Ly Monica T, Altaras Caroline, Tripodis Yorghos, Adler Charles H, Balcer Laura J, Bernick Charles, Zetterberg Henrik, Blennow Kaj, Peskind Elaine R, Banks Sarah J, Barr William B, Wethe Jennifer V, Lenio Steve, Bondi Mark W, Delano-Wood Lisa M, Cantu Robert C, Coleman Michael J, Dodick David W, Mez Jesse, Daneshvar Daniel H, Palmisano Joseph N, Martin Brett, Lin Alexander P, Koerte Inga K, Bouix Sylvain, Cummings Jeffrey L, Reiman Eric M, Shenton Martha E, Stern Robert A, Alosco Michael L
Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Boston University Alzheimer's Disease Research Center and Chronic Traumatic Encephalopathy Center, Boston, MA, USA.
Clin Neuropsychol. 2025 Jan 20:1-25. doi: 10.1080/13854046.2025.2451828.
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. 169 participants from the DIAGNOSE CTE Research Project completed neuropsychological tests of memory and executive functioning. Cognitive impairment was identified by single-test criteria (≤-1.5 on one test) and two-test criteria (<-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, p-tau, p-tau/Aβ, total tau, neurofilament light [NfL], glial fibrillary acidic protein [GFAP]) and MRI markers (hippocampal volume, cortical thickness, white matter hyperintensities). 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 (=.04). Two-test criteria were -associated with higher CSF p-tau/Aβ (=.02) and CSF NfL (=.02). The association between two-test criteria and CSF NfL remained after excluding amyloid-positive participants (=.04). Single-test criteria were not associated with any biomarkers ('s>.05). 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.
认知障碍是创伤性脑病综合征（TES）的核心特征，创伤性脑病综合征被认为是慢性创伤性脑病的临床综合征，慢性创伤性脑病是一种与重复性头部撞击（RHI）相关的神经病理学疾病。对认知障碍进行仔细的操作化定义对于提高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国橄榄球运动员中认知障碍的单测试标准与双测试标准与脑脊液和影像学生物标志物之间的关联。来自DIAGNOSE 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学测试。认知障碍通过单测试标准（一项测试得分≤-1.5）和双测试标准（一个领域内两项测试得分均<-1）来确定。通过对年龄、种族、教育程度、体重指数、单词阅读分数和APOE ε4状态进行协方差分析，评估单测试或双测试标准是否能预测脑脊液标志物（Aβ、p-tau、p-tau/Aβ、总tau、神经丝轻链[NfL]、胶质纤维酸性蛋白[GFAP]）和MRI标志物（海马体积、皮质厚度、白质高信号）。99名参与者符合认知障碍的单测试标准。66名符合双测试标准。符合双测试标准的参与者比未符合标准的参与者有更多的重复性头部撞击暴露（P =.04）。双测试标准与脑脊液中较高的p-tau/Aβ（P =.02）和脑脊液NfL（P =.02）相关。在排除淀粉样蛋白阳性参与者后，双测试标准与脑脊液NfL之间的关联仍然存在（P =.04）。单测试标准与任何生物标志物均无关联（P>.05）。认知障碍的双测试而非单测试标准与神经退行性变标志物相关。TES未来的临床研究可能会受益于应用双测试标准来定义认知障碍。
