June 09, 2023
Are individuals who experience traumatic brain injury (TBI) at increased risk of Alzheimer's disease and related dementias (ADRD)? That's a question that Mayo Clinic researchers and colleagues sought to answer in a study published in the Journal of Alzheimer's disease in 2022.
Multiple epidemiological studies have examined associations between TBI and ADRD. However, according to physiatrist Allen W. Brown, M.D., and co-authors, previous epidemiological studies have yielded conflicting results. Dr. Brown is director of brain rehabilitation research at Mayo Clinic in Rochester, Minnesota, and senior author of the 2022 publication.
Study methods
Dr. Brown and co-authors sought to examine the relationship between the presence and severity of TBI and risk of ADRD using medical record chart abstraction data available through the Rochester Epidemiology Project (REP). The REP contains medical records from all Olmsted County, Minnesota, residents and encompasses data from multiple medical care settings within that county (including outpatient, inpatient, emergency room and nursing home settings) from 1966 to the present.
Within the REP database, Dr. Brown and colleagues identified 1,418 individuals (ages 40 and older) diagnosed with TBI in Olmsted County, Minnesota, between 1985 and 2000. The researchers classified TBI severity for those individuals: 865 with possible TBI (consistent with concussive), 450 with probable TBI (consistent with mild), and 103 with definite TBI (consistent with moderate-severe). They confirmed subsequent ADRD outcomes through 2018, and then they compared the risk of ADRD among the individuals with TBI with a referent group of 2,836 age- and sex-matched individuals without TBI, including matched for nonhead trauma. And they assessed whether associations differed by sex.
TBI was defined as any traumatically induced injury that contributed to the physiological disruption of brain function, documented in the medical record by any of the following:
- Head trauma associated with loss of consciousness, post-traumatic amnesia or other neurological signs of brain injury.
- Evidence of intracerebral, subdural or epidural hematoma; cerebral or hemorrhagic contusion or brainstem injury; penetrating brain injury or skull fracture.
- Postconcussive symptoms — including dizziness, confusion, blurred vision, double vision, headache, nausea or vomiting lasting more than 30 minutes, and symptoms that were not attributable to preexisting or comorbid conditions.
Results
"The results of our analyses in the context of existing literature support including TBI as a potential risk factor for developing neurodegenerative disease. However, disparate findings in our results and the literature indicate that the assessment of TBI-associated risk will require greater clinical characterization to better understand this risk."
- Individuals with all levels of TBI severity had a significantly higher risk of any ADRD than individuals without TBI.
- When the researchers stratified the results by the three levels of TBI severity, probable and possible TBIs were associated with an increased risk of ADRD, but definite TBI was not.
"Additional research examining the relationship between TBI and ADRD is needed — and underway — particularly studies that consider socioeconomic status, genomics and epigenetic exposures, neuropathology, race and ethnicity, and medical comorbidities," explains Dr. Brown.
Building on this body of work, Dr. Brown says that Mayo Clinic's Section of Brain Rehabilitation has been funded by the U.S. Department of Defense to vastly expand its population-based research sample to include individuals of all ages who experienced TBI from 1985 to 2014.
"We will use artificial intelligence tools to identify neuroanatomic and electrophysiological biomarkers that estimate risk of subsequently developing post-traumatic epilepsy," says Dr. Brown. "This methodology will then be applied to this much larger sample to estimate the risk of developing other conditions after TBI, including ADRD."
For more information
Mielke MM, et al. Traumatic brain injury and risk of Alzheimer's disease and related dementias in the population. Journal of Alzheimer's Disease. 2022;883:1049.
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