Association between antibiotics and dementia risk: A retrospective cohort study

Abstract

Background: The possible relation between antibiotic exposure and the alteration of gut microbiota, which may affect dementia risk, has been revealed. However, the association between antibiotics and dementia incidence has rarely been studied. We aimed to determine the association between antibiotic exposure and the risk of dementia.Methods: This population-based retrospective cohort study used data from the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) in South Korea. Exposure was the cumulative days of antibiotic prescription from 2002 to 2005. Newly diagnosed overall dementia, Alzheimer’s disease (AD), and vascular dementia (VD) were identified based on diagnostic codes and prescriptions for dementia-related drugs. The follow-up investigation was carried out from 1 January 2006 to 31 December 2013. The Cox proportional hazards regression was used to assess the association between cumulative antibiotic prescription days and dementia incidence.Results: A total of 313,161 participants were analyzed in this study. Compared to antibiotic non-users, the participants who used antibiotics for 91 or more days had an increased risk of overall dementia [adjusted hazard ratio (aHR), 1.44; 95% confidence interval (CI), 1.19–1.74], AD (aHR, 1.46; 95% CI, 1.17–1.81), and VD (aHR, 1.38; 95% CI, 0.83–2.30). Those who used five or more antibiotic classes had higher risks of overall dementia (aHR, 1.28; 95% CI, 1.00–1.66) and AD (aHR, 1.34; 95% CI, 1.00–1.78) than antibiotic non-users.Conclusion: Antibiotic exposure may increase the risk of dementia in a cumulative duration-dependent manner among adult participants. Future studies are needed to assess the causality between the long-term prescription of antibiotics and dementia risk.

Safety and Tolerability of Antimicrobial Agents in the Older Patient

“…Furthermore, prolonged administration of some antimicrobial medications, such as vancomycin, ampicillin, and streptozocin, may induce profound changes in the gut microbiota composition, altering the gut–brain axis involved in the pathogenesis of several neurodegenerative disorders [ 162 – 165 ]. A cumulative duration-dependent relationship between dementia incidence and days of antibiotic exposure recently emerged in a retrospective cohort study [ 166 ]. The association was significant after adjustment for several confounding factors potentially related to cognitive decline, including infectious diseases and dysphagia [ 166 ].…”

“…A cumulative duration-dependent relationship between dementia incidence and days of antibiotic exposure recently emerged in a retrospective cohort study [ 166 ]. The association was significant after adjustment for several confounding factors potentially related to cognitive decline, including infectious diseases and dysphagia [ 166 ]. Furthermore, exposure to long-term antibiotic use during mid-life was recently associated with decline in cognitive performance [ 167 ].…”

“…The proportion of inappropriate antimicrobial treatment varied widely across studies and care settings, as a likely result of heterogeneity of criteria used to evaluate appropriateness and inappropriateness of antimicrobial prescriptions; however, despite the fact that the definition of a gold-standard measure for inappropriate antimicrobial use has not yet been provided, inappropriate antimicrobial prescribing deserves to be addressed because it is associated with poor outcomes among older individuals [ 230 ]. In order to improve the appropriateness of antibiotic prescriptions in acute and long-term care settings, several antimicrobial stewardship (AMS) strategies have been implemented and taken into consideration (Table 6 ) [ 166 , 230 – 238 ]. AMS is defined as the careful and responsible management of antimicrobial medications used to treat or prevent infections, in order to provide a prescription of the right drug, at the right time, at the correct dose, and for the appropriate duration [ 239 ].…”

“…Chronic use of renally excreted antimicrobials should be avoided 4. A rapid but timely de-escalation is recommended to reduce the duration of empirical antibiotic treatments [ 233 ] Use of outpatient broad-spectrum or parenteral antimicrobials for older people with end-stage illness or advanced dementia [ 166 ] Broad-spectrum use of antibiotics in end-stage patients have shown contrasting results [ 235 ] Caution is needed when administering antibiotics to patients with dementia because of the potential of antibiotic-induced cognitive decline. Treatment of infection in advanced dementia has led to contrasting results 1.…”

Association between Antibiotic Use and Subsequent Risk of Prostate Cancer: A Retrospective Cohort Study in South Korea

“…The possibility of an association between antibiotic usage and various types of cancer, including prostate cancer, has been suggested in previous studies [6][7][8]. Previous cohort studies have reported that long-term antibiotic exposure may be associated with the risk of other diseases such as diabetes, dementia, and obesity [9][10][11]. The effects of antibiotics on gut microbiota diversity reduction and alteration have been revealed [12].…”