Effect of SSRIs on clinical progression in amnestic mild cognitive impairment stratified by Alzheimer's disease pathology.

INTRODUCTION: This study examined whether selective serotonin reuptake inhibitors (SSRIs) treatment influenced cognitive trajectory and progression to Alzheimer's disease (AD) dementia in amnestic mild cognitive impairment (MCI) patients, stratified by AD pathology. METHODS: Four hundred fifty-seven amnestic MCI participants in the ADNI database were analyzed. AD pathology was determined by baseline amyloid beta (Aβ) and tau positron emission tomography. Kaplan-Meier survival analysis and Cox proportional hazards models evaluated MCI-to-AD progression. Linear mixed models analyzed longitudinal cognitive trajectories, amyloid accumulation, and cortical thickness. RESULTS: SSRI treatment showed no significant effect on AD dementia progression (hazard ratio = 1.64, 95% confidence interval: 0.61 to 4.38) or cognitive trajectories, regardless of AD pathology. No significant differences in Aβ accumulation or cortical thickness were observed between SSRI users and non-users. External validation confirmed no significant SSRI effect on AD progression or cognitive decline. DISCUSSION: SSRI treatment was not associated with long-term cognitive effects in amnestic MCI, irrespective of underlying AD pathology. HIGHLIGHTS: SSRI treatment was not associated with long-term AD dementia risk in MCI. SSRI treatment had no impact on long-term cognitive performance changes in MCI. SSRI treatment did not affect Aβ accumulation or cortical thickness in MCI. SSRIs had no effect on MCI progression, regardless of underlying AD pathology.