陳秀熙Horng-Huei, Liou;Chen, Hsiu-Hsi臺灣大學:預防醫學研究所溫瓊容Wen, Chiung-JungChiung-JungWen2010-06-022018-06-292010-06-022018-06-292008U0001-3007200800403600http://ntur.lib.ntu.edu.tw//handle/246246/184815一、研究背景及目的 巴金森氏症為老年人中除了阿茲海默失智症外，第二常見的神經退化性疾病。其發生率約為每十萬人口4.5～20人，其盛行率約為每十萬人口31～328人。流行病學的相關研究，顯示不同種族或相同種族間不同的居住地理環境，巴金森氏症的發生率和盛行率均有差異，因此認為基因和環境中危險因子之間的交互作用對於巴金森氏症的病因佔有重要的角色。近年來認為巴金森氏症的致病機轉有兩大理論。一是因為細胞中蛋白質不正常的折疊與堆積導致多巴胺細胞的衰退。另一個理論是認為粒腺體的功能不良與其相關的氧化還原壓力造成多巴胺細胞的衰退與死亡。經由此二理論加上流行病學的研究結果，推測生活型態或飲食習慣或許亦會透過上述的致病機轉進而影響巴金森氏症的發生。此外，不同巴金森氏症的偵測方式亦會影響各研究間發生率及盛行率的差異。 因此，本研究利用在2000-2005年參加基隆複合式篩檢的民眾，經由飲食資料的收集及巴金森氏症的篩檢及追蹤，希望達到以下兩個目的：. 瞭解巴金森氏症在社區族群的發生率及盛行率。. 探討早期與晚期巴金森氏症相關的飲食危險因子。、研究材料及方法 研究的對象是從2000年至2005年參加基隆複合式篩檢 (Keelung community-based integrated screening program, KCIS)，40歲以上的民眾。利用兩種不同偵測巴金森氏症的方式來分析與巴金森氏症的相關因子。一是由神經科醫師參與部份篩檢的進行，主動偵側巴金森氏症個案，所偵測到的個案為臨床早期個案。另一個偵測個案的方式則是由研究個案的診斷碼來判定巴金森氏症的個案，所偵測的個案為中晚期巴金森氏症個案。 料的收集包括包含體位測量、血壓測量、生化值測量、個人過去病史、飲食習慣問卷調查以及個人生活型態因子等。用邏輯式迴歸分析(Logistic regression analysis)探討各研究變項與臨床早期和中晚期巴金森氏症的相關性，篩選出與巴金森氏症相關的飲食或其他因子。、研究結果 用在2001年中，經由神經科醫師篩檢的11,330位研究個案中，有80位診斷有巴金森氏症，將這80個個案扣除後，其餘的11,250位在追蹤的四年內，共有157位發生巴金森氏症，每年的發生率約為每十萬人年232.3~366.0人。 盛行率的評估方面，經由神經科醫師主動偵測所得到的巴金森氏症盛行率，為每十萬人口706人，與其他各年度經由個案自行求診所偵測出來的盛行率（約每十萬人口190~285人），約高出二~三倍。早期巴金森氏症個案的資料分析，發現隨著年齡的增加，巴金森氏症的發生亦會增加(RR:1.11 , 95% CI: 1.01-1.14)，而女性則為巴金森氏症的保護因子(RR: 0.74, 95% CI: 0.47-1.16)。在飲食習慣的分析，攝取越多的海鮮類食物在調整年齡和性別後，與巴金森氏症的發生傾向負相關(p for trend: 0.04)。中晚期巴金森氏症個案的資料分析，年齡的增加，亦是巴金森氏症的危險因子(RR:1.09 , 95% CI: 1.08-1.10)。在飲食部分，顯示水果的攝取與巴金森氏症的發生呈現正相關(p value for trend: 0.02)，咖啡因的攝取(p value for trend: 0.004)和每日總熱量的攝取(p value for trend: 0.001)則與巴金森氏症的發生呈現負相關。餘與中晚期巴金森氏症呈現正相關的還有心血管疾病病史(RR:1.38 , 95% CI: 1.12-1.68)及骨質疏鬆症(RR:1.63 , 95% CI: 1.37-1.94)。與巴金森氏症呈現負相關的則是：抽煙(RR:0.76 , 95% CI: 0.61-0.96)、喝酒(RR:0.76 , 95% CI: 0.59-1.00)及高血脂(RR:0.78 , 95% CI: 0.67-0.92)。、討論 研究發現，與早期巴金森氏症相關的飲食習慣為海鮮攝取，且呈現負相關。咖啡因攝取與總熱量攝取與中晚期的巴金森氏症呈現負相關；水果的攝取則與中晚期巴金森氏症呈現正相關。雖然之前文獻較少直接探討海鮮類攝取與巴金森氏症的相關，但由其他相關研究推測，海鮮攝取與巴金森氏症的關係可能透過增加普林(Purine)攝取或增加脂肪酸的攝取而影響巴金森氏症的發生。啡因的攝取雖在一統合分析中，顯示其與巴金森氏症呈現負相關，但似乎還受到其他因素的影響，包括賀爾蒙的使用，或者抽煙和飲酒的影響等。年齡是巴金森氏症危險因子外，其他與巴金森氏症相關的因子，包括水果攝取、每日總熱量的攝取、抽煙、喝酒、心血管疾病病史以及骨質疏鬆症，其與巴金森氏症的相關性，尚須更多的研究來證實。、結論 本研究利用兩種不同偵測巴金森氏症個案的方式，一是神經科醫師主動至社區篩檢巴金森氏症的個案，一是利用醫療診斷系統的連結來偵測個案，評估其不同診斷的盛行率及探討有可能影響臨床早期及中晚期巴金森氏症的因子。研究顯示，巴金森氏症的盛行率隨年齡的增加而增加，在男性的盛行率較女性為高，這與之前其他的研究有相似的結果。以不同的方式來定義巴金森氏症的個案，會影響盛行率評估，以神經科醫師主動篩檢的盛行率較病人自行求診的盛行率高出二倍左右。主動偵測的巴金森氏症個案，應屬於臨床前期的個案，發現海鮮的攝取在調整年齡、性別後，仍與巴金森氏症的發生呈現負相關。 在臨床醫師診斷的巴金森氏症個案 ，應屬於臨床中期或晚期的個案，研究顯示年齡、水果攝取、心血管疾病病史及骨質疏鬆症與巴金森氏症呈現正相關，而咖啡因攝取、較高的總熱量攝取、抽煙、喝酒及高血脂則與巴金森氏症呈現負相關。 是否在本研究所發現的每個影響巴金森氏症的變項均與巴金森氏症有關，未來還需有更多的研究來探討這些因子和巴金森氏症的因果關係。鍵詞：巴金森氏症、飲食習慣、盛行率、社區篩檢、主動偵測、被動偵測Background and Study Purpose Parkinson’s disease (PD) is the second most common degenerative disorder in the aging brain after Alzheimer’s dementia with geographical variation, which suggests the possibility of interaction between genetic susceptibility and environmental risk factors related to endo- and exotoxins. One of major considerations is nutrition. From epidemiological viewpoint, there is lacking of large population-based study to report incidence and prevalence rate simultaneously and also to demonstrate the associations between various dietary habits and the risk of