Baseline CSF p-tau levels independently predict progression of hippocampal atrophy in Alzheimer disease
Baseline CSF p-tau levels independently predict progression of hippocampal atrophy in Alzheimer disease
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DOI：
10.1212/wnl.0b013e3181b879ac
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发表时间：
2009-09-22
期刊：
影响因子：
9.9
通讯作者：
van der Flier, W. M.
中科院分区：
文献类型：
--
作者：
Henneman, W. J. P.;Vrenken, H.;van der Flier, W. M.
目的：研究基线CSF生物标志物是否与海马萎缩率相关，作为阿尔茨海默病（AD）患者、轻度认知障碍（MCI）患者和对照组疾病进展的指标，控制基线神经心理学和MRI结果。（平均年龄68 ± 8岁; 39名[52%]女性），他们访问了我们的记忆诊所并接受了连续MRI扫描（扫描间隔1.7 ± 0.7年）。在基线时，获得CSF生物标志物（淀粉样蛋白β 1-42、tau和在苏氨酸181处磷酸化的tau [p-tau]）以及神经心理学数据。使用视觉评分量表评估基线MRI扫描的内侧颞叶萎缩（MTA）、整体皮质萎缩和白色高信号。结果：经年龄和性别校正后的逐步多元线性回归显示，CSF中p-tau水平的升高与年龄、性别、年龄、性别、性别、年龄、性别、年龄、性别、性别、年龄、性别、性别、（beta [标准误差]：- 0.79 [0.35]）与随后较高的海马萎缩率独立相关（p < 0.05），以及较差的记忆性能（0.09 [0.04]）和更严重的MTA（-0.60 [0.21]）。记忆功能与海马萎缩率的关联被解释为与诊断的联系，因为它从模型中消失后，我们另外纠正diagnosis.Conclusions：基线CSF水平的tau蛋白磷酸化在苏氨酸181是独立相关的随后的疾病进展，反映了海马萎缩率。这种效应独立于基线神经心理学和MRI预测因子。我们的研究结果表明，预测疾病进展可以最好地通过结合不同方式的信息来实现。神经病学（R）2009;73：935-940
Objective: To investigate whether baseline CSF biomarkers are associated with hippocampal atrophy rate as a measure of disease progression in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and controls, controlling for baseline neuropsychological and MRI findings.Methods: We assessed data from 31 patients with AD, 25 patients with MCI, and 19 controls (mean age 68 +/- 8 years; 39 [52%] female) who visited our memory clinic and had received serial MRI scanning (scan interval 1.7 +/- 0.7 years). At baseline, CSF biomarkers (amyloid beta 1-42, tau, and tau phosphorylated at threonine 181 [p-tau]) were obtained, as well as neuropsychological data. Baseline MRI scans were assessed using visual rating scales for medial temporal lobe atrophy (MTA), global cortical atrophy, and white matter hyperintensities. Hippocampal atrophy rates were estimated using regional nonlinear "fluid" registration of follow-up scan to baseline scan.Results: Stepwise multiple linear regression, adjusted for age and sex, showed that increased CSF p-tau levels (beta [standard error]: - 0.79 [0.35]) at baseline was independently associated with higher subsequent hippocampal atrophy rates (p < 0.05), together with poorer memory performance (0.09 [0.04]) and more severe MTA (- 0.60 [0.21]). The association of memory function with hippocampal atrophy rate was explained by the link with diagnosis, because it disappeared from the model after we additionally corrected for diagnosis.Conclusions: Baseline CSF levels of tau phosphorylated at threonine 181 are independently associated with subsequent disease progression, as reflected by hippocampal atrophy rate. This effect is independent of baseline neuropsychological and MRI predictors. Our results imply that predicting disease progression can best be achieved by combining information from different modalities. Neurology (R) 2009;73:935-940