作者：Susan Jeffrey
出處：WebMD醫學新聞
February 10, 2010 — 一項新研究發現年齡大於70歲的男性，當他的Trail Making Test B表現不佳，一種反應出亞皮質前額活性或是執行功能受損的認知測試，與未來發生中風風險有關。
第一作者、瑞典Uppsala大學的Bernice Wiberg醫師與研究者們的結論是，我們的研究結果顯示，腦部梗塞風險在較輕微認知功能異常亞臨床期已經增加，這可能是一個未被察覺之大腦血管損傷的指標。
資深作者、同樣來自Uppsala大學的Johan Sundstrom醫師向Medscape神經學表示，這些研究結果也顯示，Trail Making Test B可能是診間一個有用的篩檢工具，這是一個簡易、限時的紙筆測試，受試者被要求以1-A-2-B模式將點與點之間相連。
Sundstrom醫師表示，這是項觀察性研究，所以我們無法探討因果關係，但是我們確實想要盡可能早點找出處於中風風險的人們，這項測試是簡單且便宜的，甚至比心電圖或膽固醇濃度便宜，因此非常容易使用，雖然這仍需要更多的研究。
他們的報告發表在2月2日的神經學期刊。
【血管風險】
研究作者們寫到，腦血管危險因子和生物老化已經被證實與白質病灶、無症狀（寧靜）大腦梗塞及臨床中風有關。許多研究證實這些亞臨床變化會影響認知功能，以及執行功能異常反映出亞皮質前額途徑病灶，而不是記憶缺損，該特徵主要出現在初期血管認知功能受損。
他們表示，部分但非所有研究顯示那些臨床認知功能受損病患的中風風險增加。研究作者們寫到，更進一步地看變化與認知功能之間的關聯，去激勵特別是希望能針對高風險人們採取預防性治療。
Sundstrom醫師指出，阿茲海默氏症與血管性失智已經被證實有共同的危險因子。某些人想這是一體兩面。他表示，阿茲海默氏症主要是一種小動脈疾病，而血管性失智是一種大動脈疾病。
他解釋，我們試著想，因為認知功能與失智並非立刻伴隨著中風，或是顯著的血管疾病可能仍然是一種動脈疾病，認知功能檢測可能真的被視為小血管功能的一個敏感性測試。
為了發現這之間的關聯性，他們以一個稱為Uppsala的成人男性縱向研究，這是個群眾為基礎的世代研究，針對亞皮質前額功能的測試表現、迷你精神狀態檢驗（MMSE）、Trail Making Test A與B以及之後致命或非致命中風或短暫性缺血性事件（TIAs）還有不同形式中風發生率。
這個樣本包括930位男性，受試者在分析前都已經超過70歲，且從50歲後就接受後續追蹤。他們過去都沒有中風或是TIA，且當時都接受三種認知功能測試。
在13年的後續追蹤中，166位男性發生中風或是TIA，其中105位是缺血性中風。
Sundstrom醫師表示，基本上我們發現的是一些支持我們假說的證據。在這三項認知功能測試中，Trail Making Test B與中風風險最為相關。
在校正教育、社會經濟團體、以及傳統危險因子，Trail Making Test B完成時間每增加一個標準差與腦部梗塞風險增加有關，且那些該測試表現處於最低四分位數的人們，風險增加超過3倍。
表格 中風風險與Trail Making Test B表現的關係
試驗終點 | 危險比值（ 95% 信賴區間） |
Trail Making Test B 時間每增加一個標準差
| 1.48 (1.11 – 1.97) |
Trail Making Test B表現與整體中風預後或出血性中風風險之間沒有關係。Trail Making Test A測試表現或MMSE以及任何中風預後之間是沒有關係的。
Sundstrom醫師指出，這之間的差異可能取決於這些認知功能測試所評量的特定面向。舉例來說，MMSE，是補捉臨床失憶一個很好的測試。
他附帶表示，我認為在我們的試驗族群中，MMSE並非中風一個很強之預測因子的解釋，是因為我們的受試者們相當健康且MMSE分數相當高。這可能是Trail Making Test B在我們這個高認知功能範圍中是最敏感的量測工具。如果針對認知功能較差的人們，MMSE可能是更好的工具。
Sundstrom醫師附帶表示，我們有很多認知功能測試，在確認中風風險上，仍然需要找出哪一個可能是最好的。除此之外，可能還有除了中風之外的其他風險，例如死亡風險或是心肌梗塞，可能也可以透過認知功能測試來找出。
這項研究由Uppsala大學醫學教職員經費、STROKE- Riksforbundet、瑞典研究局、瑞典心臟肺臟基金會、老年基金會、Uppsala對抗心臟與肺臟疾病基金會贊助。Sundstrom醫師擔任Itrim的科學顧問團。其他作者們的資金往來列於原始文章中。
Impaired Executive Function Linked With Subsequent Stroke
By Susan Jeffrey
Medscape Medical News
February 10, 2010 — A new study finds that among men older than 70 years, poor performance on the Trail Making Test B, a cognitive test that reflects impaired subcorticofrontal activity or executive function, is associated with future stroke risk.
