The preclinical Alzheimer cognitive composite: measuring amyloid-related decline.
The preclinical Alzheimer cognitive composite: measuring amyloid-related decline.
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DOI：
10.1001/jamaneurol.2014.803
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发表时间：
2014-08
期刊：
影响因子：
29
通讯作者：
Aisen, Paul S.
中科院分区：
文献类型：
--
作者：
Donohue, Michael C.;Sperling, Reisa A.;Salmon, David P.;Rentz, Dorene M.;Raman, Rema;Thomas, Ronald G.;Weiner, Michael;Aisen, Paul S.
随着阿尔茨海默病（AD）研究转向对疾病症状前阶段的干预，我们必须开发对最早期疾病相关变化敏感的结果指标。使用ADCS临床前阿尔茨海默认知复合量表（ADCS-PACC）证明具有AD病理学证据的临床正常老年受试者的认知复合结局的可行性。ADCS-PACC结合了评估情景记忆、定时执行功能和整体认知的测试。ADCS-PACC是临床前AD的第一项临床试验（即无症状阿尔茨海默病研究中的抗淀粉样蛋白治疗）的主要结局指标。通过ADCS-PACC，我们使用在北美进行的2项观察性研究和在澳大利亚进行的另一项研究的数据得出了淀粉样蛋白相关下降的初步估计。在3项研究中，分析的参与者认知正常，平均年龄为75.81岁，71.37岁和79.42岁。对于收集Aβ水平数据的2项研究（ADNI和Aibl），我们估计了临床前AD“Aβ阳性”安慰剂组的下降，并将其与“Aβ阴性”组进行比较。对于不包括Aβ水平数据的研究（ADCS预防工具[ADCS-PI]研究），我们根据APOE-β 4的存在和临床进展对参与者进行分组。在ADNI中，Aβ阳性受试者在24个月时的ADCS-PACC评分比Aβ阴性受试者下降更多（平均[SE]差异，-1.239 [0.522] [95%CI，-2.263至-0.215]; P = 0.02）。在Aibl中，18个月（-1.009 [0.406] [95%CI，-1.805 to-0.213]; P = .01）和36个月（-1.404 [0.452] [95%CI，-2.290 to-0.519]; P = .002）的平均（SE）差异均具有显著性。在ADCS-PI研究中，APOE-β 4等位基因携带者在24个月（平均[SE]评分，−0.742 [0.294] [95%CI，−1.318至−0.165]; P = 0.01）和36个月（−1.531 [0.469] [95%CI，−2.450至−0.612]; P = 0.001）时的ADCS-PACC表现显著更差。在ADCS-PI研究中，在第12、24和36个月时，从总体临床痴呆评定评分0分进展的认知正常参与者的ADCS-PACC显著差于总体临床痴呆评定评分0分稳定的认知正常参与者（平均[SE] ADCS-PACC评分，-4.471 [0.702] [95%CI，-5.848 to-3.094]; P < .001）。使用试验性方差估计值，并假设每组500名受试者，30%的损耗和5%的α水平，我们预测80%的把握度可以检测到Δ = 0.467至0.733范围内对ADCS-PACC的影响。对高危认知正常人群的分析表明，我们可以用ADCS-PACC可靠地测量认知下降的第一个迹象。这些分析也表明了二级预防试验的可行性。
As Alzheimer disease (AD) research moves to intervene in presymptomatic phases of the disease, we must develop outcome measures sensitive to the earliest disease-related changes. To demonstrate the feasibility of a cognitive composite outcome for clinically normal elderly participants with evidence of AD pathology using the ADCS Preclinical Alzheimer Cognitive Composite (ADCS-PACC). The ADCS-PACC combines tests that assess episodic memory, timed executive function, and global cognition. The ADCS-PACC is the primary outcome measure for the first clinical trial in preclinical AD (ie, the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s study). With the ADCS-PACC, we derive pilot estimates of amyloid-related decline using data from 2 observational studies conducted in North America and another conducted in Australia. The participants analyzed had normal cognition and mean ages of 75.81, 71.37, and 79.42 years across the 3 studies. For the 2 studies that collected data on Aβ levels (ADNI and AIBL), we estimate decline in a preclinical AD “Aβ-positive” placebo group and compare them with an “Aβ-negative” group. For the study that did not include data on Aβ levels (the ADCS Prevention Instrument [ADCS-PI] study), we grouped participants by the presence of APOE-ɛ4 and by clinical progression. In ADNI, Aβ-positive participants showed more decline than did Aβ-negative participants with regard to the ADCS-PACC score at 24 months (mean [SE] difference, −1.239 [0.522] [95% CI, −2.263 to −0.215]; P = .02). In AIBL, the mean (SE) difference is significant at both 18 months (−1.009 [0.406] [95% CI, −1.805 to −0.213]; P = .01) and 36 months (−1.404 [0.452] [95% CI, −2.290 to −0.519]; P = .002). In the ADCS-PI study, APOE-ɛ4 allele carriers performed significantly worse on the ADCS-PACC at 24 months (mean [SE] score, −0.742 [0.294] [95% CI, −1.318 to −0.165]; P = .01) and 36 months (−1.531 [0.469] [95% CI, −2.450 to −0.612]; P = .001). In the ADCS-PI study, cognitively normal participants who progress from a global Clinical Dementia Rating score of 0 are significantly worse on the ADCS-PACC than cognitively normal participants who are stable with a global Clinical Dementia Rating score of 0 at months 12, 24, and 36 (mean [SE] ADCS-PACC score, −4.471 [0.702] [95% CI, −5.848 to −3.094]; P < .001). Using pilot estimates of variance and assuming 500 participants per group with 30% attrition and a 5% α level, we project 80% power to detect effects in the range of Δ = 0.467 to 0.733 on the ADCS-PACC. Analyses of at-risk cognitively normal populations suggest that we can reliably measure the first signs of cognitive decline with the ADCS-PACC. These analyses also suggest the feasibility of secondary prevention trials.
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影响因子：
11.2
作者：
Landau, Susan M.;Mintun, Mark A.;Joshi, Abhinay D.;Koeppe, Robert A.;Petersen, Ronald C.;Aisen, Paul S.;Weiner, Michael W.;Jagust, William J.
通讯作者：
Jagust, William J.
影响因子：
9.9
作者：
Derby, Carol A.;Burns, Leah C.;Lipton, Richard B.
通讯作者：
Lipton, Richard B.
影响因子：
9.9
作者：
Doraiswamy, P. Murali;Sperling, Reisa A.;Pontecorvo, Michael J.
通讯作者：
Pontecorvo, Michael J.
DOI：
10.1016/j.jalz.2013.10.003
发表时间：
2014-10
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Donohue MC;Jacqmin-Gadda H;Le Goff M;Thomas RG;Raman R;Gamst AC;Beckett LA;Jack CR Jr;Weiner MW;Dartigues JF;Aisen PS;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative
DOI：
10.1097/01.wad.0000213870.40300.21
发表时间：
2006-10-01
影响因子：
2.1
作者：
Ferris, Steven H.;Aisen, Paul S.;Thal, Leon J.
通讯作者：
Thal, Leon J.