血漿乙型澱粉樣蛋白值變化可以預測晚年的認知衰退

作者：Caroline Cassels  
出處：WebMD醫學新聞

　　October 15, 2009 — 新研究認為，中年時，乙型澱粉樣蛋白胜肽(Aβ)40和42的比值，可以視為晚年認知衰退的預測因子。
　　
　　麻州波士頓布萊根婦女醫院研究者進行的一篇大型社區基礎研究顯示，中壯年時血漿Aβ40和Aβ42的比值高，且此一比值在後來10多年繼續增加者，與晚年的認知功能衰退顯著有關。
　　
　　主要研究者Olivia Okereke醫師在聲明中表示，藉由可預測後來認知衰退的早期可測量型風險標記，我們希望有一天可以利用這些血液生化標記，在發生認知衰退之前幾年就找出那些有風險的人。
　　
　　Okereke醫師指出，這對於失智預防和早期介入來說，邁出重要的一步。
　　
　　這項研究登載於10月12日出版的神經醫學誌。
　　
　　【憂鬱傾向】
　　研究對象是「Nurses' Health Study」這項研究中的481名健康參與者，研究者檢測中壯年研究對象(平均年紀63.6歲)的血漿中Aβ40和Aβ42值，且在10年後(平均年紀74.6歲)再度檢測。第一次抽血之後將近10年時，這些女性以大約2年的間隔接受認知檢測3次。
　　
　　檢測包括認知狀態的電話訪視，以瞭解一般認知情況，以及使用東波士頓記憶檢測(East Boston Memory Test)進行立即性和延遲性回憶試驗。該研究的主要結果是一般認知以及言語記憶。研究者指出，言語記憶特別是最終發生阿茲海默氏症的強力預測因子。
　　
　　這些研究對象的健康與生活型態特徵都相似。中年時，根據Aβ40和Aβ42的比值將這些研究對象分四組。研究者報告指出，整體而言，各組的特徵相似。不過，他們指出，當Aβ40和Aβ42的比值增加時，憂鬱的盛行率也有增加趨勢。
　　
　　此外，Aβ40和Aβ42比值最低的婦女，心臟病和有抽菸習慣的盛行率較低，她們也被認為有較高的體能活力。
　　
　　【價值在於及早確認】
　　校正多種干擾因素之後，中年時的血漿Aβ40和Aβ42的比值，與晚年時整體認知顯著惡化有關，若單以血漿Aβ42值來看則無關。
　　
　　同樣的，若Aβ40 和Aβ42的比值從中年到老年時隨著時間增加，則晚年時的認知衰退率更快，若單以血漿Aβ42值來看則無關。
　　
　　根據研究者表示，這是首次以大型研究檢視中年血漿Aβ值及其隨時間之變化與預測認知衰退的能力。因此，我們的研究發現有獨特貢獻。
　　
　　根據作者指出，此研究的好處顯而易見：中年Aβ40和Aβ42的比值可預測晚年時的認知衰退，此比值之價值在於及早辨識那些認知功能不佳風險較高的人。
　　
　　不過，他們指出，需要以其他大型縱向研究來確認這些發現。
　　
　　作者們皆宣告沒有相關財務關係。

Changes in Plasma Beta Amyloid Levels May Predict Late-Life Cognitive Decline

By Caroline Cassels
Medscape Medical News

October 15, 2009 — A high ratio of beta amyloid peptides (Aβ) 40 and 42 in midlife may be a predictor of future cognitive decline in late life, new research suggests.

A large community-based study conducted by researchers at Brigham and Women's Hospital, Boston, Massachusetts, shows that individuals with higher plasma Aβ 40:42 ratios in late midlife and then increases in these ratios 10 years later were significantly associated with greater decline in cognitive function in later life.

"By showing that there are earlier measurable risk markers of future cognitive decline, we have hope in the possibility of someday using blood biomarkers to find people at risk years before cognitive decline becomes apparent," principal investigator Olivia Okereke, MD, said in a statement.

"This is an important step in the effort to prevent and to provide early intervention against dementia," Dr. Okereke added.

The study is published in the October 12 issue of the Archives of Neurology.

Trend Toward Depression

Using 481 health participants from the Nurses' Health Study, investigators measured plasma Aβ40 and Aβ42 levels in late midlife (mean age, 63.6 years) and again 10 years later (mean age, 74.6 years). Approximately 10 years after the initial blood draw, women underwent cognitive testing 3 times at approximately 2-year intervals.

Testing included the Telephone Interview for Cognitive Status to test general cognition, as well as immediate- and delayed-recall trials for the East Boston Memory Test.

General cognition and verbal memory were the study's primary outcomes. The researchers note that verbal memory in particular is a strong predictor of eventual Alzheimer's disease.

Health and lifestyle characteristics of the subjects were similar. At midlife, participants were divided into quartiles according to ratios of Aβ40 to Aβ42. Overall, the investigators report, the characteristics were similar across quartiles. However, they note, there was a trend toward increased prevalence of depression with increasing Aβ40 and Aβ42 ratios.

In addition, women with the lowest Aβ40 to Aβ42 ratios tended to have a lower prevalence of heart disease and current smoking, and there was a suggestion that they also had higher levels of physical activity.

Value Lies in Early Identification

After adjustment for multiple confounders, midlife plasma Aβ40 to Aβ42 ratios, but not Aβ42 plasma levels alone, were associated with significantly worse late-life decline in global cognition.

Similarly, over time, a greater increase in Aβ40 and Aβ42 ratios, but not in Aβ42 levels alone, from midlife to late life predicted a significantly faster rate of cognitive decline.

According to investigators, this is the first large-scale study to examine the ability of midlife plasma Aβ levels and change in plasma Aβ levels over time to predict cognitive decline."Therefore, our findings contribute uniquely to the literature," they write.

According to the authors, the benefits of this research are clear: "Midlife Aβ40 to Aβ42 ratios alone predicted late-life cognitive decline, which suggests that this ratio may prove valuable for early identification of those at high risk of cognitive impairments," they write.

However, they add, these findings need to be confirmed by other large-scale longitudinal studies.

The authors have disclosed no relevant financial relationships.

Arch Neurol. 2009;66:1247–1253.