Department of Psychiatry, University Hospital, Angers, France.
Centre Inserm U1219 Bordeaux Population Health, CIC1401-EC, Institut de Santé Publique, d'Epidémiologie et de Développement, Université de Bordeaux, CHU de Bordeaux, Pôle Santé Publique, Bordeaux, France.
Am J Geriatr Psychiatry. 2024 Jun;32(6):665-677. doi: 10.1016/j.jagp.2023.10.002. Epub 2023 Oct 19.
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.
我们试图研究在基线时有单纯记忆主诉或轻度认知障碍的非痴呆老年人群中，来自于使用 2-脱氧-2-氟-D-葡萄糖（FDG）正电子发射断层扫描（PET）的 MEMENTO 临床队列的慢性苯二氮䓬类药物（BZD）使用与脑代谢之间的关联。
我们的分析集中在 3 个水平：（1）全脑标准化摄取值（SUVR）的平均值，（2）阿尔茨海默病（AD）特异性感兴趣区（ROI），和（3）大脑总 SUVR 与不同解剖 ROI 的比值。脑代谢来自于 2-脱氧-2-氟-D-葡萄糖-FDG-PET，并使用经过年龄、性别、教育、APOE ε4 拷贝数、认知和神经心理学评估、重性抑郁发作史和抗抑郁药使用调整的多元线性回归来比较慢性 BZD 使用者与非使用者之间的差异。
我们发现，在整个大脑（β=0.03；p=0.038）和右侧杏仁核（β=0.32；p=0.012）中，慢性 BZD 使用者（n=192）的 SUVR 显著高于非使用者（n=1122）。BZDs 的半衰期（短作用和长作用 BZDs）（p=0.051）和 Z 类药物催眠治疗（p=0.060）与右侧杏仁核的 SUVR 呈趋势相关。在其他 ROI 中未发现显著相关性。
我们的研究首次发现慢性 BZD 使用者的整体代谢更高，右侧杏仁核的特定代谢更高。由于 BZDs 的急性给药往往会降低脑代谢，这些发现可能与大脑适应全球代谢上调的代偿机制相对应，而右侧杏仁核则是特定的焦点。
