Currently a student at Fluminense Federal University, Niteroi, Brazil2Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin3Wisconsin Alzheimer's Institute, University of Wisconsin School of.
Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin3Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison4Wisconsin Alzheimer's Disease Rese.
JAMA Neurol. 2015 Jun;72(6):699-706. doi: 10.1001/jamaneurol.2015.0098.
Although advancing age is the strongest risk factor for the development of symptomatic Alzheimer disease (AD), recent studies have shown that there are individual differences in susceptibility to age-related alterations in the biomarkers of AD pathophysiology.
To investigate whether cognitive reserve (CR) modifies the adverse influence of age on key cerebrospinal fluid (CSF) biomarkers of AD.
DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional cohort of 268 individuals (211 in a cognitively normal group and 57 in a cognitively impaired group) from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center participated in this study. They underwent lumbar puncture for collection of CSF samples, from which Aβ42, total tau (t-tau), and phosphorylated tau (p-tau) were immunoassayed. In addition, we computed t-tau/Aβ42 and p-tau/Aβ42 ratios. Cognitive reserve was indexed by years of education, with 16 or more years taken to confer high reserve. Covariate-adjusted regression analyses were used to test whether the effect of age on CSF biomarkers was modified by CR. The study dates were March 5, 2010, to February 13, 2013.
Cerebrospinal fluid levels of Aβ42, t-tau, p-tau, t-tau/Aβ42, and p-tau/Aβ42.
There were significant age × CR interactions for CSF t-tau (β [SE] = -6.72 [2.84], P = .02), p-tau (β [SE] = -0.71 [0.27], P = .01), t-tau/Aβ42 (β [SE] = -0.02 [0.01], P = .02), and p-tau/Aβ42 (β [SE] = -0.002 [0.001], P = .004). With advancing age, individuals with high CR exhibited attenuated adverse alterations in these CSF biomarkers compared with individuals with low CR. This attenuation of age effects by CR tended to be more pronounced in the cognitively impaired group compared with the cognitively normal group. There was evidence of a dose-response relationship such that the effect of age on the biomarkers was progressively attenuated given additional years of schooling.
In a sample composed of a cognitively normal group and a cognitively impaired group, higher CR was associated with a diminution of age-related alterations in CSF biomarkers of AD. This suggests one pathway through which CR might favorably alter lifetime risk for symptomatic AD.
虽然年龄的增长是发生症状性阿尔茨海默病（AD）的最强危险因素，但最近的研究表明，在与年龄相关的 AD 病理生理学生物标志物的改变方面，个体存在易感性的差异。
研究认知储备（CR）是否会改变年龄对 AD 关键脑脊液（CSF）生物标志物的不利影响。
设计、地点和参与者：这项研究纳入了来自威斯康星州阿尔茨海默病预防登记处和威斯康星州阿尔茨海默病研究中心的 268 名个体（211 名认知正常组和 57 名认知障碍组）的横断面队列。他们接受了腰椎穿刺，以采集 CSF 样本，从中免疫测定 Aβ42、总 tau（t-tau）和磷酸化 tau（p-tau）。此外，我们还计算了 t-tau/Aβ42 和 p-tau/Aβ42 比值。CR 通过受教育年限来衡量，16 年或以上的受教育年限被认为是高储备。采用协变量调整回归分析来检验 CR 是否改变了年龄对 CSF 生物标志物的影响。研究日期为 2010 年 3 月 5 日至 2013 年 2 月 13 日。
脑脊液 Aβ42、t-tau、p-tau、t-tau/Aβ42 和 p-tau/Aβ42 水平。
在 CSF t-tau（β[SE]=-6.72[2.84]，P=.02）、p-tau（β[SE]=-0.71[0.27]，P=.01）、t-tau/Aβ42（β[SE]=-0.02[0.01]，P=.02）和 p-tau/Aβ42（β[SE]=-0.002[0.001]，P=.004）方面，均存在显著的年龄×CR 交互作用。与 CR 较低的个体相比，CR 较高的个体在这些 CSF 生物标志物方面表现出对年龄相关不利变化的衰减。与认知正常组相比，这种 CR 对年龄效应的衰减在认知障碍组中更为明显。有证据表明存在剂量-反应关系，即随着受教育年限的增加，年龄对生物标志物的影响逐渐减弱。
在由认知正常组和认知障碍组组成的样本中，较高的 CR 与 AD 相关的 CSF 生物标志物的年龄相关改变减少有关。这表明 CR 可能通过一种途径改变发生症状性 AD 的终生风险。
