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

• What is the primary question addressed by this study? This study explores the association between chronic BZD use and FDG-PET brain metabolism in the MEMENTO clinical cohort of nondemented older adults with isolated memory complaint or mild cognitive impairment. • What is the main finding of this study? The authors found that brain metabolism was significantly greater in chronic BZD users compared to non-users in the whole brain and in the right amygdala, independent of potential confounders. • What is the meaning of the finding? Chronic BZD use may induce a compensatory mechanism which consists in a global metabolism upregulation in the brain, with a specific focus on the right amygdala as a specific target for BZD action. 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. [ABSTRACT FROM AUTHOR]