March 23, 2022

expert reaction to study looking at cognitive decline in women taking antibiotics in later life

A study published in PLOS ONE looks at midlife antibiotic use and subsequent cognitive function in women.

Prof Tom Dening, Professor of Dementia Research and Honorary Consultant in Old Age Psychiatry at the University of Nottingham, said:

“I think it is premature to regard this hypothesis as any more than speculative based on the data in this paper. One problem is that the participants were not randomly assigned to antibiotics versus no antibiotics. One presumes that there were good medical reasons for the decision to prescribe, and therefore that a woman receiving antibiotics for more than two months might well have worse general health than a woman who did not. For example, people taking antibiotics for more than two months were more likely to be current smokers, more likely to have long-term conditions such as hypertension, diabetes and chronic lung disease, and more likely to be receiving antidepressant medication. All of these factors could themselves contribute to the differences in cognitive decline seen between the two groups. The authors do briefly acknowledge this at the end of the paper. They have made some attempts to adjust the statistics to allow for these differences, but it is always difficult to adjust for multiple potential confounding variables.

“It should also be noted that the authors have a relatively young sample of participants (mean age<62 at the time of last cognitive assessment); and they are describing measures of cognitive decline, not incident dementia. Also, nurses may or may not be representative of the general female population.

“There isn’t any direct evidence produced in the paper that changes in gut flora are responsible for any cognitive changes, so this remains an interesting but unverified hypothesis. The question as to whether receiving antibiotics is a risk factor for dementia is however an important one and one that could be investigated by exploration of population-based general practice databases.”

Prof David Curtis, Honorary Professor, UCL Genetics Institute, said:

“This study notes that female nurses reporting chronic antibiotic use in middle age are less healthy and, when tested years later, have slightly lower cognitive function. It provides no evidence at all that antibiotic use actually causes reduced cognitive functioning. Although the authors admit this in the text, they make the claim in the abstract that their results ‘underscore the importance of antibiotic stewardship, especially among aging populations’. I’m afraid there’s no justification for this claim. Antibiotics should be used carefully and only when there are appropriate indications but there is no evidence that antibiotic usage harms cognitive function. Indeed, if somebody has a medical condition for which antibiotic treatment is indicated then not taking antibiotics could result in serious consequences.”

Prof Tara Spires-Jones, Deputy Director of the Centre for Discovery Brain Sciences, University of Edinburgh, said:

“This study from Dr Mehta and team observed that women who took antibiotics for more than two months in their 50s had slightly poorer cognition in their 60s than people who had not taken antibiotics for an extended period. While the authors attempted to statistically control for things that affect cognition during ageing like alcohol intake and body mass index, this type of study cannot prove that the antibiotic use directly impacted cognition.  It is possible that the long illnesses requiring antibiotic use were the contributors to cognitive decline instead of the antibiotics themselves.  These data would not stop me from taking antibiotics if needed, but overall of course we should be careful with antibiotic use for other reasons like antibiotic resistance.”

Prof Paul Matthews, Centre Director at the UK Dementia Research Institute at Imperial College London, Edmond and Lily Safra Chair, NIHR Senior Investigator, and Head of the Department of Brain Sciences, said:

“This large retrospective population study has identified an association between differences in cognition chronic antibiotic use.  This observation is interpreted as evidence that altering the microbiome with antibiotics could influence cognition in mid-life. However, this conclusion seems unwarranted as the investigators could not independently assess the potential influence of factors, such as chronic inflammation, that led to the need for the antibiotics.  As the populations were not independently randomised, other characteristics relevant to cognitive trajectories in later life also could have accounted for the observation.  The results therefore raise an important question, but do not provide a clear answer.”

Dr Susan Kohlhaas, Director of Research from Alzheimer’s Research UK, said:

“Our brains don’t exist in isolation from the rest of the body, but are connected in a variety of ways. Antibiotics are commonly prescribed for numerous treatable conditions and have revolutionised healthcare; however, little has been done to investigate their long-term effects on memory and thinking.

“Researchers found the changes in memory and thinking in this group of women were small and results do not suggest people who take antibiotics in midlife are any more likely to develop dementia. However, this research does suggest that it’s important to consider the longer-term outcomes of medication on memory and thinking.

“We can’t be sure of cause and effect in this sort of observational study and the authors highlight that these findings present a direction for future research, rather than being conclusive evidence of a link between antibiotics and memory and thinking skills.

“This study did not look at the direct impact antibiotics had on the gut bacteria, and while researchers have linked the makeup of the intestinal microbiome to brain health, this was not investigated directly in this study. The relationship identified in this research could be a result of the infections that antibiotics were used to treat, rather than the drugs themselves. It is important to properly manage treatable health conditions and people who have concerns about any aspect of their health should speak to their GP.

“Midlife is increasingly being seen as a time to act, and there are things we can do to reduce our risk of dementia. This includes not smoking, only drinking in moderation, staying mentally and physically active, eating a balanced diet, and keeping cholesterol and blood pressure levels in check can all help to keep our brains healthy as we age. Find information and advice on brain health at www.thinkbrainhealth.org.uk”

‘Association of midlife antibiotic use with subsequent cognitive function in women’ by Raaj S. Mehta et al. was published in PLOS ONE at 6pm UK time on Wednesday 23 March.

DOI: https://doi.org/10.1371/journal.pone.0264649

Declared interests

Prof Paul Matthews: “none to declare.”

Prof Tom Dening: “I have no conflicts of interest to declare.”

Prof Tara Spires-Jones: “I have no conflicts with this paper.”

Prof David Curtis: “I have no conflict of interest to declare.”

No others received.