| 摘要: | 研究背景
失智症為一種神經退化性疾病，此疾病如今是老年疾病最重要的議題之一。2015年世界上有將近4,750萬失智症的病人，隨著全球急速老化，之後會以每20年增加一倍的速度迅速成長。在2014年的台灣老年人口當中，有4.8%的人有使用抗膽鹼藥物。全世界有許多老年人暴露於膽鹼藥物當中，然而抗膽鹼藥品應避免用於老年人身上。目前抗膽鹼藥品已被研究得知與輕微認知障礙、阿茲海默症與失智症有關，但各類抗膽鹼藥物之強度與其累積劑量和失智症之相關性仍不清楚。
研究目的
本篇研究目的是針對台灣65歲以上老年族群，評估不同類型抗膽鹼藥品或是不同累積劑量的抗膽鹼藥品使用與失智症發生的風險的相關性。
研究方法
本研究利用台灣全民健保資料庫進行回溯性世代研究，研究族群為2002年1月1日至2004年12月31日間年紀大於等於65歲的老年人。兩個主要自變項為：(1)抗膽鹼藥品的類型與(2)抗膽鹼藥品的累積劑量。
本研究個案於收案期間至少有一次抗膽鹼藥品之處方及定義為抗膽鹼藥品使用者，並將第一次處方抗膽鹼藥品的日期設為起始日，並依照起始日當天所暴露抗膽鹼用藥強度加以分類。藥品的定義與分類是依照Anticholinergic Cognitive Burden (ACB)，累積劑量部分是根據世界衛生組織所定義之藥品定義每日劑量進行換算。藥品新使用個案定義上必須於起始日前一年內無任何抗膽鹼藥品，並且排除於起始日前有接受任何失智症相關診斷或治療紀錄者。個案從起始日開始計算三年間抗膽鹼藥品的暴露劑量，後續追蹤四年以評估失智症發病情形。個案於追蹤時間內，若住院資料或者門診資料中有任一失智症相關診斷，即分類到發病組。本研究利用傾向分數配對以平衡弱效抗膽鹼藥品暴露與強效抗膽鹼藥品暴露量組間可能之干擾因子，並利用邏輯式迴歸與Cox比例風險模式分析抗膽鹼藥品使用與老人失智症之間的相關性。
研究結果
本次個案共有12,263名老年人使用抗膽鹼藥品，其中有36.1%的使用者使用強效抗膽鹼藥品。經過傾向分數配對後，兩組各4,205名個案。後續於追蹤期的四年間，強效抗膽鹼使用者得到失智症的風險並無顯著高於弱效抗膽鹼藥品使用者(Hazard ratio=1.03, 95%CI=0.87-1.22; Odds ratio=1.04, 95%CI=0.87-1.23)。抗膽鹼藥累積劑量超過1095 cDDD者，相較於低累積劑量使用者有顯著較高罹患失智症的風險(hazard ratio =1.55, 95% CI=1.07-2.25; odds ratio =1.57, 95% CI=1.08-2.30)。
結論
本篇研究結果發現年紀大於或等於65歲以上的老年人，使用抗膽鹼劑量增加與其增加失智症之間具有相關性。並且發現強效抗膽鹼藥品使用者得到失智症的風險，並無顯著高於弱效抗膽鹼藥品使用者。因此健康照護者與提供者應更加留意長期使用抗膽鹼藥品以及高累積劑量者可能產生潛在的失智症風險。
Background
Dementia, a syndrome of progressive decline in memory and cognitive function, has become one of the most important neurological disease among the elders. With the global ageing population, 47.5 million people were expected to be diagnosed with dementia in 2015, and the number will double every 20 years. In Taiwan, the prevalence of dementia among people aged 65 years and older was 4.8% in 2014. Medication with anticholinergic effects is often prescribed to the elderly in the worldwide. Furthermore, some anticholinergics were recommended to avoid using at the elder adult. Although some anticholinergics had been reported to be associated an increased risk of Alzheimer’s disease and dementia, the association between different type of anticholinergic and different cumulative dose with the risk of dementia remained unclear.
Objective
The purpose of this study was to investigate the association between different types and different cumulative doses of anticholinergic and the risk of dementia among older adults in Taiwan.
Methods
This study is a retrospective cohort study with a new drug user design using the National Health Insurance Research Database (NHIRD) in Taiwan. Patients will be eligible for being included in the study if they were aged 65 years or older between January 1, 2001 and December 31, 2004. Two major independent variables were in this study: (1) the type of anticholinergic medications and (2) the cumulative dose effect.
For the anticholinergic users, the date of first prescription of any anticholinergic medication during the enrollment period was defined as the index date. In this study, we used Anticholinergic Cognitive Burden (ACB) scale to define different types of anticholinergic and cumulative defined daily doses (cDDDs) to account the exposed level of each individual. To identify anticholinergic new users, Patients were excluded if they received any anticholinergic medications within one year before the index date. The patients were excluded if they had ever been diagnosed with dementia or received any treatment for dementia before the index date. Three-years after each index date was set as the exposure period, and follow-up for four years after the exposure period. To evaluate the disease onset period, the person time was accounted by the index date to case date of each individual. The outcome variable was defined as patients who obtained one or more inpatient or outpatient diagnosis of dementia in the follow-up period.
Propensity score matching was used to balance the selected confounders between strong anticholinergic exposed group and mild anticholinergic exposed group. The logistic regression models and Cox proportional hazard models were used to evaluate the association between anticholinergic use and the risk of dementia.
Results
Among patients with anticholinergic used (N=12,263), an estimated 36.1% elder users used ACB 2 or 3 medication. After using propensity score matching, the hazard ratio (HR) and the odds ratio (OR) of dementia were non-significant higher among patients with strong anticholinergic exposed than those with mild anticholinergic exposed (hazard ratio=1.03, 95%CI=0.87-1.22; odds ratio=1.04, 95%CI=0.87-1.23). Compared to low cumulative dose, patients with more than 1,095 cDDDs had a highest risk of dementia (hazard ratio =1.55, 95%CI=1.07-2.25; odds ratio =1.57, 95%CI=1.08-2.30).
Conclusion
We found that anticholinergic users with a higher cumulative dose were associated with an increased risk of dementia than users with lower than 90 cDDDs exposed. In this study, health care providers should be aware of this association with dementia when considering any anticholinergics for their older patients. |
