Demographic Studies, German Center for Neurodegenerative Diseases, Bonn, Germany.
Institut für Biologische Informationsprozesse, Strukturbiochemie (IBI-7), Forschungszentrum Jülich GmbH, Jülich, Germany.
J Alzheimers Dis. 2023;93(4):1329-1339. doi: 10.3233/JAD-221153.
Antibiotics for systemic use may increase the risk of neurodegeneration, yet antibiotic therapy may be able to halt or mitigate an episode of neurodegenerative decline.
To investigate the association of sporadic use of antibiotics and subsequent dementia risk (including Alzheimer's disease).
We used data from the largest public health insurance fund in Germany, the Allgemeine Ortskrankenkasse (AOK). Each of the 35,072 dementia cases aged 60 years and older with a new dementia diagnosis during the observation period from 2006 to 2018 was matched with two control-patients by age, sex, and time since 2006. We ran conditional logistic regression models for dementia risk in terms of odds ratios (OR) as a function of antibiotic use for the entire antibiotic group and for each antibiotic subgroup. We controlled for comorbidities, need for long-term care, hospitalizations, and nursing home placement.
Antibiotic use was positively associated with dementia (OR = 1.18, 95% confidence interval (95% CI):1.14-1.22), which became negative after adjustment for comorbidities, at least one diagnosis of bacterial infection or disease, and covariates (OR = 0.93, 95% CI:0.90-0.96). Subgroups of antibiotics were also negatively associated with dementia after controlling for covariates: tetracyclines (OR = 0.94, 95% CI:0.90-0.98), beta-lactam antibacterials, penicillins (OR = 0.93, 95% CI:0.90-0.97), other beta-lactam antibacterials (OR = 0.92, 95% CI:0.88-0.95), macrolides, lincosamides, and streptogramins (OR = 0.88, 95% CI:0.85-0.92), and quinolone antibacterials (OR = 0.96, 95% CI:0.92-0.99).
Our results suggest that there was a decreased likelihood of dementia for preceding antibiotic use. The benefits of antibiotics in reducing inflammation and thus the risk of dementia need to be carefully weighed against the increase in antibiotic resistance.
全身性使用抗生素可能会增加神经退行性变的风险,但抗生素治疗也许能够阻止或减轻神经退行性下降的发作。
研究散发性使用抗生素与随后发生痴呆风险(包括阿尔茨海默病)之间的关联。
我们使用了德国最大的公共健康保险公司 Allgemeine Ortskrankenkasse(AOK)的数据。在 2006 年至 2018 年的观察期间,对于每一位年龄在 60 岁及以上且新诊断为痴呆的 35072 例痴呆病例,我们均按照年龄、性别和自 2006 年以来的时间,与两位对照患者进行匹配。我们根据比值比(OR),利用条件逻辑回归模型,分析了作为整个抗生素组和每个抗生素亚组的痴呆风险函数的抗生素使用情况。我们还控制了合并症、长期护理需求、住院和疗养院安置情况。
抗生素的使用与痴呆呈正相关(OR=1.18,95%置信区间(95%CI):1.14-1.22),但在调整了合并症、至少一次细菌感染或疾病诊断以及混杂因素后,该相关性变为负相关(OR=0.93,95%CI:0.90-0.96)。在控制了混杂因素后,抗生素的亚组也与痴呆呈负相关:四环素(OR=0.94,95%CI:0.90-0.98)、β-内酰胺类抗菌药物、青霉素(OR=0.93,95%CI:0.90-0.97)、其他β-内酰胺类抗菌药物(OR=0.92,95%CI:0.88-0.95)、大环内酯类、林可酰胺类和链阳菌素类(OR=0.88,95%CI:0.85-0.92)和喹诺酮类抗菌药物(OR=0.96,95%CI:0.92-0.99)。
我们的研究结果表明,先前使用抗生素可能会降低痴呆的发生几率。在权衡抗生素治疗减少炎症和降低痴呆风险的益处时,需要仔细考虑抗生素耐药性的增加。