Toyama Kensuke, Sugiyama Seigo, Oka Hideki, Hamada Mari, Iwasaki Yuri, Horio Eiji, Rokutanda Taku, Nakamura Shinichi, Spin Joshua M, Tsao Philip S, Ogawa Hisao
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan.
Intern Med. 2017;56(6):641-649. doi: 10.2169/internalmedicine.56.7703. Epub 2017 Mar 17.
Objective Hypercholesterolemia, a risk factor in cognitive impairment, can be treated with statins. However, cognitive decline associated with "statins" (HMG-CoA reductase inhibitors) is a clinical concern. This pilot study investigated the effects of combining statins and regular exercise on cognitive function in coronary artery disease (CAD) patients with prior mild cognitive decline. Methods We recruited 43 consecutive CAD patients with mild cognitive decline. These patients were treated with a statin and weekly in-hospital aerobic exercise for 5 months. We measured serum lipids, exercise capacity, and cognitive function using the mini mental state examination (MMSE). Results Low-density lipoprotein cholesterol levels were significantly decreased, and maximum exercise capacity (workload) was significantly increased in patients with CAD and mild cognitive decline after treatment compared with before. Combined statin-exercise therapy significantly increased the median (range) MMSE score from 24 (22-25) to 25 (23-27) across the cohort (p<0.01). Changes in body mass index (BMI) were significantly and negatively correlated with changes in the MMSE. After treatment, MMSE scores in the subgroup of patients that showed a decrease in BMI were significantly improved, but not in the BMI-increased subgroup. Furthermore, the patients already on a statin at the beginning of the trial displayed a more significant improvement in MMSE score than statin-naïve patients, implying that exercise might be the beneficial aspect of this intervention as regards cognition. In a multivariate logistic regression analysis adjusted for age >65 years, sex, and presence of diabetes mellitus, a decrease in BMI during statin-exercise therapy was significantly correlated with an increase in the MMSE score (odds ratio: 4.57, 95% confidence interval: 1.05-20.0; p<0.05). Conclusion Statin-exercise therapy may help improve cognitive dysfunction in patients with CAD and pre-existing mild cognitive decline.
目的 高胆固醇血症是认知功能障碍的一个危险因素，可用他汀类药物治疗。然而，与“他汀类药物”（HMG-CoA还原酶抑制剂）相关的认知功能下降是一个临床关注点。这项前瞻性研究调查了他汀类药物与规律运动相结合对既往有轻度认知功能下降的冠状动脉疾病（CAD）患者认知功能的影响。方法 我们连续招募了43例有轻度认知功能下降的CAD患者。这些患者接受他汀类药物治疗，并每周进行5个月的院内有氧运动。我们使用简易精神状态检查表（MMSE）测量血脂、运动能力和认知功能。结果 与治疗前相比，CAD合并轻度认知功能下降的患者治疗后低密度脂蛋白胆固醇水平显著降低，最大运动能力（工作量）显著增加。他汀类药物与运动联合治疗使整个队列的MMSE评分中位数（范围）从24（22 - 25）显著提高到25（23 - 27）（p<0.01）。体重指数（BMI）的变化与MMSE的变化显著负相关。治疗后，BMI降低的患者亚组的MMSE评分显著改善，但BMI升高的亚组未改善。此外，试验开始时已服用他汀类药物的患者的MMSE评分改善比未服用他汀类药物的患者更显著，这意味着就认知而言，运动可能是这种干预的有益方面。在对年龄>65岁、性别和糖尿病存在情况进行校正的多因素逻辑回归分析中，他汀类药物与运动联合治疗期间BMI的降低与MMSE评分的增加显著相关（优势比：4.57，95%置信区间：1.05 - 20.0；p<0.05）。结论 他汀类药物与运动联合治疗可能有助于改善CAD合并既往轻度认知功能下降患者的认知功能障碍。
