Article(id=1240738483069842335, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240738480549065614, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202501176, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1736438400000, receivedDateStr=2025-01-10, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773744706170, onlineDateStr=2026-03-17, pubDate=1746806400000, pubDateStr=2025-05-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773744706170, onlineIssueDateStr=2026-03-17, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773744706170, creator=13701087609, updateTime=1773744706170, updator=13701087609, issue=Issue{id=1240738480549065614, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', 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=1773744705569, creator=13701087609, updateTime=1773744787657, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1240738824918192654, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240738480549065614, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1240738824922386959, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240738480549065614, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1537, endPage=1543, ext={EN=ArticleExt(id=1240738483766096823, articleId=1240738483069842335, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Study on the association between obesity status and dementia in patients with cardiovascular metabolic diseases, columnId=1240413921954295836, journalTitle=Modern Preventive Medicine, columnName=Epidemiology and Statistical Methods, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the relationship between different obesity statuses in patients with cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM) and the incidence of all-cause dementia and its subtypes.

Methods

Based on data from the UK Biobank, study subjects were categorized into five obesity states—underweight, normal weight, simple central or simple generalized obesity, combined overweight, and combined obesity—according to BMI and waist circumference. The Cox proportional hazards regression model was employed to analyze the hazard ratios (HR) and 95% confidence intervals (CI) for dementia incidence among patients with cardiovascular metabolic diseases across different obesity statuses.

Results

A total of 63 066 CVD patients and 33 872 T2DM patients were included in the study. Compared to normal weight CVD patients, underweight individuals exhibited a 135% increased risk of vascular dementia (VD) (HR=2.35, 95%CI: 1.09-5.09). The risk of all-cause dementia and Alzheimer’s disease (AD) in patients with simple central or simple generalized obesity decreased by 26% (0.74, 0.61-0.90) and 30% (0.70, 0.51-0.95),respectively. For combined overweight patients, the risk of all-cause dementia and AD decreased by 28% (0.72, 0.64-0.82) and 29%(0.71, 0.58-0.87), respectively. In combined obesity patients, the risk of all-cause dementia, AD, and VD decreased by 35% (0.65,0.58-0.74), 40% (0.60, 0.49-0.74), and 27% (0.73, 0.57-0.93), respectively. Compared to normal weight T2DM patients, combined overweight patients showed a 39% (0.61, 0.46-0.81) and 46% (0.54, 0.36-0.81) reduction in the risk of all-cause dementia and AD,respectively. The risk of all-cause dementia, AD, and VD in combined obesity patients decreased by 35% (0.53, 0.41-0.69), 40%(0.45, 0.31-0.66), and 27% (0.53, 0.32-0.87), respectively.

Conclusion

There is an “obesity paradox” in dementia risk among patients with cardiovascular metabolic diseases, with a significant reduction in the incidence of dementia among patients with simple central or simple generalized obesity, combined overweight, and combined obesity.

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目的

探讨心血管疾病(CVD)患者和2型糖尿病患者(T2DM)患者不同肥胖状态与全因痴呆及其亚型的关系。

方法

基于英国生物银行(UK Biobank)数据,根据BMI和腰围将研究对象分为低体重、正常体型、单纯中心性或单纯全身肥胖、复合超重和复合肥胖5种状态,采用Cox比例风险回归模型分析不同肥胖状态心血管代谢疾病患者的痴呆发病风险比(HR)值及其95%CI

结果

CVD患者共纳入63 066名研究对象,T2DM患者共纳入33 872名研究对象。以正常体型CVD患者为对照,低体重患者发生血管性痴呆(VD)的风险增高135%(HR=2.35,95%CI:1.09~5.09)。单纯中心性或单纯全身肥胖患者的全因痴呆和阿尔茨海默病(AD)的发病风险分别下降26%(HR=0.74,95%CI:0.61~0.90)、30%(HR=0.70,95%CI:0.51~0.95)。复合超重患者的全因痴呆和AD的发病风险分别下降28%(HR=0.72,95%CI:0.64~0.82)和29%(HR=0.71,95%CI:0.58~0.87)。复合肥胖患者的全因痴呆、AD和VD的发病风险分别下降35%(HR= 0.65,95%CI:0.58~0.74)、40%(HR=0.60,95%CI:0.49~0.74)和27%(HR=0.73,95%CI:0.57~0.93)。以正常体型T2DM患者为对照,复合超重患者出现全因痴呆和AD的风险分别下降39%(HR=0.61,95%CI:0.46~0.81)和46%(HR=0.54,95%CI:0.36~0.81)。复合肥胖患者的全因痴呆、AD和VD的发病风险分别下降35%(HR=0.53,95%CI:0.41~0.69)、40%(HR= 0.45,95%CI:0.31~0.66)和27%(HR=0.53,95%CI:0.32~0.87)。

结论

心血管代谢疾病患者痴呆风险存在“肥胖悖论”现象,单纯中心性或单纯全身肥胖、复合超重、复合肥胖患者的痴呆发病风险明显降低。

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朱东山,E-mail:
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张小宇(2001—),女,硕士在读,研究方向:慢性病流行病学

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张小宇(2001—),女,硕士在读,研究方向:慢性病流行病学

