According to a new study, traumatic brain injury (TBI) with a loss of consciousness (LOC) may be associated with development of some neurodegenerative diseases like Parkinson’s disease (PD) later in life, but not Alzheimer’s disease (AD) or incident dementia.
The Centers for Disease Control and Prevention estimates that more than 1.3 million Americans seek emergency care for head injuries each year. Most traumatic brain injuries (TBIs) are mild and most people return to their prior level of functioning. Still, concern over late-life effects of TBIs has grown with increased awareness of repetitive head trauma in athletes and in service members injured during military conflicts. Only a few studies show a definitive correlation between TBI with LOC and the future development of either Parkinson’s or Alzheimer’s disease.
A new study published in JAMA Neurology focused narrowly on the long-term effects of one instance of trauma to the head, especially involving loss of consciousness, among older people. The research team compiled head injury data from three large, longitudinal, prospective studies including members of a Seattle-area health care delivery system (ACT), priests and nuns living in orders across the United States (ROS), and Chicago-area adults in retirement communities (MAP). The studies involved 7,130 participants on whom annual (ROS and MAP) or biennial (ACT) testing was performed and data was accrued from 1994 to April 1, 2014. On average, study participants were 80 years old at the time of this report, and did not have dementia, PD, or AD when they enrolled in the original studies; forty percent were men. Of this group, 865 people had suffered TBI with LOC at some point before the study began. Of the 865, 142 had been unconscious for more than one hour.
The data was analyzed for both clinical outcomes – including dementia, AD, PD, Parkinsonism, and mild cognitive impairment and neuropathologic outcomes – including neurofibrillary tangles, neuritic plaques, microinfarcts, cystic infarcts, Lewy bodies, and hippocampal sclerosis. Brain autopsies were done on close to 23 percent of the total group, or 1,589 people, to determine whether a link exists between TBI and neuropathological findings, thus helping in the diagnosis of neurodegenerative disease.
Among the 7,130 participants, 1,537 developed some form of dementia, another 1,322 developed AD and 117 developed PD during follow-up. No statistically significant relationship between TBI with LOC and dementia risk was discovered when the study group was compared with the 1,537 dementia patients, providing no signs that head injury was more common in this group. Results for AD, diagnosed in 1,322 study participants, were similar. However, regression data showed a strong association between TBI with LOC greater than an hour and PD (117 cases during the study).
Neuropathological findings at autopsy (1,652 autopsy cases) showed no association between TBI with LOC and beta amyloid plaques or neurofibrillary tangles (accumulation of tau proteins), the hallmark indicators of AD. However, the autopsies found an increased risk for Lewy bodies (abnormal toxic aggregates of alpha-synuclein protein) in TBI with LOC less than an hour and an increased risk of cortical cerebral microinfarcts (microscopic strokes) in TBI with LOC more than an hour. Individuals whose TBI with LOC occurred before age 25 years also had an increased risk for microinfarcts and Lewy bodies, especially in the frontal or temporal cortex implicating an increased risk for PD.
Among the findings, TBI with LOC was positively associated with incident PD in the ACT study (hazard ratio of 3.56 for a TBI with LOC lasting longer than one hour) and with progression of Parkinson signs in the ROS and MAP (odds ratio of 2.23 for TBI lasting longer than one hour). It was also found that TBI with LOC lasting longer than one hour was associated with presence of Lewy bodies (relative risk of 2.64 in the ACT study) and with cerebral microinfarcts (relative risk of 2.12 in ROS and MAP).
Although most people recover to normal functioning after a traumatic brain injury, this study suggests that a single blow to the head causing a loss of consciousness for more than an hour, even in one’s 20s is not innocuous and may lead to a three-fold increased risk of neurodegenerative disease (Parkinson’s) decades later.
The study limitations include that a self-reported TBI might bring inaccuracies such as LOC duration. In addition, it seems from the methods that these TBI with dementia or cognitive impairments were excluded, which might explain why no significant association was found between TBI with LOC and risk of dementia/AD. Moreover, the study included data from participants who may not be broadly representative of ethnically diverse populations and there were systematic differences in research practices.
Although the vast majority of people who experience head injury will not develop Parkinson’s, this study may provide clinicians with an additional diagnostic tool. For example, asking patients about history of head injury, amongst other symptoms and risk factors, may prove a valuable means of ascertaining the likelihood of a PD diagnosis and might provide ideas for possible interventions for reducing risk of PD. Prospective TBI brain donation studies can further help to characterize post-TBI neurodegeneration, identify risk factors, and develop effective treatments.
Written By: Dr. Pratibha Bharti, PhD Biotechnology