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Meta-Analysis
. 2023 Apr;19(4):1292-1299.
doi: 10.1002/alz.12768. Epub 2022 Aug 31.

Effect of reduction in brain amyloid levels on change in cognitive and functional decline in randomized clinical trials: An instrumental variable meta-analysis

Menglan Pang  1   2 , Ling Zhu  1   2 , Audrey Gabelle  1   2 , Arie R Gafson  1   2 , Robert W Platt  3 , James E Galvin  4 , Pierre Krolak-Salmon  5   6 , Ivana Rubino  2 , Carl de Moor  1   2 , Shibeshih Belachew  1   2 , Changyu Shen  1   2
Affiliations
Meta-Analysis

Effect of reduction in brain amyloid levels on change in cognitive and functional decline in randomized clinical trials: An instrumental variable meta-analysis

Menglan Pang et al. Alzheimers Dement. 2023 Apr.

Abstract

Introduction: 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.

Keywords: Alzheimer's disease; amyloid; causal effect; clinical trials; cognitive decline.

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References

REFERENCES

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