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Midlife and late-life obesity and the risk of dementia: cardiovascular health study[J].Archives of Neurology, 2009, 66(3): 336-342., articleTitle=Midlife and late-life obesity and the risk of dementia: cardiovascular health study, refAbstract=null), Reference(id=1241081880750117752, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, doi=null, pmid=null, pmcid=null, year=2003, volume=289, issue=20, pageStart=2663, pageEnd=2672, url=null, language=null, rfNumber=[25], rfOrder=28, authorNames=Rapp SR, Espeland MA, Shumaker SA, journalName=JAMA: the Journal of the American Medical Association, refType=null, unstructuredReference=Rapp SR, Espeland MA, Shumaker SA, et al. Effect of estrogen plus progestin on global cognitive function in postmenopausal women:the Women's Health Initiative Memory Study: a randomized controlled trial[J]. JAMA: the Journal of the American Medical Association, 2003, 289(20): 2663-2672., articleTitle=Effect of estrogen plus progestin on global cognitive function in postmenopausal women:the Women's Health Initiative Memory Study: a randomized controlled trial, refAbstract=null), Reference(id=1241081880863363965, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, doi=null, pmid=null, pmcid=null, year=2021, volume=13, issue=13, pageStart=16974, pageEnd=16989, url=null, language=null, rfNumber=[26], rfOrder=29, authorNames=Cho YK, Lee J, Kim HS, journalName=Aging(Albany NY), refType=null, unstructuredReference=Cho YK, Lee J, Kim HS, et al. The risk of Alzheimer's disease according to dynamic changes in metabolic health and obesity: a nationwide population-based cohort study[J]. Aging(Albany NY),2021, 13(13): 16974-16989., articleTitle=The risk of Alzheimer's disease according to dynamic changes in metabolic health and obesity: a nationwide population-based cohort study, refAbstract=null)], funds=[Fund(id=1241081873506554449, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, awardId=82273702, language=CN, fundingSource=国家自然科学基金资助项目(82273702), fundOrder=null, country=null), Fund(id=1241081873657549408, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, awardId=2022HWYQ-030, language=CN, fundingSource=山东省优秀青年学者资助项目(2022HWYQ-030), fundOrder=null, country=null), Fund(id=1241081873808544359, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, awardId=tsqnz20221103, language=CN, fundingSource=泰山学者项目专项基金(tsqnz20221103), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1241081864627212437, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, xref=1., ext=[AuthorCompanyExt(id=1241081864639795350, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, companyId=1241081864627212437, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China), AuthorCompanyExt(id=1241081864648183960, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, companyId=1241081864627212437, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东大学齐鲁医学院公共卫生学院流行病学系,山东 济南 250012)]), AuthorCompany(id=1241081864732070044, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, xref=2., ext=[AuthorCompanyExt(id=1241081864753041565, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, companyId=1241081864732070044, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.山东大学临床流行病学和循证医学中心,山东 济南 250012)])], figs=[ArticleFig(id=1241081871849804224, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, language=EN, label=Figure 1, caption=Forest plot of subgroup analysis by gender and age of different obesity status and dementia in patients with cardiovascular metabolic diseases, figureFileSmall=JQKp2OlFYH+KvjIWFIdANA==, figureFileBig=nxoh2uFwcL/LnxlvWl8QXQ==, tableContent=null), ArticleFig(id=1241081871992410577, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, language=CN, label=图1, caption=心血管代谢疾病患者不同肥胖状态与痴呆的性别、年龄的亚组分析森林图, figureFileSmall=JQKp2OlFYH+KvjIWFIdANA==, figureFileBig=nxoh2uFwcL/LnxlvWl8QXQ==, tableContent=null), ArticleFig(id=1241081872109851104, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, language=EN, label=Figure 2, caption=Sensitivity analysis forest plot using different exclusion criteria in patients with cardiovascular metabolic diseases, figureFileSmall=VTg4lQCSihktFsd9g/DMZg==, figureFileBig=e+fiJ8/sXU3UF71nqpMtVg==, tableContent=null), ArticleFig(id=1241081872218903016, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, language=CN, label=图2, caption=心血管代谢疾病患者中采用不同排除标准进行的敏感性分析森林图, figureFileSmall=VTg4lQCSihktFsd9g/DMZg==, figureFileBig=e+fiJ8/sXU3UF71nqpMtVg==, tableContent=null), ArticleFig(id=1241081872374092276, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, language=EN, label=Table 1, caption=

Baseline characteristics of the CVD patient population [n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
特征合计正常体型低体重单纯中心性或
单纯全身肥胖
复合超重复合肥胖
基线年龄 (岁)
<6020 9112 248(36.8)99(41.1)1 121(35.4)6 116(30.0)11 327(34.2)
≥6042 1553 864(63.2)142(58.9)2 050(64.7)14 265(70.0)21 834(65.8)
性别
23 5933 859(63.1)163(67.6)2 267(71.5)5 796(28.4)11 508(34.7)
39 4732 253(36.9)78(32.4)904(28.5)14 585(71.6)21 653(65.3)
人种
白人60 1365 869(96.0)230(95.4)3 065(96.7)19 409(95.2)31 563(95.2)
非白人2 930243(4.0)11(4.6)106(3.3)972(4.8)1 598(4.8)
教育水平 (年)
≤1037 5133 180(52.0)142(58.9)1 826(57.6)11 432(56.1)20 933(63.1)
11~126 218721(11.8)26(10.8)330(10.4)2 017(9.9)3 124(9.4)
>1219 3352 211(36.2)73(30.3)1 015(32.0)6 932(34.0)9 104(27.5)
家庭人均年收入 (£)
<18 00020 3621 985(32.5)104(43.2)985(31.1)5 977(29.3)11 311(34.1)
18 000~30 99917 1711 628(26.6)62(25.7)898(28.3)5 700(28.0)8 883(26.8)
31 000~51 99913 7781 330(21.8)32(13.3)700(22.1)4 692(23.0)7 024(21.2)
≥52 00011 7551 169(19.1)43(17.8)588(18.5)4 012(19.7)5 943(17.9)
体力活动水平 (MET)
轻度 (<600)15 7541 120(18.3)61(25.3)573(18.1)4 372(21.5)9 628(29.0)
中度 (600~3 000)24 8022 372(38.8)95(39.4)1 220(38.5)8 266(40.6)12 849(38.8)
重度 (≥3 000)22 5102 620(42.9)85(35.3)1 378(43.5)7 743(38.0)10 684(32.2)
吸烟状况
从不吸烟27 3493 144(51.4)93(38.6)1 769(55.8)8 889(43.6)13 454(40.6)
戒烟27 6291 890(30.9)49(20.3)1 075(33.9)8 750(42.9)15 865(47.8)
吸烟8 0881 078(17.6)99(41.1)327(10.3)2 742(13.5)3 842(11.6)
饮酒频率
从不饮酒3 119331(5.4)18(7.5)179(5.6)817(4.0)1 774(5.4)
戒酒3 331310(5.1)40(16.6)159(5.0)883(4.3)1 939(5.9)
经常56 6165 471(89.5)183(75.9)2 833(89.3)18 681(91.7)29 448(88.8)
TD2M
54 7435 928(97.0)233(96.7)3 049(96.2)18 685(91.7)26 848(81.0)
8 323184(3.0)8(3.3)122(3.9)1 696(8.3)6 313(19.0)
高血压
32 2384 251(69.6)173(71.8)1 995(62.9)11 775(57.8)14 044(42.4)
30 8281 861(30.5)68(28.2)1 176(37.1)8 606(42.2)19 117(57.7)
抑郁状况
46 7724 542(74.3)165(68.5)2 372(74.8)15 697(77.0)23 996(72.4)
16 2941 570(25.7)76(31.5)799(25.2)4 684(23.0)9 165(27.6)
APOE*
47 6004 505(73.7)176(73.0)2 291(72.3)15 262(74.9)25 366(76.5)
15 4661 607(26.3)65(27.0)880(27.8)5 119(25.1)7 795(23.5)
), ArticleFig(id=1241081872512504317, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, language=CN, label=表1, caption=

CVD患者人群基线特征[n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
特征合计正常体型低体重单纯中心性或
单纯全身肥胖
复合超重复合肥胖
基线年龄 (岁)
<6020 9112 248(36.8)99(41.1)1 121(35.4)6 116(30.0)11 327(34.2)
≥6042 1553 864(63.2)142(58.9)2 050(64.7)14 265(70.0)21 834(65.8)
性别
23 5933 859(63.1)163(67.6)2 267(71.5)5 796(28.4)11 508(34.7)
39 4732 253(36.9)78(32.4)904(28.5)14 585(71.6)21 653(65.3)
人种
白人60 1365 869(96.0)230(95.4)3 065(96.7)19 409(95.2)31 563(95.2)
非白人2 930243(4.0)11(4.6)106(3.3)972(4.8)1 598(4.8)
教育水平 (年)
≤1037 5133 180(52.0)142(58.9)1 826(57.6)11 432(56.1)20 933(63.1)
11~126 218721(11.8)26(10.8)330(10.4)2 017(9.9)3 124(9.4)
>1219 3352 211(36.2)73(30.3)1 015(32.0)6 932(34.0)9 104(27.5)
家庭人均年收入 (£)
<18 00020 3621 985(32.5)104(43.2)985(31.1)5 977(29.3)11 311(34.1)
18 000~30 99917 1711 628(26.6)62(25.7)898(28.3)5 700(28.0)8 883(26.8)
31 000~51 99913 7781 330(21.8)32(13.3)700(22.1)4 692(23.0)7 024(21.2)
≥52 00011 7551 169(19.1)43(17.8)588(18.5)4 012(19.7)5 943(17.9)
体力活动水平 (MET)
轻度 (<600)15 7541 120(18.3)61(25.3)573(18.1)4 372(21.5)9 628(29.0)
中度 (600~3 000)24 8022 372(38.8)95(39.4)1 220(38.5)8 266(40.6)12 849(38.8)
重度 (≥3 000)22 5102 620(42.9)85(35.3)1 378(43.5)7 743(38.0)10 684(32.2)
吸烟状况
从不吸烟27 3493 144(51.4)93(38.6)1 769(55.8)8 889(43.6)13 454(40.6)
戒烟27 6291 890(30.9)49(20.3)1 075(33.9)8 750(42.9)15 865(47.8)
吸烟8 0881 078(17.6)99(41.1)327(10.3)2 742(13.5)3 842(11.6)
饮酒频率
从不饮酒3 119331(5.4)18(7.5)179(5.6)817(4.0)1 774(5.4)
戒酒3 331310(5.1)40(16.6)159(5.0)883(4.3)1 939(5.9)
经常56 6165 471(89.5)183(75.9)2 833(89.3)18 681(91.7)29 448(88.8)
TD2M
54 7435 928(97.0)233(96.7)3 049(96.2)18 685(91.7)26 848(81.0)
8 323184(3.0)8(3.3)122(3.9)1 696(8.3)6 313(19.0)
高血压
32 2384 251(69.6)173(71.8)1 995(62.9)11 775(57.8)14 044(42.4)
30 8281 861(30.5)68(28.2)1 176(37.1)8 606(42.2)19 117(57.7)
抑郁状况
46 7724 542(74.3)165(68.5)2 372(74.8)15 697(77.0)23 996(72.4)
16 2941 570(25.7)76(31.5)799(25.2)4 684(23.0)9 165(27.6)
APOE*
47 6004 505(73.7)176(73.0)2 291(72.3)15 262(74.9)25 366(76.5)
15 4661 607(26.3)65(27.0)880(27.8)5 119(25.1)7 795(23.5)
), ArticleFig(id=1241081872818688528, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, language=EN, label=Table 2, caption=

