慢性幽門桿菌感染和老人認知功能障礙之關聯研究

Association between the Chronic Infection of Helicobacter pylori and Cognitive Impairment in the Elderly

韓明倫(Ming-Lun Han)

指導教授 ： 程蘊菁

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/博士(2019年)

https://doi.org/10.6342/NTU201902522

摘要

背景
許多文獻提出慢性幽門螺旋桿菌感染可能導致認知功能障礙。然而，之前的研究結果並不一致。在西元2016年，一個集合了7篇研究的統合分析顯示幽門螺旋桿菌感染和失智症有顯著相關性，其匯集勝算比(pooled odds ratio)為1.71。但是一篇最近發表的大型世代追蹤研究卻沒有顯示此關聯性。

材料與方法
本研究是橫斷性研究，招募了587位於2011及2013年間參加台大醫院老人健康檢查65歲以上之老人。我們使用酵素免疫法檢測血清中幽門螺旋桿菌免疫球蛋白G濃度，並使用各種神經精神測試來評估整體和特定領域的認知功能，再利用多變量線性回歸和邏輯斯回歸模型來評估血清幽門桿菌免疫球蛋白G濃度(IgG) 與認知功能障礙之間的關聯。

結果
與幽門螺旋桿菌免疫球蛋白G濃度的最低四分位數的老人（Q1）相比，最高四分位數（Q4）的長者其語言流暢度(蔬菜項目)（β係數= -0.24, 95％信賴區間= -0.45, -0.03; 勝算比= 1.53, 95 ％信賴區間= 0.88, 2.66），專注功能領域(數字記憶跨度-正向)( β係數= -0.19, 95％信賴區間= -0.42, -0.04; 勝算比= 1.83, 95％信賴區間= 1.03-3.24)和專注功能因子（β係數= -0.20, 95％信賴區間= -0.37, -0.02; 勝算比= 2.67,95％信賴區間= 1.51, 4.73）的表現較差。整體認知功能和幽門螺旋桿菌免疫球蛋白G濃度沒有顯著的關聯。分層分析顯示，在男性中，血清幽門螺旋桿菌免疫球蛋白G濃度為最高四分位數的老人其語言流暢度(蔬菜項目)表現較差（β係數= -0.38, 95％信賴區間= -0.66, -0.09; 勝算比= 3.01, 95％信賴區間= 1.42, 6.38）。

結論
我們的研究結果顯示，較高的血清幽門螺旋桿菌免疫球蛋白G濃度與語言及專注功能的認知障礙風險有關聯。

公共衛生上的應用
本研究顯示根除幽門螺桿菌也許可以做為認知功能障礙的初段預防方法。我們使用血清學檢測評估幽門螺桿菌感染，此方法屬於非侵入檢查且價格較低廉，適用於社區老年族群的大規模篩查和檢測。

關鍵字

幽門桿菌 ； 感染 ； 認知功能障礙 ； 老人

並列摘要

Background/purpose: Helicobacter pylori (H. pylori) infection has been positively associated with cognitive impairment. However, previous studies have shown inconsistent findings. In 2016, one meta-analysis including 7 studies found a significant association between H. pylori infection and dementia with a pooled odds ratio of 1.71 but a recent large cohort study did not confirm these findings.

Material & Methods: This cross-sectional study included 587 elderly participants (age ≥ 65) from the annual elderly health checkup program at National Taiwan University Hospital from 2011 to 2013. H. pylori infection was assessed by a serology test of IgG using a commercial enzyme immunoassay (EIA). Both global and domain-specific cognition were assessed using various neuropsychological tests. Factor analysis, multivariable linear regression and logistic regression models were utilized to assess the association between the serum H. pylori IgG level and cognitive impairment.

Results: Compared with the lowest quartile of H. pylori IgG (Q1), the highest quartile (Q4) was associated with lower performance on verbal fluency-vegetables [(β=-0.24, 95% confidence interval (CI)= -0.45, -0.03; odds ratio (OR) =1.53, 95% confidence interval (CI)= 0.88, 2.66)], attention domain [digit span-forward: β=-0.19, 95% confidence interval (CI) = -0.42, -0.04; odds ratio (OR) =1.83, 95% confidence interval (CI) = 1.03, 3.24], and attention factor (β=-0.20, 95% confidence interval (CI) = -0.37, -0.02; OR= 2.67, 95% CI = 1.51, 4.73). No significant association was observed for global cognition. Stratified analyses revealed that, among men, the highest quartile (Q4) of serum H. pylori IgG was associated with poor performance on verbal fluency-vegetables (β= -0.38, 95% CI=-0.66, -0.09; OR=3.01, 95% CI=1.42, 6.38).

Conclusion: Our findings disclosed a positive association between serum H. pylori level and cognitive impairment of verbal fluency and attention function.

Public health implication
Our study provides important information for the primary prevention of cognitive impairment through the eradication of H. pylori. To assess H. pylori infection, we performed a serology test that is relatively non-invasive, inexpensive and suitable for mass screening and early detection of the high-risk group in the community dwelling elderly.

並列關鍵字

Helicobacter pylori ； Infection ； Cognitive impairment ； Elders

參考文獻

1. 2016 Alzheimer's disease facts and figures. Alzheimers Dement, 2016. 12(4): p. 459-509.

2. Sun, Y., H.J. Lee, S.C. Yang, et al., A nationwide survey of mild cognitive impairment and dementia, including very mild dementia, in Taiwan. PLoS One, 2014. 9(6): p. e100303.

3. Gelinas, D.S., K. DaSilva, D. Fenili, et al., Immunotherapy for Alzheimer's disease. Proc Natl Acad Sci U S A, 2004. 101 Suppl 2: p. 14657-62.

4. Farrer, L.A., L.A. Cupples, J.L. Haines, et al., Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA, 1997. 278(16): p. 1349-56.

5. Andersen, K., L.J. Launer, M.E. Dewey, et al., Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. EURODEM Incidence Research Group. Neurology, 1999. 53(9): p. 1992-7.