Traumatic Brain Injury and Alzheimer’s Disease
How it works
This literature review investigates traumatic brain injury and Alzheimer’s disease using various experimental methods. Participants were drawn from a range of demographic areas and were either observed or experimented upon. Blunt force trauma to the cranium has shown an association with late-onset Alzheimer’s disease in both animal models and human observations. The results in all studies are consistent with the previously accepted notion that traumatic brain injury is highly correlated with the development of Alzheimer’s disease. Methodologies included experiments on mouse models, induction of traumatic brain injuries, and the observation of traumatic brain injuries in practical environments.
Further research is needed to establish a definitive correlation between traumatic brain injury and Alzheimer’s disease.
The Correlation of Traumatic Brain Injury and Alzheimer’s Disease: A Literature Review
Research on neurodegenerative diseases has begun to focus on discovering their underlying causes and correlations. Alzheimer’s Disease (AD) has been the leading cause of dementia for over a century (Nogueira et al., 2016). However, there are discrepancies between research and diagnosis; very few cases of AD have a definitive cause. Traumatic brain injury (TBI) has been linked to AD in many circumstances. These range from spontaneous accidents causing blunt trauma to the head, battleground combat in the military, and even widely accepted sports such as American football and professional fighting. Cases of TBI are increasing exponentially, and interestingly enough, so is the incidence of AD. Researchers are continuously searching for answers and ways to circumvent or mitigate the effects of TBI, which could potentially lower the rate of AD development in our society.
Neuropathology of AD
AD is a form of dementia; it is a neurodegenerative disease that affects the natural cognitive functions of a normally functioning brain. Alzheimer’s has a couple of main signs that characterize the pathology of the disease. This form of dementia intrinsically affects cholinergic neuronal cell lines by a rogue protease that incorrectly cuts a protein, called the amyloid precursor protein (APP), causing amyloid-beta deposits or plaques to build up in the extracellular matrix of a neuronal cell (Kondo et al., 2015). The second sign of AD is from the hyperphosphorylation of tau protein that is responsible for microtubule formation. The hyperphosphorylation induces an event called catastrophe, which is the sudden degradation of microtubule formation causing neurofibrillary tangles to accumulate in the intracellular matrix of a neuronal cell. Both of these processes cause defects in cell communication and neuronal plasticity, ultimately causing the prevailing symptoms of memory loss, language impairment, and reasoning deficits. A plethora of suggestions are made depicting the origin of AD, but a sole cause is not yet defined.
Synopsis of TBI
Severe trauma anywhere in the human body will have detrimental effects and can be treated naturally or with modern medicine; however, traumatic brain injury (TBI), which presents no definitive treatment options, poses a unique challenge. Our brain defines our character and uniqueness; severe trauma to this organ can result in irreversible damage affecting cognitive ability. Consequences of TBI may lead to impairments in memory, reasoning, and motor skills (O’Connor et al., 2013). Symptoms manifest themselves in various ways; immediate signs of ailments and debilitations may be evident, or manifestations could take weeks or even months to appear post-trauma. Current research has discussed the relationship of TBI with various neurodegenerative diseases. Further research is needed to establish connections between brain trauma and cognitive diseases. Hypothesis: If more research on the correlation between AD and TBI is recognized and disseminated, then policies can be put in place to mitigate the contraction of AD.
Participants used in all studies had shown signs of TBI, signs of AD, or were patients of late-onset AD due to unexplainable corollaries. Empirical studies were conducted on model organisms to assess the consequences of TBI over a period of time by biochemically analyzing their neuronal development. All human studies required participants to have a documented case of TBI or AD with telltale signs of amyloid-beta plaques and fibrils.
Physical stress and TBI: Medical professionals and researchers are well aware of how TBI occurs – blunt force trauma to the head is caused by injury, physical attack, or forceful impact to the cranium (Gileen, Greenwood, & David, 2013). In all research reviewed, physical stress and TBI were analyzed by various experiments to determine their holistic effects. Physical stress and trauma were either mechanically induced to a model organism or observed within many of the participants. All studies observed show features of amyloid-beta and tau protein accumulation alongside dysfunction in neuronal-cell plasticity in relation to TBI and physical stress (Nogueira, Epelbaum, Steyaert, Dubois, & Schwartz, 2016). These studies inform researchers about the harmful effects of TBI and its severity. Continued research would aid in making connections with blunt-force trauma and deficits in our working memory.
Assessment of working memory. In all studies conducted, the comprehensive objective was to assess the effects of TBI and analyze relationships to working memory. The hippocampus plays a critical role in memory acquisition and consolidation; trauma to these regions could manifest into deficits in function, including memory and lack of awareness (Gilleen, Greenwood, & David, 2013; O’Connor et al., 2013). The severity of the effects TBI elicits can vary across patients, but the more severe injuries can cause enduring damage (O’Connor et al., 2013). These findings help show the interconnection between TBI and hippocampal dysfunction, creating a possible parallel between brain trauma and neurodegenerative disorders.
TBI elicits signs of AD. Since the widely accepted signs of AD are so prevalent, studies have been done to observe the correlations between TBI and the accepted signs of AD. In the studies reviewed, results suggest that exposure to cranial traumatic stress is associated with decreased memory performance and motor deficits (Shishido et al., 2016; Weiner et al., 2017; Gileen et al., 2013). Injury to the brain affects learning and memory acquisition at an escalated rate as age increases (O’Connor et al., 2013). Although there are no studies that show a definitive causal relationship between TBI and AD, the results show a significant correlation. Shishido et al. (2016) found that mice exposed to TBI show an increased concentration of amyloid-beta plaques and tau fibrils in their cholinergic neurons. Further empirical studies depicting the relationship between TBI and AD are imperative for finding ways to prevent forms of dementia.
