Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy

Alzheimers Dement. 2024 May;20(5):3378-3387. doi: 10.1002/alz.13807. Epub 2024 Apr 1.

Abstract

Introduction: We aimed to assess the effect of antidepressant use on dementia risk, cognitive decline, and brain atrophy.

Methods: In this prospective cohort study, we included 5511 dementia-free participants (Mini-Mental State Examination [MMSE] > 25) of the Rotterdam study (57.5% women, mean age 70.6 years). Antidepressant use was extracted from pharmacy records from 1991 until baseline (2002-2008). Incident dementia was monitored from baseline until 2018, with repeated cognitive assessment and magnetic resonance imaging (MRI) every 4 years.

Results: Compared to never use, any antidepressant use was not associated with dementia risk (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.92-1.41), or with accelerated cognitive decline or atrophy of white and gray matter. Compared to never use, dementia risk was somewhat higher with tricyclic antidepressants (HR 1.36, 95% CI 1.01-1.83) than with selective serotonin reuptake inhibitors (HR 1.12, 95% CI 0.81-1.54), but without dose-response relationships, accelerated cognitive decline, or atrophy in either group.

Discussion: Antidepressant medication in adults without indication of cognitive impairment was not consistently associated with long-term adverse cognitive effects.

Highlights: Antidepressant medications are frequently prescribed, especially among older adults. In this study, antidepressant use was not associated with long-term dementia risk. Antidepressant use was not associated with cognitive decline or brain atrophy. Our results support safe prescription in an older, cognitively healthy population.

Keywords: MRI; antidepressant use; cognitive decline; depression; population‐based.

MeSH terms

  • Aged
  • Antidepressive Agents* / adverse effects
  • Antidepressive Agents* / therapeutic use
  • Atrophy*
  • Brain* / diagnostic imaging
  • Brain* / pathology
  • Cognitive Dysfunction*
  • Dementia* / epidemiology
  • Female
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors