Scientists studying Alzheimer’s disease are increasingly finding clues that the brain begins to deteriorate years before a person shows symptoms of dementia.
研究阿茲海默症的科學家發現有越來越多的證據顯示，早在一個人出現癡呆徵兆的多年之前，他的大腦即已開始退化。

Research on a large extended family of 5,000 people in Colombia with a genetically driven form of Alzheimer’s has found evidence that the precursors of the disease begin even earlier than previously thought.
科學家以哥倫比亞一個許多成員有遺傳型老年癡呆症的5000口大家族為研究對象，蒐集的證據顯示，阿茲海默症的早期徵兆出現得比醫學界此前認為的還要早。

The studies, published this month in the journal Lancet Neurology, found that the brains of people destined to develop Alzheimer’s clearly show changes at least 20 years before they have any cognitive impairment. In the Colombian family, researchers saw these changes in people ages 18 to 26; on average, members of this family develop symptoms of mild cognitive impairment at 45 and of dementia at 53.
發表在11月號《刺胳針神經學》期刊的研究報告指出，註定罹患阿茲海默症者在認知能力受到任何損傷之前的至少20年，大腦即已出現明顯的變化。以這個哥倫比亞家族而言，研究人員在18到26歲之間的年輕成員身上觀察到這些變化。平均而言，這個家族的成員45歲出現輕微的認知損傷症狀，53歲則出現癡呆症狀。

These brain changes occur earlier than the first signs of plaques made from a protein called beta amyloid or a-beta, a hallmark of Alzheimer’s. Researchers detected higher-than-normal levels of amyloid in the spinal fluid of these young adults. They found suggestions that memory-encoding parts of the brain were already working harder than in normal brains. And they identified indications that brain areas known to be affected by Alzheimer’s may be smaller than in those who do not have the Alzheimer’s gene.
乙型澱粉樣蛋白（或稱a-beta）是阿茲海默症的特徵。大腦的變化比這種蛋白形成的類澱粉斑更早出現。研究人員在這些年輕成人的脊髓液中測得的澱粉濃度高於正常值。他們發現，大腦負責把記憶譯為密碼的部位此時工作起來已經比正常大腦吃力。他們還發現，大腦受阿茲海默症影響的部位可能比無阿茲海默基因者小。

“This is one of the most important pieces of direct evidence that individual persons have the disease and all the pathology many years before,” said Dr. Kaj Blennow, a professor in clinical neurochemistry at the University of Gothenburg in Sweden, who was not involved in the research.
並未參與這項研究的瑞典哥特堡大學神經化學教授布蘭諾說：「這是顯示部分個人會罹患阿茲海默症，同時多年前便出現全部病變的最重要直接證據之一。」

Dr. Nick Fox, a neurologist at University College London, who was also not part of the research, said the findings suggested that “some of the things that we thought were more downstream may not be quite so downstream; they may be happening earlier.”
同樣並未參與前述研究的倫敦大學學院神經學專家福克斯表示，這項發現意味，「我們以前所認為一些比較下游的問題可能不是那麼下游，可能發生得更早」。

That, in turn, said Dr. Fox, who wrote a commentary about the findings in Lancet Neurology, could have implications for when and how to treat people, because “there may be targets to attack, whether it’s high levels of a-beta or whatever, when people are still functioning very well.”
福克斯曾經為文評論《刺胳針神經學》刊登的這分報告。他表示，這可能對治療的時機及方法具有意義，因為「無論它是高濃度的a-beta或其他東西，當人們認知功能還很好時，可能就已有必須鎖定攻擊的目標」。

The Colombian family suffers from a rare form of Alzheimer’s that is caused by a genetic mutation; it strikes about a third of its members in midlife.
這個哥倫比亞家族遺傳的阿茲海默症非常罕見。它因基因突變而起，影響整個家族約1/3的中年成員。

Because the family is so large and researchers can identify who will get the disease, studying the family provides an unusual opportunity to learn about Alzheimer’s causes and pathology.
由於這個家族枝繁葉茂，研究人員得以找出最終將患病的成員，使他們有機會深入探索阿茲海默症的肇因與病理。

