Kathryn V. Papp, PhD, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115; Tel: +1 617-643-5322; E-mail:
J Prev Alzheimers Dis. 2022;9(2):255-261. doi: 10.14283/jpad.2022.17.
Cognitive composites commonly serve as primary outcomes in Alzheimer's disease (AD) secondary prevention trials.
To evaluate the association between amyloid (Aβ) burden level (+/-) and performance on three separate composite endpoints: Preclinical Alzheimer's Cognitive Composite (PACC), PACC+Semantic Fluency (PACC5), and Repeatable Battery for Neuropsychological Status (RBANS).
Screening data from the randomized, double-blind, placebo-controlled, phase 2b/3 atabecestat EARLY study in preclinical AD participants were used in this analysis.
The EARLY study was conducted at 143 centers across 14 countries.
3,569 cognitively unimpaired older adults (Clinical Dementia Rating of 0; aged 60-85 years) screened for inclusion in the EARLY study with Aβ status and at least PACC or RBANS at screening were included. Participants were categorized as those with non-pathological Aβ levels (Aβ-, n=2,824) and those with pathological Aβ levels (Aβ+, n=745) based on florbetapir uptake or levels of cerebrospinal fluid Aβ1-42.
Analysis of Covariance models controlling for age, sex, and education were used to examine the difference in PACC, PACC5, and RBANS between Aβ groups. Nonparametric bootstrap was used to compare sensitivity of composites to differentiate between Aβ status.
Of 3,569 participants, 2,116 were women (59%); 3,006 were Caucasian (84%); mean (SD) age was 68.98 (5.28) years. Aβ+ participants performed worse versus Aβ- participants on all cognitive composites though the magnitude of the Aβ effect was generally small. The Aβ+/- effect size for the PACC (Cohen's d=-0.15) was significantly greater than the RBANS (d=-0.097) while the PACC5 effect size (d=-0.139) was numerically larger than the RBANS. When examining subscores from the composites, memory tests (i.e., Free and Cued Selective Reminding Test, Figure Recall) and speed of processing (i.e., Digit-Symbol/Coding on the PACC/RBANS) exhibited the largest Aβ+/- effect sizes.
Cross-sectional relationships between Aβ and cognition among clinically unimpaired older adults are detectable on multi-domain cognitive composites but are relatively small in magnitude. The Aβ+/- group effect was statistically larger for PACC and marginally larger for PACC5 versus RBANS. However, interpretation of composite sensitivity to Aβ status cross-sectionally cannot be generalized to sensitivity to change over time.
认知综合常用于阿尔茨海默病（AD）二级预防试验的主要结局。
评估淀粉样蛋白（Aβ）负担水平（+/-）与三个独立复合终点表现之间的关系：临床前阿尔茨海默病认知复合（PACC）、PACC+语义流畅性（PACC5）和重复神经心理状态测试（RBANS）。
使用这项分析筛查了在临床前 AD 参与者中进行的随机、双盲、安慰剂对照、2b/3 期 atabecestat EARLY 研究的筛查数据。
EARLY 研究在 14 个国家的 143 个中心进行。
3569 名认知正常的老年人（临床痴呆评定 0；年龄 60-85 岁）接受包括 Aβ 状态在内的筛查，筛查时至少有 PACC 或 RBANS 的参与者被纳入研究。根据 florbetapir 摄取或脑脊液 Aβ1-42 水平，参与者分为无病理性 Aβ 水平（Aβ-，n=2824）和病理性 Aβ 水平（Aβ+，n=745）。
使用协方差分析模型，控制年龄、性别和教育，比较 Aβ 组之间 PACC、PACC5 和 RBANS 的差异。非参数自举用于比较综合评分对区分 Aβ 状态的敏感性。
在 3569 名参与者中，2116 名为女性（59%）；3006 名参与者为白种人（84%）；平均（SD）年龄为 68.98（5.28）岁。与 Aβ-参与者相比，Aβ+参与者在所有认知综合测试中表现较差，尽管 Aβ 效应的程度通常较小。PACC（Cohen's d=-0.15）的 Aβ+/−效应量明显大于 RBANS（d=-0.097），而 PACC5 的效应量（d=-0.139）在数值上大于 RBANS。在检查综合评分的子评分时，记忆测试（即自由和线索选择性回忆测试、图形回忆）和处理速度（即 PACC/RBANS 的数字符号/编码）表现出最大的 Aβ+/−效应量。
在临床无明显障碍的老年人中，淀粉样蛋白与认知之间的横断面关系可在多领域认知综合中检测到，但在数量上相对较小。与 RBANS 相比，PACC 和 PACC5 的 Aβ+/−组效应在统计学上更大，在 PACC5 上略大。然而，综合评分对 Aβ 状态的敏感性的横断面解释不能推广到随时间变化的敏感性。
