【摘要】：目的:本研究目的是尋找中國(guó)北方≥60y老年人輕度認(rèn)知障礙(Mild Cognitive Impairment,MCI)的影響因素。通過(guò)分析生活方式、膳食因素、生化指標(biāo)、免疫指標(biāo)、血漿脂肪酸(Fatty Acid,FA)與MCI的關(guān)系,探究MCI的影響因素,為尋找MCI的有效干預(yù)手段以及為以后對(duì)MCI進(jìn)一步的研究提供新的線(xiàn)索。方法:在河北省石家莊市用簡(jiǎn)單隨機(jī)抽樣的方法隨機(jī)抽取三個(gè)社區(qū)開(kāi)展一項(xiàng)病例對(duì)照研究,以三個(gè)社區(qū)的所有60y的老年人為研究對(duì)象。本研究研究對(duì)象的選取分為兩步:首先根據(jù)社區(qū)居民健康檔案按照納入和排除標(biāo)準(zhǔn)對(duì)所有老年人進(jìn)行初步篩選;然后再進(jìn)行基本資料調(diào)查后,結(jié)合納入和排除標(biāo)準(zhǔn)對(duì)老年人進(jìn)行再次篩選。最后根據(jù)MCI的診斷標(biāo)準(zhǔn)、問(wèn)卷和體檢數(shù)據(jù),由衛(wèi)生部北京醫(yī)院精神內(nèi)科專(zhuān)家做出最終診斷,找出該三個(gè)社區(qū)中的全部MCI患者;再根據(jù)正常認(rèn)知診斷標(biāo)準(zhǔn)確定三個(gè)社區(qū)中的全部正常認(rèn)知者,利用簡(jiǎn)單隨機(jī)抽樣的方法抽取得到對(duì)照組,使對(duì)照組與MCI組的數(shù)量比為1:1。本研究的工作主要包括對(duì)研究對(duì)象進(jìn)行認(rèn)知狀況、生活方式和膳食因素等資料的調(diào)查;并及時(shí)開(kāi)展血液生化指標(biāo)、免疫指標(biāo)以及血漿FA等指標(biāo)的實(shí)驗(yàn)室檢測(cè)。在后期數(shù)據(jù)處理中,本文將通過(guò)分析生活方式、膳食因素、血脂指標(biāo)、免疫指標(biāo)、脂肪酸(Fatty Acid,FA)與MCI的關(guān)系,尋找MCI的影響因素,具體分析過(guò)程為:先對(duì)各項(xiàng)指標(biāo)在兩組中的分布進(jìn)行初步分析;然后用單因素logistic回歸分析探討生活方式、膳食因素、生化指標(biāo)、代謝性疾病、免疫指標(biāo)以及血漿脂肪酸各自對(duì)MCI的影響;在進(jìn)行單因素分析后,將單因素分析中有統(tǒng)計(jì)學(xué)意義的變量納入多因素logistic回歸模型,得出MCI的獨(dú)立影響因素。在結(jié)果分析中,分類(lèi)變量的描述用例數(shù)(n)和構(gòu)成比(%),定量變量的描述用均數(shù)(x)±標(biāo)準(zhǔn)差(S)或中位數(shù)(M)和上下四分位數(shù)(Q1,Q3)表示;分類(lèi)變量的兩組間比較采用χ2檢驗(yàn),不符合條件者采用秩和檢驗(yàn);定量變量的兩組間比較采用t檢驗(yàn),不符合使用條件者采用wilcoxon符號(hào)秩和檢驗(yàn)。MCI的影響因素探究先使用單因素logistic回歸分析,然后使用多因素logistic回歸模型進(jìn)行分析。結(jié)果:1各項(xiàng)指標(biāo)在不同認(rèn)知狀況人群中的分布年齡(p=0.0114)、受教育程度(p0.0001)與MCI有明顯的關(guān)系。與對(duì)照組相比,MCI組中低年齡段60-64y所占比例低(42.74%55.65%),中間年齡段65-69y(33.87%23.39%)、70-74y(17.74%8.87%)所占比例高于對(duì)照組,而高年齡段75-y(5.65%12.1%)占的比例又再次低于對(duì)照組。MCI中受教育程度較高的人群占的比例低于對(duì)照組;MCI組中參加學(xué)習(xí)活動(dòng)的比例低于對(duì)照組(12.1%18.55%),MCI的做家務(wù)時(shí)間明顯少于對(duì)照組(p.0001);MCI組偶爾吸煙(6.45%5.65%)和經(jīng)常吸煙(11.29%4.03%,p=0.0908)的人占的比例均高于對(duì)照組;而兩組中居住狀況(p=0.7757)、娛樂(lè)活動(dòng)(p=0.9265)、飲酒(p=0.3903)、靜坐時(shí)間(p=0.1599)、睡眠時(shí)間(p=0.5955)的分布沒(méi)有明顯差異。膳食因素中,對(duì)照組攝入蛋類(lèi)的頻次多于MCI組、而堅(jiān)果類(lèi)的攝入頻率比MCI少。米面雜糧等、蔬菜菌藻、水果、禽肉、畜肉、淡水魚(yú)貝類(lèi)、海水魚(yú)貝類(lèi)、豆類(lèi)及制品等在MCI組和正常組中的分布也沒(méi)有差異。MCI組中 HDL-C(1.141.18)、ApoA-1(1.511.42)的水平均低于對(duì)照組,而ApoB(0.910.83)、ApoE(4.193.58)的水平均高于對(duì)照組,但是兩組中其他指標(biāo) TC、TG、LDL-C、HDL-C/LDL-C、PL(a)、LP-PLA2 的水平在兩組中的差異并不明顯。MCI中患高血壓(54.03%40.32%)、血脂異常(46.77%32.26%)、糖尿病(17.74%8.06%)的比例均高于對(duì)照組。血脂異常包含的三種疾病高膽固醇血癥、高甘油三酯血癥、低高密度脂蛋白膽固醇血癥、貧血在兩組的分布并沒(méi)有明顯的差別。免疫指標(biāo)CRP、IL-6、TNF-α在MCI和對(duì)照組水平的分布沒(méi)有明顯的差異。本研究還重點(diǎn)分析了血漿FA在MCI組和對(duì)照組中的分布。SFA的總含量在兩組中沒(méi)有差異,但是其組分C16:0(p=0.0061)在MCI組的含量低于對(duì)照組。MUFA在兩組的分布沒(méi)有明顯差異。PUFA中n-3 PUFA的總含量在兩組沒(méi)有差異,但是其組分C22:6n-3的水平在對(duì)照組中較高(p=0.0057);而MCI組中n-6PUFA的總含量(p0.0001)及其組分C18:2n-6c的水平均比對(duì)照組高(p=0.0003);PUFA 總含量比值 n-3/n-6PUFA(p=0.0140)和 C22:6n-3/C20:4n-6(p=0.0294)在正常組中的水平均高于MCI組。2各項(xiàng)指標(biāo)與MCI關(guān)系的單因素logistic回歸分析通過(guò)單因素logistic回歸分析后,年齡、受教育程度、失眠情況、視力狀況、吸煙、做家務(wù)時(shí)間等都是MCI的影響因素。