Baseline characteristics of patients with type 2 diabetes mellitus (T2DM) [n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
特征合计正常体型低体重单纯中心性或
单纯全身肥胖
复合超重复合肥胖
基线年龄 (岁)
<6013 730454(41.0)23(48.9)306(42.6)2 410(33.6)10 537(42.5)
≥6020 142654(59.0)24(51.1)412(57.4)4 769(66.4)14 283(57.6)
性别
13 459706(63.7)30(63.8)505(70.3)2 320(32.3)9 898(39.9)
20 413402(36.3)17(36.2)213(29.7)4 859(67.7)14 922(60.1)
人种
白人30 477986(89.0)42(89.4)643(89.6)6 176(86.0)22 630(91.2)
非白人3 395122(11.0)5(10.6)75(10.5)1 003(14.0)2 190(8.8)
教育水平 (年)
≤1020 809577(52.1)30(63.8)418(58.2)4 100(57.1)15 684(63.2)
11~123 457144(13.0)6(12.8)85(11.8)742(10.3)2 480(10.0)
>129 606387(34.9)11(23.4)215(29.9)2 337(32.6)6 656(26.8)
家庭人均年收入 (£)
<18 00011 452369(33.3)20(42.6)244(34.0)2 300(32.0)8 519(34.3)
18 000~30 9999 033280(25.3)12(25.5)193(26.9)2 007(28.0)6 541(26.4)
31 000~51 9997 296252(22.7)7(14.9)162(22.6)1 556(21.7)5 319(21.4)
≥52 0006 091207(18.7)8(17.0)119(16.6)1 316(18.3)4 441(17.9)
体力活动水平(MET)
轻度 (<600)10 288226(20.4)13(27.7)155(21.6)1 785(24.9)8 109(32.7)
中度 (600~3 000)13 166415(37.5)16(34.0)275(38.3)2 922(40.7)9 538(38.4)
重度 (≥3 000)10 418467(42.2)18(38.3)288(40.1)2 472(34.4)7 173(28.9)
吸烟状况
从不吸烟14 795593(53.5)22(46.8)395(55.0)3 127(43.6)10 658(42.9)
戒烟14 794343(31.0)8(17.0)235(32.7)3 006(41.9)11 202(45.1)
吸烟4 283172(15.5)17(36.2)88(12.3)1 046(14.6)2 960(11.9)
饮酒频率
从不饮酒2 45371(6.4)5(10.6)65(9.1)556(7.7)1 756(7.1)
戒酒2 27981(7.3)7(14.9)44(6.1)402(5.6)1 745(7.0)
经常29 140956(86.3)35(74.5)609(84.8)6 221(86.7)21 319(85.9)
高血压
13 703724(65.3)38(80.9)400(55.7)3 582(49.9)8 959(36.1)
20 169384(34.7)9(19.2)318(44.3)3 597(50.1)15 861(63.9)
心血管疾病
25 212941(84.9)35(74.5)599(83.4)5 483(76.4)18 154(73.1)
8 660167(15.1)12(25.5)119(16.6)1 696(23.6)6 666(26.9)
抑郁状况
23 905788(71.1)29(61.7)526(73.3)5 403(75.3)17 159(69.1)
9 967320(28.9)18(38.3)192(26.7)1 776(24.7)7 661(30.9)
APOE*
26 535856(77.3)37(78.7)546(76.0)5 632(78.5)19 464(78.4)
7 337252(22.7)10(21.3)172(24.0)1 547(21.6)5 356(21.6)
), ArticleFig(id=1241081872936129048, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, language=CN, label=表2, caption=

T2DM患者人群基线特征[n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
特征合计正常体型低体重单纯中心性或
单纯全身肥胖
复合超重复合肥胖
基线年龄 (岁)
<6013 730454(41.0)23(48.9)306(42.6)2 410(33.6)10 537(42.5)
≥6020 142654(59.0)24(51.1)412(57.4)4 769(66.4)14 283(57.6)
性别
13 459706(63.7)30(63.8)505(70.3)2 320(32.3)9 898(39.9)
20 413402(36.3)17(36.2)213(29.7)4 859(67.7)14 922(60.1)
人种
白人30 477986(89.0)42(89.4)643(89.6)6 176(86.0)22 630(91.2)
非白人3 395122(11.0)5(10.6)75(10.5)1 003(14.0)2 190(8.8)
教育水平 (年)
≤1020 809577(52.1)30(63.8)418(58.2)4 100(57.1)15 684(63.2)
11~123 457144(13.0)6(12.8)85(11.8)742(10.3)2 480(10.0)
>129 606387(34.9)11(23.4)215(29.9)2 337(32.6)6 656(26.8)
家庭人均年收入 (£)
<18 00011 452369(33.3)20(42.6)244(34.0)2 300(32.0)8 519(34.3)
18 000~30 9999 033280(25.3)12(25.5)193(26.9)2 007(28.0)6 541(26.4)
31 000~51 9997 296252(22.7)7(14.9)162(22.6)1 556(21.7)5 319(21.4)
≥52 0006 091207(18.7)8(17.0)119(16.6)1 316(18.3)4 441(17.9)
体力活动水平(MET)
轻度 (<600)10 288226(20.4)13(27.7)155(21.6)1 785(24.9)8 109(32.7)
中度 (600~3 000)13 166415(37.5)16(34.0)275(38.3)2 922(40.7)9 538(38.4)
重度 (≥3 000)10 418467(42.2)18(38.3)288(40.1)2 472(34.4)7 173(28.9)
吸烟状况
从不吸烟14 795593(53.5)22(46.8)395(55.0)3 127(43.6)10 658(42.9)
戒烟14 794343(31.0)8(17.0)235(32.7)3 006(41.9)11 202(45.1)
吸烟4 283172(15.5)17(36.2)88(12.3)1 046(14.6)2 960(11.9)
饮酒频率
从不饮酒2 45371(6.4)5(10.6)65(9.1)556(7.7)1 756(7.1)
戒酒2 27981(7.3)7(14.9)44(6.1)402(5.6)1 745(7.0)
经常29 140956(86.3)35(74.5)609(84.8)6 221(86.7)21 319(85.9)
高血压
13 703724(65.3)38(80.9)400(55.7)3 582(49.9)8 959(36.1)
20 169384(34.7)9(19.2)318(44.3)3 597(50.1)15 861(63.9)
心血管疾病
25 212941(84.9)35(74.5)599(83.4)5 483(76.4)18 154(73.1)
8 660167(15.1)12(25.5)119(16.6)1 696(23.6)6 666(26.9)
抑郁状况
23 905788(71.1)29(61.7)526(73.3)5 403(75.3)17 159(69.1)
9 967320(28.9)18(38.3)192(26.7)1 776(24.7)7 661(30.9)
APOE*
26 535856(77.3)37(78.7)546(76.0)5 632(78.5)19 464(78.4)
7 337252(22.7)10(21.3)172(24.0)1 547(21.6)5 356(21.6)
), ArticleFig(id=1241081873070346788, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, language=EN, label=Table 3, caption=

