Neurodegenerative Disease Death Certification Among National Football League Players With Dementia

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Importance Researchers frequently use death certificate data to evaluate occupational risks among National Football League (NFL) players, demonstrating elevated neurodegenerative mortality risk. Robust epidemiologic data suggest deaths attributable to neurodegenerative disease (NDD) are frequently underreported on death certificates, leading to substantial underascertainment of neurodegenerative mortality. Better characterization of the factors underlying neurodegenerative death certification is critical to addressing underreporting of NDDs, informing disease surveillance and resource allocation. Objective To elucidate clinical, exposure, and neuropathologic factors associated with neurodegenerative death certification. Design, Setting, and Participants This cohort study included 202 brain donors with clinician-adjudicated dementia who underwent postmortem neuropathologic assessment and retrospective clinical assessment with informants from February 15, 2008, to December 30, 2021, to ascertain clinical and lifetime exposure history. Statistical analysis was performed from October 2025 to June 2026. Exposure NFL career. Main Outcomes and Measures Neuropathologic diagnosis based on established diagnostic criteria, as well as informant-reported clinical measures and exposure history. Multiple logistic regression analysis was conducted to examine the association between factors and NDD death certification, adjusted for age at death, race and ethnicity, and educational level. Results Of 202 male brain donors (mean [SD] age at death, 73.1 [10.5] years) with clinician-adjudicated dementia, 62 (30.7%) had a neurodegenerative underlying cause of death listed on their death certificate. Behavior Rating Inventory of Executive Function–Adult Version (BRIEF-A) Global Executive Composite T-score (odds ratio [OR], 1.04; 95% CI, 1.01-1.06), BRIEF-A Metacognition Index T-score (OR, 1.03; 95% CI, 1.01-1.06), Cognitive Difficulties Scale score (OR, 1.02; 95% CI, 1.01-1.03), and Functional Activities Questionnaire score (OR, 1.13; 95% CI, 1.06-1.21), as well as a history of emergency department treatment for head injury (OR, 4.11; 95% CI, 1.72-9.82), were associated with increased odds of neurodegenerative death certification. High Alzheimer disease neuropathology (OR, 5.27; 95% CI, 1.93-14.40), frontotemporal lobar degeneration (OR, 4.48; 95% CI, 1.61-12.50), Braak stage IV to VI (OR, 2.99; 95% CI, 1.54-5.79), frequent diffuse plaques (OR, 4.21; 95% CI, 1.56-11.38), moderate to severe neuritic plaques (OR, 3.42; 95% CI, 1.55-7.54), and Thal phase 4 (OR, 4.50; 95% CI, 1.39-14.60) were associated with increased odds of neurodegenerative death certification. Conclusions and Relevance This cohort study found that only 30.7% of brain donors with clinician-adjudicated dementia had neurodegenerative death certification. These results add to growing evidence of frequent NDD underascertainment where more severe disease is associated with neurodegenerative death certification, offering insight into factors that must be considered when using death certificate data to assess NDD burden. Factors such as worsened executive functioning and cognitive symptoms, greater functional impairment, and more severe neuropathology may be associated with an increased likelihood of neurodegenerative death certification among NFL players.