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In an effort to identify potentially modifiable risk factors for the development of dementia, there has been an increasing interest in the potential role of head injury on subsequent dementia risk. In a 2020 study published in Neurology, the authors found that the risk for dementia was roughly 2-3 times higher in patients with traumatic brain injury (TBI) compared to those without TBI.1 While some studies have not demonstrated support for this association, findings largely suggest that even mild TBI may increase dementia risk.1-6
The link between head injury and dementia was further confirmed in a recent prospective cohort study with a 25-year follow-up period. As reported in September 2021 in Alzheimer’s and Dementia, researchers analyzed data from 14,376 participants in the Atherosclerosis Risk in Communities (ARIC) Study, including a combination of cognitive assessments, diagnostic and death certificate codes, self-report, and informant interviews.5
The results showed an association between head injury and dementia risk (hazard ratio [HR], 1.44; 95% (confidence interval) CI, 1.3-1.57) in a dose-dependent manner, with HRs of 1.25 (95% CI, 1.13-1.39) for 1 head injury and 2.14 (95% CI, 1.86-2.46) for 2 or more head injuries. The results also showed stronger associations among female participants (HR, 1.69; 95% CI, 1.51-1.90) compared to male participants (HR, 1.15; 95% CI, 1.00-1.32) and among White participants (HR, 1.55; 95% CI, 1.40-1.72) compared to Black participants (HR, 1.22; 95% CI, 1.02-1.45).
“The 2020 Lancet Commission on Dementia added TBI as 1 of 12 potentially modifiable risk factors for dementia,” lead author Andrea L. Schneider, MD, PhD, assistant professor in the department of neurology at the University of Pennsylvania Perelman School of Medicine told Neurology Advisor.7 Dr Schneider stated that this along with her findings suggests there’s a dose-response association between the number of prior head injuries and dementia risk. She believes this highlights the importance of both primary and secondary prevention of head injuries. Future research in this area should focus on “prevention and intervention strategies aimed at reducing dementia after head injury,” said Dr Schneider.
A closer look at the connection between head injury and dementia was discussed in interviews with Mario Mendez, MD, PhD, professor of neurology and psychiatry at the David Geffen School of Medicine at the University of California, Los Angeles, and director of neurobehavior at the VA Greater Los Angeles; and Erica Kornblith, PhD, neuropsychologist and clinical researcher at the San Francisco VA Medical Center and assistant professor of psychiatry at the Weill Institute for Neurosciences at the University of California, San Francisco, School of Medicine. Dr Kornblith is the author of the 2020 Neurology study mentioned above.1
What does the bulk of the evidence suggests about dementia risk following head injury?
Dr Mendez: There is a significantly increased prevalence of a history of TBI among patients with dementia. This increased prevalence transcends dementia types and has been reported in Alzheimer disease (AD), frontotemporal dementia, and other conditions. The preponderance of the evidence suggests that folks who have a history of one or more head injuries have increased risk for developing dementia as they age.
The risk of dementia after head injury is not straightforward. It can be associated with a prior history of mild TBIs, particularly if repetitive, and even if they are subconcussive. There seems to be a cumulative effect of head injuries, such that many mild ones may be more significant than one major injury in terms of subsequent dementia risk.
What are the proposed mechanisms potentially driving this link?
Dr Mendez: The are 2 main mechanisms, with others proposed. First, head trauma decreases neuronal and associated cognitive reserve, which means that there is less of a “cushion” for the emergence of dementia with aging. Another mechanism relates to chronic traumatic encephalopathy (CTE), a phenomenon most commonly reported among participants in collision sports such as American football or boxing that results in the accumulation of abnormal tau around blood vessels deep in the sulci, particularly of the frontal lobes.
Dr Kornblith: The mechanisms driving this increased risk are not clear and are an active topic of research. There are several hypothesized pathways: 1) TBI causes structural damage to the brain that results in cognitive impairment; 2) TBI triggers a cascade of neurochemical changes that results in build-up of the plaques and tangles8 associated with AD and other neurodegenerative processes; 3) that same cascade of neurochemical changes may lead to a number of central nervous system changes including arterial stiffness, chronic inflammation, and damage to the blood-brain barrier, and may increase risk of stroke, thereby resulting in cognitive impairment; 4) repeated TBIs are associated with CTE, which may result in a clinical dementia presentation.