在60-74y范圍內(nèi),年齡越小,發(fā)生MCI的風(fēng)險(xiǎn)越小(均有p0.05,且與60-64y組相比,65-69y、70-74y兩組發(fā)生MCI的風(fēng)險(xiǎn)分別為1.885倍、2.603倍);但75-y組MCI的發(fā)生風(fēng)險(xiǎn)與60-64y組沒(méi)有差異(p=0.3121)。受教育程度越高,發(fā)生MCI的風(fēng)險(xiǎn)越低。失眠、視力下降、吸煙等均是MCI的危險(xiǎn)因素,做家務(wù)每增加一個(gè)小時(shí),MCI的發(fā)生風(fēng)險(xiǎn)變?yōu)樵瓉?lái)的0.621倍。對(duì)食物攝入頻率與MCI做單因素logistic回歸分析,發(fā)現(xiàn)膳食因素與MCI的關(guān)系并不明顯。將生化指標(biāo)按照三分位數(shù)劃分為低水平組、中等水平組、高水平組。HDL-C(高水平組OR=0.532)、ApoA-1(高水平組OR=0.490)是MCI的保護(hù)因素。ApoB(中等水平組、高水平組OR=1.882、2.294)、ApoE(高水平組OR=2.368)是MCI的危險(xiǎn)因素。TC(OR=0.517)、LP(a)(OR=0.491)僅在中等水平對(duì)MCI有保護(hù)作用。而免疫指標(biāo)與MCI并沒(méi)有表現(xiàn)出明顯的關(guān)系。代謝性疾病中,高血壓(OR=1.740)、糖尿病(OR=2.458)、血脂異常(OR=1.845)是MCI的危險(xiǎn)因素(OR1)。而血脂異常的三種具體類(lèi)型與MCI沒(méi)有表現(xiàn)出明顯的關(guān)系。SFA組分C16:0在MCI組的含量低于對(duì)照組(p=0.0061)。MUFA在MCI組和對(duì)照組中并沒(méi)有明顯差異(p=0.2782)。PUFA中n-3PUFA的總含量在兩組沒(méi)有差異,但是其組分C22:6n-3的水平在對(duì)照組中較高(p=0.0057);n-6PUFA的總含量在MCI組中較高(p.0001),其組分C18:2n-6c的水平在MCI組中較高(p=0.0003)。兩組中比值 n-3/n-6 PUFA(p=0.0140)和 C22:6n-3/C20:4n-6(p=0.0294)在正常組中的水平均高于MCI組。將各種FA按照三分位數(shù)分為三組,分別為低水平組、中等水平組、高水平組,分析FA在不同水平時(shí)對(duì)MCI的影響。在MCI組和對(duì)照組中C16:0、C22:6n-3、n-6PUFA 總含量、C18:2n-6c 以及兩個(gè)比值 n-3/n-6PUFA 和 C22:6n-3/C20:4n-6 在MCI組和對(duì)照組中的部分分組之間仍然有明顯的差距,此外,n-3PUFA總含量(p=0.0330)、C20:4n-6(p=0.0005)在MCI組和對(duì)照組中的分布也存在明顯差異。3各項(xiàng)指標(biāo)與MCI關(guān)系的多因素logistic回歸分析將生活方式、載脂蛋白、LP(a)、LP-PLA2、代謝性疾病、血漿FA中單因素logistic回歸分析中有統(tǒng)計(jì)學(xué)意義的指標(biāo)納入多因素logistic分析模型中。生活方式中的受教育程度、做家務(wù)時(shí)間,代謝性疾病中的血脂異常以及血漿FA中的C20:4n-6、比值n-3/n-6PUFA都是MCI的獨(dú)立影響因素。受教育程度越高(與小學(xué)及以下學(xué)歷相比,中學(xué)中專(zhuān)和大專(zhuān)大學(xué)及以上學(xué)歷OR分別為0.248、0.133)、做家務(wù)時(shí)間越長(zhǎng)(做家務(wù)時(shí)間每增加1h,OR=0.605)、比值n-3/n-6PUFA越大(與低水平組相比,高水平組的OR=0.361),MCI發(fā)生的風(fēng)險(xiǎn)越小,這些是MCI的獨(dú)立保護(hù)因素;而中等水平的C20:4n-6是MCI的危險(xiǎn)因素(與低水平組相比,中等水平OR=2.600,但高水平組與低水平組發(fā)生MCI的風(fēng)險(xiǎn)無(wú)明顯差異),血脂異常(OR=3.075)是MCI發(fā)生的獨(dú)立危險(xiǎn)因素。4結(jié)論生活方式中年齡、受教育程度是MCI的影響因素,其中MCI發(fā)生的危險(xiǎn)性在60-74y內(nèi)隨年齡增加而增加,而在75-y時(shí)危險(xiǎn)性降低;受教育程度是MCI的獨(dú)立影響因素;做家務(wù)能防止和延緩MCI的發(fā)生和發(fā)展。膳食因素中食物攝入頻次對(duì)MCI的影響不明顯。生化指標(biāo)中HDL-C以及載脂蛋白ApoA-1、ApoB、ApoE均是MCI的影響因素。代謝性疾病也是MCI的危險(xiǎn)因素,其中血脂是MCI的獨(dú)立危險(xiǎn)因素。在本研究中并未發(fā)現(xiàn)免疫指標(biāo)與MCI有關(guān)系。FA與MCI有密切的關(guān)系。SFA中C16:0是認(rèn)知的保護(hù)因素。n-3PUFA中的C18:3n-3在中等水平時(shí)對(duì)認(rèn)知有損害作用;C22:6n-3對(duì)MCI有保護(hù)作用,且有一個(gè)有效作用的界值。n-6PUFA對(duì)認(rèn)知有損害作用,一方面可能會(huì)通過(guò)抑制n-3PUFA進(jìn)入和在組織內(nèi)分布;一方面可能會(huì)與n-3PUFA競(jìng)爭(zhēng)合成過(guò)程中的酶,進(jìn)而抑制n-3PUFA的作用。
[Abstract]:AIM: To explore the influencing factors of mild cognitive impairment (MCI) in elderly people (> 60 y) in northern China. To explore the relationship between MCI and lifestyle, dietary factors, biochemical indicators, immune indicators, plasma fatty acid (FA), and to explore the influencing factors of MCI. Methods: A case-control study was conducted in three communities randomly selected from Shijiazhuang City, Hebei Province. All 60y elderly in three