Risk ratios (HRs) and 95% confidence intervals (CI) of different obesity states and dementia subtypes in patients with cardiovascular metabolic diseases

, figureFileSmall=null, figureFileBig=null, tableContent=
不同疾病患者的不同肥胖状态全因痴呆AD VD
CVD患者a
正常体型1.001.001.00
低体重1.38 (0.84~2.28)0.84 (0.31~2.27)2.35 (1.09~5.09)
单纯中心性或单纯全身肥胖0.74 (0.61~0.90)0.70 (0.51~0.95)0.99 (0.70~1.41)
复合超重0.72 (0.64~0.82)0.71 (0.58~0.87)0.81 (0.63~1.04)
复合肥胖0.65 (0.58~0.74)0.60 (0.49~0.74)0.73 (0.57~0.93)
T2DM患者b
正常体型1.001.001.00
低体重2.29 (0.92~5.71)1.73 (0.41~7.29)3.42 (0.79~14.86)
单纯中心性或单纯全身肥胖0.78 (0.51~1.19)0.56 (0.29~1.09)1.06 (0.51~2.18)
复合超重0.61 (0.46~0.81)0.54 (0.36~0.81)0.63 (0.38~1.06)
复合肥胖0.53 (0.41~0.69)0.45 (0.31~0.66)0.53 (0.32~0.87)
), ArticleFig(id=1241081873179398704, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240738483069842335, language=CN, label=表3, caption=

心血管代谢疾病患者不同肥胖状态与痴呆亚型的风险比(HR)和95%CI

, figureFileSmall=null, figureFileBig=null, tableContent=
不同疾病患者的不同肥胖状态全因痴呆AD VD
CVD患者a
正常体型1.001.001.00
低体重1.38 (0.84~2.28)0.84 (0.31~2.27)2.35 (1.09~5.09)
单纯中心性或单纯全身肥胖0.74 (0.61~0.90)0.70 (0.51~0.95)0.99 (0.70~1.41)
复合超重0.72 (0.64~0.82)0.71 (0.58~0.87)0.81 (0.63~1.04)
复合肥胖0.65 (0.58~0.74)0.60 (0.49~0.74)0.73 (0.57~0.93)
T2DM患者b
正常体型1.001.001.00
低体重2.29 (0.92~5.71)1.73 (0.41~7.29)3.42 (0.79~14.86)
单纯中心性或单纯全身肥胖0.78 (0.51~1.19)0.56 (0.29~1.09)1.06 (0.51~2.18)
复合超重0.61 (0.46~0.81)0.54 (0.36~0.81)0.63 (0.38~1.06)
复合肥胖0.53 (0.41~0.69)0.45 (0.31~0.66)0.53 (0.32~0.87)
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心血管代谢疾病患者肥胖状态与痴呆的关联研究
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张小宇 1 , 王琪 1 , 付春迎 1 , 谢博 1 , 王仲璇 1 , 张露艺 1 , 李响 1 , 朱东山 1, 2
现代预防医学 | 流行病与统计方法 2025,52(9): 1537-1543
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现代预防医学 | 流行病与统计方法 2025, 52(9): 1537-1543
心血管代谢疾病患者肥胖状态与痴呆的关联研究
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张小宇1, 王琪1, 付春迎1, 谢博1, 王仲璇1, 张露艺1, 李响1, 朱东山1, 2
作者信息
  • 1.山东大学齐鲁医学院公共卫生学院流行病学系,山东 济南 250012
  • 2.山东大学临床流行病学和循证医学中心,山东 济南 250012
  • 张小宇(2001—),女,硕士在读,研究方向:慢性病流行病学

通讯作者:

朱东山,E-mail:
Study on the association between obesity status and dementia in patients with cardiovascular metabolic diseases
Xiao-yu ZHANG1, Qi WANG1, Chun-ying FU1, Bo XIE1, Zhong-xuan WANG1, Lu-yi ZHANG1, Xiang LI1, Dong-shan ZHU1, 2
Affiliations
  • Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
出版时间: 2025-05-10 doi: 10.20043/j.cnki.MPM.202501176
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目的

探讨心血管疾病(CVD)患者和2型糖尿病患者(T2DM)患者不同肥胖状态与全因痴呆及其亚型的关系。

方法

基于英国生物银行(UK Biobank)数据,根据BMI和腰围将研究对象分为低体重、正常体型、单纯中心性或单纯全身肥胖、复合超重和复合肥胖5种状态,采用Cox比例风险回归模型分析不同肥胖状态心血管代谢疾病患者的痴呆发病风险比(HR)值及其95%CI

