AI Article Synopsis
- Alzheimer's disease (AD) shows variability in how patients respond to amyloid beta removal therapy, impacting individual treatment benefits.
- A study utilized random forest models on the EMERGE trial to create an individual-level treatment response (ITR) score, highlighting significant differences in treatment effects among patients.
- Findings revealed that the top 25% of responders had distinct characteristics, such as lower hippocampal volume and more advanced disease, suggesting that precision medicine approaches could enhance future AD research and treatment strategies.*
Article Abstract
Introduction: 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.
Methods: 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).
Results: 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.
Discussion: This ITR analysis provides a proof of concept for precision medicine in future AD research and drug development.
Highlights: 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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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917030 | PMC |
| http://dx.doi.org/10.1002/alz.13431 | DOI Listing |
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