Article(id=1240972422162206967, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240972413354176744, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202312324, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1702915200000, receivedDateStr=2023-12-19, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773800481596, onlineDateStr=2026-03-18, pubDate=1715270400000, pubDateStr=2024-05-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773800481596, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773800481596, creator=13701087609, updateTime=1773800481596, updator=13701087609, issue=Issue{id=1240972413354176744, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='9', pageStart='1537', pageEnd='1728', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773800479495, creator=13701087609, updateTime=1773800596829, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1240972905568334240, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240972413354176744, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1240972905568334241, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240972413354176744, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1708, endPage=1712, ext={EN=ArticleExt(id=1240972422569054491, articleId=1240972422162206967, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Effect of serum uric acid on cognitive function in patients with Alzheimer’s disease based on trajectory model classification, columnId=1228016569138213037, journalTitle=Modern Preventive Medicine, columnName=Clinical Medicine and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To analyze the effect of serum uric acid (UA) on cognitive function in patients with Alzheimer’s disease (AD).

Methods

The cognitive function of 259 patients with AD who were followed up more than 3 times in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) follow-up cohort were measured by Mini-Mental State Examination (MMSE). The trajectory analysis model was used to classify the subjects according to the changing trend of MMSE scores during the follow-up period. Taking different trajectory groups as dependent variables and serum UA as independent variables, multi-classification Logistic regression analysis was used to explore the effect of serum UA on cognitive function in patients with different types of AD after adjusting various confounding factors.

Results

According to the trajectory model, the subjects were divided into three subgroups: cognitive sudden decline group, cognitive slow decline group, and cognitive stationary group. There was significant difference in serum UA among different trajectory subgroups (F=4.910, P=0.008). After adjusting for the influence of bio-behavioral-disease potential confounding factors, multi-classification Logistic regression found that serum UA was an independent risk factor for the outcome of cognitive slow decline group (cognitive slow decline group: OR=1.35, 95%CI: 1.03-1.77).With each increase of 10 mg/L in UA level, the risk of cognitive decline in AD patients in cognitive slow decline group was 35%higher than that in cognitive stable group. In the cognitive sudden decline group, there was no risk association between UA and cognitive function.

Conclusion

Compared with those with stable cognitive development, high level of serum UA is a risk factor for slow cognitive decline in patients with AD.

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目的

分析血清尿酸对阿尔茨海默病(Alzheimer disease,AD)患者认知功能的影响。

方法

研究对象来自阿尔茨海默病神经影像学计划随访队列中随访≥3次的AD患者259例,采用简易精神状态评价量表( mini-mental state examination,MMSE)测定患者的认知功能。使用轨迹分析模型依据随访期间MMSE得分的变化趋势对研究对象进行归类。以不同轨迹组作为因变量,血清尿酸作为自变量,采用多分类logistic回归分析探讨在调整各种混杂因素后,血清尿酸对不同类型AD患者认知功能的影响。

结果

轨迹模型将研究对象分为三个亚组,分别为认知骤降组、认知缓降组和认知平稳组。不同轨迹亚组间血清尿酸差异有统计学意义(F=4.910,P=0.008)。多分类logistic回归在调整了生物-行为-疾病潜在混杂因素影响后,发现血清尿酸是认知缓降组结局的独立危险因素(认知缓降组OR=1.35,95%CI:1.03~1.77),尿酸水平每升高10 mg/L,认知缓降组AD患者发生认知水平下降的风险较认知平稳组增加35%。而在认知骤降组结局中,未见尿酸与认知功能有风险关联。

