Cerebral Metabolic Signature of Chronic Benzodiazepine Use in Nondemented Older Adults: An FDG-PET Study in the MEMENTO Cohort.

We sought to examine the association between chronic Benzodiazepine (BZD) use and brain metabolism obtained from 2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) in the MEMENTO clinical cohort of nondemented older adults with an isolated memory complaint or mild cognitive impairment at baseline. Our analysis focused on 3 levels: (1) the global mean brain standardized uptake value (SUVR), (2) the Alzheimer's disease (AD)-specific regions of interest (ROIs), and (3) the ratio of total SUVR on the brain and different anatomical ROIs. Cerebral metabolism was obtained from 2-deoxy-2-fluoro-D-glucose-FDG-PET and compared between chronic BZD users and nonusers using multiple linear regressions adjusted for age, sex, education, APOE ε 4 copy number, cognitive and neuropsychiatric assessments, history of major depressive episodes and antidepressant use. We found that the SUVR was significantly higher in chronic BZD users (n = 192) than in nonusers (n = 1,122) in the whole brain (beta = 0.03; p = 0.038) and in the right amygdala (beta = 0.32; p = 0.012). Trends were observed for the half-lives of BZDs (short- and long-acting BZDs) (p = 0.051) and Z-drug hypnotic treatments (p = 0.060) on the SUVR of the right amygdala. We found no significant association in the other ROIs. Our study is the first to find a greater global metabolism in chronic BZD users and a specific greater metabolism in the right amygdala. Because the acute administration of BZDs tends to reduce brain metabolism, these findings may correspond to a compensatory mechanism while the brain adapts with global metabolism upregulation, with a specific focus on the right amygdala.

Informations de copyright

Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

CONFLICT OF INTEREST TD reports personal fees from Lundbeck, Otsuka and Eisai. WE reports personal fees from Eisai, Janssen, Lundbeck, Otsuka, UCB, Roche and Chugai. VC reports personal fees from Janssen and Bristol Meyers Squibb. All other authors declare no competing interests. To the best of our knowledge, among the pharmaceutical companies mentioned here, only Roche is involved in the production of benzodiazepines (namely, diazepam, in its marketed form of valium in France). Neither Roche nor any of the other pharmaceutical companies mentioned here were consulted regarding the planning or analysis of the study.