结果

CVD患者共纳入63 066名研究对象,T2DM患者共纳入33 872名研究对象。以正常体型CVD患者为对照,低体重患者发生血管性痴呆(VD)的风险增高135%(HR=2.35,95%CI:1.09~5.09)。单纯中心性或单纯全身肥胖患者的全因痴呆和阿尔茨海默病(AD)的发病风险分别下降26%(HR=0.74,95%CI:0.61~0.90)、30%(HR=0.70,95%CI:0.51~0.95)。复合超重患者的全因痴呆和AD的发病风险分别下降28%(HR=0.72,95%CI:0.64~0.82)和29%(HR=0.71,95%CI:0.58~0.87)。复合肥胖患者的全因痴呆、AD和VD的发病风险分别下降35%(HR= 0.65,95%CI:0.58~0.74)、40%(HR=0.60,95%CI:0.49~0.74)和27%(HR=0.73,95%CI:0.57~0.93)。以正常体型T2DM患者为对照,复合超重患者出现全因痴呆和AD的风险分别下降39%(HR=0.61,95%CI:0.46~0.81)和46%(HR=0.54,95%CI:0.36~0.81)。复合肥胖患者的全因痴呆、AD和VD的发病风险分别下降35%(HR=0.53,95%CI:0.41~0.69)、40%(HR= 0.45,95%CI:0.31~0.66)和27%(HR=0.53,95%CI:0.32~0.87)。

结论

心血管代谢疾病患者痴呆风险存在“肥胖悖论”现象,单纯中心性或单纯全身肥胖、复合超重、复合肥胖患者的痴呆发病风险明显降低。

体质指数  /  腰围  /  心血管代谢疾病  /  痴呆症
Objective

To investigate the relationship between different obesity statuses in patients with cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM) and the incidence of all-cause dementia and its subtypes.

Methods

Based on data from the UK Biobank, study subjects were categorized into five obesity states—underweight, normal weight, simple central or simple generalized obesity, combined overweight, and combined obesity—according to BMI and waist circumference. The Cox proportional hazards regression model was employed to analyze the hazard ratios (HR) and 95% confidence intervals (CI) for dementia incidence among patients with cardiovascular metabolic diseases across different obesity statuses.

Results

A total of 63 066 CVD patients and 33 872 T2DM patients were included in the study. Compared to normal weight CVD patients, underweight individuals exhibited a 135% increased risk of vascular dementia (VD) (HR=2.35, 95%CI: 1.09-5.09). The risk of all-cause dementia and Alzheimer’s disease (AD) in patients with simple central or simple generalized obesity decreased by 26% (0.74, 0.61-0.90) and 30% (0.70, 0.51-0.95),respectively. For combined overweight patients, the risk of all-cause dementia and AD decreased by 28% (0.72, 0.64-0.82) and 29%(0.71, 0.58-0.87), respectively. In combined obesity patients, the risk of all-cause dementia, AD, and VD decreased by 35% (0.65,0.58-0.74), 40% (0.60, 0.49-0.74), and 27% (0.73, 0.57-0.93), respectively. Compared to normal weight T2DM patients, combined overweight patients showed a 39% (0.61, 0.46-0.81) and 46% (0.54, 0.36-0.81) reduction in the risk of all-cause dementia and AD,respectively. The risk of all-cause dementia, AD, and VD in combined obesity patients decreased by 35% (0.53, 0.41-0.69), 40%(0.45, 0.31-0.66), and 27% (0.53, 0.32-0.87), respectively.

Conclusion

There is an “obesity paradox” in dementia risk among patients with cardiovascular metabolic diseases, with a significant reduction in the incidence of dementia among patients with simple central or simple generalized obesity, combined overweight, and combined obesity.

