title: Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players.
abstract: The term "repetitive head impacts" (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), quantitative analysis of this relationship has not yet been examined because of the lack of validated tools to quantify lifetime RHI exposure. The objectives of this study were: 1) to develop a metric to quantify cumulative RHI exposure from football, which we term the "cumulative head impact index" (CHII); 2) to use the CHII to examine the association between RHI exposure and long-term clinical outcomes; and 3) to evaluate its predictive properties relative to other exposure metrics (i.e., duration of play, age of first exposure, concussion history). Participants included 93 former high school and collegiate football players who completed objective cognitive and self-reported behavioral/mood tests as part of a larger ongoing longitudinal study. Using established cutoff scores, we transformed continuous outcomes into dichotomous variables (normal vs. impaired). The CHII was computed for each participant and derived from a combination of self-reported athletic history (i.e., number of seasons, position[s], levels played), and impact frequencies reported in helmet accelerometer studies. A bivariate probit, instrumental variable model revealed a threshold dose-response relationship between the CHII and risk for later-life cognitive impairment (p < 0.0001), self-reported executive dysfunction (p < 0.0001), depression (p < 0.0001), apathy (p = 0.0161), and behavioral dysregulation (p < 0.0001). Ultimately, the CHII demonstrated greater predictive validity than other individual exposure metrics.
authors.affiliation: 1 Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine , Boston, Massachusetts.|2 Department of Anatomy and Neurobiology, Boston University School of Medicine , Boston, Massachusetts.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Montenigro
authors.affiliation: 1 Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine , Boston, Massachusetts.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Alosco
authors.affiliation: 3 Data Coordinating Center, Boston University School of Public Health , Boston, Massachusetts.
authors.forename: Brett M
authors.initials: BM
authors.lastname: Martin
authors.affiliation: 1 Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine , Boston, Massachusetts.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Daneshvar
authors.affiliation: 1 Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine , Boston, Massachusetts.|4 Department of Neurology, Boston University School of Medicine , Boston, Massachusetts.
authors.forename: Jesse
authors.initials: J
authors.lastname: Mez
authors.affiliation: 1 Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine , Boston, Massachusetts.|3 Data Coordinating Center, Boston University School of Public Health , Boston, Massachusetts.|5 Department of Biostatistics, Boston University School of Public Health , Boston, Massachusetts.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Chaisson
authors.affiliation: 1 Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine , Boston, Massachusetts.|6 Concussion Legacy Foundation , Waltham, Massachusetts.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Nowinski
authors.affiliation: 4 Department of Neurology, Boston University School of Medicine , Boston, Massachusetts.|7 Framingham Heart Study, Boston University School of Medicine , Boston, Massachusetts.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
authors.affiliation: 1 Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine , Boston, Massachusetts.|4 Department of Neurology, Boston University School of Medicine , Boston, Massachusetts.|8 Department of Pathology, Boston University School of Medicine , Boston, Massachusetts.|9 VA Boston Healthcare System , Boston, Massachusetts.
authors.forename: Ann C
authors.initials: AC
authors.lastname: McKee
authors.affiliation: 1 Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine , Boston, Massachusetts.|6 Concussion Legacy Foundation , Waltham, Massachusetts.|10 Department Neurosurgery, Boston University School of Medicine , Boston, Massachusetts.|11 Department of Neurosurgery, Emerson Hospital , Concord, Massachusetts.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Cantu
authors.affiliation: 12 Environmental Health, Boston University School of Public Health , Boston, Massachusetts.
authors.forename: Michael D
authors.initials: MD
authors.lastname: McClean
authors.affiliation: 1 Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine , Boston, Massachusetts.|2 Department of Anatomy and Neurobiology, Boston University School of Medicine , Boston, Massachusetts.|4 Department of Neurology, Boston University School of Medicine , Boston, Massachusetts.|10 Department Neurosurgery, Boston University School of Medicine , Boston, Massachusetts.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Stern
authors.affiliation: 1 Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine , Boston, Massachusetts.|5 Department of Biostatistics, Boston University School of Public Health , Boston, Massachusetts.
authors.forename: Yorghos
authors.initials: Y
authors.lastname: Tripodis
mesh_terms: D000328:Adult; D057565:Apathy / Q000502:physiology; D001924:Brain Concussion / Q000150:complications / Q000175:diagnosis* / Q000523:psychology; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000209:etiology / Q000523:psychology; D003863:Depression / Q000175:diagnosis* / Q000209:etiology / Q000523:psychology; D056344:Executive Function / Q000502:physiology; D005538:Football / Q000293:injuries* / Q000523:psychology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012008:Recurrence; D012189:Retrospective Studies; D012574:Schools / Q000639:trends; D057566:Self Report; D013334:Students / Q000523:psychology; D014495:Universities / Q000639:trends
keywords: behavior; cognition; concussion; football; long-term impairment; subconcussive impacts