預測老年人失智的新風險指標


  May 25, 2009 — 一項可能改善未來病患選擇的介入性研究顯示,包括傳統與全新確認之失智危險因子的15分新指標,在預測老年失智症的準確度達81%。
  
  來自於舊金山加州大學Deborah E. Barnes博士及其同事們於5月13日神經學線上期刊的文獻中描述了一項晚年失智風險指標。
  
  研究團隊針對3,375位受試者(平均年齡為76歲)測試這項新的指標,這些病患都收納在心血管健康認知研究中,其中59%為女性、15%為非裔美人,所有受試者在參與研究前都沒有失智症。
  
  該指標包括高齡、認知功能測試表現不佳、身體質量指數、有一個以上的脂蛋白原E4對偶基因、腦部核磁共振造影(MRI)顯示有白質疾病、腦部MRI顯示腦室變大、超音波顯示內頸動脈變厚、有繞道手術病史、理學表現緩慢以及沒有飲酒。
  
  有14%的病患(共480位)在六年內發生失智症,其中56%受試者的分數較高(高於8分)、23%受試者分數中等(4~7分)、4%受試者分數較低(0~3分)。
  
  Barn醫師向Medscape精神醫學表示,該指標必須在不同試驗族群中確效,而其中許多危險因子在過去的一些失智症研究中已經確認過,因此並不令人意外。
  
  Barnes醫師表示,我們假設該指標將包括許多心血管危險因子,例如高血壓、糖尿病,但最終將不像腦部MRI或低認知功能分數那樣直接反映預測能力,而是比較可能直接反映失智症對腦部的影響力。
  
  【常規使用過於昂貴?】
  馬里蘭巴爾的摩約翰霍普金斯灣景醫學中心的Constantine Lyketsos醫師向Medscape精神學表示,該指標對於研究者們來說是非常有用的,如果這經過確效,將可用於臨床試驗中,把失智風險作為研究變項。
  
  記憶與阿茲海默氏症治療中心主任、老年精神學與神經精神學部門主任Lyketsos醫師表示,這在臨床上將是有用的,一項指標必須包括可廣泛獲得且不會過於昂貴的變項。
  
  他附帶表示,包含指標的許多評量,例如迷你精神狀態檢驗修改版,測試整體認知功能、Digit字母加減測試、頸動脈都卜勒超音波來評估血管內層厚度、以及特定型式的MRI定量法,都不是一般常用的量測方法。
  
  Lyketsos醫師表示,對一般大眾來說,這將會是一系列昂貴的檢驗,估計要數千美元,而我們目前對於高分病患並沒有特定的介入措施。
  
  Lyketsos醫師將臨床醫師的注意力引導到一項有趣的發現─沒有飲酒是失智的危險因子之一。他指出,人們將飲酒視為對認知功能有損害,但大部分的數據顯示,低至中度的飲酒確實是有幫助的。
  
  【收納非裔美人增強研究強度】
  紐約州立大學雪城醫學院分校老年醫學部門主任Sharon A. Brangman醫師表示,這項研究的一個重點是其中收納了15%的非裔美人。
  
  Brangman醫師表示,有鑑於老年族群的種族及民俗差異性,以及非裔美人與拉丁美裔族群的阿茲海默氏症高比例(可能與這些族群的糖尿病與高血壓比例較高有關),我們需要涵蓋這些族群與其他族群的數據。Brangman醫師認為,這篇文獻中收納的15%非裔美人比其他研究好。
  
  Brangman醫師指出,臨床上,這個指標可能協助長期計畫的家人們以及希望早期治療的醫師們。但是,當我面對判斷一個沒有治癒方法的末期疾病時,我總是潸然淚下。當我們預測一個不一定發生的末期疾病時,是否曾加了情緒負擔。當我們以臨床風險指標評估,如果我們無法提供治癒的方法,那其中的倫理考量於何?
  
  我認為我們風險指標是很重要的,這提升了我們對於疾病進程的瞭解,特別是在早期時,可以協助我們進一步瞭解這個疾病,最終找出有益的治療方法。
  
  巴西里約熱內盧Psiquiatria機構阿茲海默氏症中心的Jerson Laks醫師表示,這個指標最終對於研究與臨床將會是有益的。然而,他也提醒,這應該被證明具有高敏感度與專一性,以在錯誤率很低的情況下預測失智症的預後。
  
  研究者們目前正在尋找發展出臨床用途更好且變項較少的指標。
  
  這項研究由國家心臟、肺臟與血液機構;國家老化機構;國家神經及並與中風機構;國家衛生研究院贊助。研究者們表示沒有相關資金上的往來。
  

New Risk Index Predicts Dementia in Elderly

By Janis Kelly
Medscape Medical News

May 25, 2009 — A new 15-point index that includes both conventional and newly identified dementia risk factors was 81% accurate at identifying older adults who would subsequently develop dementia — a finding that may improve patient selection for future intervention studies.

