Examining the Relationship between Head Trauma and Neurodegenerative Disease: A Review of Epidemiology, Pathology and Neuroimaging Techniques

Abstract

Traumatic brain injuries (TBI) are induced by sudden acceleration-deceleration and/or rotational forces acting on the brain. Diffuse axonal injury (DAI) has been identified as one of the chief underlying causes of morbidity and mortality in head trauma incidents. DAIs refers to microscopic white matter (WM) injuries as a result of shearing forces that induce pathological and anatomical changes within the brain, which potentially contribute to significant impairments later in life. These microscopic injuries are often unidentifiable by the conventional computed tomography (CT) and magnetic resonance (MR) scans employed by emergency departments to initially assess head trauma patients and, as a result, TBIs are incredibly difficult to diagnose. The impairments associated with TBI may be caused by secondary mechanisms that are initiated at the moment of injury, but often have delayed clinical presentations that are difficult to assess due to the initial misdiagnosis. As a result, the true consequences of these head injuries may go unnoticed at the time of injury and for many years thereafter. The purpose of this review is to investigate these consequences of TBI and their potential link to neurodegenerative disease (ND). This review will summarize the current epidemiological findings, the pathological similarities, and new neuroimaging techniques that may help delineate the relationship between TBI and ND. Lastly, this review will discuss future directions and propose new methods to overcome the limitations that are currently impeding research progress. It is imperative that improved techniques are developed to adequately and retrospectively assess TBI history in patients that may have been previously undiagnosed in order to increase the validity and reliability across future epidemiological studies. The authors introduce a new surveillance tool ((Retrospective Screening of Traumatic Brain Injury Questionnaire, RESTBI) to address this concern.

Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer’s disease.

“…Specifically, the authors concluded that a remote TBI with LOC was associated with increased Lewy bodies and cerebral microinfarcts, but not AD pathology in the 213 cases that came to autopsy. Although other lines of evidence suggest that Lewy bodies can accumulate following traumatic axonal injury (Sundman, Hall, & Chen, 2014; Uryu et al, 2007), one possible explanation for the lack of an association observed with AD may relate to the use of a very high threshold to define AD pathology in that study (i.e., the authors’ quantified NFTs in the neocortex, or only Braak Stages V and VI), and the results may have differed if more inclusive criteria were used. Alternatively, it is possible that some neuropathological features may plateau early in the disease process (Serrano-Pozo, Frosch, Masliah, & Hyman, 2011), thus making it difficult to measure an increase in neuropathological features at autopsy.…”

Biological links between traumatic brain injury and Parkinson’s disease

“…TBI has been implicated as a risk factor for several neurodegenerative diseases, including Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS), and PD [148]. Compelling evidence from three prospective cohort studies aimed at determining the relationship between TBI, AD, and PD supports the relationship between TBI and PD pathology [8,9,30,76].…”

Microwave & magnetic proteomics of macrophages from patients with HIV-associated cognitive impairment

“…Five enzymes related to glucose metabolism were identified as differentially expressed in HACI. These were glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), fructose-bisphosphate aldolase (Aldolase), phosphoglycerate kinase 1 (PGK-1), and 6-phosphogluconate dehydrogenase (6PGD) [ 23 – 25 ]. These showed up-regulation with a p <0.05 and a practical significance threshold of +1.5 F.C.…”