Alzheimer’s disease (AD) is a neurological disorder with variability in pathology and clinical progression. AD patients may differ in individual-level benefit from amyloid beta removal therapy.
Random forest models were applied to the EMERGE trial to create an individual-level treatment response (ITR) score which represents individual-level benefit of high-dose aducanumab relative to the placebo. This ITR score was used to test the existence of heterogeneity in treatment effect (HTE).
We found statistical evidence of HTE in the Clinical Dementia Rating–Sum of Boxes (CDR-SB;P =  0.034). The observed CDR-SB benefit was 0.79 points greater in the group with the top 25% of ITR score compared to the remaining 75% (P = 0.020). Of note, the highest treatment responders had lower hippocampal volume, higher plasma phosphorylated tau 181 and a shorter duration of clinical AD at baseline.
This ITR analysis provides a proof of concept for precision medicine in future AD research and drug development.

Emerging trials have shown a population-level benefit from amyloid beta (Aβ) removal in slowing cognitive decline in early Alzheimer’s disease (AD).
This work demonstrates significant heterogeneity of individual-level treatment effect of aducanumab in early AD.
The greatest clinical responders to Aβ removal therapy have a pattern of more severe neurodegenerative process.

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This post is Copyright: Menglan Pang,
Audrey Gabelle,
Paramita Saha‐Chaudhuri,
Willem Huijbers,
Arie Gafson,
Paul M. Matthews,
Lu Tian,
Ivana Rubino,
Richard Hughes,
Carl de Moor,
Shibeshih Belachew,
Changyu Shen | October 26, 2023

Wiley: Alzheimer’s & Dementia: Table of Contents