Cognitive Effects of the BET Protein Inhibitor Apabetalone: A Prespecified Montreal Cognitive Assessment Analysis Nested in the BETonMACE Randomized Controlled Trial
| Autor: | Henrik Zetterberg, Bengt Winblad, Chris Halliday, Kamyar Kalantar-Zadeh, Jeffrey L. Cummings, Gregory G. Schwartz, Kausik K. Ray, Stephen J. Nicholls, Aziz Khan, Michael O. Sweeney, Jan O. Johansson, Peter P. Toth, Ewelina Kulikowski, Kenneth Lebioda, Henry N. Ginsberg, Norman C.W. Wong |
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| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | Journal of Alzheimer's Disease |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-210570 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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