PD. Thus, the aim of the present study is firstly to estimate the incidence and prevalence of PD in the community in Taiwan, and secondly, to elucidate the effect of a series of life-style, dietary habits, and their related biological markers on the risk of PD using a population-based cohort study.aterial and Methods Study subjects enrolled in our study for the following analysis are originated form the participants involved in Keelung community-based integrated screening program (KCIS) from 2000 to 2005. A one-stage neurological survey for idiopathic PD was also conducted in 2001. As our study subjects are from community-based residents, we have two ways of detecting PD, active and passive method. In active method, we used one-stage method in a cross-sectional survey to detect PD by the Neurologists in 2001. In passive method, we exploited data on the enrollment of screenee between 2001 and 2005 to estimate prevalence rate in each year by the linkage of these screenee with health insurance claimed record to find 701 PD cases. Information on anthropometric measurement, blood pressure measurement, biochemical markers, personal medical history, food intake questionnaire, and life style factors were collected. Logistic regression model with adjustment for potential confounders was used to estimate the association between different dietary factors and PD risks.esult Among 11,330 participants who received screening for PD by the neurologists in 2001, 80 PD cases were detected. Of remain 11,250 participants who were free from PD in 2001, 157 participants were diagnosed as PD in the following 4 years. The incidence rate was around 232.3~366.0 per 105 person-years. The prevalence rate was 706 per 105population when using active method to detect PD cases. The prevalence rate was about two-fold when comparing with the passive detection method. In early PD analysis, which PD cases was detected by active method, we found that age was a risk factor for PD (RR:1.11 , 95% CI: 1.01-1.14). Female gender is a protective factor for PD though it was not statistically significant (RR: 0.74, 95% CI: 0.47-1.16). Seafood intake was inversely associated with PD (p for trend: 0.04). In late PD analysis, which PD cases was detected by passive method, the risk for PD also increased with age (RR:1.09 , 95% CI: 1.08-1.10). For dietary habits, an increase in intake of fruit was positively associated with the risk of PD (p for trend: 0.02). Intake of caffeine (p for trend: 0.004) and high total calorie intake per day (p for trend: 0.001) were inversely associated with the risk for PD. Those who had cardiovascular disease history (RR:1.38, 95% CI:1.12-1.68) and osteoporosis(RR:1.63, 95% CI:1.37-1.94) were more prone to having late PD than those who were in the absence of corresponding diseases or disease history. Smoking (RR:0.76 , 95% CI: 0.61-0.96), alcohol drinking(RR:0.76 , 95% CI: 0.59-1.00) and chronic disease with hyperlipidemia (RR:0.78 , 95% CI: 0.67-0.92) were inversely associated with the risk of PD.onclusion Our study used two ways of detecting PD, active and passive method. The prevalence rate using active method of detecting PD was about two-fold higher than passive method. By