Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98493, USA.
J Alzheimers Dis. 2012;31(2):401-10. doi: 10.3233/JAD-2012-120202.
Alzheimer's disease (AD) and other dementias are likely preceded by a protracted preclinical state. Thus, identification of biomarkers that signal potential points of intervention during this prodromal phase (during which patients are largely able to compensate for their cognitive deficits) is of paramount importance. Insulin is a pancreatic hormone with potent central nervous system effects, and insulin dysregulation has been implicated in the pathogenesis of both AD and vascular dementia. The aim of the current study was to determine whether circulating insulin differs as a function of mild cognitive impairment (MCI) diagnosis, and whether this relationship is mediated by sex and apolipoprotein E (APOE) genotype. A sample of 549 nondemented participants aged 65 and over from the Adult Changes in Thought community-based cohort underwent cognitive testing and blood draw to determine fasting levels of plasma insulin. Subjects were categorized as having normal cognitive functioning, amnestic MCI, or nonamnestic MCI. Results showed that the relationship between insulin and diagnostic category is moderated by sex, such that men with nonamnestic or amnestic MCI have higher fasting plasma insulin than cognitively normal men, while women with amnestic MCI have lower fasting plasma insulin than cognitively normal women. Exploratory analyses suggest that APOE ε4 genotype may further influence the relationship between sex and insulin. Future research will help determine whether insulin dysregulation results in differential effects on vascular function and AD pathology as a function of sex and/or APOE genotype.
阿尔茨海默病（AD）和其他痴呆症可能在前临床阶段就已经存在很长一段时间了。因此，识别在这个前驱期（在此期间，患者在很大程度上能够补偿他们的认知缺陷）中发出潜在干预点信号的生物标志物是至关重要的。胰岛素是一种具有强大中枢神经系统作用的胰腺激素，胰岛素失调与 AD 和血管性痴呆的发病机制都有关。本研究的目的是确定循环胰岛素是否会因轻度认知障碍（MCI）的诊断而有所不同，以及这种关系是否受性别和载脂蛋白 E（APOE）基因型的影响。一个由 549 名年龄在 65 岁及以上的、来自成人思想变化社区为基础的队列的非痴呆参与者组成的样本接受了认知测试和血液抽取，以确定空腹血浆胰岛素水平。研究对象被分为认知功能正常、遗忘性 MCI 或非遗忘性 MCI。结果表明，胰岛素与诊断类别的关系受到性别的调节，即患有非遗忘性或遗忘性 MCI 的男性空腹血浆胰岛素水平高于认知正常的男性，而患有遗忘性 MCI 的女性空腹血浆胰岛素水平低于认知正常的女性。探索性分析表明，APOE ε4 基因型可能进一步影响性别和胰岛素之间的关系。未来的研究将有助于确定胰岛素失调是否会因性别和/或 APOE 基因型的不同而对血管功能和 AD 病理产生不同的影响。
