Antibiotic use in midlife women for at least two months associated with small decrease in cognition scores

8th April 2022

Antibiotic use among midlife women for two months and longer is linked to lower cognition scores when assessed approximately 7 years later

Antibiotic use for at least two months among midlife women has been found to be associated with a minor, but significant reduction in overall cognition scores when re-assessed approximately 7 years later. This was the conclusion of an analysis of women in the Nurses’ Health Study II by researchers from the Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, US.

Research has increasingly pointed to a connection between the gut-brain axis, linking emotional and cognitive centres of the brain with intestinal functions and especially the influence of the gut microbiota in these interactions. In fact, it is already established that there are microbiome composition links with mental health including quality of life and depression.

Antibiotic use negatively affect the balance of the gut microbiota and in fact, some evidence suggests that in women, use of antibiotics (for ≥ 2 months) in late adulthood is associated with a significant increased risk of cardiovascular disease.

Nevertheless, whether antibiotic use, which affects microbiome diversity, might also have a detrimental impact upon cognition is unclear although early exposure to antibiotics in the first 24 months of life may be associated with detrimental neuro-developmental outcomes, 11 years later. There is also some data showing how gut microbial alterations may also be associated with Alzheimer’s disease.

For the present study, the US team examined midlife antibiotic use among women and subsequent cognitive function which was assessed 7 years later. They used data from the Nurses’ Health Study II, which is an on-going prospective cohort study and in which participants complete detailed lifestyle, medication and health-related questionnaires every 2 years. In 2009, participants were asked to report on their total duration of antibiotic use into 7 categories, ranging from none to > 3 years, over the preceding 4 years. Since at the time, the mean age of participants was 54.7 years, this was called midlife antibiotic use. Approximately 7 years after 2009, the researchers administered the CogState battery which assesses global cognition, psychomotor function, learning and working memory. Antibiotic use was categorised as none, 1 – 14 days, 15 days to 2 months and 2 months+.

Regression analysis was undertaken to assess the relationship between the use of antibiotics and cognitive decline, adjusting for several factors including body mass index, smoking status, educational attainment.

Antibiotic use and cognition scores

A total of 14,542 women with a mean age of 61.7 years completed the cognitive testing and were included in the analysis.

Compared to non-antibiotic users, women using antibiotics for at least 2 months or longer, had mean global cognition scores that were lower by -0.08 standard units (95% CI -0.12 to – 0.073 p for trend = 0.002) in fully adjusted models. Similarly, for psychomotor speed and attention, the mean scores were -0.10 (95% CI -0.16 to -0.04, p = 0.004) and -0.06 (95% CI -0.11 to – 0.01, p = 0.03) for learning and working memory.

The authors concluded that chronic antibiotic use in midlife were associated with minor decreases in cognitive scores when assessed approximately 7 years later.

Citation
Mehta RS et al. Association of midlife antibiotic use with subsequent cognitive function in women PLoS One 2022

Medication for sleep disturbance among midlife women of little benefit over longer-term

28th May 2021

Medicines for sleep disturbance are recommended for short-term use only although little is known about the effectiveness of such treatments when taken over longer periods of time.

Sleep disturbances are a common problem that can manifest in at least three different ways, e.g., difficulties in getting to sleep, remaining asleep or early morning awakening. There are several prescription treatments available for sleep disturbance including benzodiazepines, Z-drugs (e.g., zopiclone, zolpidem) and sedating antidepressants such as trazodone. While these medicines are only recommended for short-term use, for some patients, the chronic nature of the condition invariably results in continued use of treatment, either intermittently or regularly, for extended periods of time. In an effort to examine the effects of sleep medicines on patient-reported measures of sleep disturbance, a team from the Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, US, set out to examine the impact of sleep medicines among a cohort of midlife women. Eligible participants were drawn from the Study of Women’s Health Across the Nation (SWAN), which is an ongoing longitudinal study examining the biological and psychological changes that occur during the menopause transition. On an annual basis, women were asked to self-report on three aspects of sleep: difficulty initiating, frequent awakening and early morning awakening and anyone who reported on these disturbances at least once, were eligible for inclusion in the study. Women were asked about their sleep medication during each study visit and women were asked, using a 5-point Likert scale, to report their level of difficulty to each of the three sleep aspects and the authors also included a matched cohort of non-sleep medicine users. Furthermore, as sleep disturbances may arise because of depression, anxiety and pain, individuals also completed questionnaires to identify the impact of each of these factors.

Findings
The study included 238 women who had an initial prescription for sleep medication and who were matched to 447 non-users. There were no significant differences between the two groups with respect to depression, anxiety or pain scores. The mean age of those using sleep medicines was 49.5 years and at baseline, the mean score for initiating sleep was 2.7, waking frequently 3.8 and early morning wakening 2.8. Among non-users, the corresponding mean values were similar; 2.6, 3.7 and 2.7 respectively. After 1 year of use, the mean scores among sleep medicine users were 2.6 (initiating sleep) vs 2.3 (non-users), 3.6 (frequent wakening) vs 3.5 (non-users) and 2.8 (early morning wakening) vs 2.5 (non-users) and none of these differences were statistically significant. In addition, there was no difference in mean scores between the two main classes of sleep medicines, benzodiazepines and Z-drugs compared with non-users for the same three aspects of sleep. Furthermore, there were also no important differences between sleep medicine users/non-users after 2 years of follow-up. A further finding was how none of the patients in either group, reported a worsening of sleep disturbance over the two year follow-up period.

Commenting on these results, the authors noted that over the longer term, no sleep medicines were associated with a reduction in the three main aspects of sleep disturbance compared with those who did not use such treatments. They concluded that while sleep medicines are often used off-license, over longer periods of time, the results of the study demonstrate little benefit from continued use.

Citation
Soloman DH et al. Prescription medication for sleep disturbances among midlife women during 2 years of follow-up: a SWAN retrospective cohort study. BMJ Open 2021