作者：Barbara Boughton 齣處：WebMD醫學新聞 　　June 16, 2009 — 根據一項發錶在6月16日神經醫學期刊的前瞻性研究結果 那些遺忘性失語的輕度認知功能受損（aMCI MCI病患的憂鬱癥可以預測惡化成阿茲海默氏癥 - 趣味新聞網

發表日期 2009-07-02T08:02:01+08:00

     作者：Barbara Boughton
齣處：WebMD醫學新聞

June 16, 2009 — 根據一項發錶在6月16日神經醫學期刊的前瞻性研究結果，那些遺忘性失語的輕度認知功能受損（aMCI）病患，如果發生憂鬱癥，可以預測之後惡化成阿茲海默氏癥（AD）。然而，該研究結果顯示，以阿茲海默氏癥治療藥物donepezil（Aricept，Elsai/輝瑞藥廠）使用於有憂鬱癥狀與aMCI的病患，可能延緩這些病患惡化成失智癥。

主要作者、洛杉磯加州大學David Geffen醫學院的神經學助理教授Po Lu精神博士錶示，早期研究報告指齣，神經行為癥狀，特彆是冷漠與憂鬱，看起來會加速惡化成失智癥的速度；我們的研究確認瞭這項假說。

Lu博士附帶錶示，他們也檢視以藥物治療是否有任何好處，特彆是donepezil；然而，其他研究顯示donepezil會使阿茲海默氏癥行為癥狀減少，我們的研究也發現，相較於安慰劑與維他命E，donepezil確實會減緩失智癥的惡化。

【憂鬱癥越嚴重 惡化速度越快】
研究團隊追蹤208位憂鬱癥病患與548位沒有憂鬱癥狀的病患，長達三年，這些病患的年齡都介於55至91歲之間。試驗前，所有病患都以Beck憂鬱量錶（BDI）評估，並且分類為憂鬱（BDI分數10分以上）或是非憂鬱（BDI分數低於10分）。

這些結果顯示，BDI分數每增加一分，惡化成阿茲海默氏癥的風險高瞭3%（P=0.03）。研究團隊也以一項隨機分派、雙盲、平行設計來比較donepezil治療（10 mg）相較於安慰劑或是維生素E（2000 IU）的效果。其研究結果顯示，donepezil更可能顯著地減緩aMCI與憂鬱病患的失智癥狀，但是對於無憂鬱癥的aMCI病患作用不大。

當追蹤到1.7年時，那些有aMCI與憂鬱癥且使用donepezil的病患，有11%發展成阿茲海默氏癥，使用維生素E與安慰劑組則是25%（P=0.023）。在2.2年時，那些有憂鬱癥aMCI且使用donepezil的病患，有14%發展成阿茲海默氏癥，使用維生素E與安慰劑且有憂鬱癥的aMCI病患，則有29%演變成阿茲海默氏癥（P=0.025）。

他們錶示，即使以donepzil治療2.7年後，惡化的比例仍然是比較低的；而治療組中非憂鬱癥受試者的存活麯綫並沒有差異。

研究團隊排除在過去兩年間被診斷為憂鬱癥或是其他精神疾病異常的病患，其他排除條款包括中樞神經（CNS）栓塞、感染或是使用維他命或是其他營養補充品。Lu博士錶示，受試者們被允許使用穩定劑量的抗憂鬱藥物，在試驗前處方達一個月，隻要憂鬱癥被認為是失智疾病進程的一部分，且不是臨床重鬱癥的病徵。

研究團隊錶示，在他們的文獻中，憂鬱可能代錶瞭一個AD起始的錶現型標記以及使用donepezil的良好反應。除此之外，憂鬱與AD之間的關係仍然未知。Lu博士錶示，他們假設憂鬱可能與其下CNS疾病病理生成有關。隨著阿茲海默氏癥惡化，而可能與憂鬱癥狀有關。

由於aMCI病患是個差異性很大的族群，這對於針對那些有憂鬱癥狀而以donepezil治療之病患的臨床醫師來說可能是有幫助的。Lu博士指齣，使用這個藥物治療可以延緩失智發作，也可以提供較好的生活品質。

【武斷地處理憂鬱癥】
紐約Albert Einstin醫學院行為科學與精神學助理教授Angela Scicutella醫師錶示，這項研究的顯著性，以這項研究的前瞻性設計，提供瞭支持憂鬱與失智之關聯性的進一步證據。

Scicutella醫師附帶錶示，這項研究強調臨床醫師必須要更武斷地提齣後期的憂鬱癥狀，因為這些情緒癥狀經常伴隨著認知功能缺損。

她強調，有憂鬱癥與aMCI的病患，於疾病早期以donepezil治療，可能可以延緩阿茲海默氏癥的進展。Scicutella醫師錶示，這對於病患及其傢屬來說，是個很重要的治療介入。

