研究背景:
根據台灣衛福部 2015 年資料顯示肺阻塞（COPD）造成七十歲以下的生命年數損失約十年。肺阻塞病人可出現許多共病症，之前的研究認為，肺阻塞病人可觀察到認知功能障礙。然而，關於肺阻塞和失智症之間關係的研究很少。肺阻塞是一種全身性的發炎疾病，發炎因子的影響對於包括失智症在內的各種認知功能障礙扮演著重要的角色。我們認為肺阻塞病人與無肺阻塞相比，患失智症的風險更高。不論是肺阻塞或失智症都是常見的臨床疾病，也影響病人的預後，因此需要進一步探討相互間的關係及其臨床的預後。
研究目的:
在研究肺阻塞與失智症之前，我們計劃先驗證肺阻塞診斷的準確性。藉由驗證診斷碼的正確性後，才能進一步利用全民健康保險研究資料庫(NHIRD)探討肺阻塞病人是否增加失智症的風險，並進而探討這類肺阻塞合併失智症的病人，在住院時的預後是否較差？若肺阻塞病人在開始時有較好的藥物順從性，是否可以減少之後失智症的發生？
研究方法:
首先，由2011年1月1日至2011年12月31日，永康奇美醫院出院並被診斷患有肺阻塞(ICD-9-CM codes 490, 491, 492, or 496)病歷中，選取四十歲以上的住院資料，看病人肺阻塞的診斷與實行肺功能檢查之間的比例，以評估肺阻塞與肺功能之間的一致性。其次，我們使用全民健康保險研究資料庫篩選在2002年1月1日至2011年12月31日的住院期間，年齡大於40歲並且沒有阿茲海默症或帕金森氏症病史(ICD-9-CM codes:331, 332)的肺阻塞病人，分析相較於其他非肺阻塞的病人，追蹤之後發生失智症的機會是否較高？入院的第一天被定義為肺阻塞的指標日期。病人共病症的評估來自指標日期前一年的門診或住院中的ICD-9-CM代碼。第三，研究患有肺阻塞的病人合併有失智症，相較於單純只有肺阻塞的病人，在住院時的死亡率，發生嚴重的敗血症和各種器官衰竭是否有差異? 最後，使用藥品日數覆蓋比例（proportion of days covered, PDC) 計算從肺阻塞到發生失智症期間的藥物順從性，並定義PDC ≥80%為高順從性，PDC<80% 為低順從性，觀察兩組發生失智症的差異。我們使用卡方檢定來比較類別變量，Student’s t-tests來比較連續變項。P值<0.05具顯著統計意義。多變量邏輯回歸分析，對可能影響結果的因子進行校正，來評估失智症的風險和失智症對預後的影響。
結果:
首先，在2011年中利用出院ICD-9-CM診斷碼，共選取130位病人做分析。其中有92位男性和38位女性，其平均年齡為76.48歲。有98位(75.4%)有肺功能檢測，而肺功能符合肺阻塞診斷的有91位(占總人數的70%)。其次，調整年齡，性別，冠狀動脈疾病，腦梗塞，高脂血症，高血壓，糖尿病後，與無肺阻塞病人相比，肺阻塞病人發生失智症的校正風險比值(adjusted HR)為1.65（95% 信賴區間= 1.43–1.90）。第三，肺阻塞合併失智症的病人在住院時，相較於肺阻塞沒有失智症者，在控制了潛在的變異因素之後，有較高的敗血症比例，校正勝算比（adjusted OR）為1.38（95％信賴區間：1.10-1.72），和較高的住院死亡率，校正勝算比為1.69（95％信賴區間：1.18-2.43）。失智症也會增加急性呼吸衰竭，校正勝算比為1.39，(95％信賴區間：1.09-1.77）。高藥物順從性(PDC≥80％)的肺阻塞病人，無法降低失智症風險。
結論:
肺阻塞增加了失智症的風險，肺阻塞合併失智症增加了急性呼吸衰竭，嚴重敗血症和住院死亡率。在藥物順從性高的肺阻塞族群可能無法減少失智症的發生。

Background:
According to Taiwan's Ministry of Health and Welfare report in 2015, COPD caused patients loss of life expectancy of 10 years in patients less than 70 years. Previous studies have reported that cognitive dysfunction was observed in COPD patients. However, research identifying the association between COPD and dementia is scarce. COPD is an inflammatory systemic diseases and cytokine may play a key role in promoting the degenerative processes involved in a wide variety of cognitive disorders, including dementia. We hypothesized COPD patients had higher risk of dementia compared with patients without COPD. Both COPD and dementia are common diseases in clinical, they also affect the patients’ outcome. We need further research to evaluate the relationship between COPD and dementia and their clinical outcome.