Body mass index  /  Waist circumference  /  Cardiovascular metabolic diseases  /  Dementia
张小宇, 王琪, 付春迎, 谢博, 王仲璇, 张露艺, 李响, 朱东山. 心血管代谢疾病患者肥胖状态与痴呆的关联研究. 现代预防医学, 2025 , 52 (9) : 1537 -1543 . DOI: 10.20043/j.cnki.MPM.202501176
Xiao-yu ZHANG, Qi WANG, Chun-ying FU, Bo XIE, Zhong-xuan WANG, Lu-yi ZHANG, Xiang LI, Dong-shan ZHU. Study on the association between obesity status and dementia in patients with cardiovascular metabolic diseases[J]. Modern Preventive Medicine, 2025 , 52 (9) : 1537 -1543 . DOI: 10.20043/j.cnki.MPM.202501176
痴呆症是以认知功能进行性减退为特征的综合征,常表现为记忆、语言、执行功能等高级皮层功能障碍[1],其最常见亚型为阿尔茨海默病(Alzheimer disease, AD)和血管性痴呆(vascular dementia,VD)[2]。全球现有约5 000万痴呆症患者,预计2030年将增至6 600万。痴呆症对患者身心健康及家庭造成沉重负担,已成为21世纪全球重大公共卫生挑战[3-6]。心血管代谢疾病是以代谢紊乱(如糖尿病、肥胖等)为核心诱因,导致动脉粥样硬化及心脑血管事件的一类综合征,其病程与认知衰退密切相关[7-12]。尽管超重、肥胖是心血管代谢疾病的独立风险因素,而先前的研究表明超重、肥胖人群与正常体重人群相比,其病死率相对较低或生存预后较好,这种现象被称为“肥胖悖论”,但其对认知功能的影响尚未明确[13-15]。因此,本研究联合BMI与腰围两种肥胖指标,探讨不同肥胖状态对心血管代谢疾病患者痴呆风险的影响,为今后心血管代谢疾病患者预防认知功能下降、制定相应的干预措施提供理论依据。
此次研究的数据来自英国生物银行(UKB)的已批准项目(项目编号227947),UKB已获得英国西北多中心研究伦理委员会伦理批准(编号:11/NW/0382)。本研究采用前瞻性设计,如果参与者在随访期间患有痴呆并患有心血管疾病(cardiovascular disease,CVD)或2型糖尿病(type 2 diabetes mellitus,T2DM),则其CVD或T2DM的诊断必须早于痴呆。在排除数据缺失(如关键协变量信息等)以及基线已确诊为痴呆的参与者后,共纳入63 066名CVD患者和33 872名T2DM患者进行前瞻性分析。
通过与UKB数据库的初级保健、住院和死亡登记记录的关联数据,使用国际疾病分类第10版(ICD-10)代码定义CVD患者和T2DM患者。全身肥胖以身体质量指数(body mass index, BMI)作为判断指标:BMI=体重(kg)/身高的二次方(m2),分为体重过低(<18.5 kg/m2)、体重正常(18.5 kg/m2≤BMI<24 kg/m2)、超重(24.0 kg/m2≤BMI<28.0 kg/m2)和肥胖(≥28.0 kg/m2)。以腰围作为中心性肥胖判断指标:腰围正常(男性<85 cm,女性<80 cm)、中心性肥胖(男性≥85 cm,女性≥80 cm)。按照BMI和腰围将研究对象分为五种状态:低体重(体重过低/腰围正常)、正常体型(体重正常/腰围正常)、单纯中心性(体重正常/中心性肥胖)或单纯全身肥胖(超重或肥胖/腰围正常)、复合超重(超重/中心性肥胖)、复合肥胖(肥胖/中心性肥胖)。
结果变量为全因痴呆,包括AD和VD痴呆亚型。ICD-10代码F00、F01、G30和ICD-9代码290·1用于定义全因痴呆的参与者。ICD-10代码F00、G30和ICD-9代码290·1用于定义痴呆亚型AD。ICD-10代码F01用于定义痴呆亚型VD。
基于既往研究证据[16],我们在模型中校正了以下变量:基线年龄、性别、种族/民族、教育水平、家庭人均年收入、体力活动水平、吸烟状况、饮酒状况、高血压状况、心血管病状况、T2DM状况、抑郁状况和APOE等位基因状况。
数据分析使用SAS 9.4和R 4.3.3。用(均数±标准差)描述连续性变量,用频率和构成比描述分类变量。采用Cox比例风险回归模型估计CVD患者和T2DM患者的不同肥胖状态(以正常体型为参照组)与痴呆(包括全因痴呆、AD和VD)之间的风险比(HR)和95%CI。对于经历过痴呆症的参与者,随访时间计算为他们被诊断为痴呆症时的年龄减去基线年龄;对于没有经历痴呆的参与者,随访时间定义为他们在最后随访时的年龄减去基线年龄。通过排除随访前2年内和前5年内被诊断为痴呆的参与者后进行敏感性分析。检验水准α=0.05。
在CVD患者的不同肥胖状态分析中基线时纳入63 066名参与者,其中37.4%为女性。CVD患者低体重的全因痴呆发病率和VD发病率最高,分别为6.64%和2.90%,复合肥胖的全因痴呆发病率和AD发病率最低,分别为4.48%和1.53%。见表1
在T2DM患者的不同肥胖状态分析中基线时纳入33 872名参与者,其中39.7%为女性。T2DM患者低体重的全因痴呆发病率、AD发病率和VD发病率最高,分别为10.64%、4.26%、4.26%,复合肥胖的全因痴呆发病率、AD发病率和VD发病率最低,分别为3.7%、1.31%、1.22%。见表2
在CVD患者中以正常体型患者为对照,低体重患者出现VD的风险增高135%(HR=2.35,95%CI:1.09~ 5.09),单纯中心性或单纯全身肥胖患者发生全因痴呆和AD的风险分别下降26%(HR=0.74,95%CI:0.61~0.90)、30%(HR=0.70,95%CI:0.51~0.95),复合超重患者的全因痴呆和AD的发病风险分别下降28%(HR=0.72,95%CI:0.64~0.82)、29%(HR=0.71,95%CI:0.58~0.87),复合肥胖患者的全因痴呆、AD和VD的发病风险分别下降35%(HR=0.65,95%CI:0.58~0.74)、40%(HR=0.60,95%CI:0.49~0.74)、27%(HR=0.73,95%CI:0.57~0.93)。