她附帶錶示，這項研究也提齣瞭一個令人耐人尋味的問題，憂鬱但並未符閤正式aMCI診斷標準的老年病患使用donepezil，是否可以幫助延緩阿茲海默氏癥的進展。

Lu與Scicutella醫師錶示沒有相關資金上的往來。這項研究由國傢高齡化機構、阿茲海默氏癥學會、阿茲海默疾病聯閤研究經費、阿茲海默氏癥研究中心、Jim Easton與Sidell Kagan基金會贊助。

Depression in MCI Patients Predicts Progression to Alzheimer's Disease

By Barbara Boughton
Medscape Medical News

June 16, 2009 — Depression in those with amnesic mild cognitive impairment (aMCI) is predictive of progression to Alzheimer's disease (AD), according to a new prospective study published in the June 16 issue of Neurology. However, treatment with the Alzheimer's drug donepezil (Aricept, Elsai/Pfizer) may slow the progression to dementia for those patients who exhibit symptoms of both depression and aMCI, the study found.

"Earlier reports have suggested that neurobehavioral symptoms, particularly apathy and depression, seem to accelerate the rate of progression to dementia," said lead author Po Lu, PsyD, assistant professor of neurology at the David Geffen School of Medicine, at the University of California, Los Angeles. "Our study did verify this hypothesis."

They also looked to see whether treatment, specifically donepezil, had any beneficial effects, Dr. Lu added. "While other studies show [donepezil] causes reduced behavioral symptoms in Alzheimer's disease, our study also found that donepezil did delay the progression to dementia compared with placebo and vitamin E."

More Depression, Faster Decline

Researchers followed 208 depressed patients and 548 patients without depressive symptoms, all between the ages of 55 and 91 years, for 3 years. At baseline, all patients were assessed using the Beck Depression Inventory (BDI), and stratified into depressed (with a BDI score of 10 or greater) or nondepressed (with a BDI score of less than 10).

The results indicated that every point increase in the BDI was associated with a 3% higher risk for progression to Alzheimer's disease (P = .03). The researchers also used a randomized, double-blind, parallel-group design to compare donepezil treatment (10 mg) with placebo or vitamin E (2000 IU). Their results revealed that donepezil was significantly more likely to delay dementia symptoms in those with aMCI and depression but had little effect on aMCI patients without depression.

At 1.7 years, 11% of those who had aMCI and depression who took donepezil developed Alzheimer's disease, vs 25% in the depressed group who took vitamin E or placebo (P =.023). At 2.2 years, 14% of those with aMCI and depression who took donepezil went on to develop Alzheimer's compared with 29% with aMCI and depression in the vitamin E and placebo groups (P = .025).

The proportion who progressed remained "marginally lower" with donepezil treatment even at 2.7 years, they note. Survival curves did not differ between treatment groups in the nondepressed participants.

The researchers excluded those who had been diagnosed with depression or another psychiatric disorder within the past 2 years. Other exclusion criteria included central-nervous system (CNS) infarct, infection, or taking vitamins or other supplements. Subjects were allowed to take stable doses of antidepressants prescribed up to 1 month before baseline, as long as the depression was considered part of the dementia disease process and not a sign of major clinical depression, Dr. Lu said.

The researchers noted in their paper that depression may serve as a phenotypic marker for the onset of AD as well as a favorable response to donepezil. Still, the relationship between depression and AD remains poorly understood, they noted. They hypothesized that depression may be a result of underlying CNS pathology. "As Alzheimer's disease spreads, it may also be responsible for the symptoms of depression," Dr. Lu said.

While aMCI patients are a heterogeneous group, it may be helpful for clinicians to target those with depression for treatment with donepezil. "That may delay the onset of dementia and provide a longer quality of life," Dr. Lu said.

"Assertive" Management of Depression

"The significance of this study, with its prospective design, is that it provides further evidence in support of the correlation between depression and dementia," said Angela Scicutella, MD, PhD, associate professor of psychiatry and behavioral sciences at Albert Einstein College of Medicine, in the Bronx, NY.

"The study emphasizes the need for clinicians to be more assertive in addressing late-life depression symptoms, since these mood symptoms are often accompanied by cognitive deficits," Dr. Scicutella added.

Treating patients with depression and aMCI early in the disease process with donepezil could possibly delay the progression to Alzheimer's, she emphasized. "It would be an important therapeutic intervention for patients and their families," Dr. Scicutella said.

The study also raises the intriguing question of whether using donepezil in elderly patients who are depressed — but do not meet the formal diagnostic criteria for aMCI — might help slow the progression to Alzheimer's disease, she added.

Dr. Lu and Dr. Scicutella disclosed no relevant financial relationships. The study was supported by the National Institute on Aging, the Alzheimer's Association, the Alzheimer's Disease Cooperative Study grant, the Alzheimer's Disease Research Center, Jim Easton, and the Sidell Kagan Foundation.

Neurology 2009;72:2115-2121.

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