Researchers, led by Dr. Eric Reiman of the Banner Alzheimer’s Institute in Phoenix, Arizona, and in Colombia by Dr. Francisco Lopera, a neurologist at the University of Antioquia, recently received a grant from the National Institutes of Health to conduct a clinical trial to test a drug on family members before they develop symptoms, to see if early brain changes can be halted or slowed.
亞利桑納州鳳凰城班納阿茲海默症研究所的芮曼，以及哥倫比亞安迪奧基亞大學的神經學專家羅培拉共同主持這項研究。研究團隊最近獲得馬里蘭州美國國立衛生研究院補助，準備對尚未出現症狀的該家族成員進行臨床藥物實驗，以研判能否遏止或減緩早期腦部變化。

The studies in Lancet Neurology used several tests, including spinal taps, brain imaging and functional magnetic resonance imaging.
《刺胳針神經學》的研究採用了數種檢測方法，包括抽骨髓、腦部造影，以及功能磁振造影。

“The prevailing theory has been that development of Alzheimer’s disease begins with the progressive accumulation of amyloid in the brain,” Dr. Reiman said. “This study suggests there are changes that are occurring before amyloid deposition.”
芮曼博士說：「最主要的理論一直認為，如果大腦不斷累積澱粉，就會引發阿茲海默症。這項研究顯示，在澱粉累積之前，一些變化已經開始出現。」

One possibility is that brain areas are already impaired.
一種可能是，大腦的某些部位已經受損。

Another possibility, experts said, is that these brain differences may go back to the young developing brain.
專家說，另一種可能是，這些腦部的差異也許可以追溯到大腦還在成長、發育的時期。

“It is a genetic disease, and it’s not hard to imagine that your gene results in some differences in the way your brain is formed,” said Dr. Adam Fleisher, director of brain imaging at the Banner Institute and an author of the studies.
這篇報告的撰寫人之一，班納阿茲海默症研究所腦部造影部門主管傅雷瑟說：「這是一種遺傳性疾病。不難想像，基因會使大腦的形成過程出現一些差異。」

In one of the Lancet Neurology studies, researchers examined 44 relatives between ages 18 to 26. Twenty had the mutation that causes Alzheimer’s. The cerebrospinal fluid of those with the mutation contained more amyloid than that of relatives without it. This was striking because researchers know that when people develop amyloid plaques levels in their spinal fluid are lower than normal. That is believed to be because the fluid form of amyloid gets absorbed into the plaque form, Dr. Reiman said.
在《刺胳針神經學》刊登的一項研究中，研究人員檢查44名18到26歲之間的親屬。其中20人的大腦出現足以引發阿茲海默症的突變。他們的腦脊髓液澱粉濃度高過無突變的其他親屬。這令人相當驚訝，因為研究人員原本已知，如果某人的腦部出現澱粉斑，腦脊髓液的澱粉濃度會低於正常。芮曼表示，這可能是因為液狀的澱粉會被吸收，最後成為斑狀。

The researchers are analyzing data from family members ages 7 to 17 to see if some of the brain changes occur at an even younger age.
研究人員正在分析該家族7至17歲成員的資料，以確定部分腦部變化是否出現得更早。

“Some people think that that may be scary, that you can see it so many years before,” Dr. Reiman said. “But it seems to me that that provides potential opportunities for the development of future therapies.”
芮曼說：「有些人認為，早這麼多年看到這些徵兆可能有點嚇人。不過我認為，這可以為未來開發治療方法提供潛在的機會。」

原文參照：
http://www.nytimes.com/2012/11/13/health/alzheimers-precursors-founds-at-earlier-age.html

Video: Fear Grips a Family
http://nyti.ms/RTMKZ4  

Interactive Multimedia:
http://www.nytimes.com/interactive/2010/06/02/health/te_alzheimers.html

2012-11-27聯合報/G5版/UNITEDDAILYNEWS 陳世欽譯 原文參見紐時週報十版右