What are the current implications for clinicians regarding dementia screening and prevention in patients with prior head injury?
Dr Kornblith: This is such an important question. Clinicians should be aware that if an older patient has a known history of TBI, that patient’s risk for dementia is increased compared to an older patient without history of TBI. In this case, clinicians can explore with their patient whether a doctor’s visit or clinical evaluation is indicated when cognitive decline is suspected, and they may raise with the patient the possibility of including family members in this discussion.
Younger patients with head injury history may express concern about CTE, as this diagnosis is discussed in the media due to its association with professional athletes. Clinicians can refer these patients to a physician or neuropsychologist for screening.
What should be the focus of future research and public health efforts in this area?
Dr Mendez: Prevention is hugely important, and there should be a major focus on this very preventable risk factor, with an emphasis on the use of helmets and minimizing head trauma in contact sports. In addition, the public needs to be educated on the fact that even minor head injuries can increase your risk of dementia in later life.
Dr Kornblith: There is much work to be done around optimizing healthy cognitive aging for folks with a history of head injury. Our lab’s [The Kristine Yaffe Lab] ongoing work is centered around understanding which individuals and groups are at greatest risk for dementia and why, and how to ameliorate that risk. TBI clearly increases risk but is not the whole picture; there are other contributing factors that are not yet fully understood.
For example, we are currently investigating the impact of social determinants of health such as education, income, access to medical care, social support, and community and neighborhood variables, as well as the role of systematic racism and discrimination, on the risk for dementia after head injury. We want to understand how these factors may operate differently for folks from different racial and ethnic backgrounds.
Regarding education, it is important for patients to know that while they can’t change their history of TBI exposure, they can wear helmets and seatbelts and avoid risky activities to reduce the chance of a head injury in the future. My mentor and senior author on this study, Kristine Yaffe, MD, showed in a landmark study that up to 30% of dementia risk may be modifiable, and it is essential for patients to understand that there is much they can do daily to decrease their risk of dementia.9 Physical activity is extremely important, as is managing any chronic health conditions, particularly vascular risk factors like diabetes and hypertension, along with reducing stress and receiving social connection and support from friends and family.
References
1. Kornblith E, Peltz CB, Xia F, et al. Sex, race, and risk of dementia diagnosis after traumatic brain injury among older veterans. Neurology. Published online September 29, 2020. doi:10.1212/WNL.0000000000010617
2. LoBue C, Munro C, Schaffert J, et al. Traumatic brain injury and risk of long-term brain changes, accumulation of pathological markers, and developing dementia: a review. J Alzheimers Dis. Published online August 3, 2019. doi:10.3233/JAD-190028
3. Turk KW, Marin A, Schiloski KA, et al. Head injury exposure in veterans presenting to memory disorders clinic: an observational study of clinical characteristics and relationship of event-related potentials and imaging markers. Front Neurol. Published online June 14, 2021. doi:10.3389/fneur.2021.626767
4. Peterson K, Veazie S, Bourne D, Anderson J. Association between traumatic brain injury and dementia in veterans: a rapid systematic review. J Head Trauma Rehabil. 2020;35(3):198-208. doi:10.1097/HTR.0000000000000549
5. Schneider ALC, Selvin E, Latour L, et al. Head injury and 25-year risk of dementia. Alzheimers Dement. Published online March 9, 2021. doi:10.1002/alz.12315
6. Barnes DE, Byers AL, Gardner RC, et al. Association of mild traumatic brain injury with and without loss of consciousness with dementia in US military veterans. JAMA Neurol. Published online September 1, 2018. doi:10.1001/jamaneurol.2018.0815
7. Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. Published online July 30, 2020. doi:10.1016/S0140-6736(20)30367-6
8. Risacher SL, West JD, Deardorff R, et al. Head injury is associated with tau deposition on PET in MCI and AD patients. Alzheimers Dement (Amst). Published online August 13, 2021. doi:10.1002/dad2.12230
9. Norton S, Matthews FE, Barnes DE, et al. Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. Lancet Neurol. Published online August 1, 2014. doi:10.1016/S1474-4422(14)70136-X
