. 2019 Sep 21;90(11):1221–1233. doi: 10.1136/jnnp-2017-317557

Table 1.

Key studies summarising the relationship of TBI and neurodegenerative disease

Study	N	Design	TBI exposure	Outcome	Conclusion
Barnes et al ¹²	357 558	Cohort 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	2 794 852	Cohort 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	325 870	Cohort 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	2133	Autopsy-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	3 329 360	Cohort 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	2 013 197	Meta-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	40 639	Cohort 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	511 016	Meta-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	7130	Multiple 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	649	Cohort 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	97 372	Meta-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	346	Meta-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.