Vijverberg Everard G B, Dols Annemiek, Krudop Welmoed A, Del Campo Milan Marta, Kerssens Cora J, Gossink Flora, Prins Niels D, Stek Max L, Scheltens Philip, Teunissen Charlotte E, Pijnenburg Yolande A L
Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands; Department of Neurology, HagaZiekenhuis, The Hague, The Netherlands.
Department of Old Age Psychiatry, GGZ InGeest, Amsterdam, The Netherlands.
Alzheimers Dement (Amst). 2017 Mar 2;7:99-106. doi: 10.1016/j.dadm.2017.01.009. eCollection 2017.
To prospectively determine the diagnostic value of cerebrospinal fluid (CSF) levels total-tau (tau) to amyloid-β ratio (Aβ) ratio (tau/Aβ ratio), phosphorylated-tau (p-tau) to tau ratio (p-tau/tau ratio), neurofilament light chain (NfL) and YKL40 in the late-onset frontal lobe syndrome, in particular for the differential diagnosis of behavioral variant frontotemporal dementia (bvFTD) versus primary psychiatric disorders (PSY).
We included patients with a multidisciplinary 2-year-follow-up diagnosis of probable/definite bvFTD ( = 22) or PSY ( = 25), who underwent a detailed neuropsychiatric clinical examination, neuropsychological test battery, and magnetic resonance imaging at baseline. In all cases, CSF was collected through lumbar puncture at baseline. We compared CSF biomarker levels between the two groups and measured the diagnostic accuracy for probable/definite bvFTD, using the follow-up diagnosis as the reference standard.
The best discriminators between probable/definite bvFTD and PSY were the levels of CSF NfL (area under the curve [AUC] 0.93, < .001, 95% confidence interval [CI] 0.85-1.00), p-tau/tau ratio (AUC 0.87, < .001, 95% CI 0.77-0.97), and YKL40 (AUC 0.82, = .001, 95% CI 0.68-0.97). The combination of these three biomarkers had a sensitivity of 91% (95% CI 66%-100%) at a specificity of 83% (95% CI 65%-95%) with an AUC of 0.94 ( < .001, 95% CI 0.87-1.00) for bvFTD. CSF tau/Aβ ratio was less accurate in differentiating between bvFTD and PSY.
We found a good diagnostic accuracy for higher levels of CSF NfL and YKL40 and reduced p-tau/tau ratio in distinguishing bvFTD from PSY. We advocate the use of these CSF biomarkers as potential additional tools to neuroimaging in the diagnosis of bvFTD versus PSY.
前瞻性地确定脑脊液（CSF）中总tau蛋白（tau）与淀粉样β蛋白（Aβ）比值（tau/Aβ比值）、磷酸化tau蛋白（p-tau）与tau蛋白比值（p-tau/tau比值）、神经丝轻链（NfL）和YKL40在晚发性额叶综合征中的诊断价值，特别是用于行为变异型额颞叶痴呆（bvFTD）与原发性精神障碍（PSY）的鉴别诊断。
我们纳入了经过多学科2年随访诊断为可能/确诊bvFTD（n = 22）或PSY（n = 25）的患者，这些患者在基线时接受了详细的神经精神临床检查、神经心理测试组套和磁共振成像。所有病例在基线时均通过腰椎穿刺采集脑脊液。我们比较了两组之间的脑脊液生物标志物水平，并以随访诊断作为参考标准，测量了可能/确诊bvFTD的诊断准确性。
在区分可能/确诊bvFTD和PSY方面，最佳的鉴别指标是脑脊液NfL水平（曲线下面积[AUC]为0.93，P <.001，95%置信区间[CI]为0.85 - 1.00）、p-tau/tau比值（AUC为0.87，P <.001，95% CI为0.77 - 0.97）和YKL40（AUC为0.82，P =.001，95% CI为0.68 - 0.97）。这三种生物标志物的组合对bvFTD的敏感性为91%（95% CI为66% - 100%），特异性为83%（95% CI为65% - 95%），AUC为0.94（P <.001，95% CI为0.87 - 1.00）。脑脊液tau/Aβ比值在区分bvFTD和PSY方面准确性较低。
我们发现脑脊液NfL和YKL40水平升高以及p-tau/tau比值降低在区分bvFTD和PSY方面具有良好的诊断准确性。我们主张将这些脑脊液生物标志物作为在bvFTD与PSY诊断中辅助神经影像学的潜在工具。