using a neurological survey we found an inverse relationship of seafood to early PD among Chinese people. Regarding progression to symptomatic PD we also found coffee, high calorie intake per day, smoking, alcohol drinking and hyperlipidemia were negatively associated with the risk of PD. The presence of osteoporosis and cardiovascular disease history are positively related to the risk of PD. The influence of some risk factors is rather elusive and need further study to conform these relationships.中文摘要………………………………………………………………………………….…I文摘要……………………………………………………………………………...…….V一章 前言………………………………………………………………………………...1一、前言………………………………………………………………………………...…1二、研究目的………………...……………………………………………………………2二章 文獻回顧…………………………………...………………………………………3一、巴金森氏症的盛行率……………………………………………………………...3二、巴金森氏症的致病機轉……………………………...……………………………4三、飲食因子與巴金森氏症的相關………………………………………….………5　1. 抗氧化物與巴金森氏症的相關…………………………………………...……5　2. 乳製品與巴金森氏症的相關性……………………………………………...…6　3. 脂肪類食物與巴金森氏症的相關性……………………………………...……7　4. 葉酸、維生素B6、維生素B12與巴金森氏症的相關性…………………...……8　5. 咖啡與巴金森氏症的相關性……………………………………………...……9　6. 高尿酸飲食與巴金森氏症的相關性……………………………………...……10三章 研究材料及方法……………………………………………….…………………12一、研究對象及研究設計………………………………………………………….....12二、巴金森氏症的診斷……………………………………………………………….14三、資料收集………………………………………………………………………….15四、統計分析………………………………………………………………………….19四章 研究結果………………………………………………………………………….20一、巴金森氏症的發生率、盛行率及疾病程度……………………………….....20二、基本資料分析………………………………...................................................21三、各變項與巴金森氏症的相關性………………………………......................23五章 討論……………………………………………………………………………….29一、巴金森氏症盛行率………………………………………………………………….29二、飲食因子與巴金森氏症的相關…………………………………………………….29三、抽煙與巴金森氏症的相關………………………………………………………….32四、疾病與巴金森氏症的相關性……………………………………………………….32五、本研究的考量及限制……………………………………………………………….34六章 結論……………………………………………………………………………….35考文獻…………………………………………………………………………………...36錄(一)………………………………………………………………………………........60目錄1………………………………………………………………………………………39 2-1………………………………………………………………………………………402-2………………………………………………………………………………………40目錄able 1……………………………………………………………………………………41able 2……………………………………………………………………………………42able 3-1……………………………………………………………………………………43able 3-2……………………………………………………………………………………43able 3-3……………………………………………………………………………………44able 3-4……………………………………………………………………………………44able 3-5……………………………………………………………………………………44able 4……………………………………………………………………………………46able 5……………………………………………………………………………………46able 6……………………………………………………………………………………47able 7……………………………………………………………………………………47able 8-1……………………………………………………………………………………48able 8-2……………………………………………………………………………………48able 9-1……………………………………………………………………………………49able 9-2……………………………………………………………………………………50able 10-1…………………………………………………………………………………51able 10-2…………………………………………………………………………………52able 11……………………………………………………………………………………53able 12……………………………………………………………………………………54able 13……………………………………………………………………………………55able 14……………………………………………………………………………………56able 15……………………………………………………………………………………57able 16……………………………………………………………………………………58able 17……………………………………………………………………………………59application/pdf515519 bytesapplication/pdfen-US巴金森氏症飲食習慣盛行率社區篩檢主動偵測被動偵測Parkinson’s diseasedietary habitsprevalencecommunity-based screeningactive detectionpassive detection[SDGs]SDG3thesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/184815/1/ntu-97-R95846009-1.pdf