Pharmacological interventions for reducing the risk of cognitive decline and dementia after stroke/transient ischemic attack: A systematic review

BACKGROUND: Stroke is a leading cause of death and disability worldwide. Advances in stroke care have improved survival and recovery, but it remains unclear whether pharmacological treatments can prevent long-term consequences including cognitive decline and dementia. This systematic review examined whether pharmacological interventions reduce the risk of cognitive decline, mild cognitive impairment (MCI), or dementia in adults with a history of stroke or symptomatic transient ischemic attack (TIA). METHODS: We searched Medline, EMBASE, PsychINFO, and Cochrane Central from inception to January 23, 2025, for systematic reviews and meta-analyses of randomized controlled trials (RCTs). Eligible studies included adults with prior stroke or symptomatic TIA receiving pharmacological interventions, blood pressure-lowering, antithrombotic, and lipid-lowering drugs, compared with placebo, no treatment, or usual care. Primary outcomes were incident dementia, MCI, and cognitive decline assessed at least three months post-event. Methodological quality was assessed with AMSTAR 2, and certainty of evidence using GRADE. The protocol was registered in PROSPERO (CRD420251000825). RESULTS: Of 1343 records screened, 8 systematic reviews met inclusion criteria. The most comprehensive systematic review, including all relevant RCTs, was selected for detailed data extraction. Certainty of evidence was mostly low, with a few exceptions of moderate to high certainty. Across drug classes and outcomes, pharmacological interventions generally showed no meaningful reductions in dementia, MCI, and cognitive decline over a mean follow-up of 2.0-4.9 years. CONCLUSIONS: Current evidence does not support pharmacological interventions after a cerebrovascular event for reducing risk of cognitive decline, MCI, or dementia. Further high-quality studies with longer follow-ups are needed.