作者：Allison Gandey
出處：WebMD醫學新聞
October 21, 2009 (巴爾的摩) — 一篇隨機安慰劑控制試驗的事後分析結果顯示，rivastigmine (商品名Exelon，Novartis製造)緩解巴金森氏症失智病患的症狀。在美國神經協會第134屆年會的發表中，研究者顯示這個膽鹼脂酶抑制劑可改善執行功能。
研究者表示，rivastigmine最初獲得美國核准用於治療阿茲海默氏症，最近核准用於巴金森氏症失智，對病患有幫助。
這是與會聽眾難以錯過的訊息，海報展覽區也有許多有關此效果的事後分析與回溯分析結果。研究者表示，這是他們面臨所謂「產生最多假設的研究」的研究限制。
印第安那大學的Martin Farlow醫師向Medscape Neurology提到他的兩篇海報，這些資料來自原本的24週rivastigmine試驗，也就是讓rivastigmine獲得美國和歐洲核准用於巴金森氏症的重要研究：「The Exelon in Parkinson's disease dementia study」，也稱為EXPRESS試驗，包括了來自多個中心的541名病患。
這篇新分析，一樣是由肯塔基州Lexington郡Sanders-Brown老化研究中心的Frederick Schmitt博士領導，評估該試驗的次級結果以及分析執行功能。研究者使用Delis-Kaplan執行功能系統(D-KEFS)之次檢測以及符號數字形式測驗。病患有巴金森氏症2年以上且有輕微到中度失智。
研究者報告指出，分析數字少是因為並非每個地方都有進行執行功能檢測。
【有提供執行功能檢測資料的病患數】 檢測
檢測 | Rivastigmine 3 – 12 mg/ 天 | 安慰劑 |
D-KEFS 字母流暢性 | 258 | 144 |
D-KEFS 卡片分類 | 49 | 22 |
D-KEFS 色字干擾 | 62 | 35 |
符號數字形式 | 43 | 22 |
海報上發表之結果所描述的一系列數字列出rivastigmine的好處，但是作者並未提供D-KEFS 字母流暢性、D-KEFS 卡片分類、D-KEFS色字干擾、符號數字形式等次檢測的完整數值分析。
在D-KEFS色字干擾檢測中，作者們報告指出，相較於安慰劑，以rivastigmine治療獲得較少的自我校正錯誤(治療組n = 29人、分數為負0.6分；安慰劑組n = 11人、分數為1.1 分)。研究者報告指出，指名、閱讀與抑制任務等方面沒有明顯的治療差異。
Farlow醫師在受訪時表示，這藥物是有幫助的。不只有記憶和一般功能效果，其他方面如需多步驟的動作也有所改善。
Farlow醫師認為，多達70%巴金森氏症病患在病程中會發生失智。他表示，本研究顯示出治療認知症狀的好處。
在會議中有這麼多事後分析發表的這樣一個研究，可能很容易令大家忘記這些資料都是來自單一個臨床試驗。
加拿大Wilfrid Laurier大學的Quincy Almeida博士接受Medscape Neurology邀請進行評論時表示，我們有許多病患處方有rivastigmine，此研究結果大有可為。
他指出，很樂於在DKEFS的各項檢測中看到顯著的改善，另外也須考量巴金森動作不佳狀態對於速度檢測的整體影響。舉例而言，智力遲鈍經常會和講話緩慢產生混淆。這相當值得後續研究。
Novartis藥廠支持本研究。資深作者、Jason Olin是Novartis藥廠的員工，他也是會議中其他rivastigmine海報的共同作者。
美國神經協會第134屆年會：壁報T66。發表於2009年10月13日。
Rivastigmine May Improve Executive Function in Parkinson's Dementia
By Allison Gandey
Medscape Medical News
October 21, 2009 (Baltimore, Maryland) — Results from a post hoc analysis of data from a randomized placebo-controlled trial suggest that rivastigmine (Exelon, Novartis) eases symptoms in patients with Parkinson's dementia. Presenting here at the 134th annual meeting of the American Neurological Association, investigators showed the cholinesterase inhibitor may improve executive function.
Researchers say rivastigmine, first approved in the United States for Alzheimer's disease, and more recently for Parkinson's dementia, is benefiting patients.
It was a message that attendees might have been hard pressed to miss at the meeting, with multiple post hoc and retrospective analyses to this effect presented during the poster session. Investigators were the first to admit the limitations of what they called "mostly hypothesis-generating" studies.
"These data are derived from the original 24-week trial of rivastigmine," Martin Farlow, MD, from Indiana University at Indianapolis, told Medscape Neurology about 2 of his posters. "It was that pivotal study that first got rivastigmine approved in Parkinson's in the United States and Europe." The Exelon in Parkinson's disease dementia study, known as EXPRESS, included 541 patients from multiple centers.
The new analysis, also led by Frederick Schmitt, PhD, from the Sanders-Brown Center on Aging in Lexington, Kentucky, evaluated secondary outcome measures from the trial and assessed executive function. The investigators used Delis-Kaplan Executive Function System (D-KEFS) subtests and the Symbol Digit Modalities test. Patients had Parkinson's for 2 or more years and were experiencing mild to moderate dementia.
Researchers report the numbers for this analysis were small because executive-function tests were not performed at all sites.
Number of Patients Who Provided Data on Executive Function
| Test | Rivastigmine 3 – 12 mg per day | Placebo |
| D-KEFS letter fluency | 258 | 144 |
| D-KEFS card sorting | 49 | 22 |
| D-KEFS color-word | 62 | 35 |
| Symbol digit modalities | 43 | 22 |
The results presented on the poster depict a series of figures outlining a benefit of rivastigmine, but the authors did not provide a clear numerical breakdown for the D-KEFS letter fluency, card sorting, or symbol digit modalities tests.
In the D-KEFS color-word interference test, the authors report that treatment with rivastigmine resulted in fewer self-corrected errors vs placebo (n = 29 and ?0.6 points vs n = 11 and 1.1 points). The researchers report no significant treatment differences for the naming, reading, and inhibition tasks.
"The medication is helpful," Dr. Farlow said during an interview. "The effects clearly aren't just with memory and general functioning but are improving other areas as well, such as tasks that require multiple steps."
Dr. Farlow suggested that as many as 70% of Parkinson's patients will develop dementia at some point during the course of their illness. "This is one study that demonstrates a beneficial effect of treating cognitive symptoms," he said.
One study, but with so many post hoc analyses presented at the meeting, it might have been easy to forget that all of the data were based on a single clinical trial.
Asked by Medscape Neurology to comment, Quincy Almeida, PhD, from Wilfrid Laurier University in Waterloo, Ontario, Canada, said, "We have many patients that are being prescribed rivastigmine, and so the results of the study are promising."
He added, "It would have been nice to see significant improvements on more subtests of DKEFS, and it is also important to consider how Parkinson motor deficits might have an overall influence on speed tests." For example, he noted, bradyphrenia can often be confused with slow speech initiation and production. "It certainly appears to be worthy of further investigation."
This study was supported by Novartis Pharmaceuticals. Senior author Jason Olin is a Novartis employee, and he coauthored the other rivastigmine posters at the meeting.
American Neurological Association 134th Annual Meeting: Poster T66. Presented October 13, 2009.
