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系統識別號 U0026-2607201813510100
論文名稱(中文) 空氣污染與失智症發生風險之病例對照研究
論文名稱(英文) A population-based case-control study on the associations between air pollution and risk of dementia
校院名稱 成功大學
系所名稱(中) 公共衛生研究所
系所名稱(英) Graduate Institute of Public Health
學年度 106
學期 2
出版年 107
研究生(中文) 李建欣
研究生(英文) Chien-Hsin Li
電子信箱 cych07197@gmail.com
學號 T86054042
學位類別 碩士
語文別 中文
論文頁數 108頁
口試委員 指導教授-李中一
口試委員-黃彬芳
口試委員-古鯉榕
口試委員-賴秋蓮
中文關鍵字 空氣污染物  失智症  阿茲海默氏症  血管性失智症  劑量效應 
英文關鍵字 air pollutants  dementia  vascular dementia  dose-responsive effects 
學科別分類
中文摘要 背景與目的:過去研究空氣污染對人體健康的危害主要集中在心血管疾病和肺臟疾病,近十年來,愈來愈多的流行病學研究發現空氣污染會造成較差的認知功能和認知功能退化,推論進一步可能會造成神經退化性疾病,例如阿茲海默氏症,懷疑可能和空氣污染會造成系統性發炎和神經發炎反應有關。由於過去的研究主要針對一般失智症,並未對不同的失智症類型作分析,而阿茲海默氏症和血管性失智症的病理變化完全不同,對空氣污染暴露的效應理論上不能混為一談。此外,空氣污染物質在不同的濃度下,在短期和長期的暴露時間是否對失智症發生造成影響。為此, 本研究探討台灣地區2005-2013年的新發失智症和失智診斷前空氣污染物(包括:PM10、SO2、CO、O3、NO2)暴露的關係;也進一步探討短期和長期空氣污染暴露對失智症發生對失智發生是否有不同影響。

方法:本研究採用巢式病例對照研究設計,資料來源為全民健康保險資料2005年百萬人承保歸人檔。病例組為2005-2013年主次診斷診斷碼為65歲以上失智症相關代碼者,並將失智症根據診斷代碼區分為阿茲海默氏症,血管性失智症,和其他失智症。對照組則依據病例組之年齡、性別、與診斷年份,以隨機抽樣方式進行病例/對照1:4比例之配對。本研究使用之空氣污染物濃度資料則是取自我國環境保護署空氣品質監測站資料,包括:PM10、SO2、O3、NO2、與CO的月平均暴露濃度,回溯研究對象在失智症診斷前3年、5年、和7年期間各種空氣污染暴露濃度。研究對象之推估居住地(鄉鎮市區)是依其就醫情形進行推估,並以地理資訊系統之一般克利金(Ordinary Kriging)空間分析方法模擬出各鄉鎮市區各種空氣污染物濃度之月平均值。本研究藉由條件式羅吉斯迴歸進行統計分析,估計不同濃度和不同期間各種空氣污染暴露對阿茲海默氏症和血管性失智症發生風險之勝算比(Odds Ratio,OR)及其95%信賴區間(Confidence Interval,CI)。

結果: 本研究共納入2005-2013年所有新發失智症病例組個案共有7,053人,對照組共28,212人。在控制潛在干擾因子以及其他空氣污染物之下,發現過去3年、5年、和7年期間的PM10、O3、NO2和CO對所有失智症的風險都沒有顯著影響,然而,較高濃度的SO2暴露(>第75百分位)和所有失智症的風險有顯著負相關,校正勝算比為0.8 (95% CI= 0.72-0.90)。另一方面,過去3年、5年、和7年期間,較高濃度的PM10暴露(>第75百分位;> 67.98-68.28 ug/m3)會增加阿茲海默氏症的風險,校正勝算比分別為1.47 (95% CI= 1.15-1.88)、1.66 (95% CI= 1.30-2.13)、和1.59 (95% CI= 1.25-2.04)。在過去3年和5年前間,較高濃度的O3暴露 (>第75百分位;O3: > 28.28-28.44 ppb)會增加阿茲海默氏症的風險,校正勝算比分別為1.44 (95% CI= 1.10-1.88)和1.58 (95% CI= 1.19-2.09)。不同百分位濃度的PM10和O3對阿茲海默氏症的影響有劑量效應,每增加10ug/m3的PM10,約增加2%的阿茲海默氏症風險;每增加1ppb的O3,約增加4%的阿茲海默氏症風險,但是O3在過去7年期間平均暴露對於阿茲海默氏症的風險沒有達到顯著效應。在過去3年、5年、和7年期間,較高濃度的CO暴露(>第75百分位)和阿茲海默氏症的風險有顯著負相關,校正勝算比分別為0.74 (95% CI= 0.55-0.99),0.74 (95% CI= 0.67-1.05),與0.67 (95% CI= 0.52-0.87)。在三個暴露期間,較高濃度的SO2和NO2對阿茲海默氏症的風險都沒有顯著影響。較高濃度的PM10、O3、CO、SO2(>第75百分位)在三個暴露期間對於血管性失智症的風險都沒有顯著影響。雖然過去5年和7年期間,較高濃度的NO2(>第75百分位;>21.03-21.5 ppb)似乎會增加血管失智症的風險,校正勝算比分別為2.06 (95% CI= 1.22-3.47)和1.94 (95% CI= 1.18-3.19),都沒有達到顯著意義,但是敏感度分析發現,NO2不用透過腦中風、高血壓、和糖尿病的途徑,會顯著增加血管性失智症的風險,約2.22倍。

結論:本研究發現在3年、5年、和7年期間,較高濃度的SO2暴露和所有失智症的風險有顯著負相關。在3年和5年期間,較高濃度的PM10和O3暴露會增加阿茲海默氏症的風險;在7年期間,較高濃度的PM10暴露也會增加阿茲海默氏症的風險,但是較高濃度的CO暴露和阿茲海默氏症的風險有顯著負相關。在5和7年期間,較高濃度的NO2有傾向可能會增加血管性失智症的風險。
英文摘要 This case-control study, including 7,053 subjects with dementia and 28,212 matched controls identified from medical calims of 1-million Taiwan’s Natinal Health Inusrance program beneficiaries in 1997-2013, was conducted to investigate the association between air pollutants and risk of dementia that was classified into three types of dementia including all dementia, Alzhiemer’s disease, and vascular dementia. After controlling for potential confounders, an increase of 1 inter quartile range (IQR) in exposures to NO2 during 7 years period prior to the onset of dementia significantly increased the risk of developing all dementia; but similar exposure to SO2 significantly decreased the risk of all dementia. While air pollution exposure was categorized into quartile, we noted a dose-response relationship between exposure to PM10 and O3 and risk of Alzheimer’s disease in all three exposure periods in time. There was a trend that higher level of NO2 exposure was related to increased risk of vascular dementia but did not reach significant effect. The correlations between exposure to PM10, NO2, and O3 and risk of dementia became stronger after considering stroke as a mediating factor.
