Yaffe Kristine, Barrett-Connor Elizabeth, Lin Feng, Grady Deborah
Departments of Psychiatry and Neurology, University of California, San Francisco, 4150 Clement St, Campus Box 111G, San Francisco, CA 94121, USA.
Arch Neurol. 2002 Mar;59(3):378-84. doi: 10.1001/archneur.59.3.378.
Few strategies are available for the prevention of cognitive impairment in elderly persons. Serum lipoprotein levels may be important predictors of cognitive function, and drugs that lower cholesterol may be effective for the prevention of cognitive impairment.
To determine whether serum lipoprotein levels, the 4-year change in serum lipoprotein levels, and the use of statin drugs are associated with cognition in older women without dementia.
DESIGN, SETTING, AND PARTICIPANTS: An observational study of 1037 postmenopausal women with coronary heart disease enrolled in the Heart and Estrogen/progestin Replacement Study (participants at 10 of 20 centers).
The Modified Mini-Mental State Examination was administered at the end of the study after 4 years of follow-up. Women whose score was less than 84 points (>1.5 SDs below the mean) were classified as having cognitive impairment. Lipoprotein levels (total, high-density lipoprotein, and low-density lipoprotein [LDL] cholesterol and triglycerides) were measured at baseline and at the end of the study; statin use was documented at each visit.
Compared with women in the lower quartiles, women in the highest LDL cholesterol quartile at cognitive testing had worse mean plus minus SD Modified Mini-Mental State Examination scores (93.7 plus minus 6.0 vs 91.9 plus minus 7.6; P =.002) and an increased likelihood of cognitive impairment (adjusted odds ratio, 1.76; 95% confidence interval, 1.04-2.97). A reduction in the LDL cholesterol level during the 4 years tended to be associated with a lower odds of impairment (adjusted odds ratio, 0.61; 95% confidence interval, 0.36-1.03) compared with women whose levels increased. Higher total and LDL cholesterol levels, corrected for lipoprotein(a) levels, were also associated with a worse Modified Mini-Mental State Examination score and a higher likelihood of impairment, whereas high-density lipoprotein cholesterol and triglyceride levels were not associated with cognition. Compared with nonusers, statin users had higher mean plus minus SD Modified Mini-Mental State Examination scores (92.7 plus minus 7.1 vs 93.7 plus minus 6.1; P =.02) and a trend for a lower likelihood of cognitive impairment (odds ratio, 0.67; 95% confidence interval, 0.42-1.05), findings that seemed to be independent of lipid levels.
High LDL and total cholesterol levels are associated with cognitive impairment, and lowering these lipoprotein levels may be a strategy for preventing impairment. The association between statin use and better cognitive function in women without dementia requires further study.
预防老年人认知障碍的策略有限。血清脂蛋白水平可能是认知功能的重要预测指标，而降胆固醇药物可能对预防认知障碍有效。
确定血清脂蛋白水平、血清脂蛋白水平的4年变化以及他汀类药物的使用是否与无痴呆的老年女性的认知情况相关。
设计、场所和参与者：对参加心脏与雌激素/孕激素替代研究（20个中心中的10个中心的参与者）的1037名绝经后冠心病女性进行的一项观察性研究。
在4年随访结束时进行改良简易精神状态检查。得分低于84分（比平均值低>1.5个标准差）的女性被归类为有认知障碍。在基线和研究结束时测量脂蛋白水平（总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白[LDL]胆固醇以及甘油三酯）；每次就诊时记录他汀类药物的使用情况。
与处于较低四分位数的女性相比，认知测试时处于LDL胆固醇最高四分位数的女性的改良简易精神状态检查平均得分（±标准差）更差（93.7±6.0对91.9±7.6；P = 0.002），且认知障碍的可能性增加（调整后的优势比，1.76；95%置信区间，1.04 - 2.97）。与LDL胆固醇水平升高的女性相比，在4年期间LDL胆固醇水平降低的女性发生障碍的几率往往较低（调整后的优势比，0.61；95%置信区间，0.36 - 1.03）。校正脂蛋白(a)水平后，较高的总胆固醇和LDL胆固醇水平也与更差的改良简易精神状态检查得分和更高的障碍可能性相关，而高密度脂蛋白胆固醇和甘油三酯水平与认知无关。与未使用者相比，他汀类药物使用者的改良简易精神状态检查平均得分（±标准差）更高（92.7±7.1对93.7±6.1；P = 0.02），且认知障碍可能性有降低趋势（优势比，0.67；95%置信区间，0.42 - 1.05），这些结果似乎与血脂水平无关。
高LDL和总胆固醇水平与认知障碍相关，降低这些脂蛋白水平可能是预防障碍的一种策略。他汀类药物使用与无痴呆女性更好的认知功能之间的关联需要进一步研究。
