Precision medicine analysis of heterogeneity in individual-level treatment response to amyloid beta removal in early Alzheimer's disease.
Alzheimers Dement
; 20(2): 1102-1111, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-37882364
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 (Aß) 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 Aß removal therapy have a pattern of more severe neurodegenerative process.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
/
Disfunção Cognitiva
Limite:
Humans
Idioma:
En
Revista:
Alzheimers Dement
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos