Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Banner Alzheimer's Institute, Stead Family Memory Center, Phoenix, AZ, USA.
J Alzheimers Dis. 2020;75(3):903-910. doi: 10.3233/JAD-191090.
The apolipoprotein epsilon 4 (APOE4) allele is a well-established genetic risk factor for Alzheimer's disease (AD). However, there are mixed findings as to how the APOE4 allele modifies the effects of both higher low-density lipoprotein cholesterol (LDL) and statin use on cognitive functioning.
This study sought to examine the effects of LDL levels and statin use on verbal learning and memory, as modified by the presence of the APOE4 allele, in a sample of cognitively unimpaired, older adults at risk for AD.
Neuropsychological, LDL, statin use, and APOE4 data were extracted from an ongoing longitudinal study at the Banner Alzheimer's Institute in Arizona. Participants were cognitively unimpaired based on Mini-Mental State Examination scores within a normal range, aged 47-75, with a family history of probable AD in at least one first-degree relative.
In the whole sample, higher LDL was associated with worse immediate verbal memory in APOE4 non-carriers, but did not have an effect on immediate verbal memory in APOE4 carriers. In APOE4 non-carriers, statin use was associated with better verbal learning, but did not have an effect on verbal learning in APOE4 carriers. Among women, higher LDL in APOE4 carriers was associated with worse verbal learning than in APOE4 non-carriers, and statin use in APOE4 non-carriers was associated with better verbal learning and immediate and delayed verbal memory but worse performances on these tasks in APOE4 carriers.
LDL and statin use may have differential effects on verbal learning and/or memory depending on genetic risk for AD. Women appear to be particularly vulnerable to statin use depending on their APOE4 status.
载脂蛋白 E psilon 4（APOE4）等位基因是阿尔茨海默病（AD）的一个公认的遗传风险因素。然而，APOE4 等位基因如何修饰较高的低密度脂蛋白胆固醇（LDL）和他汀类药物使用对认知功能的影响存在混合结果。
本研究旨在检查 LDL 水平和他汀类药物使用对认知未受损的、有 AD 风险的老年人群的言语学习和记忆的影响，这些人群的 APOE4 等位基因存在差异。
从亚利桑那州班纳阿尔茨海默病研究所的一项正在进行的纵向研究中提取神经心理学、LDL、他汀类药物使用和 APOE4 数据。参与者的认知功能正常，基于 Mini-Mental State Examination 评分在正常范围内，年龄在 47-75 岁之间，至少有一位一级亲属有明确的 AD 家族史。
在整个样本中，APOE4 非携带者的 LDL 较高与即时言语记忆较差相关，但在 APOE4 携带者中 LDL 对即时言语记忆没有影响。在 APOE4 非携带者中，他汀类药物使用与更好的言语学习相关，但在 APOE4 携带者中没有影响。在女性中，APOE4 携带者的 LDL 较高与言语学习较差相关，而 APOE4 非携带者的他汀类药物使用与更好的言语学习以及即时和延迟言语记忆相关，但在 APOE4 携带者中这些任务的表现更差。
LDL 和他汀类药物的使用可能根据 AD 的遗传风险对言语学习和/或记忆产生不同的影响。女性的 APOE4 状态可能使其特别容易受到他汀类药物使用的影响。
