A Trial of Cilostazol in Patients With Mild Cognitive Impairment (COMCID)
Status:
Completed
Trial end date:
2020-12-01
Target enrollment:
Participant gender:
Summary
Epidemiological, clinicopathological and animal studies show that vascular disease in various
forms contributes to cognitive decline. Increasing age is the strongest risk for dementia
irrespective of whether it results from a vascular etiology or neurodegenerative disease
processes such as in Alzheimer's disease (AD). AD and vascular cognitive impairment, the two
most common causes of dementia, represent two extremes of a spectrum of disorders; however, a
number of entities, which possess varying degrees of neurodegenerative and vascular
pathologies, occur in between. The pure forms of the disorders are preferred for convenience
to label, treat or manage but conditions within the spectrum are the norm rather than the
exception as dementia advances. Therefore, combinatorial therapy directed at both vascular
and neurodegenerative aspects of dementia is a promising approach for the treatment of
dementia in the elderly.
Cilostazol acts as an antiplatelet agent and has other pleiotropic effects based on
phosphodiesterase-3-dependent mechanisms. Increasing evidence suggests that cilostazol offers
endothelial protection, via pleiotropic effects. Intriguingly, cilostazol has been shown to
decrease amyloid beta (Abeta) accumulation and protect Abeta-induced cognitive deficits in an
experimental model. In a pilot study of 10 patients with moderate AD (mean MMSE score, 11.9
points) who received donepezil, cilostazol add-on treatment for 5-6 months demonstrated
significantly increased MMSE score in comparison to baseline. Moreover, cilostazol was shown
to be effective in preventing cognitive decline in patients with AD with cerebrovascular
diseases, mild cognitive impairment (MCI), and mild dementia who received donepezil.
These results highlight the need for a comprehensive prospective cohort study to analyze the
effect of cilostazol on the preservation of cognitive function in patients with early-stage
cognitive impairment, namely MCI.