communities were selected as subjects. The study was divided into two steps: first, according to the health status of community residents. According to the inclusion and exclusion criteria, all the elderly were initially screened, then the basic data were investigated, and then the elderly were screened again according to the inclusion and exclusion criteria. All the MCI patients in the study group were identified according to the diagnostic criteria of normal cognition, and all the normal cognitive people in the three communities were selected by simple random sampling to control group. The ratio between the control group and MCI group was 1:1. In the later data processing, this paper will analyze the life style, dietary factors, blood lipid index, immune index, the relationship between fatty acid (FA) and MCI, and find out the influencing factors of MCI. The specific analysis process is as follows: first of all, the various indicators. The distribution of MCI in the two groups was analyzed preliminarily; then the effects of lifestyle, dietary factors, biochemical indicators, metabolic diseases, immune indicators and plasma fatty acids on MCI were investigated by univariate logistic regression analysis; after univariate analysis, the statistically significant variables in univariate analysis were included in multivariate logistic regression analysis. In the result analysis, the descriptive use cases (n) and constituent ratio (%) of the classified variables, the descriptions of the quantitative variables were expressed by mean (x) + standard deviation (S) or median (M) and upper and lower quartile (Q1, Q3); the comparison between the two groups of the classified variables was performed by_2 test, and the rank sum test was used for those who did not meet the criteria. The comparison between the two groups was conducted by t test, and those who did not meet the use conditions were tested by Wilcoxon symbolic rank sum test. The influencing factors of MCI were analyzed by single factor Logistic regression, and then analyzed by multi-factor logistic regression model. Compared with the control group, the proportion of 60-64y in MCI group was lower (42.74% 55.65%), 65-69y in the middle age group (33.87% 23.39%), 70-74y (17.74% 8.87%) was higher than that in the control group, and 75-y in the high age group (5.65% 12.1%) was lower than that in the control group again. The proportion of participants in the MCI group was lower than that in the control group (12.1% 18.55%) and the time spent on housework in the MCI group was significantly less than that in the control group (p.0001); the proportion of occasional smokers (6.45% 5.65%) and frequent smokers (11.29% 4.03%, P = 0.0908) in the MCI group was higher than that in the control group; while the living conditions (p = 0.7757) and recreational activities (p = 0.92%) in the MCI group were higher than that in the control group. 