Deborah E. Barnes, PhD, MPH, from the University of California, San Francisco, and colleagues describe the late-life dementia risk index in a study published online May 13 in Neurology.

The researchers tested the new scale in 3375 participants (mean age, 76 years) in the Cardiovascular Health Cognition Study. Fifty-nine percent were women and 15% were African American. None had dementia at baseline.

The index items include older age, poor cognitive test performance, body mass index, ?1 apolipoprotein E4 alleles, white matter disease on cerebral magnetic resonance imaging (MRI), ventricular enlargement on cerebral MRI, internal carotid artery thickening on ultrasound, history of bypass surgery, slow physical performance, and lack of alcohol consumption.

Fourteen percent of the patients (n?= 480) developed dementia within 6 years of baseline. This included 56% of subjects with high scores (8 or more points), 23% of subjects with moderate scores (4 to 7 points), and 4% of subjects with low scores (0 to 3 points).

Dr. Barnes told Medscape Psychiatry that the index needs to be validated in different study populations but that most of the risk factors had been identified in previous dementia studies, so there were no true surprises.

"We had hypothesized that the index would include a combination of cardiovascular risk factors, such as hypertension and diabetes, but these turned out to not be as predictive as variables such as brain MRI findings or low cognitive test scores, which are likely to be markers that directly reflect the impact of dementia on the brain," Dr. Barnes said.

Too Expensive for Routine Use?

Constantine Lyketsos, MD, from Johns Hopkins Bayview Medical Center, Baltimore, Maryland, told Medscape Psychiatry that the index is likely to be very helpful for researchers. "If validated, this will enable us to use dementia risk as a research variable in clinical trials," he said.

Dr. Lyketsos, who is also codirector of the Division of Geriatric Psychiatry and Neuropsychiatry and director of the Memory and Alzheimer's Treatment Center, noted that to be clinically useful, an index must include variables that are widely available and not too expensive.

He added that several measures included in the index, such as the Modified Mini-Mental State Exam measure of global cognitive function, the Digit Symbol Substitution Test, carotid Doppler ultrasound to measure intima medial thickness, and the particular type of MRI quantification used, are not routine tests.

"This would be an expensive package of tests for the average person, amounting to thousands of dollars," Dr. Lyketsos said, "particularly as we do not yet have an intervention that we would use for someone with a high-risk score."

Dr. Lyketsos called clinicians' attention to 1 interesting finding — that lack of alcohol consumption is a risk factor for dementia. "People think of alcohol as damaging to cognition, but most data show that low to moderate alcohol consumption actually helps you," he said.

Inclusion of African Americans a Strength

Sharon A. Brangman, MD, who heads the Geriatrics Division at SUNY Upstate Medical University in Syracuse, New York, noted that 1 strong point of this study is 15% of the subjects were African American.

"Given the increasing racial/cultural diversity of the geriatric population, and the higher rates of Alzheimer's disease that are documented in African American and Latino populations (maybe due to the high rates of diabetes and hypertension in these groups), we need to have data that includes these groups and others. I think 15% African American inclusion in this paper is better than most studies," Dr. Brangman said.

Clinically, Dr. Brangman said that this index might help families with long-term planning and physicians in starting therapy early.

"But I am always torn when faced with the dilemma of identifying a terminal condition for which there is no cure," Dr. Brangman said. "Do we increase the emotional burden when we predict a terminal illness that may or may not occur? What are the ethical considerations when using the risk index in the clinical setting if we cannot offer a cure?

"I do think it is important that we are thinking in terms of a risk index, since increasing our understanding of the disease process, especially in its early stages, can only help in better understanding the disease and the eventual identification of beneficial therapies."

Jerson Laks, MD, director of the Alzheimer Center at the Instituto de Psiquiatria in Rio de Janeiro, Brazil, said that the index would potentially be useful in both research and clinical settings. "However, it should prove to have a high sensitivity/specificity, so that the outcome of dementia may be predicted with a low chance of mistake," he warned.

The researchers are currently seeking funding to develop a shorter index that might have greater clinical utility.

The study was supported by the National Heart, Lung and Blood Institute; the National Institute on Aging; the National Institute of Neurological Disorders and Stroke; and the National Institutes of Health. The researchers have disclosed no relevant financial relationships.

Neurology. Published online before print May 13, 2009.

    
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