臺灣地區多氯聯苯暴露老年人的神經認知功能探討

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臺灣地區多氯聯苯暴露老年人的神經認知功能探討

Neuro-Cognitive Function of Polychlorinated Biphenyls (PCBs) Exposed Elderly in Taiwan

林高章 , Masters　　Advisor：郭育良;郭乃文　　

繁體中文

認知記憶；老年人；多氯聯苯；神經功能； Neuro-Cognitive Evaluation ； Neuropsychological Tests ； Elderly ； PCBs

Abstract │ Reference (72) │ Altmetrics

Abstract 〈TOP〉

前言: 1979年中台灣爆發米糠油中毒事件(稱為油症)，約有2061人暴露於環境毒物多氯聯苯及多氯夫喃造成健康危害。由於這些化學物質之脂溶性特質，對中樞神經系統的影響更為深遠。已知文獻指出多氯聯苯造成嬰幼兒智力低下、動作遲緩、記憶減退的障礙；即使持續追蹤，智力功能亦比正常兒童來得低下。少有研究指出此種暴露對於易感族群的老年人，是否會造成智力功能之影響。

研究目的:
1)了解六十歲以上之油症患者的認知、記憶功能是否與對照組不同? 
2)是否該種功能的影響，對於男女有所差別? 
3)是否血清生化指標及甲狀腺激素在油症患者與對照組有所不同? 
4)是否認知功能的影響，是由於生化指標或甲狀線激素之變化所造成?

研究方法:採回朔性世代研究，選取年齡≧60歲居住台中、彰化兩地且登錄於中央衛生機關，多氯聯苯暴露的老年人，依性別、年齡、居住地區等找出配對組，經由問卷及神經功能測試及抽血比較。量表採標準化中文版【簡易認知功能測試之台灣神經學會共識版，世界衛生組織之數字符號，魏式成年智力量表之注意力及記憶廣度、語言記憶、學習能力、30分鐘延遲回憶，魏式記憶量表修正三版的視覺記憶廣度，老年憂鬱量表之測試，修正Luria的運動、感覺系統評估，及日常生活量表等】，經居家訪視，排除干擾因子後，結果以統計軟體依student T測試、卡方、單變項及多變項迴歸，比對兩者是否顯著差異。

結果:暴露組166人(57%)及對照組162人(61%)完成訪視。平均年齡69.5±5.9歲，男女比例49:51，教育程度平均為4.3±3.5年。在兩者的神經功能比較上，校正年齡、性別、教育程度，呈現顯著的有注意力及記憶廣度(前序測試,p=0.0002)、視覺記憶廣度(逆序測試,p=0.01)，學習能力(P=0.03)外，30分鐘延遲記憶及語言記憶測試具傾向意義(p=0.06)，其餘如簡易認知功能測試(P=0.12)、運動(p=0.49)、感覺(p=0.70)、憂鬱(p=0.99)、數字符號(p=0.09)及日常生活量表(p=0.35)，皆不顯著。在性別上，簡易認知功能測試、數字符號、注意力及記憶廣度、視覺記憶等具有女性較男性分數低的結果(P<0.05)。而比對與1980-1982所測多氯聯苯濃度與認知功能測驗結果，除注意力記憶廣度呈現劑量效應外，延遲回憶、數字符號及視覺記憶，亦呈現傾向劑量相關意義。另外生化顯示暴露者的甲狀腺功能低下(T3)的異常比例偏高，具顯著性(P=0.0002)，然而中毒者之智力並非經由甲狀線功能之影響所造成。

討論:利用多變項回歸校正干擾因子後，以學習能力與記憶缺失為最顯著。此結果與在因食用多氯聯苯所污染的湖魚而對成年人記憶功能的傷害相似，提供了環境毒物遲緩性對人類中樞神經記憶功能的危害證據。另外發現有憂鬱傾向的比例，占受試的82%，雖與暴露無關，卻與年齡有關(p=0.006)，顯示當地居住老年人生活的不滿意度，值得進一步探討。對於暴露劑量的關係研究，由於只使用多氯聯苯的濃度，而缺乏多氯夫喃之資料，其劑量效應之關聯僅呈部分之相關性。

結論:本研究指出，多氯聯苯及多氯夫喃之暴露，會造成視覺及語言記憶、注意力、學習能力等明顯或傾向性的低下，並在注意力及記憶廣度之影響，呈現與多氯聯苯有劑量效應之關係。本篇為國內第一篇環境毒物中毒者之世代研究，呈現出神經毒物-多氯聯苯-造成老年人中樞功能受損的結論。對於未來從環境保護的觀點，預防老年人之智力受損，必須避免如多氯聯苯及夫喃之類化合物之暴露，提供了更直接更有力的證據。

