A new study suggests a link between antibiotic use in midlife and small decreases in cognitive test scores later in life.
The study, led by researchers from Harvard Medical School and Rush Medical College, found that women who reported at least 2 months of antibiotic exposure in their mid-50s had lower mean scores on a standard cognitive assessment 7 years later compared with those who weren't exposed to antibiotics. The relationship persisted after adjustment for other lifestyle risk factors.
The results were published this week in PLOS One.
Participants tested 7 years after antibiotic exposure
To investigate a potential link between midlife antibiotic exposure and subsequent cognition, the researchers conducted a population-based cohort study among participants in the Nurses' Health Study II (NHS2), an ongoing prospective study that began in 1989 with the enrollment of 116,430 female nurses ages 25 to 42.
Every 2 years, participants in NHS2 fill out a questionnaire with detailed information on lifestyle, medication, and health-related factors. NHS2 and the original Nurses Health Study, established in 1976, are two of the largest investigations into risk factors for major chronic diseases in women.
In 2009, NHS2 participants (mean age 57.4) were asked to report their total duration of antibiotic use in seven categories over the preceding 4 years, and the reasons antibiotics were used. Seven years after primary antibiotic exposure was ascertained from the 2009 survey, the researchers administered CogState—a standardized, online cognitive test that measures psychomotor function and information processing speed, vigilance and visual attention, visual learning and short-term memory, and attention and working memory. The mean age of participants at the time of testing was 61.7 years.
The researchers then used multivariate linear regression models to examine midlife antibiotic use in relation to composite scores for psychomotor speed and attention, learning and working memory, and global cognition. They adjusted the models for age at the time of cognitive assessment and educational attainment of participants' parents and spouses, along with factors such as body mass index, symptoms of depression or antidepressant use, smoking status, and comorbidities.
Of the 15,129 women who completed the CogState battery, 14,542 were included in the analysis. Compared with women who did not use antibiotics in midlife, women who used antibiotics for at least 2 months had mean CogState scores that were lower by 0.11 standard units for global cognition (Ptrend = 0.002), 0.13 for psychomotor speed and attention (Ptrend = 0.004), and 0.10 for learning and working memory (Ptrend = 0.03).
The association remained after adjusting for confounding factors, and similar associations were found in subgroup analyses.
The mean difference in score associated with each additional year of age was (–0.03) for global cognition, (–0.04) for psychomotor speed and attention, and (–0.03) for learning and working memory.
"Thus the relation of antibiotic use to cognition was roughly equivalent to that found for three to four years of aging," the study authors wrote.
Among the limitations noted are the fact that antibiotic information was self-reported several years after use, and thus may be subject to recall bias, and that the data are limited to women.
The gut-brain axis
Although the study does not provide evidence of a causal link between chronic antibiotic use in midlife and the lower scores on the CogState test, the authors note that experimental studies in mice have suggested a relationship between antibiotics and cognition. Also, epidemiologic data have found associations between antibiotic exposure in infancy and lower cognitive score later in life.
In addition, a 2012 clinical trial in patients with Alzheimer's disease found that 12 months of antibiotic use led to declines in cognitive scores compared with placebo.
The possible mechanism linking antibiotic use to cognitive function could be the gut-brain axis. Antibiotic use has been found to have a profound impact on the microbial composition of the gut, and antibiotic-induced alterations of gut microbiota have been found to persist for years. Since research in both humans and animals suggests that differences in the gut microbiome may be connected to neuropsychiatric illnesses via the gut-brain axis, the authors hypothesize there could be a connection to cognitive function, as well.
"These data provide a better understanding of potential complications of antibiotics throughout life, as well as generate hypotheses about the role of the gut microbiome in cognition," they wrote.
