Cilostazol Augmentation Study in Dementia

• Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog) [ Time Frame: Baseline, 3-month, 6-month ] [ Designated as safety issue: No ]
• Mini-Mental State Examination [ Time Frame: baseline, 3-month, 6-month ] [ Designated as safety issue: No ]
• Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) [ Time Frame: baseline, 3-month, 6-month ] [ Designated as safety issue: No ]
• Caregiver-Administered Neuropsychiatric Inventory (NPI) [ Time Frame: baseline, 3-month, 6-month ] [ Designated as safety issue: No ]
• Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) [ Time Frame: baseline, 3-month, 6-month ] [ Designated as safety issue: No ]

The purpose of this study is to examine the effects of cilostazol augmentation in mild to moderate Alzheimer disease patients with subcortical white matter hyperintensities (WMHI) treated by donepezil.

Dementia is the most disabling disease in the old age. The prevalence of dementia is 5-10% of the elders. AchEIs (donepezil, galantamine, rivastigmine) are used to treat mild to moderate dementia, but these drugs only relate to symptomatic improvement and the response rates are less than 30%.

Cilostazol is a cyclic adenosine monophosphate phosphodiesterase 3 inhibitor (PDE3I) and used as antiplatelet agent in subcortical vascular disease (WMHI). And it upregulates phosphorylation of cyclic adenosine monophosphate-pathway response element binding protein (CREB) which plays a crucial role in memory enhancement and synaptic plasticity related to neurodegeneration prevention.

The investigators will try cilostazol augmentation in dementia patients with WMHI receiving donepezil to see the addictive effects of cilostazol using cognitive tasks and PET imaging.

• Drug: Cilostazol
  Cilostazol 100mg bid per day will be administered orally and the period is total 24 weeks. The first week is a period for increasing the quantity, and during this period, cilostazol 50mg bid per day will be administered orally.
• Drug: Placebo
  Placebo with similar shape and color to cilostazol 100mg bid per day will be administered orally and the period is total 24 weeks. The first week is a period for increasing the quantity, and during this period, placebo 50mg bid per day will be administered orally.

• Experimental: Cilostazol
  Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation.
  Intervention: Drug: Cilostazol
• Placebo Comparator: Placebo
  Placebo group means dementia patients group receiving donepezil with placebo.
  Intervention: Drug: Placebo

Inclusion Criteria:

• Men/women over sixty years old
• Patients with slight and moderate dementia (MMSE score is over 10 under 26.)
• Patients with probable Alzheimer's disease according to the standard of NINCDS-ADRDA
• Patients accompanied with WMHI on Brain MRI (Fazeka's scale 1~3)

Exclusion Criteria:

• Those who do not agree to the test in a written form
• Patients who accompany other diseases except cerebral atrophy or change of subcortical white matter due to Alzheimer's disease on brain MRI
• Patients who should not use Cilostazol (① patients with bleeding tendency ② patients with congestive heart failure ③ patients who have a medical history of hypersensitivity to this medicine or constituent of this medicine ④ those who use anticoagulant and clot buster)
• Patients who suffer from nerve diseases or mental diseases which have influence on cognitive function except Alzheimer's disease (for example, schizophrenia, severe depression, mental retardation and etc.)
• Patients who are suspected to have a personal history of drug addiction or alcoholism within recent 10 years
• Patients who have severe problems in eye sight or hearing so that it is impossible to conduct the test smoothly
• Patients who the researchers think are inappropriate for taking part in the test