Pang Menglan, Zhu Ling, Gabelle Audrey, Gafson Arie R, Platt Robert W, Galvin James E, Krolak-Salmon Pierre, Rubino Ivana, de Moor Carl, Belachew Shibeshih, Shen Changyu
Biogen Digital Health, Biogen, Cambridge, Massachusetts, USA.
Biogen, Cambridge, Massachusetts, USA.
Alzheimers Dement. 2023 Apr;19(4):1292-1299. doi: 10.1002/alz.12768. Epub 2022 Aug 31.
Whether the reduction in brain amyloid beta (Aβ) plaque alone may substantially slow cognitive and functional decline in patients with dementia or mild cognitive impairment due to Alzheimer's disease (AD) remains debated.
An instrumental variable meta-analysis was performed to infer the effect of change in positron emission tomography (PET)-measured Aβ standardized uptake value ratio (SUVR) on cognitive and functional decline.
Pooling data from 16 randomized trials demonstrates that each 0.1-unit decrease in PET Aβ SUVR is associated with a reduction (95% confidence interval) by 0.09 (0.034-0.15), 0.33 (0.12-0.55), and 0.13 (0.017-0.24) point in the average change of the Clinical Dementia Rating-Sum of Boxes, the Alzheimer's Disease Assessment Scale-Cognitive Subscale, and the Mini-Mental State Examination, respectively.
This meta-analysis provides statistically significant evidence of a likely causal relationship between a reduction in Aβ plaque and a reduction in cognitive and functional decline in patients with AD.
A widely cited meta-analysis article concluded amyloid beta reduction does not substantially improve cognition. We identified data inconsistencies in the initial publication and found new trial data. We repeated the meta-analysis after correcting data inconsistencies and adding new trial data. Updated results suggested statistically significant clinical benefit of amyloid beta reduction. Amyloid beta is a viable biological target for the treatment and prevention of AD.
仅脑淀粉样β蛋白（Aβ）斑块的减少是否能显著减缓因阿尔茨海默病（AD）导致的痴呆或轻度认知障碍患者的认知和功能衰退，仍存在争议。
进行了一项工具变量荟萃分析，以推断正电子发射断层扫描（PET）测量的Aβ标准化摄取值比率（SUVR）变化对认知和功能衰退的影响。
汇总16项随机试验的数据表明，PET Aβ SUVR每降低0.1个单位，临床痴呆评定量表-总盒数、阿尔茨海默病评估量表-认知分量表和简易精神状态检查的平均变化分别降低（95%置信区间）0.09（0.034 - 0.15）、0.33（0.12 - 0.55）和0.13（0.017 - 0.24）分。
这项荟萃分析提供了具有统计学意义的证据，表明Aβ斑块减少与AD患者认知和功能衰退减少之间可能存在因果关系。
一篇被广泛引用的荟萃分析文章得出结论，淀粉样β蛋白减少并不能显著改善认知。我们在最初发表的文章中发现了数据不一致之处，并找到了新的试验数据。在纠正数据不一致并添加新的试验数据后，我们重复了荟萃分析。更新后的结果表明，淀粉样β蛋白减少具有统计学意义的临床益处。淀粉样β蛋白是治疗和预防AD的一个可行的生物学靶点。
