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Cited by 56Dementia and Cognitive Impairment ResearchTreatment of Major DepressionPharmaceutical Practices and Patient Outcomes

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Antidepressant Use and Cognitive Decline: The Health and Retirement Study

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Saczynski, Jane S., Rosen, Allison B., McCammon, Ryan J., Zivin, Kara, Andrade, Susan E., Langa, Kenneth M., Vijan, Sandeep, Pirraglia, Paul A., Briesacher, Becky A.·2015·The American Journal of Medicine
DOI 10.1016/j.amjmed.2015.01.007PMC PMC4618694
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Abstract

Background Depression is associated with cognitive impairment and dementia, but whether treatment for depression with antidepressants reduces the risk for cognitive decline is unclear. We assessed the association between antidepressant use and cognitive decline over 6 years. Methods Participants were 3714 adults aged 50 years or more who were enrolled in the nationally representative Health and Retirement Study and had self-reported antidepressant use. Depressive symptoms were assessed using the 8-item Center for Epidemiologic Studies Depression Scale. Cognitive function was assessed at 4 time points (2004, 2006, 2008, 2010) using a validated 27-point scale. Change in cognitive function over the 6-year follow-up period was examined using linear growth models, adjusted for demographics, depressive symptoms, comorbidities, functional limitations, and antidepressant anticholinergic activity load. Results At baseline, cognitive function did not differ significantly between the 445 (12.1%) participants taking antidepressants and those not taking antidepressants (mean, 14.9%; 95% confidence interval, 14.3-15.4 vs mean, 15.1%; 95% confidence interval, 14.9-15.3). During the 6-year follow up period, cognition declined in both users and nonusers of antidepressants, ranging from -1.4 change in mean score in those with high depressive symptoms and taking antidepressants to -0.5 change in mean score in those with high depressive symptoms and not taking antidepressants. In adjusted models, cognition declined in people taking antidepressants at the same rate as those not taking antidepressants. Results remained consistent across different levels of baseline cognitive function, age, and duration of antidepressant use (prolonged vs short-term). Conclusions Antidepressant use did not modify the course of 6-year cognitive change in this nationally representative sample.

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  • Few published studies have examined the effect of antidepressant use on cognitive decline.

    “but few published studies have examined the effect of antidepressant use on cognitive decline, 11,16”

    From Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy (2024) · cites this paper as [16]

    The Discussion says that many clinical trials, mostly small, have assessed antidepressant treatment and cognitive decline. It limits the scarcity of published work to population-based studies, a qualification absent from the citing sentence. (LLM, conf=0.86)

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    Experimental — accuracy not yet measured

  • Other studies have found no association between antidepressant use and dementia risk.

    “other studies have found no association between antidepressant use and dementia risk [18, 19, 23, 41].”

    From Long-Term Antidepressant Use and Dementia Risk: A Propensity Score-Matched Study of Swiss Older Adults, with an Anticholinergic-Specific Analysis (2026) · cites this paper as [41]

    The Discussion and Conclusions report no significant association between antidepressant use and six-year change in cognitive function. The study did not establish a null association with dementia risk, which is a different outcome. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The absence of a consistent association with dementia risk, cognitive decline, and brain atrophy is in concordance with earlier findings.

    “The absence of a consistent association with dementia risk, cognitive decline, and brain atrophy is in concordance with earlier findings. 15-17”

    From Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy (2024) · cites this paper as [16]

    The Conclusions (page not available in our copy) report no significant association between antidepressant use and six-year cognitive change in older adults. The study did not assess brain atrophy or incident dementia risk; its discussion of dementia does not establish an absence of association with dementia risk. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Prior cohort studies on antidepressant use and dementia risk have produced contrasting results.

    “Long-term observational data are needed, but cohort studies to date have produced contrasting results. While various studies observed increased risk of dementia in antidepressant users, 4,8-14 several others did not. 15-19”

    From Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy (2024) · cites this paper as [16]

    The Conclusions (page not available) report no significant association between antidepressant use and six-year cognitive change, supporting the cited sentence’s no-association side. The Discussion describes differing findings in earlier studies, but this paper measured cognitive change rather than incident dementia, so it does not directly support the claim about dementia risk. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Citations

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Metadata

Authors
Saczynski, J. S., Rosen, A. B., McCammon, R. J., Zivin, K., Andrade, S. E., Langa, K. M., Vijan, S., Pirraglia, P. A., & Briesacher, B. A.
Affiliations
  • University of Massachusetts Chan Medical School (US)
  • University of Michigan (US)
  • Brown University (US)
  • Northeastern University (US)
Corresponding author
Saczynski, Jane S.
ORCID
Venue
The American Journal of Medicine
Publisher
Elsevier BV
Published
2015-07
Volume
128
Issue
7
Pages
739-746
ISSN
0002-9343 (ISSN-L)
DOI
10.1016/j.amjmed.2015.01.007
PMC
PMC4618694
OpenAlex
W2032828904
Cited by
56
References
3
Citations by year
2026: 5 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 2 · 2017: 9 · 2016: 5 · 2015: 2
FWCI
4.06
Type
journal article
Language
en
Open access
Licence
Locations
  • The American Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders
  • Health Services Research and Development (CD2 07-206-1, VA IIR 10-176-3)
  • National Institute on Aging (U01 AG09740, K01AG33643)
  • National Heart, Lung, and Blood Institute (P01AG031098, U01HL105268)
  • U.S. Department of Veterans Affairs
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
Keywords
antidepressants, cognitive decline, depression, cognitive impairment, dementia, older adults, anticholinergic activity, depressive symptoms, cognitive function
MeSH terms
Aged, Aged, 80 and over, Antidepressive Agents, Cognition, Cross-Sectional Studies, Depressive Disorder, Female, Follow-Up Studies, Humans, Male, Middle Aged, Surveys and Questionnaires, Reference Values, United States, Geriatric Assessment, Incidence, Age Distribution, Sex Distribution, Risk Assessment

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