Xiong Chengjie, Jasielec Mateusz S, Weng Hua, Fagan Anne M, Benzinger Tammie L S, Head Denise, Hassenstab Jason, Grant Elizabeth, Sutphen Courtney L, Buckles Virginia, Moulder Krista L, Morris John C
From the Charles F. and Joanne Knight Alzheimer's Disease Research Center (C.X., M.S.J., H.W., A.M.F., T.L.S.B., D.H., J.H., E.G., C.L.S., V.B., K.L.M., J.C.M.), Departments of Neurology (V.B., K.L.M., A.M.F., J.H., J.C.M., C.L.S.), Pathology and Immunology (J.C.M.), Physical Therapy (J.C.M.), and Occupational Therapy (J.C.M.), Division of Biostatistics (C.X., M.S.J., H.W., E.G.), and Departments of Psychology (D.H., J.H.), Radiology (T.L.S.B., D.H.), and Neurological Surgery (T.L.S.B.), Washington University School of Medicine, St. Louis, MO.
Neurology. 2016 Apr 19;86(16):1499-506. doi: 10.1212/WNL.0000000000002593. Epub 2016 Mar 23.
To determine whether and how longitudinal rates of change in MRI volumetrics, CSF concentrations of Alzheimer-related proteins, molecular imaging of cerebral fibrillar amyloid with PET using the [(11)C] benzothiazole tracer, Pittsburgh compound B (PiB), and cognition were associated among asymptomatic middle-aged to older individuals.
Multivariate mixed models for repeated measures were used to assess the correlations on the rates of changes across markers.
Among 209 asymptomatic middle-aged to older individuals longitudinally followed for up to 11 years (mean 6.7 years), a faster intraindividual decrease in CSF Aβ42 was associated with a faster increase in PiB mean cortical standardized uptake value ratio (MCSUVR, p = 0.04), but not others. The rate of change in CSF tau (and Ptau181) was correlated with the rate of change in PiB MCSUVR (p = 0.002), hippocampal volume (p = 0.04), and global cognition (p = 0.008). The rate of change in hippocampal volume was correlated with the rate of change in global cognition (p = 0.04). Only 3 significant correlations were observed at baseline: CSF Aβ42 and PiB MCSUVR (p < 0.001), CSF tau and PiB MCSUVR (p < 0.001), and CSF Aβ42 and global cognition (p = 0.01).
CSF tau (Ptau181), PiB MCSUVR, and hippocampal volume were all longitudinally correlated with each other, whereas CSF Aβ42 was correlated only with PiB binding. Unlike the baseline values, the longitudinal change in CSF tau (Ptau181) and hippocampal volume were correlated with the longitudinal change in global cognition, validating the role of these biomarkers in Alzheimer disease prevention trials.
确定在无症状的中年至老年个体中，MRI体积测量的纵向变化率、阿尔茨海默病相关蛋白的脑脊液浓度、使用[(11)C]苯并噻唑示踪剂匹兹堡化合物B（PiB）进行PET脑纤维淀粉样蛋白分子成像以及认知之间是否存在关联以及如何关联。
采用重复测量的多变量混合模型来评估各标志物变化率之间的相关性。
在209名无症状的中年至老年个体中进行了长达11年（平均6.7年）的纵向随访，脑脊液Aβ42个体内更快的下降与PiB平均皮质标准化摄取值比率（MCSUVR）更快的升高相关（p = 0.04），但与其他指标无关。脑脊液tau（和Ptau181）的变化率与PiB MCSUVR的变化率（p = 0.002）、海马体积的变化率（p = 0.04）以及整体认知的变化率（p = 0.008）相关。海马体积的变化率与整体认知的变化率相关（p = 0.04）。在基线时仅观察到3个显著相关性：脑脊液Aβ42与PiB MCSUVR（p < 0.001）、脑脊液tau与PiB MCSUVR（p < 0.001）以及脑脊液Aβ42与整体认知（p = 0.01）。
脑脊液tau（Ptau181）、PiB MCSUVR和海马体积在纵向均相互关联，而脑脊液Aβ42仅与PiB结合相关。与基线值不同，脑脊液tau（Ptau181）和海马体积的纵向变化与整体认知的纵向变化相关，证实了这些生物标志物在阿尔茨海默病预防试验中的作用。
