International Psychogeriatrics

Research Article

Depressive symptoms, antidepressant use, and future cognitive health in postmenopausal women: the Women's Health Initiative Memory Study

Joseph S. Goveasa1 c1, Patricia E. Hogana2, Jane M. Kotchena3, Jordan W. Smollera4, Natalie L. Denburga5, JoAnn E. Mansona6, Aruna Tummalaa1, W. Jerry Mysiwa7, Judith K. Ockenea8, Nancy F. Woodsa9, Mark A. Espelanda2 and Sylvia Wassertheil-Smollera10

a1 Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

a2 Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

a3 Department of Population Health, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

a4 Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA

a5 Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa, USA

a6 Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

a7 Department of Physical Medicine and Rehabilitation, Ohio State University Medical Center, Columbus, Ohio, USA

a8 Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA

a9 Family and Child Nursing, University of Washington, Seattle, Washington, USA

a10 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, New York, USA


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.

(Received October 04 2011)

(Revised October 30 2011)

(Revised December 05 2011)

(Accepted December 12 2011)

(Online publication February 03 2012)


c1 Correspondence should be addressed to: Joseph S. Goveas, MD, Assistant Professor, Department of Psychiatry and Behavioral Medicine Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. Phone: +414-955-8983; Fax: +414-955-6299. Email: