Brickman Adam M, Provenzano Frank A, Muraskin Jordan, Manly Jennifer J, Blum Sonja, Apa Zoltan, Stern Yaakov, Brown Truman R, Luchsinger José A, Mayeux Richard
Arch Neurol. 2012 Dec;69(12):1621-7. doi: 10.1001/archneurol.2012.1527.
BACKGROUND New-onset Alzheimer disease (AD) is often attributed to degenerative changes in the hippocampus. However, the contribution of regionally distributed small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging, remains unclear. OBJECTIVE To determine whether regional WMHs and hippocampal volume predict incident AD in an epidemiological study. DESIGN A longitudinal community-based epidemiological study of older adults from northern Manhattan, New York. SETTING The Washington Heights/Inwood Columbia Aging Project. PARTICIPANTS Between 2005 and 2007, 717 participants without dementia received magnetic resonance imaging scans. A mean (SD) of 40.28 (9.77) months later, 503 returned for follow-up clinical examination and 46 met criteria for incident dementia (45 with AD). Regional WMHs and relative hippocampal volumes were derived. Three Cox proportional hazards models were run to predict incident dementia, controlling for relevant variables. The first included all WMH measurements; the second included relative hippocampal volume; and the third combined the 2 measurements. MAIN OUTCOME MEASURE Incident AD. RESULTS White matter hyperintensity volume in the parietal lobe predicted time to incident dementia (hazard ratio [HR] = 1.194; P = .03). Relative hippocampal volume did not predict incident dementia when considered alone (HR = 0.419; P = .77) or with the WMH measures included in the model (HR = 0.302; P = .70). Including hippocampal volume in the model did not notably alter the predictive utility of parietal lobe WMHs (HR = 1.197; P = .049). CONCLUSIONS The findings highlight the regional specificity of the association of WMHs with AD. It is not clear whether parietal WMHs solely represent a marker for cerebrovascular burden or point to distinct injury compared with other regions. Future work should elucidate pathogenic mechanisms linking WMHs and AD pathology.
新发阿尔茨海默病（AD）通常归因于海马体的退行性变化。然而，磁共振成像显示为白质高信号（WMHs）的局部分布的小血管脑血管疾病的作用仍不清楚。目的：在一项流行病学研究中确定局部WMHs和海马体体积是否可预测AD的发生。设计：对纽约曼哈顿北部老年人进行的基于社区的纵向流行病学研究。地点：华盛顿高地/因伍德哥伦比亚老龄化项目。参与者：2005年至2007年期间，717名无痴呆症的参与者接受了磁共振成像扫描。平均（标准差）40.28（9.77）个月后，503人返回进行随访临床检查，46人符合新发痴呆症标准（45例为AD）。得出局部WMHs和相对海马体体积。运行三个Cox比例风险模型来预测新发痴呆症，并控制相关变量。第一个模型包括所有WMH测量值；第二个模型包括相对海马体体积；第三个模型结合了这两个测量值。主要观察指标：新发AD。结果：顶叶白质高信号体积可预测新发痴呆症的时间（风险比[HR]=1.194；P=0.03）。单独考虑时，相对海马体体积不能预测新发痴呆症（HR=0.419；P=0.77），在模型中纳入WMH测量值时也不能预测（HR=0.302；P=0.70）。在模型中纳入海马体体积并没有显著改变顶叶WMHs的预测效用（HR=1.197；P=0.049）。结论：研究结果突出了WMHs与AD关联的区域特异性。尚不清楚顶叶WMHs是仅代表脑血管负担的标志物，还是与其他区域相比指向不同的损伤。未来的工作应阐明连接WMHs和AD病理的致病机制。
