■认知功能下降是阿尔茨海默病(AD)临床研究的关键结果。
■为了确定总体淀粉样蛋白负荷以及海马和基底前脑体积对纵向速率的影响,以及通过重复测试AD频谱中特定域认知变化的实践效果,考虑队列中的非线性效应和异质性。
■我们包括来自三个队列的1,514例病例,ADNI,AIBL,和DELCODE,范围从认知正常的人到主观认知能力下降和轻度认知障碍(MCI)的人。我们使用广义贝叶斯混合效应分析淀粉样蛋白和体积效应的线性和多项式模型。使用贝叶斯随机效应荟萃分析确定跨队列效应的稳健性。
■我们发现淀粉样蛋白和海马体积具有一致的作用,但不是基底前脑容量,meta分析中三个队列的记忆变化率。淀粉样蛋白和体积标志物对执行功能的影响更为异质。我们发现实践对淀粉样蛋白阴性认知正常对照和MCI病例的记忆和执行表现有影响,但在淀粉样蛋白阳性对照中只有较小的程度,而在淀粉样蛋白阳性MCI病例中根本没有。
■我们发现了队列之间的异质性,特别是对执行功能的影响。淀粉样蛋白阴性的认知表现的初始增加,但在淀粉样蛋白阳性的MCI病例和对照中没有,这可能反映了重复测试的实践效果,这些重复测试随着脑淀粉样蛋白水平的升高而丢失。
UNASSIGNED: Cognitive decline is a key outcome of clinical studies in Alzheimer\'s disease (AD).
UNASSIGNED: To determine effects of global amyloid load as well as hippocampus and basal forebrain volumes on longitudinal rates and practice effects from repeated testing of domain specific cognitive change in the AD spectrum, considering non-linear effects and heterogeneity across cohorts.
UNASSIGNED: We included 1,514 cases from three cohorts, ADNI, AIBL, and DELCODE, spanning the range from cognitively normal people to people with subjective cognitive decline and mild cognitive impairment (MCI). We used generalized Bayesian mixed effects analysis of linear and polynomial models of amyloid and volume effects in time. Robustness of effects across cohorts was determined using Bayesian random effects meta-analysis.
UNASSIGNED: We found a consistent effect of amyloid and hippocampus volume, but not of basal forebrain volume, on rates of memory change across the three cohorts in the meta-analysis. Effects for amyloid and volumetric markers on executive function were more heterogeneous. We found practice effects in memory and executive performance in amyloid negative cognitively normal controls and MCI cases, but only to a smaller degree in amyloid positive controls and not at all in amyloid positive MCI cases.
UNASSIGNED: We found heterogeneity between cohorts, particularly in effects on executive functions. Initial increases in cognitive performance in amyloid negative, but not in amyloid positive MCI cases and controls may reflect practice effects from repeated testing that are lost with higher levels of cerebral amyloid.