Neurology:载脂蛋白 e 和可改变危险因素对老年人海马体积减少和记忆衰退的不同影响

2022-04-02 Naomi MedSci原创

近日,研究人员试图确定心血管危险因素、衰老、痴呆发生率(caide)风险评分与海马体积(hv)损失和情景记忆(em)下降的认知正常(cn)老年人分为脑β-淀粉样蛋白阴性(aβ-)或阳性aβ。

前瞻性研究表明,在认知正常 (CN)、年龄增加、携带载脂蛋白 E (APOE) ε4 等位基因脑 β-淀粉样蛋白水平 (Aβ+) 升高的老年人中,每一项都会增加认知能力下降的风险,尤其是在情景记忆中,大脑萎缩,特别是在海马体中,最终导致阿尔茨海默病 (AD) 痴呆

虽然很微妙,但 Aβ 积累可能在痴呆临床分类之前长达 30 年发生,这为实施降低这种风险的策略提供了机会。由于 APOE ε4 携带和年龄等风险因素无法改变,因此确定可能改变的 CN 成人不良认知结果和脑萎缩的其他风险因素变得很重要。流行病学研究已经确定了痴呆的危险因素,尽管这些机制尚不完全清楚。例如,血压和胆固醇水平升高、肥胖和糖尿病等生理特征,以及吸烟和受教育程度较低等行为特征都会增加痴呆风险,当综合考虑这些风险因素的影响时,它们对痴呆的预后效用得到改善。重要的是,这里的每一个风险因素都可以被调整。

心血管风险因素、衰老和痴呆症发病率 (CAIDE) 风险评分是经过充分验证的痴呆症风险评分,它包含年龄、性别、APOE ε4 状态、教育、高血压、体重指数 (BMI)、高胆固醇血症和身体不活动。CAIDE 风险评分的预测效用因人群而异,但 CAIDE 风险评分对于痴呆风险和管理的决策变得很重要,包括指导制定旨在降低老年 CN 人群痴呆风险的战略。然而,当考虑到最常见的痴呆形式 AD 的新兴生物学模型时,基于 CAIDE 风险评分降低痴呆患病率的策略是有问题的,因为 CAIDE 评分还包括无法修改的特性; 即年龄、性别和 APOE ε4。

鉴于大脑 Aβ 对 AD 风险的中心作用,以及观察到年龄和 APOE ε4 通过影响 Aβ 积累而增加 AD 痴呆风险,CAIDE 风险评分中包含的可修改风险因素可能通过增加或放大年龄或 APOE ε4 携带对 Aβ 的影响来发挥作用。尽管过程与 Aβ 无关,CAIDE 评分中包含的可修改风险因素可能会增加痴呆症的风险。随着 AD 生物标志物的广泛应用,除了 Aβ+、APOE ε4 和年龄的影响外,研究在 CAIDE 风险评分中操作的可改变痴呆风险因素如何导致 AD 痴呆风险成为可能。海马萎缩和情景记忆衰退已被可靠地证明是临床前 AD 的早期标志物,因此可用于检查该阶段不同推定 AD 风险因素的影响。

近日,研究人员展开一项前瞻性研究,试图确定心血管危险因素、衰老、痴呆发生率(caide)风险评分与海马体积(hv)损失和情景记忆(em)下降的认知正常(cn)老年人分为脑β-淀粉样蛋白阴性(aβ-)或aβ。本研究的第1个目的是确定临床前 AD (Aβ+) 10 年内 CAIDE 风险评分与早期痴呆指数(海马萎缩、情景记忆下降)之间关系的性质。第2个目的是重新检查这些关系与从风险估计中删除的不可修改的风险因素。然后,第3个目的是通过对具有阈下 Aβ 水平 (Aβ-) 的 CN 老年人的重新检查来挑战在早期 AD 中观察到的可改变或不可改变的危险因素与疾病进展之间的任何关系的特异性。

澳大利亚成像,生物标志物和生活方式研究参与者(58-91岁)完成≥2神经心理学评估和脑 aβpet 扫描(n = 592)。研究人员计算了每个参与者的(CAIDE)风险评分(年龄、性别、 E型载脂蛋白质(apoe) ε4状态、受教育程度、高血压、体重指数(bmi)、高胆固醇血症、缺乏运动)和可改变的(CAIDE)风险评分(caide-mr; education、高血压、 bmi、高胆固醇血症、缺乏运动)。Aβ 的分类是用百分比 > 25。线性混合模型评估了各CAIDE评分、 aβ 组和时间对 hv 损失和 em 下降的交互作用。年龄、性别和载脂蛋白 ε4作为独立的预测因子被包括在 caide-先生模型中,以评估不同的联系。探索性分析考察了 aβ-cn 成年人个体可改变的危险因素与结果之间的关系。

  • aβ 组 × caide × 时间交互作用对HV损失有显著影响(β (se) = 0.04(0.01) ; p < . 000) ,但对EM下降无显著影响(β (se) =-2.33(9.96) ; p = . 98)。
  • 分解显示只有 aβ 参与者存在显著的 caide × time 相互作用。
  • 分别考虑可变/不可变 caide 组分时,可观察到一个显著的 aβ× caide × 时间相互作用仅对EM下降有影响(β (se) = 3.03(1.18) ; p = . 01)。
  • 只在 aβ 参与者中观察到显著的 caide-score  × 时间相互作用。
  • 两组中 apoeε4和年龄 × 时间对HV损失和EM下降均有显著的交互作用。
  • 对 aβ-cn 参与者的探索性分析显示,BMI × 时间 与EM下降之间存在显著的交互作用(β (se) =-3.30(1.43) ; p = . 02)。

这些结果与研究表明,年龄增加、 APOE ε4 与 HV 损失率、 EM 下降率增加有关。 在 Aβ-CNs 中,可改变心血管危险因素的较低患病率与 10 年内较少的 HV 损失和 EM 下降相关,这表明减少可改变心血管危险因素的干预措施可能对该组有益。

文献来源:Rosenich E, Bransby L, Yassi N, et al. Differential Effects of APOE and Modifiable Risk Factors on Hippocampal Volume Loss and Memory Decline in AB- and AB+ Older Adults [published online ahead of print, 2022 Feb 15]. Neurology. 2022;10.1212/WNL.0000000000200118. doi:10.1212/WNL.0000000000200118

 

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    2022-06-01 yinhl1978
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    2022-04-01 ms4000002026468787

    学习了

    0

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