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Efficacy of Cilostazol Administration in Alzheimer’s Disease Patients with White Matter Lesions: A Positron-Emission Tomography Study

  • Jun-Young Lee
  • Haewoo Lee
  • Hye Bin Yoo
  • Jung-Seok Choi
  • Hee-Yeon Jung
  • Eun Jin Yoon
  • Hongrae Kim
  • Ye-Ha Jung
  • Ho-Young Lee
  • Yu Kyeong KimEmail author
Original Article

Abstract

This study tested the efficacy of the phosphodiesterase type III inhibitor cilostazol in Alzheimer’s disease patients with white matter lesions treated with donepezil in comparison with donepezil monotherapy using fluorodeoxyglucose (18F) positron-emission tomography (FDG PET). A 24-week, randomized, double-blind, placebo-controlled, parallel-group study was conducted. Thirty-six Alzheimer’s disease patients with white matter lesions who received donepezil (n = 18 each in the cilostazol and placebo groups) were enrolled. Participants underwent pre and post FDG PET imaging scans and three rounds of clinical and neuropsychological tests. The cilostazol group did not show a significant decrease of regional glucose metabolism; however, regional glucose metabolism was significantly decreased in the parietal and frontal lobes of the placebo group. The repeated measures ANOVA measuring differences in uptake change revealed that regional glucose metabolism in the left inferior frontal gyrus was significantly more preserved in the cilostazol group than that in the placebo group (p < 0.005). Mean changes from baseline on the Mini-Mental State Exam, Alzheimer’s Disease Assessment Scale-cognitive subscale, Alzheimer’s Disease Cooperative Study-Activities of Daily Living Inventory, and the Clinical Dementia Rating Sum of Boxes did not differ between the two groups. In the cilostazol group, the increase of glucose metabolism correlated with the improvment of the Alzheimer’s Disease Assessment Scale-cognitive score. We conclude that cilostazol treatment added to donepezil may delay the decline in regional cerebral metabolism in Alzheimer’s disease with white matter lesions compared with donepezil monotherapy. In additon, our results verified the efficacy of cilostazol in improving or protecting cognitive function in Alzheimer’s disease through increased glucose metabolism. However, the long-term effect of cilostazol on cognitive function and Alzheimer’s disease modification must be tested in further studies with larger sample size and longer study period. Trial registration: http://clinicaltrials.gov: NCT01409564

Key Words

Alzheimer’s disease cilostazol positron-emission tomography study 

Abbreviations

AD

Alzheimer’s disease

ADAS-cog

Alzheimer’s Disease Assessment Scale-cognitive subscale

ADCS-ADL

Alzheimer’s Disease Cooperative Study-Activities of Daily Living Inventory

CDR

Clinical Dementia Rating Scale

CDR-SB

the Sum of the Boxes of the Clinical Dementia Rating Scale

IFG

inferior frontal gyrus

CMRglc

cerebral metabolic rate of glucose consumption

Notes

Acknowledgments

The authors wish to thank all patients and their caregivers who participated in the study. The English in this document has been checked by at least two professional editors, both native speakers of English (http://textcheck.com).

Required Author Forms

Disclosure forms provided by the authors are available with the online version of this article.

Availability of Data and Materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors’ Contributions

JYL, HYL, and YKK designed the study and carried out the analyses presented in this article. JYL, HYL, and YKK provided the meta-database of clinical trials and contributed to the analysis of this dataset. JYL, HYL, YKK, HWL, HBY, JSC, HYJ, EJY, YHJ, and HRK all contributed to the writing of the manuscript and to valuable discussion. All authors read and approved the final manuscript.

Funding

JYL, EJY, and YKK was partially supported by a grant from Ministry of Science, ICT and Future Planning (Grant No: NRF-2014M3C7A1046042). Dr. Jun-Young Lee has been financially supported by the Otsuka International Asia Arab Company, limited for this research project.

Compliance with Ethical Standards

Ethics Approval and Consent to Participate

This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and was approved by the Ethics Board of Seoul National University College of Medicine & SMG-SNU Boramae Medical Center. All subjects or responsible caregivers, whichever appropriate, gave their informed consent.

Consent for Publication

Not applicable.

Competing Interests

The authors declare that they have no competing interests.

Supplementary material

13311_2018_708_MOESM1_ESM.pdf (1.7 mb)
ESM 1 (PDF 1718 kb)

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2019

Authors and Affiliations

  • Jun-Young Lee
    • 1
  • Haewoo Lee
    • 2
  • Hye Bin Yoo
    • 3
  • Jung-Seok Choi
    • 1
  • Hee-Yeon Jung
    • 1
  • Eun Jin Yoon
    • 4
  • Hongrae Kim
    • 1
  • Ye-Ha Jung
    • 1
  • Ho-Young Lee
    • 5
  • Yu Kyeong Kim
    • 4
    Email author
  1. 1.Department of Psychiatry and Neuroscience Research InstituteSeoul National University College of Medicine & SMG-SNU Boramae Medical CenterSeoulRepublic of Korea
  2. 2.Department of PsychiatrySeoul Medical CenterSeoulRepublic of Korea
  3. 3.School of Behavioral and Brain SciencesUniversity of Texas at DallasRichardsonUSA
  4. 4.Department of Nuclear MedicineSeoul National University College of Medicine & SMG-SNU Boramae Medical CenterSeoulRepublic of Korea
  5. 5.Department of Nuclear MedicineSeoul National University College of Medicine & Bundang HospitalSeongnamRepublic of Korea

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