结论

在AD患者中,与认知水平平稳发展者相比,高水平血清尿酸是认知缓慢下降的危险因素。

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刘佳,E-mail:
, copyrightStatement=本刊刊出的所有文章不代表中华预防医学会和本刊编委会的观点,除非特别声明。, copyrightOwner=中华预防医学会和四川大学华西公共卫生学院, extLink=null, articleAbsUrl=null, sourceXml=t/aQMAOScjkLzcIqHdNTFA==, magXml=9PbJQ0o8McpAhNhKxng17w==, pdfUrl=null, pdf=UPN6cmHN9pR4C06+/TuZlA==, pdfFileSize=609403, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=isq+jmMiHnJ+DAqPaxCCiA==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=1NnMgNn09vBAgG5naW4uxA==, mapNumber=null, authorCompany=null, fund=null, authors=

肖焕波(1973—),女,硕士,副教授,研究方向:慢性病流行病学

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Chinese Journal of Nervous and Mental Diseases, 2011, 37(10): 603-606., articleTitle=The effects of uric acid on learning-memory ability in the rat model of Alzheimer disease, refAbstract=null)], funds=[Fund(id=1240986268063027384, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, awardId=82304244, language=CN, fundingSource=国家自然科学基金青年项目(82304244), fundOrder=null, country=null), Fund(id=1240986268641841349, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, awardId=2022JYY422, language=CN, fundingSource=首都医科大学教育教学改革研究课题(2022JYY422), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1240986260722996039, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, xref=null, ext=[AuthorCompanyExt(id=1240986260731384648, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, companyId=1240986260722996039, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Yanjing Medical College of Capital Medical University, Beijing 101300, China), AuthorCompanyExt(id=1240986260739773257, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, companyId=1240986260722996039, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=首都医科大学燕京医学院,北京 101300)])], figs=[ArticleFig(id=1240986265491918914, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, language=EN, label=Figure 1, caption=Trajectory model curves of different subgroups, figureFileSmall=1qcf931fiQi2PiCCO7fzdg==, figureFileBig=EMpMO6ISI5nHuuLYglS34Q==, tableContent=null), ArticleFig(id=1240986265789714514, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, language=CN, label=图1, caption=不同亚组轨迹模型曲线, figureFileSmall=1qcf931fiQi2PiCCO7fzdg==, figureFileBig=EMpMO6ISI5nHuuLYglS34Q==, tableContent=null), ArticleFig(id=1240986266049761378, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, language=EN, label=Figure 2, caption=Violin diagram of serum uric acid levels in different trajectory models, figureFileSmall=JGB4xniw3Q/rBO9F3TkVdg==, figureFileBig=NhwskjTwohAI4on9py6qgA==, tableContent=null), ArticleFig(id=1240986266188173419, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, language=CN, label=图2, caption=不同轨迹模型血尿酸水平的小提琴图, figureFileSmall=JGB4xniw3Q/rBO9F3TkVdg==, figureFileBig=NhwskjTwohAI4on9py6qgA==, tableContent=null), ArticleFig(id=1240986266372722802, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, language=EN, label=Figure 3, caption=The associations between UA and different cognitive trajectories in 3 models, figureFileSmall=dADdy56ysdTm6C5aT8jFqQ==, figureFileBig=8RJECpGU02Pk+4k1jvU8Xw==, tableContent=null), ArticleFig(id=1240986266678907006, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, language=CN, label=图3, caption=3次模型拟合尿酸与不同认知轨迹的关联

注:认知骤降组、认知缓降组模型拟合均以认知平稳组做参照;模型1不调整任何因素时尿酸与认知轨迹的关联;模型2调整生物-行为因素时尿酸与认知轨迹的关联;模型3调整生物-行为-疾病因素时尿酸与认知轨迹的关联。

, figureFileSmall=dADdy56ysdTm6C5aT8jFqQ==, figureFileBig=8RJECpGU02Pk+4k1jvU8Xw==, tableContent=null), ArticleFig(id=1240986266884427907, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, language=EN, label=Table 1, caption=

