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Midlife Antibiotic Use Linked to Subsequent Cognitive Decline in Women

Key findings

  • This study examined the relationship between the duration of antibiotic use at midlife (during the sixth decade) and subsequent cognitive function in 14,542 women enrolled in the Nurses' Health Study II
  • At an average age of 55, participants estimated their total duration of antibiotic use over the preceding four years, and they completed the CogState an average of seven years later
  • Use of antibiotics for at least two months at midlife was significantly associated with subsequent poorer scores for global cognition, learning and working memory and psychomotor speed, and attention
  • This relationship persisted after adjustment for many potential confounding factors, including medical comorbidities, and in subgroups stratified by age, presence or absence of key comorbidities, and regular use or non-use of antidepressants
  • These findings represent yet another rationale for antibiotic stewardship, especially for older adults

There's emerging evidence that the brain–gut axis mediated by the gut microbiome has a role in the pathogenesis of dementia. For example, a small cross-sectional study published in Scientific Reports suggests large differences in the composition of the gut microbiome between participants with and without Alzheimer's disease.

Antibiotic use can profoundly alter the gut microbiome, and the changes can persist for years. In the first large study of its kind, Harvard University researchers analyzed data from the Nurses' Health Study II and found an association between long-term use of antibiotics in midlife and subsequent cognition.

The results are reported in PLoS One by Francine Grodstein, ScD, epidemiologist and professor of medicine at Brigham and Women's Hospital, Andrew T. Chan, MD, MPH, chief of the Clinical and Translational Epidemiology Unit and vice chair for clinical research in the Division of Gastroenterology and professor of medicine at Massachusetts General Hospital, Raaj S. Mehta, MD, instructor in medicine and gastroenterology at Mass General, and colleagues.

Methods

The Nurses' Health Study II, an ongoing nationwide prospective cohort study in the U.S., began in 1989 with an enrollment of 116,430 female nurses ages 25 to 42. Every two years, participants return questionnaires with detailed information on lifestyle, medication, and health-related factors.

In 2009, at an average age of 55, the participants were asked to report their total duration of antibiotic use over the preceding four years. An average of seven years later, the participants completed CogState, a validated battery of cognitive tests in which deficits have previously been shown to be associated with dementia.

Antibiotics and Cognition

Increasing total exposure to antibiotics in midlife was significantly associated with poorer cognitive scores. After adjustment for age and socioeconomic status, average scores were:

  • Global cognition—Lower by 0.11 standard units for women who used antibiotics for at least two months, compared with nonusers (P for trend = 0.002)
  • Psychomotor speed and attention—Lower by 0.13 standard units (P for trend = 0.004)
  • Learning and working memory—Lower by 0.10 standard units (P for trend = 0.03)

Further Analyses

The association persisted after multivariable adjustment for risk factors for cognitive decline, including medical comorbidities, and in subgroups stratified by age, presence or absence of key comorbidities and regular use or non-use of antidepressants.

Analysis of effect sizes showed the impact of antibiotic use on cognition was approximately equivalent to that found for three to four years of aging.

These data underscore the importance of antibiotic stewardship, especially for older adults.

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