BACKGROUND: Antidepressants are commonly prescribed medications in the elderly, but their relationship with incident mild cognitive impairment (MCI) and probable dementia is unknown.

METHODS: The study cohort included 6,998 cognitively healthy, postmenopausal women, aged 65-79 years, who were enrolled in a hormone therapy clinical trial and had baseline depressive symptoms and antidepressant use history assessments at enrollment, and at least one postbaseline cognitive measurement. Participants were followed annually and the follow-up averaged 7.5 years for MCI and probable dementia outcomes. A central adjudication committee classified the presence of MCI and probable dementia based on extensive neuropsychiatric examination.

RESULTS: Three hundred and eighty-three (5%) women were on antidepressants at baseline. Antidepressant use was associated with a 70% increased risk of MCI, after controlling for potential covariates including the degree of depressive symptom severity. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) were both associated with MCI (SSRIs: hazard ratios (HR), 1.78 [95% CI, 1.01-3.13]; TCAs: HR, 1.78 [95% CI, 0.99-3.21]). Depressed users (HR, 2.44 [95% CI, 1.24-4.80]), non-depressed users (HR, 1.79 [95% CI, 1.13-2.85]), and depressed non-users (HR, 1.62 [95% CI, 1.13-2.32]) had increased risk of incident MCI. Similarly, all three groups had increased risk of either MCI or dementia, relative to the control cohort.

CONCLUSIONS: Antidepressant use and different levels of depression severity were associated with subsequent cognitive impairment in a large cohort of postmenopausal women. Future research should examine the role of antidepressants in the depression-dementia relationship and determine if antidepressants can prevent incident MCI and dementia in individuals with late-life depression subtypes with different levels of severity.