作者：Susan Jeffrey 齣處：WebMD醫學新聞 　　September 25, 2009 —一篇係統性文獻迴顧指齣 第一次發生中風之前 多次發生中風比血管風險更能預測中風後失智 - 趣味新聞網

發表日期 2009-10-13T08:02:48+08:00

     本帖最後由 lsc0019 於 2009-10-15 00:15 編輯

作者：Susan Jeffrey
齣處：WebMD醫學新聞

September 25, 2009 —一篇係統性文獻迴顧指齣，第一次發生中風之前，約有10%病患有中風前失智，發生一次中風之後，有10%病患發生失智，復發中風之後，多達30%病患發生失智。

英國牛津John Radcliffe醫院的Sarah T. Pendlebury醫師與Peter Rothwell醫師，在9月24日Lancet Neurology期刊綫上版發錶的報告指齣，多次中風與中風後失智之間的強烈關聯。

Pendlebury醫師嚮Medscape Neurology錶示，中風本身以及其併發癥似乎是中風後失智病因的最主要因素。

她指齣，研究顯示，中風照護病房現在是中風治療的黃金標準，提供比一般病房照護更好的結果。我們假設，這些較佳的結果，有部份是因為透過預防低血氧與低血壓而有較好的認知結果以及較佳的復發中風預防等所緻。

【令人睏惑的文獻】
作者們寫道，雖然大緻同意中風與失智風險增加有關，但之前研究有關中風前後失智的發生率結果各有不同。

Pendlebury醫師指齣，諸多報告提齣的中風前失智比率、以及較多著墨的中風後失智比率，在不同的研究中，失智比率各異，所以，就醫師預期一個病患的中風結果時，難以得到一個清楚的結論。

在此一研究中，Pendlebury醫師與Rothwell醫師對1950至2009年5月1日間，與前述主題有關、已發錶的研究進行一個係統性迴顧，評估發錶之研究的異質性，以及確認中風前與中風後失智的可能風險因素。研究者在73篇符閤的文獻中，檢視瞭22篇醫院基礎與8篇群眾基礎的研究，共有7,511名病患。

匯整的中風前失智發生率中，醫院基礎的研究為14.4% (95%信心區間[CI]為12.0% – 16.8%)，高於群眾基礎研究的9.1% (95% CI，6.9% –11.3%)。

至於中風後失智，中風後第一年的失智發生率變化相當大。排除中風前失智之群眾基礎研究中，此比率為7.4%(95% CI，4.8% – 10.0%)，復發中風病患之醫院基礎研究中，包括中風前失智者，此比率為41.3%(95% CI，29.6% – 53.1%)。

作者們指齣，這些互異的比率中，93%可由研究設計和案例不同等因素加以解釋。他們指齣，醫院基礎的研究中，第一年之後的失智纍計發生率，每年比單就復發中風為基礎的研究預期高齣3%。

與中風前失智有強烈關聯的因素，包括內顳葉萎縮、女性、傢族失智病史。相對的，中風後失智與中風本身的特徵及併發癥有關，例如發生抽搐、低血氧、低血壓，或者，多次或多處發生病竈。

研究作者結論錶示，將研究方法與案例差異納入考量之後，估計失智發生率為：10%的病患在第一次中風之前有失智、10%在第一次中風之後發生失智、復發中風之後有三分之一以上發生失智。中風後失智與多次中風之間的強烈關聯，以及對於其他中風特徵的預後價值，強調齣中風本身不同於原本之血管風險因素的重要因果關係，因此，適當的急性中風照護與次級預防，對於降低失智發生有其效果。

【文獻的限製】
德國海德堡大學的Michael G. Hennerici醫師在迴響與反應文章中錶示，這個新發現強調瞭中風後失智與多次發生中風的關聯，而非原本的血管風險因素。

不過，他指齣，納入的研究多數是介於1970至1980年代之間，當時強調的是多發性梗塞失智的觀念，考量中風復發，而非探究中風前和中風後失智的發生機轉有何不同(例如，皮質-皮質下網絡之病患、失連接癥候群、或重疊性皮質退化)。因此，作者們當年的詮釋在今日受到質疑。

Hennerici醫師寫道，整體而言，目前的這篇文獻顯示，在確認老年人的失智和失能最重要的治療性機轉方麵，現有的資料有限。

中風不是同質性疾病，因為年長者有多種病癥，需使用新技術進行設計良好的前瞻性試驗來加以錶達中風病因與部位上的差異。Hennerici醫師寫道，一個可以提供部份解答的此類研究是「Leukoaraiosis and Disability Study」，他也是其中一名研究成員。該研究分析原本納入試驗時沒有失智者，其年紀相關的白質變化與轉為失智的關聯。

發生失智的90名病患中，僅13人有新發生的中風；其他37名病患有偶發中風但是沒有發生失智(BMJ. 2009;339:b2477)。

Hennerici醫師結論錶示，此發現支持這個明確的見解，因此，有可能加以治療的、纍積的基本機轉(即白質變化與高血壓)，而非中風對中風後失智的影響。係統性治療高血壓代錶的是對老化者之中風和失智的最佳預防策略。

Pendlebury醫師接受牛津閤夥生物醫學研究中心之支持。作者們皆宣告沒有相關財務關係。Hennerici醫師宣告他是「Leukoaraiosis and Disability Study」這項研究的共同研究成員。

Lancet Neurol. 綫上發錶於2009年9月24日。

Multiple Strokes, Not Vascular Risk, Most Predictive of Poststroke Dementia

By Susan Jeffrey
Medscape Medical News

September 25, 2009 — A systematic review of the literature suggests that prestroke dementia is present in about 10% of patients before a first stroke, that 10% of patients develop dementia after a stroke, and that upward of 30% of patients develop dementia after a recurrent stroke.

Sarah T. Pendlebury, FPhil, and Peter Rothwell, FMedSci, from John Radcliffe Hospital, Oxford, United Kingdom, report a strong association between multiple strokes and poststroke dementia in an article published online September 24 in Lancet Neurology.

"It seems that the stroke itself and its complications are of paramount importance in the etiology of poststroke dementia," Dr. Pendlebury told Medscape Neurology.

Studies have shown that stroke unit care, now the gold standard for stroke treatment, provides better outcomes than general ward care, she added. "We would hypothesize that some of the better outcome is through better cognitive outcome through prevention of secondary insults such as hypoxia [and] hypotension and in better prevention of recurrent stroke."

Literature Confusing

Although there is "broad consensus" that stroke is associated with an increased risk for dementia, the results of previous studies of the prevalence of pre- and poststroke dementia have been conflicting, the authors write.

"The reported rates of prestroke, and even more for poststroke, dementia were very different between different studies, so it was very difficult to get a clear idea as a clinician as to what to expect for an individual patient with a stroke in terms of their outcome," Dr. Pendlebury added.

In this study, Dr. Pendlebury and Dr. Rothwell conducted a systematic review of studies on the subject published between 1950 and May 1, 2009, both to assess the heterogeneity of the published studies and to identify possible risk factors for pre- and poststroke dementia. The researchers identified 22 hospital-based and 8 population-based studies including 7511 patients in 73 eligible articles.

The pooled prevalence of prestroke dementia was higher in hospital-based studies, at 14.4% (95% confidence interval [CI], 12.0% – 16.8%), than in population-based studies, where it was 9.1% (95% CI, 6.9% – 11.3%).

For poststroke dementia, the incidence of dementia in the first year after a stroke was highly variable but ranged from 7.4% in population-based studies where prestroke dementia was excluded (95% CI, 4.8% – 10.0%) to 41.3% in hospital-based studies of patients with recurrent stroke that included those with prestroke dementia (95% CI, 29.6% – 53.1%).

Of the variance in these rates, 93% could be explained by differences in factors such as study setting and case mix, the authors note. The cumulative incidence of dementia after the first year was about 3% per year higher in hospital-based studies than would be expected on the basis of recurrent stroke alone, they add.

Factors strongly associated with prestroke dementia included medial temporal lobe atrophy, female sex, and a family history of dementia. Poststroke dementia, in contrast, was associated with characteristics and complications of the stroke itself, such the occurrence of seizures, hypoxia, or hypotension, for example, or the presence of multiple lesions in time and place, they write.

"After study methods and case mix are taken into account, reported estimates of the prevalence of dementia are consistent: 10% of patients had dementia before first stroke, 10% developed new dementia soon after first stroke, and more than a third had dementia after recurrent stroke," the authors conclude. "The strong association of post-stroke dementia with multiple strokes and the prognostic value of other stroke characteristics highlight the central causal role of stroke itself as opposed to the underlying vascular risk factors and, thus, the likely effect of optimum acute stroke care and secondary prevention in reducing the burden of dementia."

Limitations of the Literature

In an accompanying Reflection and Reaction article, Michael G. Hennerici, MD, from the University of Heidelberg, Germany, says the new findings "strengthen the association of post-stroke dementia with multiple strokes rather than with underlying vascular risk factors."

However, he notes, "most of the studies included were from the 1970s and 1980s when the emphasis was on concept of multi-infarct dementia and counting stroke recurrences rather than on investigation of distinct mechanisms in the development of pre-stroke and post-stroke dementia (eg, lesions in cortico-subcortical networks, disconnection syndromes, or overlapping cortical degeneration. Therefore, the authors' interpretation of the findings could be questioned nowadays."

"Above all," Dr. Hennerici writes, the current article, "shows the limitations of the available data to identify the most important, and possibly treatable active mechanisms of dementia and disability in elderly patients."

Stroke is not a homogeneous disease, and because the elderly have multimorbidity, the variability in stroke etiology and topography must be addressed in well-designed prospective trials using new technologies. One such trial already providing some of these answers, Dr. Hennerici writes, is the Leukoaraiosis and Disability Study, on which he is a coinvestigator. This study assesses the role of age-related white matter changes and conversion to dementia in patients free of dementia at entry.

Of 90 patients who developed dementia, only 13 had a new stroke; the other 37 patients who had incident stroke did not develop dementia (BMJ. 2009;339:b2477).

"This finding lends support to the notion of distinct, and hence potentially treatable, cumulative basic mechanisms (ie, white matter changes and hypertension) rather than to stroke in general for post-stroke dementia," Dr. Hennerici concludes. "Systematic treatment of hypertension represents the best available preventive strategy for both stroke and dementia in ageing people."

Dr. Pendlebury is supported by the Oxford Partnership Biomedical Research Center. The authors have disclosed no relevant financial relationships. Dr. Hennerici has disclosed that he was a co investigator on the Leukoaraiosis and Disability Study.

Lancet Neurol. Published online September 24, 2009.

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