65), drinking (p = 0.3903), sitting time (p = 0.1599), sleeping time (p = 0.5955) were not significantly different. Among dietary factors, the frequency of eggs intake in the control group was higher than that in the MCI group, while the frequency of nuts intake was lower than that in the MCI group. The levels of HDL-C (1.141.18) and ApoA-1 (1.511.42) in MCI group were lower than those in control group, while the levels of ApoB (0.910.83) and ApoE (4.193.58) were higher than those in control group, but the levels of TC, TG, LDL-C, HDL-C/LDL-C, PL (a) and LP-PLA2 were not significantly different between the two groups. The prevalence of hypercholesterolemia, hypertriglyceridemia, hypohigh-density lipoprotein cholesterolemia, and anemia were not significantly different between the two groups. Immune indexes CRP, IL-6 and TNF-alpha in MCI and the control group were not significantly different. There was no significant difference in the distribution of plasma FA between the MCI group and the control group. There was no difference in the total content of SFA between the two groups, but the content of component C16:0 (p = 0.0061) in the MCI group was lower than that in the control group. There was no significant difference in the distribution of MUFA between the two groups. However, the levels of component C22:6n-3 were higher in the control group (p = 0.0057), the total content of n-6PUFA (p 0.0001) and its component C18:2n-6c in the MCI group were higher than those in the control group (p = 0.0003), the ratio of total content of PUFA to total content of n-3/n-6PUFA (p = 0.0140) and C22:6n-3/C20:4n-6 (p = 0.0294) in the normal group were higher than those in the MCI group. Univariate logistic regression analysis showed that age, education level, insomnia, visual acuity, smoking and housework time were all influencing factors of MCI. Within the 60-74y range, the younger the age, the lower the risk of MCI (all p0.05), and compared with the 60-64y group, the 65-69y and 70-74y groups had wind of MCI. The higher the education level, the lower the risk of MCI. Insomnia, decreased vision, and smoking were all risk factors of MCI. Every hour of housework, the risk of MCI increased to 0.621 times. Single factor Logistic regression analysis showed that the relationship between dietary factors and MCI was not obvious. The biochemical indexes were divided into low level group, middle level group and high level group according to three-digit. HDL-C (high level group OR = 0.532), ApoA-1 (high level group OR = 0.490) were protective factors of MCI. ApoB (middle level group, high level group OR = 1.882, 2.294), ApoE (high water group OR = 1.882, 2.294). TC (OR = 0.517) and LP (a) (OR = 0.491) had protective effects on MCI only at moderate levels. However, immune indexes were not significantly associated with MCI. Hypertension (OR = 1.740), diabetes mellitus (OR = 2.458) and dyslipidemia (OR = 1.845) were risk factors for MCI in metabolic diseases. There was no