阿茲海默失智症藥物治療的現況與新進展

Pharmacological Treatment of Alzheimer's Disease: The Present and the Future

阿玆海默失智症是失智症中最常見的一種退化性失智症，但目前無有效根治的療法。臨床上常用的藥物主要是針對改善記憶功能及生活功能或減緩其惡化，以及控制其精神症狀的藥物。本研究利用Cochrane資料庫探討自2000年至2012年止，搜尋所有關於阿茲海默失智症臨床試驗的系統性回顧之文章，分析用藥種類及治療效果，本回顧針對目前研究較多的及臨床常用的藥物治療，選取乙醯膽醶酶抑制劑，及N-甲基-D-天冬氨酸（N-methyl-D-aspartic acid, NMDA）接受器拮抗劑，血管預防性用藥，維他命製劑等作文獻回顧，探討其對阿茲海默失智症的療效。另外也針對免疫療法的進展作整理。結果顯示目前最多實證研究及有正面效果的仍是乙醯膽鹼酶抑制劑，有效治療對象是輕到重度之阿茲海默失智症，其療效在於改善記憶功能，生活能力及整體印象分數，有很好的結果。NMDA接受器拮抗劑用於中重度之阿茲海默失智症，在改善記憶功能及生活能力，也有很好的結果。至於神經保護劑、血管改善用藥（如降血脂藥）、及維他命製劑則還沒有足夠多的臨床證據證實其確實有預防及緩解療程惡化的效果，這還須未來更多的研究來證實。近幾年很多臨床試驗用免疫療法，清除或減少「β類澱粉蛋白」來防治失智症，有相當不錯的進展，相信不久的未來，此種治療應該有很大的突破。

Alzheimer's disease (AD) is a progressive, degenerative disorder of the brain and the most common form of dementia among the elderly. With the lack of a cure for AD, goals of drug therapy include temporary improvement, stabilization, or less -than-expected decline in cognition, daily living functions and behavior symptoms. We searched Cochrane database of systematic reviews from year 2000 to 2012 for all the clinical t rails about the pharmacological treatment of AD. The current pharmacological approach of AD treatment is mainly based on symptomatic therapy with cholinesterase inhibitors (ChEIs) and N-methyl-D-aspartic acid (NMDA) receptor antagonists. The results show that treatment with ChEIs in mild to severe dementia of AD patients and NMDA receptor antagonists in moderate to severe AD produced statistically significant improvements in cognition, daily living functions, global clinician's or caregiver's impressions, and behavior symptoms. In recent years, increased emphasis has been put on the vascular contribution to AD's pathophysiology. The two vascular risk factors mostly studied with respect to cognitive outcomes are hypertension and dyslipidemia. In the limited clinical trials using statin to treat AD or dementia, statin caused no significant difference in global function, behaviors, or daily activities, nor is there evidence thus far that statin aids in the prevention of AD or dementia. With regard to vitamin E, an antioxidant, no significant preventive effects were found for the progression from mild cognitive impairment to AD. Other vitamin agents studied for the treatment of dementia are folic acid and vitamin B12. Although these vitamins can lower serum level of homocystien (a reported possible risk factor for AD), no significant beneficial effects were found. Amyloid β (Aβ) peptides represent an important molecular target for AD intervention. Several types of Aβ peptide immunotherapy of AD are currently under investigation. Although pre-clinical studies showed that immunization against Aβ peptide provides protection from and reversal of the pathology of AD in animal models, serious adverse events have been reported like meningoencephalitis and vasogenic edema. Novel strategies have been implemented to overcome these problems. Over 10, 000 patients are enrolled in more than 40 ongoing clinical trials, most of which are expected to report final results in the near future.