General Internal Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
George Washington University Milken Institute School of Public Health, Washington, DC, USA.
J Alzheimers Dis. 2023;93(3):949-961. doi: 10.3233/JAD-221224.
Prior studies into the association of head trauma with neuropathology have been limited by incomplete lifetime neurotrauma exposure characterization.
To investigate the neuropathological sequelae of traumatic brain injury (TBI) in an autopsy sample using three sources of TBI ascertainment, weighting findings to reflect associations in the larger, community-based cohort.
Self-reported head trauma with loss of consciousness (LOC) exposure was collected in biennial clinic visits from 780 older adults from the Adult Changes in Thought study who later died and donated their brain for research. Self-report data were supplemented with medical record abstraction, and, for 244 people, structured interviews on lifetime head trauma. Neuropathology outcomes included Braak stage, CERAD neuritic plaque density, Lewy body distribution, vascular pathology, hippocampal sclerosis, and cerebral/cortical atrophy. Exposures were TBI with or without LOC. Modified Poisson regressions adjusting for age, sex, education, and APOE ɛ4 genotype were weighted back to the full cohort of 5,546 participants.
TBI with LOC was associated with the presence of cerebral cortical atrophy (Relative Risk 1.22, 95% CI 1.02, 1.42). None of the other outcomes was associated with TBI with or without LOC.
TBI with LOC was associated with increased risk of cerebral cortical atrophy. Despite our enhanced TBI ascertainment, we found no association with the Alzheimer's disease-related neuropathologic outcomes among people who survived to at least age 65 without dementia. This suggests the pathophysiological processes underlying post-traumatic neurodegeneration are distinct from the hallmark pathologies of Alzheimer's disease.
先前关于头部创伤与神经病理学关联的研究受到不完全的终生神经创伤暴露特征描述的限制。
使用三种创伤性脑损伤 (TBI) 确定方法,对尸检样本中的创伤性脑损伤后遗症进行研究,为更大的、基于社区的队列中的关联提供加权结果。
从成人思维变化研究中的 780 名年龄较大的成年人中收集每两年一次的诊所就诊中的自我报告头部创伤伴有意识丧失 (LOC) 暴露情况,这些成年人后来死亡并捐献他们的大脑进行研究。自我报告数据得到了病历摘要的补充,对于 244 人,还进行了关于终生头部创伤的结构化访谈。神经病理学结果包括 Braak 阶段、CERAD 神经原纤维缠结密度、路易体分布、血管病理学、海马硬化和大脑/皮质萎缩。暴露情况是 TBI 伴或不伴 LOC。调整年龄、性别、教育程度和 APOE ɛ4 基因型的修正泊松回归对 5546 名参与者的整个队列进行了加权。
伴有 LOC 的 TBI 与大脑皮质萎缩的存在相关(相对风险 1.22,95%CI 1.02,1.42)。伴有或不伴有 LOC 的 TBI 与其他任何结果均无关联。
伴有 LOC 的 TBI 与大脑皮质萎缩的风险增加有关。尽管我们增强了 TBI 的确定,但我们在没有痴呆且至少活到 65 岁的人群中,没有发现 TBI 与阿尔茨海默病相关的神经病理学结果之间存在关联。这表明创伤后神经退行性变的病理生理过程与阿尔茨海默病的标志性病理不同。