Objective:
In order to use the National Health Insurance Research Database (NHIRD) in Taiwan, we planned to validate COPD diagnostic accuracy before investigating the risk of dementia in COPD. Then, we evaluate the risk of dementia, included Alzheimer’s disease or Parkinsonism disease. After that, we aimed to determine the risk of mortality, severe sepsis and acute organ failure in patients with COPD and dementia. Final research was to evaluate whether the medication adherence can reduce the risk of dementia.
Methods:
Firstly, we used the diagnosis at discharge in the electronic medical records to represent the discharge diagnosis in the NHIRD. Patients who were diagnosed with COPD (International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes 490, 491, 492, or 496) and discharged from 1 January 2011 to 31 December 2011 aged 40 years or older were enrolled. Secondly, patients who received a discharge diagnosis of COPD during a hospitalization between January 1, 2002 and December 31, 2011 and older than 40 years of age with COPD without previous history of Alzheimer’s disease or Parkinsonism disease were identified from the NHIRD to survey the risk of dementia. The first date of admission was defined as the index date. Comorbidities were evaluated from 1 year before the index date according to ICD-9-CM codes in outpatient and inpatient services. Thirdly, COPD patients with dementia compared to those without dementia and three outcome measures were investigated, including hospital mortality, severe sepsis, and acute organ dysfunction. Fourthly, we used proportion of days covered (PDC) to evaluate the medication adherence in COPD patients. The measurement period for adherence was from COPD diagnosis to outcome occurred, death, or Dec. 31, 2013. The adherence was divided into high PDC (≥ 80%) and low PDC (<80%). We used chi-square tests to compare categorical variables and Student’s t-tests to compare continuous variables. Statistical significance was inferred at a two-sided P value of <0.05. The risk of dementia and specific effects of dementia on outcome measures, were assessed using multivariate logistic regression analysis adjusting for all baseline characteristics.
Results:
Firstly, we enrolled 92 males and 38 females with mean age 76.48 years for validation. There are 98 (75.4%) patients have performed pulmonary function test. Among those who had a diagnosis of COPD, 91 (70%) patients had FEV1/FVC<70. Secondly, the adjusted hazard ratio (HR) of developing dementia was 1.65 (95% confidence interval  [CI]： 1.43–1.90) in patients with COPD compared with those without COPD after adjusting for age, gender, and comorbidities. Thirdly, after controlling for potential confounding factors, dementia was found to significantly increase the odds of severe sepsis and hospital mortality with an adjusted odds ratio (OR) of 1.38 (95% CI：1.10–1.72) and 1.69 (95% CI：1.18–2.43), respectively. Dementia was also significantly associated with an increased OR of acute respiratory dysfunction (adjusted OR=1.39, 95% CI：1.09–1.77). Fourthly, we found that COPD patients with high PDC (≥80%) may not reduce the risk of dementia.
Conclusions:
COPD increased the risk of dementia and the coexistence of COPD and dementia increased risk of acute respiratory failure, severe sepsis and hospital mortality. Improvement of drug adherence may not reduce the risk of dementia in COPD.

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