Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720-3190, USA.
Ann Epidemiol. 2012 Dec;22(12):868-75. doi: 10.1016/j.annepidem.2012.09.004. Epub 2012 Oct 24.
To assess relationships between biomarkers for Alzheimer's disease (AD) and their potential contributions to AD.
Biomarkers and cognitive evaluations were assessed longitudinally in 179 patients with mild cognitive impairment, from the Alzheimer's Disease Neuroimaging Initiative from 2003 to 2006, and were used to examine, at any given time, the joint contributions of hippocampal volume, whole brain volume, and brain glucose metabolism on clinical AD progression, using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Marginal structural models were applied, and an inverse-probability of treatment weight estimation was used to account for time-dependent confounding between study variables.
At any given time, population-level differences (e.g., 1-standard deviation [SD] increase) in brain glucose metabolism (-1.036; 95% confidence interval [95% CI], -1.608, -0.464) and hippocampal volume (-1.537; 95% CI, -2.399, -0.674) independently reduced mean (ADAS-Cog), whereas a 1-SD increase in whole brain volume did not (0.372; 95% CI, -0.283, 1.027). The effects of brain glucose metabolism differed in subgroups defined by baseline covariates (e.g., age), but no subgroup effects were observed for hippocampal volume and brain volume.
Brain glucose metabolism and hippocampal volume represent relevant biological markers in subjects at risk for AD.
评估阿尔茨海默病（AD）的生物标志物之间的关系及其对 AD 的潜在贡献。
从 2003 年至 2006 年，对来自阿尔茨海默病神经影像学倡议的 179 名轻度认知障碍患者进行了纵向的生物标志物和认知评估，并用于在任何特定时间检查海马体积、全脑体积和大脑葡萄糖代谢在临床 AD 进展中的联合贡献，使用阿尔茨海默病评估量表认知子量表（ADAS-Cog）。应用边际结构模型，并使用治疗权重估计的逆概率来解释研究变量之间的时变混杂。
在任何特定时间，脑葡萄糖代谢（-1.036；95%置信区间 [95%CI]，-1.608，-0.464）和海马体积（-1.537；95%CI，-2.399，-0.674）的人群水平差异（例如，1 个标准差 [SD] 增加）独立地降低了平均（ADAS-Cog），而全脑体积的 1-SD 增加则没有（0.372；95%CI，-0.283，1.027）。脑葡萄糖代谢的影响在由基线协变量（例如年龄）定义的亚组中有所不同，但在海马体积和脑体积方面没有观察到亚组效应。
脑葡萄糖代谢和海马体积是 AD 风险患者的相关生物学标志物。
