Monica T Ly, Caroline Altaras, Yorghos Tripodis, Charles H Adler, Laura J Balcer, Charles Bernick, Henrik Zetterberg, Kaj Blennow, Elaine R Peskind, Sarah J Banks, William B Barr, Jennifer V Wethe, Steve Lenio, Mark W Bondi, Lisa M Delano-Wood, Robert C Cantu, Michael J Coleman, David W Dodick, Jesse Mez, Daniel H Daneshvar, Joseph N Palmisano, Brett Martin, Alexander P Lin, Inga K Koerte, Sylvain Bouix, Jeffrey L Cummings, Eric M Reiman, Martha E Shenton, Robert A Stern, Michael L Alosco
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Careful operationalization of cognitive impairment is essential to improving the diagnostic specificity and accuracy of TES criteria. We compared single- versus two-test criteria for cognitive impairment in their associations with CSF and imaging biomarkers in male former American football players. <b>Method:</b> 169 participants from the DIAGNOSE CTE Research Project completed neuropsychological tests of memory and executive functioning. Cognitive impairment was identified by single-test criteria (<i>z</i>≤-1.5 on one test) and two-test criteria (<i>z</i><-1 on two tests within a domain). ANCOVAs adjusting for age, race, education, body mass index, word-reading score, and APOE ε4 status assessed whether single- or two-test criteria predicted CSF markers (Aβ<sub>1-42</sub>, p-tau<sub>181</sub>, p-tau<sub>181</sub>/Aβ<sub>1-42</sub>, total tau, neurofilament light [NfL], glial fibrillary acidic protein [GFAP]) and MRI markers (hippocampal volume, cortical thickness, white matter hyperintensities). <b>Results:</b> Ninety-nine participants met single-test criteria for cognitive impairment. Sixty-six met two-test criteria. Participants who met two-test criteria had greater exposure to RHI than those who did not (<i>p</i>=.04). Two-test criteria were -associated with higher CSF p-tau<sub>181</sub>/Aβ<sub>1-42</sub> (<i>q</i>=.02) and CSF NfL (<i>q</i>=.02). The association between two-test criteria and CSF NfL remained after excluding amyloid-positive participants (<i>q</i>=.04). Single-test criteria were not associated with any biomarkers (<i>q</i>'s>.05). <b>Conclusions:</b> Two-test but not single-test criteria for cognitive impairment were associated with markers of neurodegeneration. 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Careful operationalization of cognitive impairment is essential to improving the diagnostic specificity and accuracy of TES criteria. We compared single- versus two-test criteria for cognitive impairment in their associations with CSF and imaging biomarkers in male former American football players. <b>Method:</b> 169 participants from the DIAGNOSE CTE Research Project completed neuropsychological tests of memory and executive functioning. Cognitive impairment was identified by single-test criteria (<i>z</i>≤-1.5 on one test) and two-test criteria (<i>z</i><-1 on two tests within a domain). ANCOVAs adjusting for age, race, education, body mass index, word-reading score, and APOE ε4 status assessed whether single- or two-test criteria predicted CSF markers (Aβ<sub>1-42</sub>, p-tau<sub>181</sub>, p-tau<sub>181</sub>/Aβ<sub>1-42</sub>, total tau, neurofilament light [NfL], glial fibrillary acidic protein [GFAP]) and MRI markers (hippocampal volume, cortical thickness, white matter hyperintensities). <b>Results:</b> Ninety-nine participants met single-test criteria for cognitive impairment. Sixty-six met two-test criteria. Participants who met two-test criteria had greater exposure to RHI than those who did not (<i>p</i>=.04). Two-test criteria were -associated with higher CSF p-tau<sub>181</sub>/Aβ<sub>1-42</sub> (<i>q</i>=.02) and CSF NfL (<i>q</i>=.02). The association between two-test criteria and CSF NfL remained after excluding amyloid-positive participants (<i>q</i>=.04). Single-test criteria were not associated with any biomarkers (<i>q</i>'s>.05). <b>Conclusions:</b> Two-test but not single-test criteria for cognitive impairment were associated with markers of neurodegeneration. 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引用次数: 0
摘要
目的：认知障碍是创伤性脑病综合征（TES）的核心特征，TES是慢性创伤性脑病（一种与重复性头部撞击（RHI）相关的神经病理疾病）的公认临床综合征。认知障碍的谨慎操作对于提高TES标准的诊断特异性和准确性至关重要。我们比较了男性前美式足球运动员认知障碍的单次和双次测试标准与CSF和成像生物标志物的关系。方法：来自诊断CTE研究项目的169名参与者完成了记忆和执行功能的神经心理测试。通过单次测试标准（一次测试z≤-1.5）和双次测试标准（z1-42、p-tau181、p-tau181/ a - β1-42、总tau蛋白、神经丝光[NfL]、胶质纤维酸性蛋白[GFAP]）和MRI标记（海马体积、皮质厚度、白质高信号）来识别认知障碍。结果：99名参与者符合认知障碍的单次测试标准。其中66人符合两项测试标准。符合两个测试标准的参与者比不符合标准的参与者暴露于RHI （p=.04）。两项检测标准均与CSF p-tau181/ a - β1-42升高（q= 0.02）和CSF NfL升高（q= 0.02）相关。在排除淀粉样蛋白阳性参与者后，两项测试标准与CSF NfL之间的关联仍然存在（q= 0.04）。单次检测标准与任何生物标志物均无相关性（q's>.05）。结论：认知障碍的两项测试而非单项测试标准与神经变性标志物相关。未来的临床研究可能会受益于应用双测试标准来操作认知障碍。
Single- versus two-test criteria for cognitive impairment: associations with CSF and imaging markers in former American football players.
Objective: Cognitive impairment is a core feature of traumatic encephalopathy syndrome (TES), the putative clinical syndrome of chronic traumatic encephalopathy-a neuropathological disease associated with repetitive head impacts (RHI). Careful operationalization of cognitive impairment is essential to improving the diagnostic specificity and accuracy of TES criteria. We compared single- versus two-test criteria for cognitive impairment in their associations with CSF and imaging biomarkers in male former American football players. Method: 169 participants from the DIAGNOSE CTE Research Project completed neuropsychological tests of memory and executive functioning. Cognitive impairment was identified by single-test criteria (z≤-1.5 on one test) and two-test criteria (z<-1 on two tests within a domain). ANCOVAs adjusting for age, race, education, body mass index, word-reading score, and APOE ε4 status assessed whether single- or two-test criteria predicted CSF markers (Aβ1-42, p-tau181, p-tau181/Aβ1-42, total tau, neurofilament light [NfL], glial fibrillary acidic protein [GFAP]) and MRI markers (hippocampal volume, cortical thickness, white matter hyperintensities). Results: Ninety-nine participants met single-test criteria for cognitive impairment. Sixty-six met two-test criteria. Participants who met two-test criteria had greater exposure to RHI than those who did not (p=.04). Two-test criteria were -associated with higher CSF p-tau181/Aβ1-42 (q=.02) and CSF NfL (q=.02). The association between two-test criteria and CSF NfL remained after excluding amyloid-positive participants (q=.04). Single-test criteria were not associated with any biomarkers (q's>.05). Conclusions: Two-test but not single-test criteria for cognitive impairment were associated with markers of neurodegeneration. Future clinical research in TES may benefit from applying two-test criteria to operationalize cognitive impairment.
期刊介绍：
The Clinical Neuropsychologist (TCN) serves as the premier forum for (1) state-of-the-art clinically-relevant scientific research, (2) in-depth professional discussions of matters germane to evidence-based practice, and (3) clinical case studies in neuropsychology. Of particular interest are papers that can make definitive statements about a given topic (thereby having implications for the standards of clinical practice) and those with the potential to expand today’s clinical frontiers. Research on all age groups, and on both clinical and normal populations, is considered.
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