論文目次 目錄
摘要 i
第一章 前言 1
1.1 失智症之介紹 1
1.2 研究的目的 2
第二章 文獻回顧 3
2.1失智症簡介和盛行率 3
2.2失智症的種類 3
2.3 失智症的診斷 4
2.4失智症和空氣污染的關係 4
2.5失智症之危險因子 5
2.5.1 心血管疾病危險因子 5
2.5.2 其他危險因子 7
2.5.3 教育程度 9
2.5.4 空氣污染 9
2.6空氣污染和失智症關聯性的相關文獻 10
第三章 研究方法 14
3.1資料來源 14
3.1.1全民健康保險資料 14
3.1.2空氣污染監測資料 14
3.2研究設計 15
3.3研究對象定義與選取 16
3.3.1病例組選取: 16
3.3.2對照組選取 17
3.4空氣污染物濃度之暴露評估 17
3.5影響失智症之危險因子定義 19
3.6統計分析 20
3.6.1描述性統計 20
3.6.2推論性統計 21
3.7敏感度分析 22
第四章 研究結果 23
4.1描述性統計闡述 23
4.1.1研究對象之人口學描述 23
4.1.2研究對象之空氣污染暴露濃度描述 23
4.1.3各空氣污染物日平均值之皮爾森Pearson相關係數 24
4.2各空氣污染物濃度與所有失智症發生勝算之迴歸分析結果 24
4.2.1懸浮微粒PM10與所有失智症發生之風險 (表4-1) 24
4.2.2二氧化硫與所有失智症發生之風險 (表4-2) 26
4.2.3臭氧與所有失智症發生之風險 (表4-3) 27
4.2.4二氧化氮與所有失智症發生之風險 (表4-4) 29
4.2.5一氧化碳與失智症發生之風險 (表4-5) 31
4.3各空氣污染物濃度與阿茲海默氏症發生勝算之迴歸分析結果 32
4.3.1懸浮微粒PM10與阿茲海默氏症發生之風險 (表5-1) 32
4.3.2二氧化硫與阿茲海默氏症發生之風險 (表5-2) 34
4.3.3臭氧與阿茲海默氏症發生之風險 (表5-3) 36
4.3.4二氧化氮與阿茲海默氏症發生之風險 (表5-4) 37
4.3.5一氧化碳與阿茲海默氏症發生之風險 (表5-5) 39
4.4各空氣污染物濃度與血管性失智症發生勝算之迴歸分析結果 41
4.4.1懸浮微粒PM10與血管性失智症發生之風險 (表6-1) 41
4.4.2二氧化硫與血管性失智症發生之風險 (表6-2) 42
4.4.3臭氧與血管性失智症發生之風險 (表6-3) 44
4.4.4二氧化氮與血管性失智症發生之風險 (表6-4) 45
4.4.5一氧化碳與血管性失智症發生之風險 (表6-5) 47
4.5 敏感度分析 49
第五章 討論 50
5.1 本研究主要結果 50
5.2 與過去文獻發現進行比較與討論 50
5.2.1懸浮微粒PM10與失智症發生風險研究結果討論 50
5.2.2二氧化硫SO2與失智症發生風險研究結果討論 52
5.2.3臭氧O3與失智症發生風險研究結果討論 52
5.2.4二氧化氮NO2與失智症發生風險研究結果討論 53
5.2.5 一氧化碳CO與失智症發生風險研究結果討論 54
5.3 研究優勢與限制 54
5.3.1研究優勢 54
5.3.2研究限制 55
第六章 結論 58
參考文獻 59
附錄 70
圖一、病例組和對照組個案選取流程 70
表1a、病例組與對照組之基本人口學特徵 71
表1b、病例組與對照組之基本人口學特徵 72
表2-1、失智症前3、5、7年病例組與對照組之懸浮微粒(PM10)月平均值分佈情形 73
表2-2、失智症前3、5、7年病例組與對照組之二氧化硫(SO2)月平均值分佈情形 74
表2-3、失智症前3、5、7年病例組與對照組之臭氧(O3)月平均值分佈情形 75
表2-4、失智症前3、5、7年病例組與對照組之二氧化氮(NO2)月平均值分佈情形 76
表2-5、失智症前3、5、7年病例組與對照組之一氧化碳(CO)月平均值分佈情形 77
表3、前3、5、7年空氣污染物之皮爾森相關係數分析 78
