Selective serotonin reuptake inhibitor use, age-related neuropathology and cognition in late-life

Psychiatry Res. 2023 Oct:328:115471. doi: 10.1016/j.psychres.2023.115471. Epub 2023 Sep 9.


The objective of this study was to evaluate an association of selective serotonin reuptake inhibitor (SSRI) use with late life cognitive decline and further investigate the association with brain pathology. Using the data are from two harmonized clinical-pathologic cohort studies with annual cognitive testing we found that SSRI use was associated with significantly faster global cognitive decline and this association was present in those with and without pre-existing cognitive impairment at the time of SSRI initiation. In separate analyses of persons who died during the study and underwent neuropathologic examination, SSRI use was related to higher level of paired helical filament tau tangles and faster rate of global cognitive decline. However, when SSRI use and tangles were included in the same model, the association of SSRI use with rate of global cognitive decline was reduced by more than 50% and no longer statistically significant. SSRI use was associated with higher postmortem level of tau tangles, possibly because SSRI are being used to treat neurobehavioral symptoms associated with dementia, and this relationship appears to partly account for the association of SSRI use with more rapid cognitive decline.

Keywords: Alzheimer’ disease; Behavioral impairment; Dementia; SSRI; Tau tangles.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease* / psychology
  • Cognition
  • Cognition Disorders* / diagnosis
  • Cognition Disorders* / drug therapy
  • Cognition Disorders* / etiology
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / pathology
  • Humans
  • Nervous System Diseases*
  • Selective Serotonin Reuptake Inhibitors / adverse effects


  • Selective Serotonin Reuptake Inhibitors