Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer's disease.
Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer's disease.
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DOI：
10.1093/brain/awq277
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Alzheimer's Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Jack CR Jr;Wiste HJ;Vemuri P;Weigand SD;Senjem ML;Zeng G;Bernstein MA;Gunter JL;Pankratz VS;Aisen PS;Weiner MW;Petersen RC;Shaw LM;Trojanowski JQ;Knopman DS;Alzheimer's Disease Neuroimaging Initiative
脑Aβ淀粉样蛋白沉积的生物标志物可以通过脑脊液Aβ42或匹兹堡化合物B正电子发射断层扫描成像来测量。我们的目的是评估Aβ负荷和神经退行性萎缩在磁共振成像上预测从轻度认知障碍到阿尔茨海默氏痴呆的较短进展时间的能力，并描述这些生物标志物对进展风险的影响，因为它们变得越来越异常。从阿尔茨海默病神经影像学倡议中确定了总共218名轻度认知障碍的受试者。主要结局是进展为阿尔茨海默氏痴呆的时间。测量海马体积并根据颅内体积进行调整。我们使用了一种新的方法，将脑脊液Aβ42和匹兹堡复合B正电子发射断层扫描测量值合并，以产生两种来源脑Aβ负荷的等效测量值，并使用多重插补方法分析结果。我们分两个阶段进行分析。首先，我们将受试者分为“淀粉样蛋白阳性”（n = 165，假设阿尔茨海默病在该组中占主导地位）和“淀粉样蛋白阴性”（n = 53）。在第二阶段，我们纳入了所有218名轻度认知障碍受试者，以评估我们假设包含预期病理全谱的样本中的生物标志物。在Kaplan-Meier分析中，轻度认知障碍的淀粉样蛋白阳性受试者比轻度认知障碍的淀粉样蛋白阴性受试者更有可能在2年内进展为痴呆（50%对19%）。在仅伴有轻度认知功能障碍的淀粉样蛋白阳性受试者中，海马萎缩预测了较短的进展时间（P < 0.001），而Aβ负荷没有预测（P = 0.44）。相比之下，当合并所有218例轻度认知障碍受试者（淀粉样蛋白阳性和阴性）时，海马萎缩和Aβ负荷预测至进展时间较短，把握度相当（两者四分位数间差异的风险比为2.6）;然而，在海马萎缩值范围内，风险特征呈线性，但在脑Aβ负荷值较高时达到上限。我们的研究结果与阿尔茨海默病模型一致，其中Aβ沉积启动病理级联反应，但不是认知障碍的直接原因，这一事实证明，Aβ负荷严重程度与高水平进展风险无关。相比之下，海马萎缩表明一个人在神经退行性疾病的道路上走了沿着多远，因此离发展成痴呆症有多近。我们发现许多轻度认知障碍受试者具有中等水平的Aβ负荷，对此可能的解释包括：（i）个体受试者可能在不同的绝对水平上达到Aβ负荷平台;（ii）某些受试者可能比其他受试者对Aβ更敏感;和（iii）具有中度Aβ水平的轻度认知障碍的受试者可能代表阿尔茨海默病患者，与其他疾病共存。
Biomarkers of brain Aβ amyloid deposition can be measured either by cerebrospinal fluid Aβ42 or Pittsburgh compound B positron emission tomography imaging. Our objective was to evaluate the ability of Aβ load and neurodegenerative atrophy on magnetic resonance imaging to predict shorter time-to-progression from mild cognitive impairment to Alzheimer’s dementia and to characterize the effect of these biomarkers on the risk of progression as they become increasingly abnormal. A total of 218 subjects with mild cognitive impairment were identified from the Alzheimer’s Disease Neuroimaging Initiative. The primary outcome was time-to-progression to Alzheimer’s dementia. Hippocampal volumes were measured and adjusted for intracranial volume. We used a new method of pooling cerebrospinal fluid Aβ42 and Pittsburgh compound B positron emission tomography measures to produce equivalent measures of brain Aβ load from either source and analysed the results using multiple imputation methods. We performed our analyses in two phases. First, we grouped our subjects into those who were ‘amyloid positive’ (n = 165, with the assumption that Alzheimer's pathology is dominant in this group) and those who were ‘amyloid negative’ (n = 53). In the second phase, we included all 218 subjects with mild cognitive impairment to evaluate the biomarkers in a sample that we assumed to contain a full spectrum of expected pathologies. In a Kaplan–Meier analysis, amyloid positive subjects with mild cognitive impairment were much more likely to progress to dementia within 2 years than amyloid negative subjects with mild cognitive impairment (50 versus 19%). Among amyloid positive subjects with mild cognitive impairment only, hippocampal atrophy predicted shorter time-to-progression (P < 0.001) while Aβ load did not (P = 0.44). In contrast, when all 218 subjects with mild cognitive impairment were combined (amyloid positive and negative), hippocampal atrophy and Aβ load predicted shorter time-to-progression with comparable power (hazard ratio for an inter-quartile difference of 2.6 for both); however, the risk profile was linear throughout the range of hippocampal atrophy values but reached a ceiling at higher values of brain Aβ load. Our results are consistent with a model of Alzheimer’s disease in which Aβ deposition initiates the pathological cascade but is not the direct cause of cognitive impairment as evidenced by the fact that Aβ load severity is decoupled from risk of progression at high levels. In contrast, hippocampal atrophy indicates how far along the neurodegenerative path one is, and hence how close to progressing to dementia. Possible explanations for our finding that many subjects with mild cognitive impairment have intermediate levels of Aβ load include: (i) individual subjects may reach an Aβ load plateau at varying absolute levels; (ii) some subjects may be more biologically susceptible to Aβ than others; and (iii) subjects with mild cognitive impairment with intermediate levels of Aβ may represent individuals with Alzheimer’s disease co-existent with other pathologies.
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3.7
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van der Flier, Wiesje M.
影响因子：
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作者：
Aizenstein, Howard Jay;Nebes, Robert D.;Saxton, Judith A.;Price, Julie C.;Mathis, Chester A.;Tsopelas, Nicholas D.;Ziolko, Scott K.;James, Jeffrey A.;Snitz, Beth E.;Houck, Patricia R.;Bi, Wenzhu;Cohen, Ann D.;Lopresti, Brian J.;DeKosky, Steven T.;Halligan, Edythe M.;Klunk, William E.
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Klunk, William E.