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Cognitive Effects of the BET Protein Inhibitor Apabetalone: A Prespecified Montreal Cognitive Assessment Analysis Nested in the BETonMACE Randomized Controlled Trial
- Source :
- Journal of Alzheimer's Disease
- Publication Year :
- 2021
- Publisher :
- IOS Press, 2021.
-
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.
- Subjects :
- Male
medicine.medical_specialty
BET inhibitor
Placebo
Epigenesis, Genetic
law.invention
Randomized controlled trial
law
Internal medicine
medicine
Humans
Dementia
Cognitive Dysfunction
Effects of sleep deprivation on cognitive performance
Cognitive decline
Vascular dementia
Aged
Quinazolinones
apabetalone
epigenetics
business.industry
General Neuroscience
Montreal Cognitive Assessment
clinical trial
montreal cognitive assessment
Cognition
General Medicine
Middle Aged
Mental Status and Dementia Tests
medicine.disease
Psychiatry and Mental health
Clinical Psychology
Cardiovascular Diseases
Female
Geriatrics and Gerontology
business
Alzheimer’s disease
Research Article
Subjects
Details
- ISSN :
- 18758908 and 13872877
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- Journal of Alzheimer's Disease
- Accession number :
- edsair.doi.dedup.....188b82b89f296b0c5f10f0a31785301c
- Full Text :
- https://doi.org/10.3233/jad-210570