Comparison of subgroup features of different trajectory models [(),n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
变量分组认知骤降组(n=39)认知缓降组(n=114)认知平稳组(n=106)F/χ2P
尿酸(mg/L)48.5±12.255.0±13.150.9±12.54.9100.008
年龄(岁)72.48±7.1775.85±7.8575.49±7.063.0670.048
性别20(52.6)47(41.2)48(44.9)1.5170.455
18(47.4)67(58.8)59(55.1)
吸烟25(65.8)69(60.5)65(60.7)0.3650.855
13(34.2)45(39.5)42(39.3)
饮酒35(92.1)109(95.6)99(92.5)1.1360.529
3(7.9)5(4.4)8(7.5)
肥胖34(89.5)99(86.8)96(89.7)0.4950.778
4(10.5)15(13.2)11(10.3)
高血压12(31.6)37(32.5)40(37.4)0.7470.696
26(68.4)77(67.5)67(62.6)
血脂异常26(68.4)85(74.6)77(72.0)0.5760.714
12(31.6)29(25.4)30(28.0)
糖尿病34(89.5)95(83.3)89(83.2)0.9410.695
4(10.5)19(16.7)18(16.8)
心血管疾病12(31.6)32(28.1)31(29.0)0.1710.897
26(68.4)82(71.9)76(71.0)
慢性肾病26(68.4)71(62.3)74(69.2)1.2780.541
12(31.6)43(37.7)33(30.8)
癌症33(86.8)89(78.1)82(76.6)1.8050.430
5(13.2)25(21.9)25(23.4)
ApoE4携带10(26.3)39(34.2)32(29.9)0.9850.637
28(73.7)75(65.8)75(70.1)
), ArticleFig(id=1240986267068977294, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, language=CN, label=表1, caption=

不同轨迹模型亚组特征比较[(),n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
变量分组认知骤降组(n=39)认知缓降组(n=114)认知平稳组(n=106)F/χ2P
尿酸(mg/L)48.5±12.255.0±13.150.9±12.54.9100.008
年龄(岁)72.48±7.1775.85±7.8575.49±7.063.0670.048
性别20(52.6)47(41.2)48(44.9)1.5170.455
18(47.4)67(58.8)59(55.1)
吸烟25(65.8)69(60.5)65(60.7)0.3650.855
13(34.2)45(39.5)42(39.3)
饮酒35(92.1)109(95.6)99(92.5)1.1360.529
3(7.9)5(4.4)8(7.5)
肥胖34(89.5)99(86.8)96(89.7)0.4950.778
4(10.5)15(13.2)11(10.3)
高血压12(31.6)37(32.5)40(37.4)0.7470.696
26(68.4)77(67.5)67(62.6)
血脂异常26(68.4)85(74.6)77(72.0)0.5760.714
12(31.6)29(25.4)30(28.0)
糖尿病34(89.5)95(83.3)89(83.2)0.9410.695
4(10.5)19(16.7)18(16.8)
心血管疾病12(31.6)32(28.1)31(29.0)0.1710.897
26(68.4)82(71.9)76(71.0)
慢性肾病26(68.4)71(62.3)74(69.2)1.2780.541
12(31.6)43(37.7)33(30.8)
癌症33(86.8)89(78.1)82(76.6)1.8050.430
5(13.2)25(21.9)25(23.4)
ApoE4携带10(26.3)39(34.2)32(29.9)0.9850.637
28(73.7)75(65.8)75(70.1)
), ArticleFig(id=1240986267316441242, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, language=EN, label=Table 2, caption=

Variable assignment table for multinomial logistic regression analysis

, figureFileSmall=null, figureFileBig=null, tableContent=
变量赋值
因变量1=认知平稳组
2=认知缓降组
3=认知骤降组
性别1=男;2=女
吸烟0=否;1=是
饮酒0=否;1=是
肥胖0=否;1=是
ApoE4携带0=否;1=是
高血压0=否;1=是
糖尿病0=否;1=是
血脂异常0=否;1=是
慢性肾病0=否;1=是
心血管疾病0=否;1=是
癌症0=否;1=是
), ArticleFig(id=1240986267459047589, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972422162206967, language=CN, label=表2, caption=

多分类logistic回归分析变量赋值表

, figureFileSmall=null, figureFileBig=null, tableContent=
变量赋值
因变量1=认知平稳组
2=认知缓降组
3=认知骤降组
性别1=男;2=女
吸烟0=否;1=是
饮酒0=否;1=是
肥胖0=否;1=是
ApoE4携带0=否;1=是
高血压0=否;1=是
糖尿病0=否;1=是
血脂异常0=否;1=是
慢性肾病0=否;1=是
心血管疾病0=否;1=是
癌症0=否;1=是
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基于轨迹模型分类的血清尿酸对阿尔茨海默病患者认知功能影响的研究
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肖焕波 , 张洪伟 , 纪颖 , 刘佳
现代预防医学 | 临床与预防 2024,51(9): 1708-1712
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现代预防医学 | 临床与预防 2024, 51(9): 1708-1712
基于轨迹模型分类的血清尿酸对阿尔茨海默病患者认知功能影响的研究
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肖焕波, 张洪伟, 纪颖, 刘佳
作者信息
  • 首都医科大学燕京医学院,北京 101300
  • 肖焕波(1973—),女,硕士,副教授,研究方向:慢性病流行病学

通讯作者:

刘佳,E-mail:
Effect of serum uric acid on cognitive function in patients with Alzheimer’s disease based on trajectory model classification
Huan-bo XIAO, Hong-wei ZHANG, Ying JI, Jia LIU
Affiliations
  • Yanjing Medical College of Capital Medical University, Beijing 101300, China
出版时间: 2024-05-10 doi: 10.20043/j.cnki.MPM.202312324
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目的

分析血清尿酸对阿尔茨海默病(Alzheimer disease,AD)患者认知功能的影响。

方法

研究对象来自阿尔茨海默病神经影像学计划随访队列中随访≥3次的AD患者259例,采用简易精神状态评价量表( mini-mental state examination,MMSE)测定患者的认知功能。使用轨迹分析模型依据随访期间MMSE得分的变化趋势对研究对象进行归类。以不同轨迹组作为因变量,血清尿酸作为自变量,采用多分类logistic回归分析探讨在调整各种混杂因素后,血清尿酸对不同类型AD患者认知功能的影响。

结果

轨迹模型将研究对象分为三个亚组,分别为认知骤降组、认知缓降组和认知平稳组。不同轨迹亚组间血清尿酸差异有统计学意义(F=4.910,P=0.008)。多分类logistic回归在调整了生物-行为-疾病潜在混杂因素影响后,发现血清尿酸是认知缓降组结局的独立危险因素(认知缓降组OR=1.35,95%CI:1.03~1.77),尿酸水平每升高10 mg/L,认知缓降组AD患者发生认知水平下降的风险较认知平稳组增加35%。而在认知骤降组结局中,未见尿酸与认知功能有风险关联。

结论

在AD患者中,与认知水平平稳发展者相比,高水平血清尿酸是认知缓慢下降的危险因素。

尿酸  /  认知功能  /  轨迹分析模型  /  阿尔茨海默病
Objective

To analyze the effect of serum uric acid (UA) on cognitive function in patients with Alzheimer’s disease (AD).

Methods

The cognitive function of 259 patients with AD who were followed up more than 3 times in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) follow-up cohort were measured by Mini-Mental State Examination (MMSE). The trajectory analysis model was used to classify the subjects according to the changing trend of MMSE scores during the follow-up period. Taking different trajectory groups as dependent variables and serum UA as independent variables, multi-classification Logistic regression analysis was used to explore the effect of serum UA on cognitive function in patients with different types of AD after adjusting various confounding factors.

