Table 1

Key studies summarising the relationship of TBI and neurodegenerative disease

StudyNDesignTBI exposureOutcomeConclusion
Barnes et al 12 357 558Cohort study (US Veterans Health Administration).
Mean follow-up 4.2 years.
Moderate-severe TBI (≥1).
Mild TBI (≥1) with LOC.
Mild TBI (≥1) without LOC.
Dementia.HR 3.77 (3.63–3.91)
HR 2.52 (2.29–2.76)
HR 2.36 (2.10–2.66)
Fann et al 7 2 794 852Cohort study (Danish National Patient Register).
Mean follow-up 9.9 years.
Severe TBI (single).
Mild TBI (single).
Dementia.HR 1.35 (1.26–1.45)
HR 1.17 (1.13–1.20)
Gardner et al 19 325 870Cohort study (US Veterans Health Administration).
Mean follow-up 4.6 years.
Moderate-severe TBI (≥1)
Mild TBI (≥1)
PD.HR 1.83 (1.61–2.07)
HR 1.56 (1.35–1.80)
Schaffert et al 16 2133Autopsy-confirmed cases from cohort studies (from US National Alzheimer’s Coordinating Center).TBI with LOC (≥1).AD (neuropathologically confirmed).3.6 years earlier onset and diagnosis
Nordström and Nordström6 3 329 360Cohort study (Swedish National Patient Register).
Mean follow-up 15.3 years.
Severe TBI (single).
Mild TBI (single).
Dementia.OR 2.06 (1.95–2.19)
OR 1.63 (1.57–1.70)
Li et al 5 2 013 197Meta-analysis of 21 case–control and 11 cohort studies.All severities (≥1).Dementia.
AD.
RR 1.63 (1.34–1.99)
RR 1.51 (1.26–1.80)
Raj et al 11 40 639Cohort study (Finnish Care Register).
Median follow-up 10 years. Used mild TBI controls.
Moderate-severe TBI (≥1).Dementia.
PD.
ALS.
HR 1.9 (1.6–2.2)
HR 1.3 (0.9–1.9) (NS)
HR 1.3 (0.5–3.2) (NS)
Watanabe and Watanabe21 511 016Meta-analysis of 13 case–control and 3 cohort studies.All severity TBI (single).
All severity TBI (repeated).
ALS.OR 1.23 (1.08–1.42)
OR 1.17 (0.73–1.89) (NS)
Crane et al 17 7130Multiple US cohort studies (Memory and Aging Project, Adult Changes in Thought Study and Religious Orders Study).TBI with LOC >1 hour (single).PD.
PD neuropathology.
Dementia.
AD.
AD neuropathology.
HR 3.56 (1.52–8.28)
HR 2.64 (1.40–4.99)
NS
NS
NS
Abner et al 15 649Cohort study (Kentucky Biologically Resilient Adults in Neurological Studies, ‘BRAiNS’).
Median follow-up 10.8 years.
All severities (≥1).AD neuropathology (men).
AD neuropathology (women).
OR 1.47(1.03–2.09)
OR 1.18 (0.83–1.68) (NS)
Jafari et al 18 97 372Meta-analysis of 19 case–control, 2 nested case–control and 1 cohort study.Symptomatic TBI (single).PD.OR=1.57 (1.35–1.83)
Fleminger et al 13 346Meta-analysis of 15 case–control studies.TBI with LOC (single).AD.OR=1.58 (1.21–2.06)
  • Summary of key meta-analyses or significant individual studies providing evidence about neurodegenerative diseases after TBI. All other reported tests are significant.

  • AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; LOC, loss of consciousness; NS, not significant; PD, Parkinson’s disease; RR, relative risk; TBI, traumatic brain injury.