PDF(Pubmed)
Abstract：
BACKGROUND: The Anti-Amyloid in Asymptomatic Alzheimer\'s Disease (A4) Study failed to show a treatment benefit with solanezumab, but the longitudinal consequences of elevated amyloid were observed in study participants with objective decline on the Preclinical Alzheimer Cognitive Composite (PACC) and subjective decline on the combined Cognitive Function Index (participant + study partner CFI), during the trial period.
OBJECTIVE: We sought to expand on previous findings by comparing longitudinal patterns of participant and study partner CFI separately and their associations with the PACC stratified by baseline amyloid tertile over the course of the A4 Study.
METHODS: Cognitively unimpaired older adult participants and their study partners were independently administered the CFI at screen prior to amyloid PET disclosure and then at 3 subsequent visits (week 48, week 168, week 240) of the study. PACC collected at visits concurrent with CFI administration were also examined longitudinally.
METHODS: The A4 Study was conducted at 67 sites in Australia, Canada, Japan, and the United States.
METHODS: 1,147 participants with elevated amyloid based on florbetapir PET were enrolled in the A4 Study and included in these analyses. 583 were on placebo and 564 were treated with solanezumab.
METHODS: The PACC was used to assess objective cognitive performance and the CFI was used to assess change in everyday cognitive functioning by the participant and their study partner independently. Amyloid level was characterized by Centiloid tertiles (<46.1 CL, 46.1 to 77.2 CL, >77.2 CL). Participants were aware of their elevated amyloid status, but not their CL tertile, or specific level of amyloid. Longitudinal correlations between participant and study partner CFI and PACC were examined at all visits where assessments were available. The impact of baseline amyloid tertile on CFI and PACC associations was also examined.
RESULTS: Both participant and study partner CFI increased over the duration of the study indicating worsening cognitive functioning. Results did not differ by treatment group. The association between higher CFI and worse PACC for both for participant and study partner became progressively stronger over the course of the study. PACC had a significantly higher correlation with study partner CFI than with participant CFI by week 168. The stronger correlations between study partner CFI and PACC were driven by those in the highest amyloid tertile.
CONCLUSIONS: Both participant and study partner report captured subtle changes in everyday cognitive functioning for participants with biomarker confirmed and disclosed preclinical AD. Moreover, study partner report was most highly aligned with cognitive decline, particularly among those with the highest amyloid load.
OBJECTIVE: We sought to expand on previous findings by comparing longitudinal patterns of participant and study partner CFI separately and their associations with the PACC stratified by baseline amyloid tertile over the course of the A4 Study.
METHODS: Cognitively unimpaired older adult participants and their study partners were independently administered the CFI at screen prior to amyloid PET disclosure and then at 3 subsequent visits (week 48, week 168, week 240) of the study. PACC collected at visits concurrent with CFI administration were also examined longitudinally.
METHODS: The A4 Study was conducted at 67 sites in Australia, Canada, Japan, and the United States.
METHODS: 1,147 participants with elevated amyloid based on florbetapir PET were enrolled in the A4 Study and included in these analyses. 583 were on placebo and 564 were treated with solanezumab.
METHODS: The PACC was used to assess objective cognitive performance and the CFI was used to assess change in everyday cognitive functioning by the participant and their study partner independently. Amyloid level was characterized by Centiloid tertiles (<46.1 CL, 46.1 to 77.2 CL, >77.2 CL). Participants were aware of their elevated amyloid status, but not their CL tertile, or specific level of amyloid. Longitudinal correlations between participant and study partner CFI and PACC were examined at all visits where assessments were available. The impact of baseline amyloid tertile on CFI and PACC associations was also examined.
RESULTS: Both participant and study partner CFI increased over the duration of the study indicating worsening cognitive functioning. Results did not differ by treatment group. The association between higher CFI and worse PACC for both for participant and study partner became progressively stronger over the course of the study. PACC had a significantly higher correlation with study partner CFI than with participant CFI by week 168. The stronger correlations between study partner CFI and PACC were driven by those in the highest amyloid tertile.
CONCLUSIONS: Both participant and study partner report captured subtle changes in everyday cognitive functioning for participants with biomarker confirmed and disclosed preclinical AD. Moreover, study partner report was most highly aligned with cognitive decline, particularly among those with the highest amyloid load.