Type of Study: Studies conducted show differences in experimental design, types of participants, and the level of study. Although all studies showed empirical experimentation, various studies relied on manipulating animal models in the lab while others performed quasi-like experiments on military veterans and extreme sport athletes. For example, one study investigated the effects of TBI in snowboarders between increased or decreased use of a helmet, while another study observed the effects of TBI in rat models (Hasler, Baschera, Taugwalder, Exadaktylos, & Raabe, 2015; Nogueira, Epelbaum, Steyaert, Dubois, & Schwartz, 2016). The model organisms used in these experiments help us translate our findings into tangible evidence that could be used for preventive measures.
The model organism used results are interpreted differently depending on what type of model organism was utilized in the study. External validity holds an experiment accountable for replication in the real world. Observations of TBI and AD vary in contingency, whether an animal model or a human model is assessed. In several studies, a mouse model was used to assess the consequences of TBI and their correlations to the signs of AD (Shishido et al., 2016). Current research is being conducted to show the associations of various cranial traumas to TBI and other diseases.
Associations with brain injury: Many forms of neurodegenerative diseases could be linked to TBI. The studies that were observed differed in the form of brain trauma. For example, war veterans affected by TBI were used in a study to make connections to AD. Meanwhile, a study on snowboarders and their helmet use showed compelling evidence of TBI and associations with brain trauma (Hasler, Baschera, Taugwalder, Exadaktylos, & Raabe, 2015; Weiner et al., 2017). Studies on the associations of TBI and various cognitive diseases are essential to combating the development of dementia and other dangerous ailments.
Ongoing research suggests that traumatic brain injuries (TBIs), which occur in various ways, lead to the progression of Alzheimer’s disease (AD). Dementia is simply a decline in cognitive ability severe enough to significantly reduce an organism’s ability to perform everyday activities. AD, the most common form of dementia, is a neurodegenerative disorder associated with synaptic loss, functional abnormalities within neurons, neuronal cell death, the extracellular accumulation of amyloid-B peptide (AB) plaques/fibrils, and an intracellular accumulation of hyperphosphorylated tau protein (Iqbal and Grundke-Iqbal, 2013). Accumulation of AB plaques and tau protein fibrils cause the gradual decrease in cognitive ability and possible cell death, associated with AD (Texido et al., 2012). We hypothesize that if more research is conducted on the correlation between AD and TBI, then policies can be implemented to mitigate the contraction of AD.
Studies suggest that TBI is becoming an epidemic and a public health initiative that needs addressing. Shishido et al. (2016) showed that TBI activates progressive accumulation of amyloid-beta plaques to the injured cortex within a day post injury. Moderate to severe cases of TBI are correlated with an elevated risk of dementia (O’Connor et al., 2013). Emotional consequences, behavioral impulsivity and aggression are secondary effects of TBI that lead researchers to believe there is a strong association with dementia and hippocampal abnormalities. Alterations in cognitive ability due to TBI include deficits in attention, processing speed, and executive functioning (O’Connor et al., 2013). Physical consequences of TBI can include problems with balance, fatigue, seizures, and headaches. Medical consequences of TBI raise concerns that need to be addressed, even without the association of AD or other dementias.
TBI is only one proposed correlation with AD; others could be attributable to the etiology. Gilleen, Greenwood, & David (2014) suggested that genetic predispositions are plausible causes for AD. The epidemiology is associated with deficits in the hippocampal regions of the brain, which are responsible for memory consolidation and retrieval. Chronic traumatic encephalopathy (CTE) is correlated with AD and TBI in post-mortem neuronal tissues (O’Connor et al., 2013). Athletes diagnosed with a severe concussion or TBI may also experience an increased contraction of CTE, which could cause lifelong impairment. Although there is no clinical diagnosis of CTE presently, the disease appears to show extreme pathological correlations with AD and is a consequence of TBI (O’Connor et al., 2013).
It is essential to continue empirical research on both animal models and humans to develop a baseline for treatment and prevention. Limitations in the studies observed include discrepancies between observation and experimentation, which affect the external validity of the study. Diagnosing a TBI can be difficult, especially when cases of dementia exhibit similar signs. Whether there even exists a TBI-related dementia is unknown, but further research is needed for a diagnosis template and circumvention strategy.
Suggestions for Further Studies
Inclinations of AD suggest a multitude of causes and relationships. A suggestion for further study could be a longitudinal assessment of a cohort of participants who experience TBI, or are genetically predisposed to AD, over a set amount of years. Genetic predispositions account for a large portion of dementias. However, it is imperative to understand the environmental effects, which could be addressed through practice and prevention by experimentation. Current funding for Alzheimer’s disease does not match the exponential rise in rates of diagnosed patients. Despite these growing rates, recent classes of Congress, particularly the 112th, have voted against allocating additional funding for research and prevention of Alzheimer’s disease. Diminishing the ignorance of the relevance of Alzheimer’s disease in society is critical. Funding institutions such as the National Institute of Health to conduct further research on the topic is imperative to curbing its exponential growth. Alzheimer’s affects many, but many do not recognize the pain it causes until they experience it themselves.