significant difference in the total content of n-3PUFA between MCI group and MCI group (p = 0.0061). There was no significant difference in the total content of n-3PUFA between MCI group and control group (p = 0.2782). There was no difference in the total content of n-3PUFA between the two groups, but the total content of component C22:6n-3 was higher in the control group (p = 0.0057). The ratio of n-3/n-6 PUFA (p = 0.0140) and C22:6n-3/C20:4n-6 (p = 0.0294) in the two groups were higher in the normal group than in the MCI group. The total content of C16:0, C22:6n-3, n-6PUFA, C18:2n-6c and the ratio of n-3/n-6PUFA and C22:6n-3/C20:4n-6 in MCI and control groups were still significantly different. In addition, the total content of n-3PUFA (p = 0.0330) and the distribution of C20:4n-6 (p = 0.0005) in MCI and control groups were significantly different. There were also significant differences. 3 Multivariate logistic regression analysis of the relationship between various indicators and MCI included lifestyle, apolipoprotein, LP (a), LP-PLA2, metabolic diseases, and statistically significant indicators in single-factor logistic regression analysis of plasma FA. The higher the education level (OR 0.248, 0.133 for junior secondary school, 0.133 for junior college and above) and the longer the housework time (OR = 0.605 for every hour of housework), the higher the ratio of n-3/n/n. The higher the - 6 PUFA (OR = 0.361 compared with the low level group), the lower the risk of MCI, these are independent protective factors of MCI; and the middle level of C20:4n - 6 is the risk factor of MCI (compared with the low level group, the middle level OR = 2.600, but the high level group and the low level group have no significant difference in the risk of MCI), dyslipidemia (OR = 3.075). Conclusion Age and education are the independent risk factors for MCI. The risk of MCI increases with age in 60-74y and decreases with age in 75-y. Education is an independent risk factor for MCI. Doing housework can prevent and delay the occurrence and development of MCI. HDL-C and apolipoprotein ApoA-1, ApoB and ApoE were the influencing factors of MCI. Metabolic diseases were also the risk factors of MCI. Blood lipid was an independent risk factor of MCI. No correlation was found between immune indexes and MCI. There was a close relationship between FA and MCI. C18:3n-3 in n-3PUFA is a protective factor for cognition. C18:3n-3 in n-3PUFA is harmful to cognition at moderate level; C22:6n-3 has protective effect on MCI and has a threshold of effective effect. n-6PUFA is harmful to cognition. On the one hand, it may inhibit the entry and distribution of n-3PUFA in tissues; on the other hand, it may compete with n-3PUFA in the process of synthesis. The enzyme further inhibits the action of n-3PUFA.
【學(xué)位授予單位】：中國(guó)疾病預(yù)防控制中心
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R749.1

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