在T2DM患者中以正常体型患者为对照,复合超重患者的全因痴呆和AD的发病风险分别下降39%(HR=0.61,95%CI:0.46~0.81)、46%(HR=0.54,95%CI:0.36~0.81),复合肥胖患者的全因痴呆、AD和VD的发病风险分别下降35%(HR=0.53,95%CI:0.41~0.69)、40%(HR=0.45,95%CI:0.31~0.66)、27%(HR=0.53,95%CI:0.32~0.87)。见表3
在CVD患者的性别分层分析中,男性仅复合超重(HR=0.72,95%CI:0.59~0.88)和复合肥胖(HR= 0.67,95%CI:0.55~0.81)与全因痴呆风险降低相关,而女性单纯中心性或单纯全身肥胖、复合超重和复合肥胖均显示风险降低(HR=0.66,95%CI:0.51~0.83;HR=0.77,95%CI:0.64~0.92;HR=0.66,95%CI:0.56~0.78)。年龄分层显示<60岁患者仅复合超重和复合肥胖状态的全因痴呆发病风险显著降低(HR=0.64,95%CI:0.42~0.96;HR=0.67,95%CI:0.45~0.97),≥60岁患者中单纯中心性或单纯全身肥胖、复合超重、复合肥胖均显著降低风险(HR=0.75,95%CI:0.61~0.92;HR=0.73,95%CI:0.64~0.84;HR=0.65,95%CI:0.57~0.74)。
T2DM患者性别分层分析中,男性复合超重(HR=0.51,95%CI:0.34~0.76)和复合肥胖(HR=0.46,95%CI:0.32~0.68)全因痴呆风险显著降低,女性仅复合肥胖与全因痴呆风险降低相关(HR=0.58,95%CI:0.40~0.83)。年龄分层显示<60岁患者单纯中心性或单纯全身肥胖的全因痴呆风险下降了79%,所有年龄患者中复合超重和复合肥胖状态的全因痴呆发病风险均低于正常体型组。见图1
分别剔除随访前2年内和前5年内被诊断为痴呆的参与者,调整相同的影响因素进行敏感性分析,两种剔除结果均表明与正常体型组相比,低体重CVD患者VD发病风险增加、单纯中心性或单纯全身肥胖全因痴呆发病风险降低、复合超重全因痴呆和AD发病风险降低、复合肥胖痴呆(包括全因痴呆、AD和VD)发病风险均降低,与CVD患者全研究人群分析结果基本一致。T2DM患者中复合超重的全因痴呆和AD发病风险降低、复合肥胖痴呆(包括全因痴呆、AD和VD)发病风险均降低,与T2DM患者全研究人群分析结果基本一致。见图2
本研究通过联合BMI与腰围指标,首次系统分析心血管代谢疾病患者不同肥胖状态与痴呆(全因痴呆、AD和VD)的关联。现有研究对此关注有限且结论不一,可能与人群异质性、肥胖定义差异及混杂因素控制不足有关。
现有研究提示较高体重指数对认知有积极影响[16-19],本研究也揭示了在CVD患者中,相较于正常体型者,低体重者VD发病风险显著升高,而单纯中心性或单纯全身肥胖、复合超重及复合肥胖者的全因痴呆与AD风险均呈下降趋势,其中复合肥胖者VD风险亦降低。在T2DM患者中,复合超重者全因痴呆和AD风险下降,复合肥胖者全因痴呆、AD及VD风险进一步降低。通过排除随访前2年内和前5年内痴呆病例的敏感性分析,本研究证实上述“肥胖悖论”具有生物学稳健性,而非反向因果关系所致。其潜在机制主要是虽然肥胖通常加剧代谢紊乱,但脂肪组织中分泌的瘦素等神经保护因子可通过增强海马突触可塑性,部分抵消神经退行进程,从而降低痴呆风险[20-21]
肥胖与心血管代谢疾病患者的痴呆风险存在年龄及性别差异[22]。在CVD患者中,≥60岁的单纯中心性或单纯全身肥胖全因痴呆风险显著低于正常体型人群。但在T2DM患者中,<60岁单纯中心性或单纯全身肥胖的全因痴呆风险降低。提示年龄可能是心血管代谢疾病人群“肥胖悖论”重要的影响因素之一,并且年龄对肥胖与痴呆关系的影响可能涉及多种机制,≥60岁的CVD患者身体处于慢性炎症状态下,肥胖相关脂肪因子的抗炎和神经保护作用可能占主导[23]。对于T2DM患者,年轻群体较强的代谢代偿能力可能抵消部分肥胖危害,随年龄增长其代偿能力衰退后,肥胖的保护作用就不再显著[24]。性别分析显示,女性CVD患者中单纯中心性或单纯全身肥胖构成痴呆保护因素,可能源于女性的雌激素神经递质调节、抗炎作用及绝经后的脂肪分布变化[25]。而男性T2DM患者的复合超重状态与全因痴呆风险降低相关,这可能与男性患T2DM后腹部脂肪分泌的神经保护因子(如网膜素)改善胰岛素敏感性有关[26]。上述差异提示,肥胖对痴呆风险的影响需结合特定疾病类型、年龄阶段及性别特征综合评估。
本研究也存在一些局限性。第一,研究中仅提供基线腰围和BMI数据,未考虑随访期间相关指标纵向变化可能造成的影响;第二,尽管研究中已对潜在的可能协变量进行了调整,但仍不能排除其他一些未测量因素的影响;第三,本研究样本人群仅来源于UKB,因此,研究结果在外推到其他人群时需要谨慎。综上所述,心血管代谢疾病患者痴呆风险存在“肥胖悖论”现象,单纯中心性或单纯全身肥胖、复合型超重/肥胖患者的痴呆发病风险明显降低,并且在年龄和性别中该发病风险存在着差异。今后尚需开展多中心大样本高质量的前瞻性研究以期进一步验证肥胖状态与心血管代谢疾病痴呆及其亚型风险的相关性。
  • 国家自然科学基金资助项目(82273702)
  • 山东省优秀青年学者资助项目(2022HWYQ-030)
  • 泰山学者项目专项基金(tsqnz20221103)
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2025年第52卷第9期
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doi: 10.20043/j.cnki.MPM.202501176
  • 接收时间:2025-01-10
  • 首发时间:2026-03-17
  • 出版时间:2025-05-10
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  • 收稿日期:2025-01-10
基金
国家自然科学基金资助项目(82273702)
山东省优秀青年学者资助项目(2022HWYQ-030)
泰山学者项目专项基金(tsqnz20221103)
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    1.山东大学齐鲁医学院公共卫生学院流行病学系,山东 济南 250012
    2.山东大学临床流行病学和循证医学中心,山东 济南 250012

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
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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