-Milov L, et al. Functional deficits in patients with mild cognitive impairment:prediction of AD[J]. Neurology, 2002, 58(5): 758-764
2 Petersen RC,Smith GE,Waring SC,et al.Mild cognitive impairm- ent.Clinical characterization and outcome[J].ArchNeurol,1999, 56:303- 308
3 Barbeau E,Didic M,Tramoni E,et a1.Evaluation of visual recog- nition memory in MCI patients[J].Neurology,2004,62:13l7-1322
4 Ostberg P,Fernaeus SE,Hellstrom K,et a1.Impaired verb fluency: a sign of mild cognitive impairment[J].Brain lang,2005,95:273-279
5 Feldman H,Scheltens P,Scarpini E,et a1.Behavioral symptoms in mild cognitive impairment[J].Neurology,2004,62:ll99-1201
6 Petersen RC,Steven JC,Ganguli M,et a1.Practice parameter: early detection of dementia:mild cognitive impairment(an evide- nce-based review).Report of the Quality Standards subcommittee of the American Academy of Neurology[J].Neurology,200l,56:l133- l142
7 Petersen RC,Smith GE,Waring SC,et al.Mild cognitive impairm- ent.Clinical characterization and outcome[J].ArchNeurol,1999, 56: 303-308
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9 Hall,Kathleen S.PhD,Gao,Sujuan PhD,Unverzagt,Frederick W.PhD,et al.Low education and childhood rural residence:Risk for Alzheimer’s disease in African Americans.Neurology,2000,54(1):95
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1 Petersen RC.Mild cognitive impairment:transition between agingand Alzheimer’S disease[J].Neurologia,2000,l5(3):93-l01
2 Petersen RC,Smith GE,Waring SC,et al.Mild cognitive impairm- ent. Clinical characterization and outcome[J].ArchNeurol,1999, 56:303-308
3 Barbeau E,Didic M,Tramoni E,et a1.Evaluation of visual recog- nition memory in MCI patients[J].Neurology,2004,62:13l7-1322
4 Ostberg P,Fernaeus SE,Hellstrom K,et a1.Impaired verb fluency: a sign of mild cognitive impairment[J].Brain lang,2005,95:273-279
5 Feldman H,Scheltens P,Scarpini E,et a1.Behavioral symptoms in mild cognitive impairment[J].Neurology,2004,62:ll99-1201
6 Petersen RC, Steven JC, Ganguli M, et a1. Practice parameter: early detection of dementia:mild cognitive impairment(an evide- nce-based review).Report of the Quality Standards subcommittee of the American Academy of Neurology[J].Neurology,200l,56:l133- l142
7 Andreasen N,Minthon L,Vanmechelen E,et a1.Cere-brospinal fluid tau and Abeta42 as predictors of developmentof Alzheimer’s disease in patients with mild cognitive impairment[J].Neurosci Lett, 1999,273(1):5-8
8 Riemenschneider M,Lautenschlager N,Wagenpfeil S,et al.Cere- brospinal fluid tau and beta-amyloid 42 proteins identify Alzh-eimer disease in subjects with mild cognitive impairment [J].Arch Neurol, 2002, 59(11): 1729-1734
9 Andreasen N,Vanmechelen E,Vanderstichele H,et a1. Cerebros- pinal fluid levels of total-tau,phosphor-tau and A beta 42 pre- dicts development ofAlzheimer's disease in patients with mild cognitive impairm ent[J].Acta Neurol Scand Suppl,2003, 179:47-51
10 Buerger K,Teipel SJ,Zinkowski R,et a1.CSF tau protein phos- phorylated at threonine 231 correlates with cognitive decline in MCI subjects[J]. Neurology,2002,59(4):627-629
11 Jensen M,Schroder J,Blomberg M,et a1.Cerebrospinal fluid A beta42 is increased early in sporadic Alzheimer’s disease and declines with disease progression[J].Ann Neurol,1999,45(4): 504 -511
12 Andreasen N,Mintl1on L,Davidsson P,et a1.Evaluation of CSF tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice[J].Arch Neurol,2001,58(3):373-379
13 Fukuyama R,Mizuno T,Moil S,et a1.Age dependent change in tl1e levels of Abeta40 and Abeta42 in cere-brospinal fluid from control subjects,and a decrease in tl1e ratio of Abeta42 to Abeta40 level in cerebrospinal fluid from Alzheimer’s disease patients[J].Eur Neurol,2000,43(3):155-160
14 Assini A,Cammarata S,Vitali A,et a1.Plasma levels of amyloid be ta.protein 42 are increased in women with mild cognitive impairment[J]. Neurology,2004,63(5):828-831
15 Padovani A,Borroni B,Colciaghi F,et a1.Abnorm alities in the pattern of platelet amyloid precursor protein forms in patients with mild cognitive impairm ent and Alzheimer disease[J]. Arch Neurol,2002,59(1):71-75
16 Borroni B, Colciaghi F, Cahagirone C, et a1. Platelet amyloid precursor protein abnorm alities in mild cogn itive impairm ent predict conversion to dementia of Alzheimer type:a 2-year follow-up study[J].Arch Neurol, 2003,60(12):1740-1744
17 Ikonomovic MD,Mufson EJ,Wuu J,et a1.Cholinergic plasticity in hippocampus of individuals with mild cognitive impairment: correlation with Alzheimer's neuropathology[J].J Alzheimers Dis,2003,5(1):39-48
18 Dickerson BC.Functional magnetic resonance imaging of chol- inergic modulation in mild cognitive impairm ent[J].Cur Opin Psychiatry, 2006, 19(3):299-306
19 Ravaglia G,Forti P,Maioli F,et a1.Plasma amino acid concent- rations in healthy and cognitively impaired oldest old individuals:associations with anthropometric parameters of body composition and functional disability[J]. Br J Nutr, 2002,88 (5):563-572
20 Weaver JD,Huang MH,Albert M,et a1.Interleukin.6 and risk of cognitive decline:MacArthur studies of successful aging [J]. Neurology, 2002, 59(3): 371-378
21 Magaki S, Mueller C, Dickson C, et a1. Increased production of inflammatory cytokines in mild cognitive impairment[J]. Exp Gerontol, 2007, 42(3):233-240
22 Schmidt R, Schmidt H, Curb JD, et a1. Early inflammation and dementia:a 25-year follow-uD of the Honolulu.Asia AgingStudy [J].Ann Neurol, 2002, 52(2):168-174
23 Galimberti D,Fenoglio C,Lovati C,et a1.Serum MCP 1 levels are increased in mild cogn itive impairm ent and mild Alzheimer's disease[J].Neurobiol Aging,2006,27(12):1763-1768
24 Pratico D,Clark CM,Liun,et a1.Increase of brain oxidative stress in mild cognitive impairm ent:a possible predictor of Alzheimer disease[J].Arch Neurol,2002,59(6):972-976
25 Butterfield DA,Reed T,Perluigi M,et a1.Elevated protein- bound levels of the lipid peroxidation product,4-hydroxy- 2-nonenal,in brain from persons with mild cogn itive impairm- ent[J].Neurosci Lett,2006,397(3):170-173
26 Schipper HM,Bennett DA,Liberman A,et a1.Gliheme oxygenase-1 expression in Alzheimer disease and mild cognitive impairment [J]. Neurobiol Aging,2006,27(2):252-261
27 Yao Y,Clark CM,Trojanowski JQ,et a1.Elevation of 12/15 lipoxygenase products in AD and mild cognitive impairment[J].Ann Neurol,2005, 58(4):623-626
28 Butterfield DA,Poon HF,St Clair D,et a1.Redox proteom ics identification of oxidatively modified hippocampal proteins in mild cognitive impairment:insights into the development of Alzhe- imer’s disease[J].Neurobiol Dis,2006,22(2):223-232
29 Seshadri S,Beiser A,Selhub J, et a1.Plasma homocysteine as,a risk factor for dementia and Alzheimer’s disease[J].NEnsl J Med, 2002, 346(7): 476-483
30 Religa D,Styczynska M,Peplonska B,et a1.Homocysteine,apol-ipo proteine E and methylenetetrahydrofolate reductase in Alzh- eimer’s disease and mild cognitive impairment[J].Dement Geriatr Cogn Disord, 2003, 16(2):64-70
31 Annerbo S,Wahlund LO,Lokk J.The relation between homoeysteine levels and development of Alzheimer’s disease in mild cognitive impairment patients[J].Dement Geriatr Cogn Disord,2005,20(4): 209-214
32 Papassotiropoulos A,LuOohann D,Bagli M,et a1.24S-hydroxycho- lesterol in cerebrospinal fluid is elevated in early stages of dementia[J].J Psychiatr Res,2002,36(1):27-32
33 Lovell MA,Smith JL,Xiong S,et a1.Alterations in zinc trans- porter protein-1(ZnT-1)in the brain of subjects with mild cogn- itive impairm ent,early,and late-stage Alzheimer’s disease [J]. Neurotox Res, 2005, 7(4):265-271
34 Odetti P,Piccini A,Giliberto L,et a1.Plasma levels of insulin and amyloid beta 42 are correlated in patients with amnestic Mild Cognitive Impairment[J].J Alzheimers Dis,2005,8(3):243-245
35 Yafe K,Blackwell T,Whitmer RA,et a1.Glycosylated hemoglobin level and development of mild cogn itive impairment or dementia in older women [J].J Nutr Health Aging,2006,10(4):293-295
36 Valla J,Schneider L,Niedzielko T,et a1.Impaired platelet mitochondrial activity in Alzheimer's disease and mild cognitive impairm ent [J]. Mitochondrion,2006,6(6):323-330
37 Luis CA,Loewenstein DA,Acevedo A,et a1.Mild cognitive impairm ent:directions for future research[J].Neurology,2003,61(4): 438 -444
38 Petersen RC, Wafing SC, Smith GE, et a1. Predictive value of APOE genotyping in incipient Alzheimer’s disease[J]. Ann N Y Acad sci, 1996,802(1):58-69
39 Chiappelli M,Borroni B,Archetti S,et a1.VEGF gene and phenol- type relation with Alzheimer's disease and mild cognitive impairm ent[J]. Rejuvenation Res,2006,9(4):485-493
40 Babiloni C,Benussi L,Binetti G,et a1.Genotype(cystatin C) and EEG phenotype in Alzheimer disease and mild cognitive impairment : a muhicentric study[J].Neuroimage,2006,29(3):948-964
41 Jack CR Jr,Petersen RC,Xu Y,et al.Rates of hippocampal atrophy correlate with change in clinical status in aging and AD[J].Neuroloy,2000, 55(4): 484-489
42 Tabert MH, Albert SM, Borukhova-Milov L, et al. Functional deficits in patients with mild cognitive impairment:prediction of AD[J]. Neurology, 2002, 58(5): 758-764