title: Cilostazol add-on therapy in patients with mild dementia receiving donepezil: a retrospective study.
abstract: OBJECTIVE
  Combinatorial therapy directed at both vascular and neurodegenerative aspects of dementia may offer a promising strategy for treatment of dementia, which often has a multifactorial basis in the elderly. We investigated whether the phosphodiesterase III inhibitor cilostazol, which is often used in the prevention of stroke and peripheral artery disease, may delay cognitive decline in the elderly receiving donepezil.
  
  
  METHODS
  Medical records were retrospectively surveyed to identify patients who had received donepezil for more than one year and had undergone Mini-Mental State Examination (MMSE) at least at two time points. Those with an initial MMSE score of less than 27 points were subjected to analysis (n = 156), with a cut-point of 21/22 applied to assign them to mild (n = 70) and moderate/severe (n = 86) dementia. The change of total MMSE score per year was compared between patients who had received donepezil and those given both donepezil and cilostazol.
  
  
  RESULTS
  In patients with mild dementia who had received donepezil and cilostazol (n = 34; 77.2±6.8 years old), the annual change in MMSE score was -0.5±1.6 during an observational period of 28.6±11.7 months, with those receiving donepezil only (n = 36; 78.4±6.5 years old) scoring less (-2.2±4.1) during 30.4±12.8 months with a statistical intergroup difference (p = 0.022). Multivariate analysis showed that absence of cilostazol treatment was the only significant predictor of MMSE decline. A positive effect of cilostazol was found in three subscale scores of MMSE, orientation for time or place and delayed recall. By clear contrast, in patients with moderate/severe dementia, there were no intergroup differences in decrease of total or subscale MMSE scores between the two groups.
  
  
  CONCLUSIONS
  These results suggest potential for cilostazol treatment in the suppression of cognitive decline in patients receiving donepezil with mild dementia but not in those with moderate/severe dementia.
authors.affiliation: Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center Hospital, Osaka, Japan ; Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.affiliation: Department of Neurosurgery, Sumoto Itsuki Hospital, Hyogo, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Nishino
authors.affiliation: Department of Regenerative Medicine and Research, Institute of Biomedical Research and Innovation, Hyogo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Yorito
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center Hospital, Osaka, Japan.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Department of Regenerative Medicine and Research, Institute of Biomedical Research and Innovation, Hyogo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kasahara
authors.affiliation: Department of Neurosurgery, Sumoto Itsuki Hospital, Hyogo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Takata
authors.affiliation: Department of Neurosurgery, Sumoto Itsuki Hospital, Hyogo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okada
mesh_terms: D000368:Aged; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077407:Cilostazol; D003704:Dementia / Q000188:drug therapy*; D000077265:Donepezil; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D010880:Piperidines / Q000627:therapeutic use*; D011379:Prognosis; D012189:Retrospective Studies; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D018696:Neuroprotective Agents; D010880:Piperidines; D013777:Tetrazoles; D000077265:Donepezil; D000077407:Cilostazol