Cummings, J;
Schwartz, GG;
Nicholls, SJ;
Khan, A;
Halliday, C;
Toth, PP;
Sweeney, M;
... Ray, KK; + view all
(2021)
Cognitive Effects of the BET Protein Inhibitor Apabetalone: A Prespecified Montreal Cognitive Assessment Analysis Nested in the BETonMACE Randomized Controlled Trial.
Journal of Alzheimer's Disease
10.3233/JAD-210570.
(In press).
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Abstract
BACKGROUND: Epigenetic changes may contribute importantly to cognitive decline in late life including Alzheimer's disease (AD) and vascular dementia (VaD). Bromodomain and extra-terminal (BET) proteins are epigenetic "readers" that may distort normal gene expression and contribute to chronic disorders. OBJECTIVE: To assess the effects of apabetalone, a small molecule BET protein inhibitor, on cognitive performance of patients 70 years or older participating in a randomized trial of patients at high risk for major cardiovascular events (MACE). METHODS: The Montreal Cognitive Assessment (MoCA) was performed on all patients 70 years or older at the time of randomization. 464 participants were randomized to apabetalone or placebo in the cognition sub-study. In a prespecified analysis, participants were assigned to one of three groups: MoCA score≥26 (normal performance), MoCA score 25-22 (mild cognitive impairment), and MoCA score≤21 (dementia). Exposure to apabetalone was equivalent in the treatment groups in each MoCA-defined group. RESULTS: Apabetalone was associated with an increased total MoCA score in participants with baseline MoCA score of≤21 (p = 0.02). There was no significant difference in change from baseline in the treatment groups with higher MoCA scores. In the cognition study, more patients randomized to apabetalone discontinued study drug for adverse effects (11.3% versus 7.9%). CONCLUSION: In this randomized controlled study, apabetalone was associated with improved cognition as measured by MoCA scores in those with baseline scores of 21 or less. BET protein inhibitors warrant further investigation for late life cognitive disorders.
| Type: | Article |
|---|---|
| Title: | Cognitive Effects of the BET Protein Inhibitor Apabetalone: A Prespecified Montreal Cognitive Assessment Analysis Nested in the BETonMACE Randomized Controlled Trial |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3233/JAD-210570 |
| Publisher version: | https://doi.org/10.3233/JAD-210570 |
| Language: | English |
| Additional information: | © 2021 – The authors. Published by IOS Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC 4.0). |
| Keywords: | Alzheimer’s disease, BET inhibitor, apabetalone, clinical trial, epigenetics, montreal cognitive assessment |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10135950 |
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