摘要：
背景：抗淀粉样蛋白在无症状阿尔茨海默病（A4）中的研究未能显示solanezumab的治疗益处，但是在临床前阿尔茨海默认知综合指数（PACC）客观下降和认知功能综合指数（参与者+研究伙伴CFI）主观下降的研究参与者中观察到淀粉样蛋白升高的纵向后果，在审判期间。
目的：我们试图通过在A4研究过程中分别比较参与者和研究伙伴CFI的纵向模式，以及它们与通过基线淀粉样颗粒分层的PACC的关联来扩展以前的研究结果。
方法：认知未受损的老年参与者和他们的研究伙伴在淀粉样蛋白PET公开之前进行筛查，然后在研究的3次后续访问（第48周，第168周，第240周）时独立给予CFI。还纵向检查了与CFI给药同时进行的访视时收集的PACC。
方法：A4研究在澳大利亚的67个地点进行，加拿大,Japan,和美国。
方法：1,147名基于florbetapirPET的淀粉样蛋白升高的参与者被纳入A4研究，并被纳入这些分析。583人接受安慰剂治疗，564人接受索兰珠单抗治疗。
方法：PACC用于评估客观认知表现，CFI用于评估参与者及其研究伙伴的日常认知功能变化。淀粉样蛋白水平以Centiloid三元组为特征（<46.1CL，46.1至77.2CL，>77.2CL）。参与者意识到他们的淀粉样蛋白状态升高，但不是他们的CLTertile,或特定水平的淀粉样蛋白。在评估可用的所有访视中检查参与者与研究伙伴CFI和PACC之间的纵向相关性。还检查了基线淀粉样蛋白对CFI和PACC关联的影响。
结果：参与者和研究伙伴CFI均在研究期间增加，表明认知功能恶化。治疗组的结果没有差异。在研究过程中，参与者和研究伙伴的较高CFI和较差PACC之间的关联逐渐增强。到第168周，PACC与研究伙伴CFI的相关性明显高于与参与者CFI的相关性。研究伙伴CFI和PACC之间的更强相关性是由淀粉样蛋白最高的部分驱动的。
结论：参与者和研究伙伴都报告了生物标志物证实并披露了临床前AD的参与者的日常认知功能的细微变化。此外，研究伙伴报告与认知能力下降密切相关，尤其是那些淀粉样蛋白负荷最高的人群。
目的：我们试图通过在A4研究过程中分别比较参与者和研究伙伴CFI的纵向模式，以及它们与通过基线淀粉样颗粒分层的PACC的关联来扩展以前的研究结果。
方法：认知未受损的老年参与者和他们的研究伙伴在淀粉样蛋白PET公开之前进行筛查，然后在研究的3次后续访问（第48周，第168周，第240周）时独立给予CFI。还纵向检查了与CFI给药同时进行的访视时收集的PACC。
方法：A4研究在澳大利亚的67个地点进行，加拿大,Japan,和美国。
方法：1,147名基于florbetapirPET的淀粉样蛋白升高的参与者被纳入A4研究，并被纳入这些分析。583人接受安慰剂治疗，564人接受索兰珠单抗治疗。
方法：PACC用于评估客观认知表现，CFI用于评估参与者及其研究伙伴的日常认知功能变化。淀粉样蛋白水平以Centiloid三元组为特征（<46.1CL，46.1至77.2CL，>77.2CL）。参与者意识到他们的淀粉样蛋白状态升高，但不是他们的CLTertile,或特定水平的淀粉样蛋白。在评估可用的所有访视中检查参与者与研究伙伴CFI和PACC之间的纵向相关性。还检查了基线淀粉样蛋白对CFI和PACC关联的影响。
结果：参与者和研究伙伴CFI均在研究期间增加，表明认知功能恶化。治疗组的结果没有差异。在研究过程中，参与者和研究伙伴的较高CFI和较差PACC之间的关联逐渐增强。到第168周，PACC与研究伙伴CFI的相关性明显高于与参与者CFI的相关性。研究伙伴CFI和PACC之间的更强相关性是由淀粉样蛋白最高的部分驱动的。
结论：参与者和研究伙伴都报告了生物标志物证实并披露了临床前AD的参与者的日常认知功能的细微变化。此外，研究伙伴报告与认知能力下降密切相关，尤其是那些淀粉样蛋白负荷最高的人群。
