Unexpectedly low prevalence of intracerebral hemorrhages in sporadic cerebral amyloid angiopathy - An autopsy study
Unexpectedly low prevalence of intracerebral hemorrhages in sporadic cerebral amyloid angiopathy - An autopsy study
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DOI：
10.1007/s00415-008-0674-4
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发表时间：
2008-01-01
影响因子：
6
通讯作者：
Jellinger, Kurt A.
中科院分区：
文献类型：
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作者：
Attems, Johannes;Lauda, Florian;Jellinger, Kurt A.
在一项对2060例老年受试者（平均年龄78.5 ± 6.8 SD岁）的连续尸检系列的回顾性研究中，在73.2%和98.5%的尸检证实的典型（斑块和缠结）阿尔茨海默病（AD）病例中检测到不同程度的散发性脑淀粉样血管病（CAA）。自发性（非创伤性）脑内出血（ICH）（不包括微出血）见于5.6%的总队列和7.2%的确诊AD病例; CAA见于49%的无ICH脑和48.7%的有ICH脑，无显著差异。脑出血组CAA严重程度的发生率明显高于非脑出血组（80.4% vs 30.9%，p < 0.001）。CAA患者比非CAA患者年龄大，临床痴呆和病理证实的AD发生率更高，但这些病例中分别有41例和33.6%的患者出现高血压体征（病史和/或尸检），而非CAA相关ICH患者的高血压体征发生率为70-75%。CAA相关性脑出血更常累及脑叶或半球，而非CAA相关性病变更常位于基底节和脑干。无脑出血病例中CAA的患病率低于有脑出血病例，但有脑出血和无脑出血病例中CAA的患病率相似，这一数据不支持CAA是老年人脑出血最明显的危险因素这一观点。虽然重度CAA确实与ICH相关，但在该尸检队列中，无CAA病例中大ICH的总体患病率要高得多，可能是由于其他风险因素，包括高血压，约40%的CAA相关ICH病例记录了高血压。AD患者（n = 163）的APOE β 3/4和APOE β 4/4的频率显著高于年龄匹配的对照组（n = 47），且与更严重程度的CAA相关，但未对伴或不伴CAA的ICH进行一般基因分型。因此，APOE在伴或不伴CAA的ICH发病机制中的作用需要进一步阐明。
In a retrospective study of a consecutive autopsy series of 2060 elderly subjects (mean age 78.5 +/- 6.8 SD years), sporadic cerebral amyloid angiopathy (CAA) of various degrees was detected in 73.2% and in 98.5% of autopsy-confirmed cases of typical (plaque and tangle) Alzheimer disease (AD). Spontaneous (non-traumatic) intracerebral hemorrhages (ICH) (excluding microbleeds) were seen in 5.6% of the total cohort and in 7.2% of definite AD cases; CAA was found in 49% of brains without and in 48.7% with ICH which was not significantly different. The latter groups showed a significantly higher frequency of severe degrees of CAA than those without ICH (80.4 vs 30.9%, p < 0.001). Patients with CAA were older than those without CAA, showing a higher frequency of clinical dementia and pathologically confirmed AD, but signs of hypertension (history and/or autopsy) were seen in 41 and 33.6% of these cases, respectively, compared to 70-75% in patients with non-CAA related ICHs. CAA-related ICH much more frequently involved cerebral lobes or hemispheres, while non-CAA related lesions were more often located in basal ganglia and brainstem. The data of a lower prevalence of CAA in cases without than with ICH, but a similar prevalence of ICH with and without CAA do not support the concept that CAA represents the most evident risk factor for ICH in the aged. While severe degrees of CAA were indeed associated with ICH, the general prevalence of large ICH in this autopsy cohort was much higher in cases without CAA, probably due to other risk factors including hypertension, which was documented in around 40% of cases with CAA-related ICH. APOE epsilon 3/4 and epsilon 4/4 were significantly more frequent in AD (n = 163) than in age-matched controls (n = 47) and were associated with more severe degrees of CAA, but no general genotyping in ICHs with and without CAA was performed. Hence, the role of APOE in the pathogenesis of ICH with and without CAA needs further elucidation.