中風不是同質性疾病，因為年長者有多種病症，需使用新技術進行設計良好的前瞻性試驗來加以表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。
Pendlebury醫師接受牛津合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. 線上發表於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.