Parallel Abstract 〈TOP〉

Introduction: Polychroninated biphenyls (PCBs) and dibenzofurans(PCDF) have lipophilic character and are known to affect central nervous system functioning. In 1979 Yucheng (oil disease) episode, approximately 2000 people in central Taiwan were exposed to PCBs and PCDFs, with fatigue, skin manifestations, liver diseases, and other symptoms. The exposed mothers delivered offspring with dark skin, delayed developmental milestones, and poorer neuro-cognitive functioning. The neuro-cognitive effects of such exposure are unknown in elderly people, who are more vulnerable in the neuro-cognitive functioning.

Objective: 
1). To compare the neuro-cognitive and memory functioning between PCBs/PCDFs exposed elderly and the control group; 2). To determine the association between gender and neuro-cognitive functioning; 3). If neuro-cognitive functioning is affected in the exposed people, whether dose-response relation exists; 4). To determine whether biochemical markers and thyroid hormones are affected in exposed people, and 5) To determine whether effects on thyroid function mediated the neuro-cognitive effects of PCBs/ PCDFs.

Methods: Retrospective cohort in community at Central Taiwan from the outbreak in 1979 was conducted in those aged 60 years or older in exposed and matched controls. Questionnaire and neuropsychological Test in Chinese version were done by trained interviewers. Basic information, Mini-Mental Status Examination (MMSE), Digit symbol (DS), Attention and Digit Span (ADS), Verbal memory of Recall Trials, Delay recall in 30 minutes, Learning Ability of Wechsler Adult Intelligence Scale (WAIS), Visual Memory Span of Wechsler Memory Scale-Revised (WMS-R), Geriatric Depression Scale-Short Form(GDS-SF), Activity of Daily Life (ADL), and Luria’s Motor and Tactile Performance were included in the study.

Results:166 (57%) exposed and 162 (61%) controls completed the tests with mean age 69.9±5.8years, male to female 49:51, and education in 4.3±3.5 years. Exposed people had reduced functioning in ADS (Forward, p=0.0002), VMS (Backward, p=0.02), Learning Ability (p=0.03), and trending in delay recall in 30 minutes, Verbal Memory Recall Trials (p=0.06), and similar MMSE (P=0.12), Motor (p=0.49), Sensory (p=0.70), Depression (p=0.99), DS (p=0.09) and ADL (p=0.35) scores. Women scored lower in MMSE, DS, ADS-backward and VMS as compared to men. Comparing to the exposure levels of PCBs, ADS showed significant linear trend. Although T3 levels were found in exposed subjects (p=0.0002), the neuro-cognitive effects were not mediated by the reduced T3 levels.

Discussion: The results were similar to Shantz’s study that PCBs had learning and memory deficits in exposed humans. A high incidence of depressive mood was found in 82% of the subjects and warranted further investigation. Some dose-response relationship was found, but mainly trends only. Lacking of the exposure levels of PCDFs prohibited more thorough dose-response evaluation.

Conclusion: Our study showed neuro-cognitive deficits in certain aspect of attention, visual memory and learning ability in elderly people previously exposed to PCBs, and found dose-response relationship in these impairments. It provides direct evidence that exposure to PCBs/PCDFs had effects on neuro-cognitive functioning and therefore minimizing exposure by measures, for environmental protection, is warranted.

Reference ( 72 ) 〈TOP〉

1. Chen YC, Guo YL, et al. Cognitive development of Yu-Cheng ("oil disease") children prenatally exposed to heat-degraded PCBs. JAMA 268:3213-8, 1992.
連結：
2. Yu ML, Hsu CC, Guo YL, et al. Disordered behavior in the early-born Taiwan Yucheng children. Chemosphere 29:2413-22, 1994.
連結：
4. Lai TJ, Guo YL, Yu ML, et al. Cognitive development in Yucheng children. Chemosphere 29: 2405-11, 1994.
連結：
5. Agency for Toxic Sustances and Disease Registry (ATSDR). Toxic profile for polychrorinated biphenyls. Atlanta, US Department of Health and Human Services, 1997.
連結：
6. 張火炎、李俊璋、郭育良等：多氯戴奧辛類化學物質之暴露與毒性。中華衛誌 18: 13-27,1999.
連結：

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