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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
166
National Cerebral and Cardiovascular Center
Suita, Osaka, Japan
Change from baseline in Mini Mental State Examination (MMSE)
Time frame: 96 weeks
Conversion from MCI to All-cause Dementia
Dementia is diagnosed clinically when the patient meets core clinical criteria for dementia with reference to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.
Time frame: up to 96 weeks
Cognitive Decline on Clinical dementia rating-sum of boxes (CDR-SB)
Time frame: baseline, 48 weeks, and 96 weeks
Cognitive Decline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 14
Time frame: baseline, 48 weeks, and 96 weeks
Cognitive Decline on Logical Memory subtest of the Wechsler Memory Scale-Revised (WMS-R)
Time frame: baseline, 48 weeks, and 96 weeks
Functional Decline on Alzheimer's disease Cooperative Study scale for activities of daily living in MCI (ADCS-MCI-ADL)
Time frame: baseline, 48 weeks, and 96 weeks
Hippocampal volume
Magnetization prepared rapid acquisition with gradient echo is used to assess hippocampal volume.
Time frame: baseline and 96 weeks
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