"Our results indicate that the risk of brain infarction is increased already in the subclinical phase of milder cognitive dysfunction, which may be an indicator of unrecognized cerebrovascular injury," the researchers, with first author Bernice Wiberg, MD, from Uppsala University, Sweden, conclude.
The results also suggest that the Trail Making Test B, a simple, timed pencil-and-paper test in which subjects are asked to connect dots in a 1-A-2-B pattern, may be a useful screening tool in the clinic, senior author Johan Sundstrom, MD, also from Uppsala University, told Medscape Neurology.
"It's an observational study, so we can't talk about causality, but we do want to identify people as early as possible who are at risk for stroke, and this test is easy and cheap, even cheaper than an ECG [electrocardiogram] or cholesterol level, so that should make it very accessible," Dr. Sundstrom noted, although more study is needed.
Their report is published in the February 2 issue of Neurology.
Vascular Risk
Cerebrovascular risk factors and biologic aging have been associated with white matter lesions and silent cerebral infarctions, as well as clinical stroke, the study authors write. Several lines of research have suggested that these subclinical changes can affect cognitive function and that it is executive dysfunction, reflecting lesions in subcorticofrontal pathways, rather than memory deficits, that features prominently in early vascular cognitive impairment.
Some but not all studies have suggested increased stroke risk among those with clinically impaired cognitive function, they note. This more detailed look at the connection between changes and cognitive function, the researchers write, "is motivated especially with the purpose to find persons at high risk in the hopeful view of preventive treatment."
Dr. Sundstrom pointed out that Alzheimer's disease and vascular dementia have been shown to share some risk factors. "Some people think they are perhaps 2 sides of the same coin," he said, with Alzheimer's primarily a disease of small arteries and vascular dementia a disease of the large arteries.
"We have come to think that because cognitive function and dementia that isn't really preceded by a stroke or overt vascular disease may still be a disease of the arteries, that cognitive function tests may actually be viewed as sensitive tests of function in the small arteries," he explained.
To find out, they looked at the relationship between performance on tests that specifically looked at subcorticofrontal function, the Mini-Mental State Examination (MMSE) and the Trail Making Tests A and B, and subsequent incidence of fatal or nonfatal stroke or transient ischemic attacks (TIAs) and stroke subtypes, using a population-based cohort called the Uppsala Longitudinal Study of Adult Men.
This sample of 930 men, who were all 70 years old at baseline for this analysis, has been followed up since they were 50 years of age. All were free of previous stroke or TIA, and all underwent testing using the 3 cognitive tests at that time.
During 13 years of follow-up, 166 men had a stroke or TIA, 105 of these with ischemic strokes.
"Basically what we found was somewhat supportive of our hypothesis," Dr. Sundstrom said. "Of the 3 cognitive function tests, the Trail Making Test B captured stroke risk."
After adjustment for education, social group, and traditional cardiovascular risk factors, each standard deviation increase in the Trail Making Test B completion time was associated with an increased risk for brain infarction, and those in the lowest quartile for performance on this test had a more than 3-fold increased risk.
Table. Stroke Risk Associated With Performance on Trail Making Test B
| Endpoint | Hazard Ratio (95% Confidence Interval) |
| 1-SD increase in Trail Making Test B time | 1.48 (1.11 – 1.97) |
?
There was no relationship between Trail Making Test B performance and stroke outcomes overall or with hemorrhagic stroke risk. No relationship was seen between performance on the Trail Making Test A test or the MMSE and any stroke outcome.
The difference may lie in the specific aspects of cognition these tests are measuring, Dr. Sundstrom said. The MMSE, for example, is a good test for capturing clinical dementia.
"I would say that the explanation that we had that the MMSE was not really a strong predictor of stroke in our cohort was that the participants were pretty healthy and had pretty high scores on the MMSE," he added. "It's just possible that the Trail Making Test B was a more sensitive measure in this high cognitive function range that we had in our cohort. It's possible the MMSE might have been better if you had people with a lower cognitive function to start with."
There are numerous cognitive function tests, he added, and it remains to be determined which might be the best at identifying stroke risk, Dr. Sundstrom added. Further, there may be other risks besides stroke, such as mortality risk or risk for myocardial infarction, that might also be identified using tests of cognitive function.
The study was supported by grants from the Medical Faculty at Uppsala University, STROKE-Riksforbundet, the Swedish Research Council, the Swedish Heart Lung Foundation, the Geriatric Fund, and Uppsala Association against Heart and Lung Disease. Dr. Sundstrom serves on a scientific advisory board for Itrim. Financial disclosures for the coauthors appear in the original article.
Neurology. 2010;74:379-385.
