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Effect of reduction in brain amyloid levels on change in cognitive and functional decline in randomized clinical trials: An instrumental variable meta‐analysis
Author(s) -
Pang Menglan,
Zhu Ling,
Gabelle Audrey,
Gafson Arie R.,
Platt Robert W,
Galvin James E,
KrolakSalmon Pierre,
Rubino Ivana,
de Moor Carl,
Belachew Shibeshih,
Shen Changyu
Publication year - 2023
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12768
Subject(s) - clinical dementia rating , dementia , meta analysis , cognitive decline , cognition , randomized controlled trial , neuroimaging , alzheimer's disease , medicine , alzheimer's disease neuroimaging initiative , clinical trial , confidence interval , positron emission tomography , psychology , disease , psychiatry , neuroscience
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. Methods 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. Results 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. Discussion 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. Highlights 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.