Estimating associations between antidepressant use and incident mild cognitive impairment in older adults with depression

Autoři: Fang Han aff001;  Tyler Bonnett aff004;  Willa D. Brenowitz aff005;  Merilee A. Teylan aff002;  Lilah M. Besser aff002;  Yen-Chi Chen aff002;  Gary Chan aff002;  Ke-Gang Cao aff003;  Ying Gao aff003;  Xiao-Hua Zhou aff006
Působiště autorů: Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China aff001;  National Alzheimer’s Coordinating Center, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America aff002;  Department of Neurology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China aff003;  Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, Maryland, United States of America aff004;  Department of Psychiatry, University of California, San Francisco, California, United States of America aff005;  Department of Biostatistics, Beijing International Center for Mathematical Research, Peking University, Beijing, China aff006
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227924



Previous studies have provided equivocal evidence of antidepressant use on subsequent cognitive impairment; this could be due to inconsistent modeling approaches. Our goals are methodological and clinical. We evaluate the impact of statistical modeling approaches on the associations between antidepressant use and risk of Mild Cognitive Impairment (MCI) in older adults with depression.


716 participants were enrolled. Our primary analysis employed a time-dependent Cox proportional hazards model. We also implemented two fixed-covariate proportional hazards models—one based on having ever used antidepressants during follow-up, and the other restricted to baseline use only.


Treating antidepressant use as a time-varying covariate, we found no significant association with incident MCI (HR = 0.92, 95% CI: 0.70, 1.20). In contrast, when antidepressant use was treated as a fixed covariate, we observed a significant association between having ever used antidepressants and lower risk of MCI (HR = 0.40, 95% CI: 0.28, 0.56). However, in the baseline-use only model, the association was non-significant (HR = 0.84, 95% CI: 0.60, 1.17).


Our results were dependent upon statistical models and suggest that antidepressant use should be modeled as a time-varying covariate. Using a robust time-dependent analysis, antidepressant use was not significantly associated with incident MCI among cognitively normal persons with depression.

Klíčová slova:

Alzheimer's disease – Antidepressants – Cognitive impairment – Dementia – Depression – Diabetes mellitus – Geriatric depression – Hypercholesterolemia


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