The A4 study: β-amyloid and cognition in 4432 cognitively unimpaired adults
The A4 study: β-amyloid and cognition in 4432 cognitively unimpaired adults
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DOI：
10.1002/acn3.51048
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发表时间：
2020-04-21
影响因子：
5.3
通讯作者：
Mattsson-Carlgren, Niklas
中科院分区：
文献类型：
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作者：
Insel, Philip S.;Donohue, Michael C.;Mattsson-Carlgren, Niklas
目的通过估计β-淀粉样蛋白的积累何时开始与认知变化相关来阐明阿尔茨海默病的临床前阶段。（N = 4432）接受A4试验筛选的认知未受损个体（65-85岁）评估阈下水平的β-淀粉样蛋白对认知的影响，并确定哪些认知领域首先受到影响。淀粉样蛋白积累与认知未受损参与者的显著认知功能障碍有关，在多种记忆测量中，β-淀粉样蛋白处于亚阈值水平（逻辑记忆延迟回忆，P = 0.03;自由和线索选择性提醒测试，P < 0.001），临床前阿尔茨海默氏症认知综合征（P = 0.01），并与执行功能下降（数字符号替代，P = 0.07）。显著地，在所有测量中，认知评分降低与阈上水平的β-淀粉样蛋白相关（P < 0.05）。自由和线索选择性提醒测试，列表回忆记忆测试，出现最敏感的β-淀粉样蛋白相关的平均认知得分下降，优于所有其他认知领域，包括叙事回忆记忆测试，逻辑Memory.Interpretation认知未受损β-淀粉样蛋白阳性个体的临床试验将包括大量的个人，其中β-淀粉样蛋白病理学下游的机制已经激活。这些发现对阿尔茨海默病的一级和二级预防具有重要意义。
Objective To clarify the preclinical stage of Alzheimer's disease by estimating when beta-amyloid accumulation first becomes associated with changes in cognition.Methods Here we studied a large group (N = 4432) of cognitively unimpaired individuals who were screened for inclusion in the A4 trial (age 65-85) to assess the effect of subthreshold levels of beta-amyloid on cognition and to identify which cognitive domains first become affected.Results beta-amyloid accumulation was linked to significant cognitive dysfunction in cognitively unimpaired participants with subthreshold levels of beta-amyloid in multiple measures of memory (Logical Memory Delayed Recall, P = 0.03; Free and Cued Selective Reminding Test, P < 0.001), the Preclinical Alzheimer's Cognitive Composite (P = 0.01), and was marginally associated with decreased executive function (Digit Symbol Substitution, P = 0.07). Significantly, decreased cognitive scores were associated with suprathreshold levels of beta-amyloid, across all measures (P < 0.05). The Free and Cued Selective Reminding Test, a list recall memory test, appeared most sensitive to beta-amyloid -related decreases in average cognitive scores, outperforming all other cognitive domains, including the narrative recall memory test, Logical Memory.Interpretation Clinical trials for cognitively unimpaired beta-amyloid-positive individuals will include a large number of individuals where mechanisms downstream from beta-amyloid pathology are already activated. These findings have implications for primary and secondary prevention of Alzheimer's disease.