美国橄榄球运动员物质使用的临床与神经病理学关联

Clinical and Neuropathological Correlates of Substance Use in American Football Players.

作者信息

Walsh Michael, Uretsky Madeline, Tripodis Yorghos, Nowinski Christopher J, Rasch Abigail, Bruce Hannah, Ryder Megan, Martin Brett M, Palmisano Joseph N, Katz Douglas I, Dwyer Brigid, Daneshvar Daniel H, Walley Alexander Y, Kim Theresa W, Goldstein Lee E, Stern Robert A, Alvarez Victor E, Huber Bertrand Russell, McKee Ann C, Stein Thor D, Mez Jesse, Alosco Michael L

机构信息

Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.

Department of Neurology, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.

出版信息

J Alzheimers Dis. 2024;101(3):971-986. doi: 10.3233/JAD-240300.

DOI:10.3233/JAD-240300

PMID:39269838

Abstract

BACKGROUND

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy more frequently found in deceased former football players. CTE has heterogeneous clinical presentations with multifactorial causes. Previous literature has shown substance use (alcohol/drug) can contribute to Alzheimer's disease and related tauopathies pathologically and clinically.

OBJECTIVE

To examine the association between substance use and clinical and neuropathological endpoints of CTE.

METHODS

Our sample included 429 deceased male football players. CTE was neuropathologically diagnosed. Informant interviews assessed features of substance use and history of treatment for substance use to define indicators: history of substance use treatment (yes vs no, primary variable), alcohol severity, and drug severity. Outcomes included scales that were completed by informants to assess cognition (Cognitive Difficulties Scale, BRIEF-A Metacognition Index), mood (Geriatric Depression Scale-15), behavioral regulation (BRIEF-A Behavioral Regulation Index, Barratt Impulsiveness Scale-11), functional ability (Functional Activities Questionnaire), as well as CTE status and cumulative p-tau burden. Regression models tested associations between substance use indicators and outcomes.

RESULTS

Of the 429 football players (mean age = 62.07), 313 (73%) had autopsy confirmed CTE and 100 (23%) had substance use treatment history. Substance use treatment and alcohol/drug severity were associated with measures of behavioral regulation (FDR-p-values<0.05, ΔR2 = 0.04-0.18) and depression (FDR-p-values<0.05, ΔR2 = 0.02-0.05). Substance use indicators had minimal associations with cognitive scales, whereas p-tau burden was associated with all cognitive scales (p-values <0.05). Substance use treatment had no associations with neuropathological endpoints (FDR-p-values>0.05).

CONCLUSIONS

Among deceased football players, substance use was common and associated with clinical symptoms.

摘要

背景

慢性创伤性脑病（CTE）是一种神经退行性tau蛋白病，在已故前足球运动员中更为常见。CTE具有异质性临床表现，病因多方面。既往文献表明，物质使用（酒精/药物）在病理和临床方面可导致阿尔茨海默病及相关tau蛋白病。

目的

研究物质使用与CTE的临床及神经病理学终点之间的关联。

方法

我们的样本包括429名已故男性足球运动员。通过神经病理学诊断CTE。 informant访谈评估物质使用特征和物质使用治疗史以定义指标：物质使用治疗史（是与否，主要变量）、酒精严重程度和药物严重程度。结局包括由 informant完成的量表，以评估认知（认知困难量表、BRIEF-A元认知指数）、情绪（老年抑郁量表-15）、行为调节（BRIEF-A行为调节指数、巴拉特冲动性量表-11）、功能能力（功能活动问卷），以及CTE状态和累积p-tau负担。回归模型测试物质使用指标与结局之间的关联。

结果

在429名足球运动员（平均年龄=62.07岁）中，313名（73%）尸检确诊为CTE，100名（23%）有物质使用治疗史。物质使用治疗及酒精/药物严重程度与行为调节指标（FDR-p值<0.05，ΔR2=0.04-0.18）和抑郁（FDR-p值<0.05，ΔR2=0.02-0.05）相关。物质使用指标与认知量表的关联最小，而p-tau负担与所有认知量表相关（p值<0.05）。物质使用治疗与神经病理学终点无关联（FDR-p值>0.05）。