Headache, conceptual 3d illustration, autoimmune encephalitis, brain inflammation, Credit: peterschreiber.media/Getty Images
Credit: peterschreiber.media/Getty Images

A new review published in The Lancet Neurology by researchers at Mass General Brigham presents findings indicating that cardiovascular disease risk may be increased by traumatic brain injury (TBI). The review presented evidence of the long-term associations between TBI and cardiovascular disease noting that post-injury comorbidities, as well as neuroinflammation, and changes in the brain-gut connection may be culprits in the elevated risk compared to the general population.

“Despite decades of extensive traumatic brain-injury-focused research, surprisingly, there has been minimal progress in mitigating long-term outcomes and mortality following injuries. The cardiovascular effects of TBI may be a missing link in advancing our efforts to improve long-term quality of life and reducing mortality rates in TBI patients,” said first author Saef Izzy, MD, of the Stroke and Cerebrovascular Center of Brigham and Women’s Hospital. “We have the opportunity to identify and improve targeted screening for high-risk populations, build preventative care strategies and improve outcomes for survivors of TBI.”

While past research has exhibited there is a strong link between TBI and neurodegenerative conditions such as Alzheimer’s disease and dementia, decades of research has failed to understand the mechanisms that occur after a TBI that drive these diseases. Izzy and review co-authors now suggest that there may be non-neurological effects of TBI, including cardiovascular, cardiometabolic, and endocrine dysfunction that may act as intermediaries that contribute to neurological disorders that may appear decades later.

As an example, the authors point to hypertension, hyperlipidemia, diabetes, and hypopituitarism that are known to negatively affect cognitive function and are established risk factors for dementia. The investigators demonstrate in their review of dozens of research reports that these cardiometabolic risk factors are also more prevalent in people with a history of TBI.

The investigators found a number of potential links between TBI and cognitive and cardiovascular dysfunction including:

  • Neuroinflammatory pathways triggered by TBI could predispose individuals to atherosclerosis.
  • Weight gain and sleep disturbances after an injury could pose independent or additive risks.
  • Disruptions to connections between the nervous and gastrointestinal systems could throw off the balance of microbes in the gut, contributing to cognitive and cardiovascular effects.

Research into the role of the gut microbiome is ongoing, and researchers are also developing new models of TBI to gain insight to the underlying biological mechanism of cardiovascular disease.

The review authors noted that they were not able to clearly determine the effect that multiple TBIs might have in cardiovascular risk, or the impact of age at time of the TBI, severity of the injury, or other comorbidities.

“This review is a clarion call to conduct better assessments and earlier intervention for survivors of TBI who may have increased cardiovascular risk. It calls for new or expanded datasets that capture, over time, changes in biomarkers and targets associated with cardiovascular disease,” said corresponding author Ross Zafonte, president of Spaulding Rehabilitation Network  who is also the principal investigator of the Football Players Health Study at Harvard that has published numerous articles on the effects of TBI. “There is a growing recognition that many systems interact to produce multilevel dysfunction after TBI, with a series of nuanced comorbidities. Clinicians can begin to treat some of these conditions, and in the future, management guidelines can more directly address the cardiovascular health of TBI survivors.”

Also of Interest