Results

According to the trajectory model, the subjects were divided into three subgroups: cognitive sudden decline group, cognitive slow decline group, and cognitive stationary group. There was significant difference in serum UA among different trajectory subgroups (F=4.910, P=0.008). After adjusting for the influence of bio-behavioral-disease potential confounding factors, multi-classification Logistic regression found that serum UA was an independent risk factor for the outcome of cognitive slow decline group (cognitive slow decline group: OR=1.35, 95%CI: 1.03-1.77).With each increase of 10 mg/L in UA level, the risk of cognitive decline in AD patients in cognitive slow decline group was 35%higher than that in cognitive stable group. In the cognitive sudden decline group, there was no risk association between UA and cognitive function.

Conclusion

Compared with those with stable cognitive development, high level of serum UA is a risk factor for slow cognitive decline in patients with AD.

Uric acid  /  Cognitive function  /  Trajectory analysis model  /  Alzheimer’s disease (AD)
肖焕波, 张洪伟, 纪颖, 刘佳. 基于轨迹模型分类的血清尿酸对阿尔茨海默病患者认知功能影响的研究. 现代预防医学, 2024 , 51 (9) : 1708 -1712 . DOI: 10.20043/j.cnki.MPM.202312324
Huan-bo XIAO, Hong-wei ZHANG, Ying JI, Jia LIU. Effect of serum uric acid on cognitive function in patients with Alzheimer’s disease based on trajectory model classification[J]. Modern Preventive Medicine, 2024 , 51 (9) : 1708 -1712 . DOI: 10.20043/j.cnki.MPM.202312324
阿尔茨海默病(Alzheimer disease,AD)是以进行性认知功能障碍和行为损害为特征的中枢神经系统退行性病变,是老年期痴呆最常见的类型。许多研究表明,尿酸(uric acid)在AD、帕金森病、血管性痴呆等多种疾病的发生发展中起重要作用,尿酸水平与认知表现相关[1-2]。在尿酸与AD的相关性研究中,有的研究支持高水平尿酸可能促进AD的发生和发展[3],也有研究支持低水平尿酸可能与AD认知下降相关[4-5],可见,关于尿酸水平与AD患者认知功能的关联,目前研究结论尚不统一。AD患者随着时间的推移,认知功能会呈现多种变化,应用一组认知轨迹模型不能充分展示患者多种预后趋势,也不利于探讨尿酸与AD患者认知功能改变的关系,本研究依据纵向数据使用轨迹分析模型(group-based trajectory modeling,GBTM),将研究对象按照认知功能变化轨迹进行归类,深入探讨尿酸水平与AD患者认知功能的相关性。
本研究数据来自阿尔茨海默病神经影像学计划(ADNI)数据库。纳入队列中随访至少3次,符合美国国立神经病语言障碍卒中研究所和AD及相关疾病协会中的“很可能AD”诊断标准的AD患者259例。所有对象在入组前均签署了知情同意书,所有方法均按照相关指南和规定进行,相关研究均在各ADNI研究中心获得了机构审查委员会批准(见完整列表:http://adni.loni.usc.edu)。
