Sporadic Use of Antibiotics in Older Adults and the Risk of Dementia: A Nested Case–Control Study Based on German Health Claims Data

Article type: Research Article

Authors: Rakuša, Elena^{a; *} | Fink, Anne^a | Tamgüney, Gültekin^{b; c} | Heneka, Michael T.^d | Doblhammer, Gabriele^{a; e}

Affiliations: [a] Demographic Studies, German Center for Neurodegenerative Diseases, Bonn, Germany | [b] Institut für Biologische Informationsprozesse, Strukturbiochemie (IBI-7), Forschungszentrum Jülich GmbH, Jülich, Germany | [c] Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany | [d] Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg | [e] Institute for Sociology and Demography, University Rostock, Rostock, Germany

Correspondence: [*] Correspondence to: Elena Rakuša, MSc, German Center for Neurodegenerative Diseases, Demographic Studies, Bonn, Germany. Tel.: +49 381 498 4071; E-mail: elena.rakusa@dzne.de.

Abstract: Background: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. Objective:To investigate the association of sporadic use of antibiotics and subsequent dementia risk (including Alzheimer’s disease). Methods: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. Results: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). Conclusion: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.

Keywords: Alzheimer’s disease, antibiotics, conditional logistic regression, dementia, epidemiology, nested case-control studies

DOI: 10.3233/JAD-221153

Journal: Journal of Alzheimer's Disease, vol. 93, no. 4, pp. 1329-1339, 2023