New research suggests antibiotic use in older adults is not associated with increased risk of dementia or cognitive decline.
The findings, published today in the journal Neurology, are from a post hoc analysis of data from a clinical trial involving more than 13,000 healthy Australian adults aged 70 and older. In a follow-up over 5 years, the analysis found no increase in cases of dementia or cognitive impairment among those who had taken antibiotics compared with those who hadn't, including those who had taken repeated courses of antibiotics, used them continuously, or used specific antibiotic classes.
The study authors say the findings should reassure seniors.
"Given that older adults are more frequently prescribed antibiotics and are also at higher risk for cognitive decline, these findings offer reassurance about using these medications," co-lead author Andrew Chan, MD, MPH, of Harvard Medical School, said in a press release from the American Academy of Neurology, which publishes the journal.
For the study, Chan and colleagues from the University of Iowa and Monash University in Australia analyzed antibiotic prescription data and cognitive test results from participants in the ASPREE (Aspirin in reducing events in the elderly) trial, which examined the health impacts of daily low-aspirin in more than 16,000 Australians aged 70 years and older. Launched in 2010, the trial was extended as an observational study in 2018 with patients who had not withdrawn or died.
The researchers wanted to examine potential links between antibiotic use and dementia or cognitive impairment because animal studies have hinted that the impact of antibiotics, which can kill both pathogenic and beneficial bacteria, on bacterial diversity in the gut microbiome may affect cognitive function.
"Although some species begin to re-cover after antibiotic treatment, antibiotic-induced perturbance to the gut microbial communities can persist for months to up to 2 years," they wrote. "As gut dysbiosis has been implicated in the pathophysiology of cognitive impairment, it is hypothesized that high levels of cumulative antibiotic exposure may lead to cognitive decline."
In addition, some observational studies have found early- and mid-life antibiotic use is associated with worse cognitive development or decline, respectively. But how antibiotic use later in life affects cognition has not been thoroughly investigated, the researchers said.
A total of 13,571 participants were involved in the study, all of whom were dementia-free when they entered the ASPREE trial. Using prescription data from Australia's Pharmaceutical Benefits Scheme (PBS), the researchers found that 8,481 participants (62.5%) had used any antibiotics at least once between trial enrollment and their second annual follow-up visit.
Given that older adults are more frequently prescribed antibiotics and are also at higher risk for cognitive decline, these findings offer reassurance about using these medications.
The researchers assessed changes in participant cognitive function using a series of cognitive tests that evaluate global cognition, episodic memory, psychomotor speed, and language and executive function. The tests were conducted at baseline and at the 1-year follow-up visit, then every 2 years. A panel of neurologists, neuropsychologists, and geriatricians reviewed the results of those tests to determine which participants had dementia and which had cognitive impairment, no dementia (CIND).
During a median of 4.7 years after the second annual follow-up visit, the researchers documented 461 incident dementia cases and 2,576 incident CIND cases, of which 289 and 1,626 were in antibiotic users, respectively. After adjusting for baseline cognitive testing scores, family history of dementia, sociodemographic and lifestyle factors, use of other medications known to affect cognition, and other health-related risk factors, the researchers found that antibiotic use was not associated with increased risk of dementia (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.84 to 1.25) or CIND (HR, 1.02; 95% CI, 0.94 to 1.11) compared with non-use.
When the researchers categorized participants by the cumulative frequency of antibiotic use (0 to 5 or more prescriptions) or long-term use (6 or more antibiotic dispenses within any 6-month interval), they found that neither higher antibiotic use frequency nor long-term use were associated with dementia or CIND. Similar results were found when they looked at specific antibiotic classes, including those that can reach higher concentrations in the central nervous system (e.g., tetracyclines, sulfonamide/trimethoprim, fluoroquinolones, and metronidazole).
"Our study, combining government-based, objective prescription data and rigorous clinical ascertainment of dementia and cognitive impairment status, does not support an association between antibiotic-associated disruption of the gut microbiome during later adulthood and dementia risk," the authors concluded.
Chan and his colleagues note, however, that the findings do have some limitations. Among them are the fact that the PBS data may not accurately reflect actual antibiotic use. In addition, all participants were free of dementia and independence-limiting physical disability, which means the findings may not be generalizable to all older adults. Finally, the duration of the study follow-up was relatively short, and analysis of the long-term effects of antibiotic use in older adults on cognition is needed.
In an accompanying editorial, epidemiologists with the Johns Hopkins University Bloomberg School of Public Health also note that almost all the participants were White and had a lower baseline prevalence of diabetes and chronic kidney disease than the general population in Australia.
"Readers should be cautious when interpreting and implementing these findings to inform rigorous clinical practice," Wenjie Cai, PhD, and Alden Gross, PhD, wrote. "This study offers insights for clinicians and health care providers working with healthy older adults who share similar health profiles with those in this study."
Cai and Gross say future studies should include more representative study populations, and examine precise dose and duration of antibiotic use, dose-response relationships, and the impact of different antibiotic classes on cognition.