Inserm, U1061, Montpellier, France.
J Alzheimers Dis. 2012;30(3):629-37. doi: 10.3233/JAD-2012-120064.
The aim of this prospective cohort study was to evaluate the effects of lipid lowering agent (LLA) intake on cognitive function in 6,830 community-dwelling elderly persons. Cognitive performance (global cognitive functioning, visual memory, verbal fluency, psychomotor speed, and executive function), clinical diagnosis of dementia, and fibrate and statin use, were evaluated at baseline, and 2, 4, and 7 year follow-up. Multivariate Cox models were stratified by gender and adjusted for sociodemographic characteristics, mental and physical health including vascular risk factors, and genetic vulnerability (apolipoprotein E and cholesteryl ester transfer protein). For women but not men, fibrate use was specifically associated with an increased risk over 7 years of decline in visual memory only (HR = 1.29, 95% CI = 1.09-1.54, p = 0.004), and did not increase risk for incident dementia. This association was independent of genetic vulnerability related to apolipoprotein E and cholesteryl exchange transfer protein polymorphisms and occurred only in women with higher low density lipoprotein (LDL)-cholesterol levels and treated with fibrate (HR = 1.39, 95% CI = 1.08-1.79, p = 0.01) and not in those with lower LDL-cholesterol levels irrespective of fibrate treatment. For both genders, no significant associations were found between statins (irrespective of their lipophilicity) and either cognitive decline or dementia incidence. This prospective study, adjusting for multiple confounders, found no evidence that LLA given in late life reduced the risk of cognitive decline and dementia, but did raise the possibility that women with treatment-resistant high LDL-cholesterol may be at increased risk of decline in visual memory.
本前瞻性队列研究的目的在于评估降脂药物（LLA）的摄入对 6830 名社区居住的老年人认知功能的影响。认知表现（整体认知功能、视觉记忆、言语流畅性、精神运动速度和执行功能）、痴呆的临床诊断以及贝特类药物和他汀类药物的使用情况，在基线、2 年、4 年和 7 年随访时进行评估。多变量 Cox 模型按性别分层，并根据社会人口统计学特征、精神和身体健康（包括血管危险因素）以及遗传易感性（载脂蛋白 E 和胆固醇酯转移蛋白）进行调整。对于女性而非男性，贝特类药物的使用与 7 年内视觉记忆下降的风险增加有关（HR = 1.29，95%CI = 1.09-1.54，p = 0.004），但不会增加痴呆的发病风险。这种关联独立于与载脂蛋白 E 和胆固醇酯转移蛋白多态性相关的遗传易感性，仅发生在 LDL 胆固醇水平较高且接受贝特类药物治疗的女性中（HR = 1.39，95%CI = 1.08-1.79，p = 0.01），而与 LDL 胆固醇水平较低且无论是否接受贝特类药物治疗的女性无关。对于两性，他汀类药物（无论其亲脂性如何）与认知能力下降或痴呆发生率之间均无显著关联。本前瞻性研究在调整了多种混杂因素后，没有证据表明 LLA 在生命晚期使用可以降低认知能力下降和痴呆的风险，但确实增加了一种可能性，即治疗抵抗性高 LDL 胆固醇的女性可能存在视觉记忆下降的风险增加。