表4-1a、病例組與對照組之PM10不同暴露期間之月平均值(μg/m3)分佈情形與失智症發生之勝算比 79
表4-1b、病例組與對照組之PM10不同暴露期間之月平均值(μg/m3)分佈情形與失智症發生之勝算比 80
表4-2a、病例組與對照組之SO2不同暴露期間之月平均值(ppb)分佈情形與失智症發生之勝算比 81
表4-2b、病例組與對照組之SO2不同暴露期間之月平均值(ppb)分佈情形與失智症發生之勝算比 82
表4-3a、病例組與對照組之O3不同暴露期間之月平均值(ppb)分佈情形與失智症發生之勝算比 83
表4-3b、病例組與對照組之O3不同暴露期間之月平均值(ppb)分佈情形與失智症發生之勝算比 84
表4-4a、病例組與對照組之NO2不同暴露期間之月平均值(ppb)分佈情形與失智症發生之勝算比 85
表4-4b、病例組與對照組之NO2不同暴露期間之月平均值(ppb)分佈情形與失智症發生之勝算比 86
表4-5a、病例組與對照組之CO不同暴露期間之月平均值(ppb)分佈情形與失智症發生之勝算比 87
表4-5b、病例組與對照組之CO不同暴露期間之月平均值(ppb)分佈情形與失智症發生之勝算比 88
表5-1a、病例組與對照組之PM10不同暴露期間之月平均值(μg/m3)分佈情形與阿茲海默氏症發生之勝算比 89
表5-1b、病例組與對照組之PM10不同暴露期間之月平均值(μg/m3)分佈情形與阿茲海默氏症發生之勝算比 90
表5-2a、病例組與對照組之SO2不同暴露期間之月平均值(ppb)分佈情形與阿茲海默氏症發生之勝算比 91
表5-2b、病例組與對照組之SO2不同暴露期間之月平均值(ppb)分佈情形與阿茲海默氏症發生之勝算比 92
表5-3a、病例組與對照組之O3不同暴露期間之月平均值(ppb)分佈情形與阿茲海默氏症發生之勝算比 93
表5-3b、病例組與對照組之O3不同暴露期間之月平均值(ppb)分佈情形與阿茲海默氏症發生之勝算比 94
表5-4a、病例組與對照組之NO2不同暴露期間之月平均值(ppb)分佈情形與阿茲海默氏症發生之勝算比 95
表5-4b、病例組與對照組之NO2不同暴露期間之月平均值(ppb)分佈情形與阿茲海默氏症發生之勝算比 96
表5-5a、病例組與對照組之CO不同暴露期間之月平均值(ppb)分佈情形與阿茲海默氏症發生之勝算比 97
表5-5b、病例組與對照組之CO不同暴露期間之月平均值(ppb)分佈情形與阿茲海默氏症發生之勝算比 98
表6-1a、病例組與對照組之PM10不同暴露期間之月平均值(μg/m3)分佈情形與血管性失智症發生之勝算比 99
表6-1b、病例組與對照組之PM10不同暴露期間之月平均值(μg/m3)分佈情形與血管性失智症發生之勝算比 100
表6-2a、病例組與對照組之SO2不同暴露期間之月平均值(ppb)分佈情形與血管性失智症發生之勝算比 101
表6-2b、病例組與對照組之SO2不同暴露期間之月平均值(ppb)分佈情形與血管性失智症發生之勝算比 102
表6-3a、病例組與對照組之O3不同暴露期間之月平均值(ppb)分佈情形與血管性失智症發生之勝算比 103
表6-3b、病例組與對照組之O3不同暴露期間之月平均值(ppb)分佈情形與血管性失智症發生之勝算比 104
表6-4a、病例組與對照組之NO2不同暴露期間之月平均值(ppb)分佈情形與血管性失智症發生之勝算比 105
表6-4b、病例組與對照組之NO2不同暴露期間之月平均值(ppb)分佈情形與血管性失智症發生之勝算比 106
表6-5a、病例組與對照組之CO不同暴露期間之月平均值(ppb)分佈情形與血管性失智症發生之勝算比 107
表6-5b、病例組與對照組之CO不同暴露期間之月平均值(ppb)分佈情形與血管性失智症發生之勝算比 108

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