Cilostazol Tested Against Cognitive Decline in Mild Cognitive Impairment
A Phase 2 trial explores whether cilostazol, a blood thinner with brain-protective effects, can slow memory loss in MCI patients.
Summary
Mild cognitive impairment sits at a crossroads between normal aging and dementia, making it a critical window for intervention. Cilostazol, a drug already approved as an antiplatelet agent, also appears to reduce amyloid beta buildup and protect against vascular damage in the brain — two key drivers of cognitive decline. Japanese researchers at the National Cerebral and Cardiovascular Center ran a completed Phase 2 randomized controlled trial enrolling 166 patients with MCI, comparing cilostazol against placebo. Earlier pilot data showed promising MMSE score improvements when cilostazol was added to standard Alzheimer's therapy. This trial aimed to rigorously test whether cilostazol can preserve cognitive function in people with early-stage impairment, targeting both the vascular and neurodegenerative dimensions of dementia simultaneously.
Detailed Summary
Dementia is rarely a single-pathway disease. Alzheimer's disease and vascular cognitive impairment are the two most common forms, but most patients present with overlapping features — amyloid plaques alongside small vessel disease, neurodegeneration combined with endothelial dysfunction. This biological reality has pushed researchers toward combination-style therapies that address both dimensions at once. Cilostazol, a phosphodiesterase-3 inhibitor widely used to treat peripheral artery disease, may be uniquely positioned to do exactly that.
The drug's appeal in cognitive medicine stems from its pleiotropic profile. Beyond antiplatelet effects, cilostazol improves cerebral blood flow, exerts endothelial protective actions, and — critically — has been shown in animal models to reduce amyloid beta accumulation and protect against amyloid-induced cognitive deficits. Human pilot data strengthened the case: a small study of 10 moderate Alzheimer's patients on donepezil found that adding cilostazol for five to six months significantly improved MMSE scores from baseline. Additional observational data suggested cilostazol helped prevent cognitive decline in Alzheimer's patients with comorbid cerebrovascular disease.
The COMCID trial (Cilostazol for Prevention of Cognitive Decline in MCI) was designed to formally test this hypothesis. Sponsored by the National Cerebral and Cardiovascular Center in Japan, the Phase 2 randomized, placebo-controlled trial enrolled 166 patients with mild cognitive impairment — the earliest detectable stage of cognitive decline before frank dementia. The trial ran from May 2015 to December 2020, providing a long-term window to assess whether cilostazol could meaningfully slow progression.
If results confirm benefit, cilostazol could represent a repurposed, accessible, and affordable therapeutic option for one of medicine's most pressing unmet needs. Its dual mechanism — targeting vascular risk while also reducing amyloid burden — aligns well with current thinking about dementia as a mixed-etiology syndrome.
However, important caveats remain. This summary is based solely on the trial registration abstract; outcome data are not yet available here. The pilot evidence supporting this trial was extremely small (n=10), and Phase 2 trials are primarily designed to assess safety and signal — not definitive efficacy. Results from the completed trial are eagerly awaited.
Key Findings
- Cilostazol reduces amyloid beta accumulation and vascular damage in preclinical models, suggesting a dual neuroprotective mechanism.
- A 10-patient pilot showed MMSE score improvement when cilostazol was added to donepezil in moderate Alzheimer's patients.
- Phase 2 RCT enrolled 166 MCI patients over 5+ years to rigorously test cognitive preservation with cilostazol vs. placebo.
- Targeting both vascular and neurodegenerative pathways simultaneously may be key for slowing mixed-etiology dementia.
- Cilostazol is already approved and widely used, making it a practical repurposing candidate if efficacy is confirmed.
Methodology
COMCID was a Phase 2 randomized, placebo-controlled trial enrolling 166 patients with mild cognitive impairment, sponsored by the National Cerebral and Cardiovascular Center in Japan. The trial ran approximately five and a half years (May 2015 to December 2020), providing substantial follow-up to assess cognitive trajectory. Specific primary endpoints and cognitive assessment tools were not detailed in the available abstract.
Study Limitations
This summary is based on the trial registration abstract only; full outcome data and results have not been reviewed. The pilot data motivating this trial involved only 10 patients, making preliminary effect estimates highly uncertain. As a Phase 2 trial, COMCID was not necessarily powered for definitive efficacy conclusions.
Enjoyed this summary?
Get the latest longevity research delivered to your inbox every week.
Enter your email to subscribe: