There has long been a suspected link between neurological diseases and brain damage. Given the immediate symptoms of a head injury include several symptoms such as confusion and memory loss which are also observed in those affected by dementia, it does seem likely that the two share neurological underpinnings. Those who incur a head injury may exhibit such symptoms temporarily, or permanently, depending on the severity of the brain injury (Graff-Radford, 2019).
Now, research from the professional sports world may be helping to reveal and clarify the specific interactions between these two associated conditions.
Sports Studies
A recent study from the University of Glasgow’s Brain Injury Group indicates that former professional soccer players are three and a half times more likely than the general population to suffer from dementia and other serious neurodegenerative diseases. More specifically, the study found a five-fold increase in the risk for Alzheimer’s, a four-fold increase in motor-neuron disease, and a two-fold increase in risk for Parkinson’s disease (Ingle, 2019).
Research from the American football world also indicates that neurodegenerative diseases may be linked to brain damage, as National Football League (NFL) players are three times more likely to die from a neurodegenerative disease than members of the general US population. Specifically, NFL players are four times as likely to die of Alzheimer’s and amyotrophic lateral sclerosis (ALS, which is a nervous system disease that weakens muscles and reduces physical function). It is worth noting that the NFL player’s mortality rate from Parkinson’s was also elevated, while not statistically significant.
A number of studies have found that speed (quarterback, running back, halfback, fullback, wide receiver, tight end, defensive back, safety, and linebacker) players are at greater risk for head injury and concussion than non-speed (all defensive and offensive linemen) players. Further evidence for the relationship between neurodegenerative disease and head injury was uncovered when research showed that speed players are at a higher risk for mortality due to neurodegenerative disease than non-speed players. In other words, those in positions which put them at greater risk for brain injury or damage (due to potential for buildup of momentum prior to impact) were at greater risk for neurodegenerative mortality (LeBano L, 2019).
Off the Field
In evaluations of members of the general population, meta-analyses show similar trends as those observed in professional sports players. One study found a 63 percent increase in risk for dementia and a 51 percent increase in Alzheimer’s specifically, for those who had incurred head injury (Li, et al., 2017). Further research indicates head injury is associated in not only neurodegenerative disease itself, but also with earlier onset, increased impairment, increased mortality and AD-type pathological changes (Abner, et al., 2014). Other evidence indicates that the severity of a head injury may moderate the level of risk of developing AD. Additionally, those who sustain a head injury later in life, particularly past age 55 may also be more at risk than those who sustained a head injury earlier in life. Those who have experienced repeated mild injury also increases risk for cognitive issues later down the line (Graff-Radford, 2019).
The association between brain injury and risk for some form of dementia is further supported by evidence which shows that pathogenic mechanisms which precede and promote dementia (including extracellular amyloid plaques that are composed of aggregated β-amyloid peptides and intracellular neurofibrillary tangles consisting of hyperphosphorylated tau protein) are known to occur after the event (May, Martin, & Wellington, 2011).
Interacting Factors
But not everyone who incurs a head injury eventually develops a neurodegenerative disease, so clearly there is more at play here. Research indicates other factors including one’s gender, age, type of injury, and presence of the APOE-ε4 gene, which has been linked with genetic contributions to Alzheimer’s (Ramos-Cejudo, et al., 2018).
In examining gender, one study revealed that head injury was associated with increased levels of amyloid plaque deposits in the neocortex and entorhinal cortex, and this increased the risk of AD in men, but not women. Research seems to indicate that female sex hormones may exert a protective affect on neurological structures and functions in the event of head injury.
As far as age goes, for those who already have a buildup of amyloid deposits or dystrophic neurites when they incur a brain injury will likely find that the brain damage exacerbated the pathogenesis, hence, older individuals who incur head injuries are at greater risk for neurodegenerative consequences. Additionally, analysis of the data reveals that the estimated relative risk for head trauma within 10 years of AD onset was 5.53, more than three times the relative risk for head trauma occurring more than 10 years prior to onset of AD, which was 1.63 This suggests that there may be a critical age range during which brain injury increases dementia risk the most. Those who experience a head injury exhibit reduced time to onset of AD (median 10 years) than those without prior head injury (median 18 years), which indicates that head injury may reduce time to onset of AD. However, those who experience a head injury after age 65 did not show reduced time until AD onset, suggesting other factors may have outweighed the injury. Alternately, the younger you are when brain injury occurs, the higher your likelihood of developing dementia 10, 20, or even 30 years later (Milke, 2018).
The type of brain injury may also be related to neurodegenerative outcomes. Diffuse axonal injury (DAI, a brain injury in which scattered lesions in white matter tracts as well as gray matter occur over a widespread neurological area) which accounts for 50 percent of brain injury cases is induced by rapid acceleration or deceleration. This type of injury often results in accumulation of amyloid precursor protein (APP), which is hypothesized to cause a burst of β-amyloid (Aβ) peptide production and the deposition of amyloid plaques which lead to dementia (May, Martin, & Wellington, 2011).
The Spectrum of Dementia
The study of the long term neurodegenerative effects of brain injury becomes even more complex when one considers that dementia is a spectrum, not one singular condition. What researchers are beginning to find it that there may be a common cause among one or more of the neurodegenerative diseases—though they may take different developmental paths due to unique environmental exposures or genetic susceptibility factors.
Thus, head injuries have consistently been associated with increased risk for dementia, that doesn’t necessarily mean Alzheimer’s specifically. In general, the risk for dementia appears to increase by 22 percent after one head injury, but mushrooms with increasing number of brain injuries, becoming almost three times as great for people who have sustained five or more brain injuries. It also appears that severe injuries pose greater risk for dementia, about twice as much as mild injuries. The strongest links to AD are seen for moderate to severe head injuries, which trigger the buildup of amyloid plaque previously discussed. In contrast, repetitive mild brain injuries are often associated with chronic traumatic encephalopathy (CTE), a degenerative condition which affects tau proteins. CTE, presents with symptoms which include tremor, bradykinesia, confusion and speech impediments. It is characterized by a gradual onset and a pronounced accumulation of neurofibrillary tangles in the neocortex and brainstem. Around 30% of those with CTE show amyloid deposits, further suggesting that CTE may be a distinct clinical entity from AD even though the same proteins likely contribute to it.
Other research suggests that Parkinson’s may find itself along the spectrum of neurodegenerative diseases related to brain injury. Unusual patterning of amyloid plaque accumulation has been observed post-TBI, as well as instances of more lewy-body pathology and microinfarcts in the absence of increases in amyloid plaques have been observed in Parkinson’s Disease sufferers who have also incurred a brain injury. The link between brain injury and Parkinson’s Disease is strongest for instances of moderate to severe brain injuries, and has primarily been observed in the vetran community. A history of brain injury was found to increase risk for Parkinson’s Disease by 70 percent in the vetran population, while mild brain injury raised the risk by 56 percent. Additionally, veterans who had incurred a brain injury developed Parkinson’s Disease on average two years earlier than those without (Meilke, 2018).
This evidence from the broad spectrum of neurodegenerative diseases is beginning to make clearer the complex link between head injury and AD-promoting and AD-like pathology. It shows the importance of reducing even minor impacts to the head whenever possible to maximize long term brain health and longevity, and it’s likely that major league sports may begin to see a shift in equipment and safety regulations over time. Additionally, this evidence reveals that those who have incurred multiple previous head injuries or who are genetically predisposed might want to choose to partake in physical activity which lowers risk of head injury. This evidence also highlights the importance of protecting the brain during the developmental stages, an essential takeaway for parents and caregivers.
However, while this type of evidence may make you feel like donning your helmet more permanently, tossing out your soccer cleats, and hibernating to preserve your brain function, it’s important to remember that an active mental and physical lifestyle is another crucial element of brain health.
While this information should remind us to wear seatbelts, helmets, pads, and protective gear when appropriate, it should not hold us back from living an active, brain healthy lifestyle!
References:
Ingle, S. (2019). Landmark study reveals link between football and dementia. The Guardian. Retrieved from: https://www.theguardian.com/football/2019/oct/21/landmark-study-reveals-link-between-football-dementia
LeBano L. (2019). NFL Players Have High Mortality Rate From Alzheimer’s Disease and ALS
Neurology Reviews. 2012 October;20(10):1,28. Retrieved from:https://www.mdedge.com/neurology/article/73622/alzheimers-cognition/nfl-players-have-high-mortality-rate-alzheimers-disease
Li, Y., Li, Y., Li, X., Zhang, S., Zhao, J., Zhu, X., & Tian, G. (2017). Head Injury as a Risk Factor for Dementia and Alzheimer’s Disease: A Systematic Review and Meta-Analysis of 32 Observational Studies. PloS one, 12(1), e0169650. doi:10.1371/journal.pone.0169650
Abner, E. L., Nelson, P. T., Schmitt, F. A., Browning, S. R., Fardo, D. W., Wan, L., … Kryscio, R. J. (2014). Self-reported head injury and risk of late-life impairment and AD pathology in an AD center cohort. Dementia and geriatric cognitive disorders, 37(5-6), 294–306. doi:10.1159/000355478
Ramos-Cejudo, J., Wisniewski, T., Marmar, C., Zetterberg, H., Blennow, K., de Leon, M. J., & Fossati, S. (2018). Traumatic Brain Injury and Alzheimer’s Disease: The Cerebrovascular Link. EBioMedicine, 28, 21–30. doi:10.1016/j.ebiom.2018.01.021
Graff-Radford, J. (2019) Alzheimer’s: Can a head injury increase my risk? The Mayo Clinic. Retrieved from: https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/expert-answers/alzheimers-disease/faq-20057837
Alzforum. (2018). Even Mild Traumatic Brain Injuries Raise Risk for Dementia, Parkinson’s. Alzforum. https://www.alzforum.org/news/research-news/even-mild-traumatic-brain-injuries-raise-risk-dementia-parkinsons
May, S., Martin, G., & Wellington, C. (2011). Brain injury and dementia: Is there a connection. J Neurol, 2(5).
Meilke, M. (2018). Even Mild Traumatic Brain Injuries Raise Risk for Dementia, Parkinson’s. AlzForum. https://www.alzforum.org/news/research-news/even-mild-traumatic-brain-injuries-raise-risk-dementia-parkinsons
