Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention trials.
Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention trials.
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DOI：
10.1371/journal.pone.0058816
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Australian Imaging Biomarkers, Lifestyle Flagship Study of Ageing
中科院分区：
文献类型：
--
作者：
Andrews KA;Modat M;Macdonald KE;Yeatman T;Cardoso MJ;Leung KK;Barnes J;Villemagne VL;Rowe CC;Fox NC;Ourselin S;Schott JM;Australian Imaging Biomarkers, Lifestyle Flagship Study of Ageing
人们对设计针对阿尔茨海默病 (AD) 风险个体的治疗研究以预防症状的出现非常感兴趣。皮质β-淀粉样蛋白斑块是AD病理学的第一阶段，可以使用正电子发射断层扫描(PET)在体内检测到，多项研究表明~1/3的健康老年人有明显的β-淀粉样蛋白沉积。在这里，我们评估了无症状淀粉样蛋白 PET 阳性对照是否会增加脑萎缩的发生率，这可以用作 AD 预防试验的结果衡量标准。我们评估了来自澳大利亚成像生物标志物与生活方式研究的 66 名对照受试者（年龄 = 73.5±7.3 岁；MMSE = 29±1.3），他们进行了基线匹兹堡化合物 B (PiB) PET 扫描和两次相隔约 18 个月的 3T MRI 扫描。我们计算了 PET 标准摄取值比 (SUVR)，并将个体分为淀粉样蛋白阳性/阴性。记录基线和 18 个月的 MRI 扫描，并计算大脑、海马和心室体积以及年化体积变化。 β-淀粉样蛋白负荷基线 PiB-PET 测量值的增加与海马萎缩率相关，与年龄无关 (p = 0.014)。 22 例（1/3）为 PiB 阳性（SUVR>1.40），其余 44 例为 PiB 阴性（SUVR≤1.31）。与 PiB 阴性者相比，PiB 阳性个体年龄较大（76.8±7.5 vs. 71.7±7.5，p<0.05），APOE4 阳性者较多（63.6% vs. 19.2%，p<0.01），但考虑到年龄和性别后，无论有或没有颅内总体积校正，基线脑、心室或海马体积均无差异。 PiB 阳性组的总海马损失率较高（0.06±0.08 比 0.02±0.05 毫升/年，p = 0.02），与年龄和性别无关，全脑损失率（7.1±9.4 比 4.7±5.5 毫升/年）和心室损失率（2.0±3.0 比 1.1±1.0）不显着较高。毫升/年）变化。根据观察到的效应大小，在一项为期 18 个月的治疗试验中，招募 384 名 (95% CI 195–1080) 淀粉样蛋白阳性受试者/组将提供 80% 的功效来检测海马萎缩率绝对减慢 25%。我们的结论是，海马萎缩可能是无症状淀粉样变性二级预防研究的可行结果指标。
There is considerable interest in designing therapeutic studies of individuals at risk of Alzheimer disease (AD) to prevent the onset of symptoms. Cortical β-amyloid plaques, the first stage of AD pathology, can be detected in vivo using positron emission tomography (PET), and several studies have shown that ∼1/3 of healthy elderly have significant β-amyloid deposition. Here we assessed whether asymptomatic amyloid-PET-positive controls have increased rates of brain atrophy, which could be harnessed as an outcome measure for AD prevention trials. We assessed 66 control subjects (age = 73.5±7.3 yrs; MMSE = 29±1.3) from the Australian Imaging Biomarkers & Lifestyle study who had a baseline Pittsburgh Compound B (PiB) PET scan and two 3T MRI scans ∼18-months apart. We calculated PET standard uptake value ratios (SUVR), and classified individuals as amyloid-positive/negative. Baseline and 18-month MRI scans were registered, and brain, hippocampal, and ventricular volumes and annualized volume changes calculated. Increasing baseline PiB-PET measures of β-amyloid load correlated with hippocampal atrophy rate independent of age (p = 0.014). Twenty-two (1/3) were PiB-positive (SUVR>1.40), the remaining 44 PiB-negative (SUVR≤1.31). Compared to PiB-negatives, PiB-positive individuals were older (76.8±7.5 vs. 71.7±7.5, p<0.05) and more were APOE4 positive (63.6% vs. 19.2%, p<0.01) but there were no differences in baseline brain, ventricle or hippocampal volumes, either with or without correction for total intracranial volume, once age and gender were accounted for. The PiB-positive group had greater total hippocampal loss (0.06±0.08 vs. 0.02±0.05 ml/yr, p = 0.02), independent of age and gender, with non-significantly higher rates of whole brain (7.1±9.4 vs. 4.7±5.5 ml/yr) and ventricular (2.0±3.0 vs. 1.1±1.0 ml/yr) change. Based on the observed effect size, recruiting 384 (95%CI 195–1080) amyloid-positive subjects/arm will provide 80% power to detect 25% absolute slowing of hippocampal atrophy rate in an 18-month treatment trial. We conclude that hippocampal atrophy may be a feasible outcome measure for secondary prevention studies in asymptomatic amyloidosis.
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影响因子：
--
作者：
De Meyer, Geert;Shapiro, Fred;Vanderstichele, Hugo;Vanmechelen, Eugeen;Engelborghs, Sebastiaan;De Deyn, Peter Paul;Coart, Els;Hansson, Oskar;Minthon, Lennart;Zetterberg, Henrik;Blennow, Kaj;Shaw, Leslie;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
14.5
作者：
Chetelat, Gael;Villemagne, Victor L.;Rowe, Christopher C.
通讯作者：
Rowe, Christopher C.
影响因子：
5.7
作者：
Leung, Kelvin K.;Barnes, Josephine;Ridgway, Gerard R.;Bartlett, Jonathan W.;Clarkson, Matthew J.;Macdonald, Kate;Schuff, Norbert;Fox, Nick C.;Ourselin, Sebastien
通讯作者：
Ourselin, Sebastien
影响因子：
5.7
作者：
Cardoso, M. Jorge;Clarkson, Matthew J.;Ridgway, Gerard R.;Modat, Marc;Fox, Nick C.;Ourselin, Sebastien
通讯作者：
Ourselin, Sebastien
影响因子：
11.2
作者：
Klunk, WE;Engler, H;Långström, B
通讯作者：
Långström, B