Limbic system structure volumes and associated neurocognitive functioning in former NFL players

Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts. CTE has been linked to disruptions in cognition, mood, and behavior. Unfortunately, the diagnosis of CTE can only be made post-mortem. Neuropathological evidence suggests limbic structures may provide an opportunity to characterize CTE in the living. Using 3 T magnetic resonance imaging, we compared select limbic brain regional volumes - the amygdala, hippocampus, and cingulate gyrus - between symptomatic former National Football League (NFL) players (n = 86) and controls (n = 22). Moreover, within the group of former NFL players, we examined the relationship between those limbic structures and neurobehavioral functioning (n = 75). The former NFL group comprised eighty-six men (mean age = 55.2 ± 8.0 years) with at least 12 years of organized football experience, at least 2 years of active participation in the NFL, and self-reported declines in cognition, mood, and behavior within the last 6 months. The control group consisted of men (mean age = 57.0 ± 6.6 years) with no history of contact-sport involvement or traumatic brain injury. All control participants provided neurobehavioral data. Compared to controls, former NFL players exhibited reduced volumes of the amygdala, hippocampus, and cingulate gyrus. Within the NFL group, reduced bilateral cingulate gyrus volume was associated with worse attention and psychomotor speed (r = 0.4 (right), r = 0.42 (left); both p < 0.001), while decreased right hippocampal volume was associated with worse visual memory (r = 0.25, p = 0.027). Reduced volumes of limbic system structures in former NFL players are associated with neurocognitive features of CTE. Volume reductions in the amygdala, hippocampus, and cingulate gyrus may be potential biomarkers of neurodegeneration in those at risk for CTE.

Interactive Effects of Racial Identity and Repetitive Head Impacts on Cognitive Function, Structural MRI-Derived Volumetric Measures, and Cerebrospinal Fluid Tau and Aβ

“…Using this automated method in FreeSurfer, we obtained estimated total intracranial volume (eICV), total gray matter volume (GMV), total cortical white matter volume (WMV), total subcortical gray matter volume (sGMV), right and left hippocampal volume, and volume of white matter hypointensities. Manual correction of the hippocampus using Slicer 4.1 2 (Fedorov et al, 2012) was performed using procedures described elsewhere (Lepage et al, 2018). eICV served as a covariate, whereas the other volumetric measures were examined as outcomes.…”

“…Autopsy studies of convenience samples suggest that professional American football players may be at high-risk for later-life neurological disorders (McKee et al, 2013;Mez et al, 2017b). In vivo studies show that former National Football League (NFL) players have worse cognition, as well as greater structural, functional, and molecular brain alterations (Didehbani et al, 2013;Hart et al, 2013;Strain et al, 2015;Koerte et al, 2016a;Alosco et al, 2018cAlosco et al, , 2019bLepage et al, 2018). These effects might extend to high school and college football players (Mez et al, 2017b), and other contact sport athletes (Koerte et al, 2012(Koerte et al, , 2015(Koerte et al, , 2016bLing et al, 2017).…”

Cumulative Effects of Prior Concussion and Primary Sport Participation on Brain Morphometry in Collegiate Athletes: A Study From the NCAA–DoD CARE Consortium

“…RHI differs from SRC in that they involve head impacts below the relative magnitude of concussive injury (i.e., absence of acute symptoms) and some have suggested that these different mechanisms of insult may have differing effects on long-term outcomes (2,(7)(8)(9)(10). Prior reports of smaller hippocampal and amygdala volumes as well as thinner frontal and temporal cortices have been recorded in retired athletes in relation to exposure factors or prior concussion relative to either former non-contact athletes or non-athlete controls (11)(12)(13)(14)(15)(16). Similarly, thalamic volumes have been inversely associated with level of exposure to contact sport in retired professional football players (17).…”

Chronic Traumatic Encephalopathy: A Comparison with Alzheimer's Disease and Frontotemporal Dementia

“…[115][116][117] Additionally, retired professional American football players show subcortical atrophy, including smaller thalamic volume, amygdala, and hippocampal volume, as well as cingulate gyrus volume. 118,119 Lower hippocampal and cingulate gyrus volumes correlated with lower cognitive performance 119 and thalamic volumes correlated with cumulative exposure and age at first exposure to head impacts in retired NFL players, 120 and with increased number of bouts in boxers. 121 Decreased cerebral metabolism as measured with FDG-PET was found in the cerebellum, pons, and medial temporal cortex in veterans exposed to blast injuries 122 ; in bilateral posterior cingulate cortex, parieto-occipital cortex, inferior frontal cortex, and cerebellum in boxers 123 ; in bilateral dorsolateral prefrontal cortices and right middle orbitofrontal cortex in retired boxers 124 ; and predominantly in the frontal and temporal lobes in retired American football players.…”