采用简易精神状态评价量表( mini-mental state examination,MMSE)从语言、视结构、延迟记忆、即刻记忆、空间定向力、时间定向力、注意力和计算7个方面测定患者的认知功能,该量表由20个问题30项组成,每项回答正确1分,错误或不知道0分,总分30分,分数越低认知能力越差。将连续或累积吸烟6个月或以上者判定为吸烟;将过去12个月有饮用含酒精饮料者判定为饮酒;体质指数BMI≥30 kg/m2定义为肥胖;收缩压≥140 mm Hg和/或舒张压≥90 mm Hg定义为高血压;空腹血糖≥7.0 mmol/L定义为糖尿病;总胆固醇浓度>5.17 mmol/L(200 mg/dl)或甘油三酯>2.3 mmol/L(200 mg/dl)定义为高脂血症;肾小球滤过率<60 ml/min判定为慢性肾脏病(chronic kidney disease, CKD)。
采用R软件进行统计分析,定量资料以()表示,组间比较采用方差分析;定性资料用[n(%)]表示,组间比较采用χ2检验。使用组轨迹模型(GBTM)依据不同AD患者随访期间MMSE得分的变化趋势对研究对象进行归类。以MMSE得分作为因变量,随访次数作为自变量构建GBTM,分别模拟将研究对象分为1、2、3及4个亚组时MMSE得分的变化轨迹;使用贝叶斯信息准则(BIC)等评价指标,判断不同亚组GBTM的拟合效果,直至选出最优模型。以MMSE的不同轨迹作为因变量,血清尿酸作为自变量,进行无序多分类logistic回归分析,在调整各种潜在混杂因素[6-7]后,拟合logistic回归模型,探讨血清尿酸与不同认知轨迹的关联。检验水准α=0.05。
综合BIC等评价指标,将研究对象按照MMSE得分轨迹分为3个亚组时模型拟合效果最佳。a组轨迹曲线呈大幅下降趋势,视为认知骤降组,占15.1%(39/259);b组轨迹曲线呈小幅下降趋势,视为认知缓降组,占44.0%(114/259);c组轨迹曲线呈平稳发展趋势,视为认知平稳组,占40.9%(106/259),不同亚组的轨迹模型曲线见图1
不同认知轨迹模型亚组尿酸水平分别为,认知骤降组(48.5±12.2)mg/L、认知缓降组(55.0±13.1)mg/L、认知平稳组(50.9±12.5)mg/L,不同亚组尿酸差异有统计学意义(F=4.910,P=0.008),两两比较得出认知骤降组与认知缓降组(P=0.013)、认知缓降组与认知平稳组(P=0.029)差异均有统计学意义,认知骤降组与认知平稳组(P=0.290)差异无统计学意义,见图2。不同轨迹亚组年龄差异有统计学意义(P=0.048),认知骤降组的年龄低于认知缓降组、认知平稳组。不同亚组间性别、吸烟、饮酒、肥胖、高血压、血脂异常、糖尿病、心血管疾病、CKD、癌症、ApoE4基因携带差异均无统计学意义。见表1
以不同轨迹亚组作为因变量,以认知平稳组作为参照组,进行多分类logistic回归分析,变量赋值见表2。不调整任何因素,自变量只纳入尿酸,结果显示(模型1):在认知缓降组的结局中,尿酸是认知水平下降的危险因素(OR=1.29,95%CI:1.04~1.59)。调整了年龄、性别、Apoe4基因携带、肥胖、吸烟、饮酒生物-行为因素后的logistic回归模型显示(模型2),在认知缓降组的结局中,尿酸是认知水平下降的危险因素(OR= 1.29,95%CI:1.03~1.62)。在模型2的基础上,又调整了高血压、糖尿病、血脂异常、CKD、心血管疾病、癌症疾病因素的影响后,logistic回归模型显示(模型3),在认知缓降组的结局中,尿酸仍是AD患者认知水平下降的危险因素(OR=1.35,95%CI:1.03~1.77)。为调整潜在混杂因素的影响先后进行了3次模型拟合,3个模型认知缓降组结局中,尿酸都是认知功能下降的危险因素,风险比相对稳定;3个模型认知骤降组结局中,未见尿酸与认知功能有风险关联。见图3
许多研究表明氧化应激机制与AD、血管性痴呆、帕金森病患者的认知损害密切相关[8-9]。尿酸是嘌呤代谢终末氧化产物,既有抗氧化应激作用,又有促氧化应激作用。生理浓度的尿酸具有抗氧化特性,能清除机体大约60%的自由基,但当尿酸水平过高时,又具有促氧化作用,可导致多种疾病的发生,尿酸与认知功能的关系密切,但报道结果不一[10]
本研究发现AD患者3组认知轨迹模型中,尿酸水平与AD患者认知功能的影响不一致。认知缓降组尿酸水平最高,多因素分析在调整了生物-行为-疾病这些潜在混杂因素影响后表明尿酸是认知功能下降的独立危险因素,尿酸水平每升高10 mg/L,认知缓降组AD患者发生认知水平下降的风险较认知平稳组增加35%。认知骤降组尿酸水平最低,数值上虽低于认知平稳组,但多因素分析尚未得出认知骤降组结局中尿酸水平对认知功能有影响的统计学结论。
