Department of Psychiatry and Neuroscience Research Institute, Seoul National University College of Medicine & SMG-SNU Boramae Medical Center, Dongjak-gu, Seoul, Republic of Korea.
Department of Psychiatry, Seoul Medical Center, Jungnang-gu, Seoul, Republic of Korea.
Neurotherapeutics. 2019 Apr;16(2):394-403. doi: 10.1007/s13311-018-00708-x.
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 (F) 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.
本研究旨在比较磷酸二酯酶 3 型抑制剂西洛他唑与多奈哌齐单药治疗对伴有脑白质病变的阿尔茨海默病患者的疗效，使用氟脱氧葡萄糖（F）正电子发射断层扫描（FDG PET）进行评估。这是一项为期 24 周的随机、双盲、安慰剂对照、平行分组研究。共纳入 36 例接受多奈哌齐治疗（西洛他唑组和安慰剂组各 18 例）且伴有脑白质病变的阿尔茨海默病患者。所有患者均进行 FDG PET 成像扫描前和扫描后的检测，并接受三轮临床和神经心理学测试。结果显示，西洛他唑组的局部葡萄糖代谢并未出现显著下降，而安慰剂组的顶叶和额叶的局部葡萄糖代谢则显著下降。重复测量方差分析显示，左侧额下回的局部葡萄糖代谢在西洛他唑组的保留程度显著高于安慰剂组（p<0.005）。简易精神状态检查量表、阿尔茨海默病评估量表认知分量表、阿尔茨海默病合作研究日常生活活动量表和临床痴呆评定量表总分的组间变化平均值无显著差异。西洛他唑组葡萄糖代谢的增加与阿尔茨海默病评估量表认知评分的改善相关。综上所述，与多奈哌齐单药治疗相比，西洛他唑联合多奈哌齐治疗可能延缓伴有脑白质病变的阿尔茨海默病患者的区域性脑代谢下降。此外，本研究结果证实了西洛他唑通过增加葡萄糖代谢改善或保护阿尔茨海默病患者认知功能的疗效。然而，西洛他唑对认知功能和阿尔茨海默病的长期影响还需在更大样本量和更长研究周期的进一步研究中进行验证。试验注册：http://clinicaltrials.gov：NCT01409564。
