Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults
Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults
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DOI：
10.1212/wnl.0b013e3182166e96
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发表时间：
2011-04-01
期刊：
影响因子：
9.9
通讯作者：
deToledo-Morrell, L.
中科院分区：
文献类型：
--
作者：
Dickerson, B. C.;Stoub, T. R.;deToledo-Morrell, L.
目的：由于阿尔茨海默病（AD）神经病理被认为比痴呆早几年发生，因此有可能在阿尔茨海默病的临床前检测到与AD相关的细微萎缩。在这里，我们假设，先前在轻度AD痴呆患者中发现的AD相关皮层变薄的“疾病特征”，将作为一种生物标志物，在纵向随访后，在认知正常（CN）的AD痴呆患者中检测与AD一致的解剖异常。方法：我们研究了2个独立的成人样本，扫描时均为CN。在样本1中，有8人在平均11.1年后发展为AD痴呆（CN-AD转换者），与25人保持CN （CN-稳定）进行比较。在样本2中，7名CN-AD转换者（平均随访7.1年）与25名cn稳定个体进行了比较。结果：两个样本的CN-AD转换器ad特征皮层变薄非常相似，约为0.2 mm （p < 0.05）。尽管绝对差异很小，但这些差异的科恩效应量非常大（bbb1）。在11名基线AD特征厚度较低（>=低于队列平均值1个标准差）的CN个体中，55%的人在接下来的十年中发展为AD痴呆，而9名AD特征厚度较高的个体（>=高于平均值1个标准差）没有人发展为痴呆。该指标预测痴呆诊断所需时间（风险比= 3.4,p < 0.0005）；1个SD变薄会使痴呆风险增加3.4。结论：通过关注已知受阿尔茨海默氏症影响的皮质区域，在痴呆前近10年的无症状个体中可以识别出细微但可靠的萎缩，使这一测量成为早期神经退行性变的潜在重要成像生物标志物。神经病学(R) 2011；76: 1395 - 1402
Objective: Since Alzheimer disease (AD) neuropathology is thought to develop years before dementia, it may be possible to detect subtle AD-related atrophy in preclinical AD. Here we hypothesized that the "disease signature" of AD-related cortical thinning, previously identified in patients with mild AD dementia, would be useful as a biomarker to detect anatomic abnormalities consistent with AD in cognitively normal (CN) adults who develop AD dementia after longitudinal follow-up.Methods: We studied 2 independent samples of adults who were CN when scanned. In sample 1, 8 individuals developing AD dementia (CN-AD converters) after an average of 11.1 years were compared to 25 individuals who remained CN (CN-stable). In sample 2, 7 CN-AD converters (average follow-up 7.1 years) were compared to 25 CN-stable individuals.Results: AD-signature cortical thinning in CN-AD converters in both samples was remarkably similar, about 0.2 mm (p < 0.05). Despite this small absolute difference, Cohen d effect sizes for these differences were very large (> 1). Of the 11 CN individuals with baseline low AD-signature thickness (>= 1 SD below cohort mean), 55% developed AD dementia over nearly the next decade, while none of the 9 high AD-signature thickness individuals (>= 1 SD above mean) developed dementia. This marker predicted time to diagnosis of dementia (hazard ratio = 3.4, p < 0.0005); 1 SD of thinning increased dementia risk by 3.4.Conclusions: By focusing on cortical regions known to be affected in AD dementia, subtle but reliable atrophy is identifiable in asymptomatic individuals nearly a decade before dementia, making this measure a potentially important imaging biomarker of early neurodegeneration. Neurology (R) 2011; 76: 1395-1402