目前有的研究支持高水平尿酸与AD患者的认知功能障碍相关[3]。Latourte A等[11]在一个随访时间超过12年的大型前瞻性队列研究中发现,高尿酸水平与老年人痴呆的风险增加有关,特别是血管性或混合性痴呆。本研究也发现高尿酸水平(认知缓降组轨迹模型)是AD患者认知功能下降的独立危险因素。这可能是当尿酸水平升高时,体内抗氧化应激水平降低,不能及时地将体内的氧自由基清除,这时血管的炎性反应及氧化应激水平会增高,造成患者血管内皮功能发生紊乱,从而对认知功能产生影响。邵晓妮等[12]用代谢组学方法研究了高尿酸血症诱发大鼠认知功能障碍模型,认为高尿酸诱发认知功能障碍机制可能与能量代谢的糖酵解和三羧酸循环、氨基酸代谢、氧化应激、神经递质转化以及细胞膜功能的紊乱等有关。
也有大量证据表明低尿酸水平与AD的发生和进展有关[4-5]。本研究也发现AD患者认知骤降轨迹组有较低的尿酸水平,但尚未发现尿酸对患者认知功能有影响的统计学关联,可能是本研究认知骤降组样本量过少,未得出有统计学意义的结果。Ye等[4]在校正了其他因素后也发现较高的血清尿酸水平与较慢的纵向认知恶化速率相关,尿酸水平对纵向认知衰退具有独立的保护作用。Geng等[13]在一项基于NHANES数据库的大型人群研究中得出,尿酸和美国老年人的认知得分之间存在正相关,尿酸在正常范围内的轻微上升有利于增强认知能力。我国学者Chen等[14]分析了健康老龄化和生物标志物队列研究(HABCS)9年的随访数据,得出高血清尿酸水平与我国老年人轻度认知障碍风险降低相关,也证实了尿酸在老年人群中的神经保护作用。Lee等[15]使用ADNI数据集评估了血清尿酸对纵向认知和脑代谢的影响,发现较高的尿酸水平对正常认知者表现出有害影响,而在认知障碍患者中则观察到有保护趋势,认为尿酸对脑代谢氧化应激介导的认知衰退具有有益作用。
宋彦等[16]在动物实验中发现,尿酸在一定剂量范围内能改善AD大鼠的学习记忆能力,这一作用存在量-效关系,超过此剂量范围尿酸的保护作用降低甚至消失,说明尿酸在一定范围内具有抗氧化应激能力,低于或高于这一范围反而会通过氧化应激反应损伤机体细胞。本研究通过分析AD患者不同认知轨迹模型,也发现认知轨迹快速下降组尿酸水平较低,认知轨迹缓慢下降组尿酸水平较高,认知轨迹相对平稳组尿酸处于适中水平。但本研究有一定的局限性,一是样本量不足,尤其认知骤降组人数较少,而且ADNI招募的受试者可能不能代表一般人群。二是ADNI数据集并非旨在研究血清尿酸水平对AD的影响,缺乏膳食因素的数据。因此本文研究结果还需要更多前瞻性大人群队列研究证实。
  • 国家自然科学基金青年项目(82304244)
  • 首都医科大学教育教学改革研究课题(2022JYY422)
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2024年第51卷第9期
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doi: 10.20043/j.cnki.MPM.202312324
  • 接收时间:2023-12-19
  • 首发时间:2026-03-18
  • 出版时间:2024-05-10
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  • 收稿日期:2023-12-19
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国家自然科学基金青年项目(82304244)
首都医科大学教育教学改革研究课题(2022JYY422)
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    首都医科大学燕京医学院,北京 101300

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2种不同金属材料的力学参数

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genus
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species
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Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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