Long-Term Treatment with Citicoline May Improve Poststroke Vascular Cognitive Impairment
Long-Term Treatment with Citicoline May Improve Poststroke Vascular Cognitive Impairment
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DOI：
10.1159/000346602
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发表时间：
2013-01-01
影响因子：
2.9
通讯作者：
Roman, Gustavo C.
中科院分区：
文献类型：
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作者：
Alvarez-Sabin, Jose;Ortega, Gemma;Roman, Gustavo C.
背景：卒中后认知功能下降比卒中复发更常见。中风使痴呆的风险加倍，是血管性认知障碍和血管性痴呆的主要原因。尽管如此，很少有药理学研究涉及卒中后血管性认知障碍。我们评估了胞磷胆碱长期给药的安全性及其在预防首次缺血性卒中患者卒中后认知功能下降方面的可能疗效。方法：胞磷胆碱与常规治疗的开放标签、随机、平行研究。所有受试者在遭受合格中风后6周被选择，并按年龄、性别、教育和中风类型随机分配到胞二磷胆碱（1 g/天）与无胞二磷胆碱（对照组）平行组中，持续12个月。医疗管理在其他方面也是类似的。所有患者均于卒中后1个月、6个月和1年进行神经心理学评估。综合测试结果，给出6个神经认知领域的指标：注意与执行功能、记忆、语言、空间知觉、运动速度和时间定向。使用调整的逻辑回归模型，我们确定了胞磷胆碱治疗与6个月和12个月时每个神经认知领域认知能力下降之间的相关性。结果如下：我们招募了347名受试者（平均年龄67.2岁，186名男性（56.6%），平均教育5.7年）; 172名（49.6%）接受了12个月的胞二磷胆碱治疗（与对照组n = 175无显著差异）。两组的人口统计学数据、危险因素、初始卒中严重程度（NIHSS）、临床和病因学分类相似。仅37例受试者（10.7%）在6个月时停止治疗（10.5%胞磷胆碱vs. 10.9%对照）; 30例（8.6%）因死亡（16例（9.3%）胞磷胆碱vs. 14例（8.0%）对照，p = 0.740），7例失访或治疗不正确，4例（2.3%）因胞磷胆碱发生不良事件而未停药。199例患者在1年时接受了神经心理学评估。整个组在卒中后6个月和12个月的认知功能得到改善，但与对照组相比，胞二磷胆碱治疗组患者在注意力-执行功能方面表现出更好的结果（6个月时OR 1.721，95% CI 1.065-2.781，p = 0.027; 12个月时OR 2.379，95% CI 1.269-4.462，p = 0.007）和时间方向（6个月时OR 1.780，95% CI 1.020-3.104，p = 0.042; 12个月时OR 2.155，95% CI 1.017-4.566，p = 0.045）。此外，胞二磷胆碱组表现出更好的功能结果（改良兰金量表
Background: Cognitive decline after stroke is more common than stroke recurrence. Stroke doubles the risk of dementia and is a major contributor to vascular cognitive impairment and vascular dementia. Nonetheless, few pharmacological studies have addressed vascular cognitive impairment after stroke. We assessed the safety of long-term administration and its possible efficacy of citicoline in preventing post-stroke cognitive decline in patients with first-ever ischemic stroke. Methods: Open-label, randomized, parallel study of citicoline vs. usual treatment. All subjects were selected 6 weeks after suffering a qualifying stroke and randomized by age, gender, education and stroke type into parallel arms of citicoline (1 g/day) for 12 months vs. no citicoline (control group). Medical management was similar otherwise. All patients underwent neuropsychological evaluation at 1 month, 6 months and 1 year after stroke. Tests results were combined to give indexes of 6 neurocognitive domains: attention and executive function, memory, language, spatial perception, motor speed and temporal orientation. Using adjusted logistic regression models we determined the association between citicoline treatment and cognitive decline for each neurocognitive domain at 6 and 12 months. Results: We recruited 347 subjects (mean age 67.2 years, 186 male (56.6%), mean education 5.7 years); 172 (49.6%) received citicoline for 12 months (no significant differences from controls n = 175). Demographic data, risk factors, initial stroke severity (NIHSS), clinical and etiological classification were similar in both groups. Only 37 subjects (10.7%) discontinued treatment (10.5% citicoline vs. 10.9% control) at 6 months; 30 (8.6%) due to death (16 (9.3%) citicoline vs. 14 (8.0%) control, p = 0.740), 7 lost to follow-up or incorrect treatment, and 4 (2.3%) had adverse events from citicoline without discontinuation. 199 patients underwent neuropsychological evaluation at 1 year. Cognitive functions improved 6 and 12 months after stroke in the entire group but in comparison with controls, citicoline-treated patients showed better outcome in attention-executive functions (OR 1.721, 95% CI 1.065-2.781, p = 0.027 at 6 months; OR 2.379, 95% CI 1.269-4.462, p = 0.007 at 12 months) and temporal orientation (OR 1.780, 95% CI 1.020-3.104, p = 0.042 at 6 months; OR 2.155, 95% CI 1.017-4.566, p = 0.045 at 12 months) during the follow-up. Moreover, citicoline group showed a better functional outcome (modified Rankin scale