Multimodal MR Imaging Signatures of Cognitive Impairment in Active Professional Fighters

Abstract

Purpose To investigate whether combining multiple magnetic resonance (MR) imaging modalities such as T1-weighted and diffusion-weighted MR imaging could reveal imaging biomarkers associated with cognition in active professional fighters. Materials and Methods Active professional fighters (n = 297; 24 women and 273 men) were recruited at one center. Sixty-two fighters (six women and 56 men) returned for a follow-up examination. Only men were included in the main analysis of the study. On the basis of computerized testing, fighters were separated into the cognitively impaired and nonimpaired groups on the basis of computerized testing. T1-weighted and diffusion-weighted imaging were performed, and volume and cortical thickness, along with diffusion-derived metrics of 20 major white matter tracts were extracted for every subject. A classifier was designed to identify imaging biomarkers related to cognitive impairment and was tested in the follow-up dataset. Results The classifier allowed identification of seven imaging biomarkers related to cognitive impairment in the cohort of active professional fighters. Areas under the curve of 0.76 and 0.69 were obtained at baseline and at follow-up, respectively, with the optimized classifier. The number of years of fighting had a significant (P = 8.8 × 10) negative association with fractional anisotropy of the forceps major (effect size [d] = 0.34) and the inferior longitudinal fasciculus (P = .03; d = 0.17). A significant difference was observed between the impaired and nonimpaired groups in the association of fractional anisotropy in the forceps major with number of fights (P = .03, d = 0.38) and years of fighting (P = 6 × 10, d = 0.63). Fractional anisotropy of the inferior longitudinal fasciculus was positively associated with psychomotor speed (P = .04, d = 0.16) in nonimpaired fighters but no association was observed in impaired fighters. Conclusion Without enforcement of any a priori assumptions on the MR imaging-derived measurements and with a multivariate approach, the study revealed a set of seven imaging biomarkers that were associated with cognition in active male professional fighters. RSNA, 2017 Online supplemental material is available for this article.

Understanding white matter structural connectivity differences between cognitively impaired and nonimpaired active professional fighters

“…In addition, paths involving cingulum, hippocampus, parahippocampus, amygdala, and thalamus showed a significantly lower WM connectivity in cognitively impaired fighters, and all these regions have been implicated to be involved in memory (Johns, ). Furthermore, in this same cohort, volumetric loss in thalamus and its association with neuropsychological outcomes (Bernick et al, ) has been indicated to predict cognitive decline (Mishra et al, ) due to RHI. These findings suggest that the RHI in fighters exhibiting cognitive decline had a significant WM connectivity damage in regions involving executive and working memory which may be responsible for their poor functional outcome.…”

“…Finally, perfusion measures using arterial spin labeling (ASL) MRI has also shown significant deficits in the thalamus, cingulate gyri, cerebellum, cuneus, and temporal lobes (Eierud et al, ; Koerte et al, ; Mishra et al, ). Even multivariate MRI measures combining voxelwise volumetric, perfusion, and dMRI‐derived measures (Mishra et al, , ) have identified deficits in several brain regions that were correlated with exposure and neuropsychological scores in participants with RHI.…”

“…For instance, various structural neuroimaging studies of RHI due to combat sports and in veterans with blast injuries have shown changes in various gray matter volumes such as thalamus, ventromedial prefrontal cortices, right fusiform gyrus, and frontotemporolimbic regions involving hippocampus, medial temporal lobe, and frontal lobes Bigler, 2013;Gooijers et al, 2013;Lopez-Larson et al, 2013;Mishra et al, 2017Mishra et al, , 2018Montenigro, Bernick, & Cantu, 2015;Ng et al, 2014). Similarly, voxelwise dMRI-derived measures such as fractional anisotropy (FA) and mean diffusivity (MD) have shown differences in the temporo-occipital white matter tracts and forceps major (Hulkower, Poliak, Rosenbaum, Zimmerman, & Lipton, 2013;Mishra et al, 2017;Ng et al, 2014;Orrison et al, 2009;Shin et al, 2014;Wintermark, Sanelli, Anzai, Tsiouris, & Whitlow, 2015;Zhang et al, 2003;Zhang, Heier, Zimmerman, Jordan, & Ulug, 2006). Finally, perfusion measures using arterial spin labeling (ASL) MRI has also shown significant deficits in the thalamus, cingulate gyri, cerebellum, cuneus, and temporal lobes (Eierud et al, 2014;Koerte et al, 2015;Mishra et al, 2018).…”

Single-scale time-dependent window-sizes in sliding-window dynamic functional connectivity analysis: A validation study

“…Both static and dynamic FC were used as features to classify cognitive impairment status of fighters. Classification framework included an automated feature selection step and a radial basis functional classifier step (see Mishra et al, 2017 , for details). A ten-fold cross-validation was used to determine the classification accuracy.…”

Risk Factors for Chronic Traumatic Encephalopathy: A Proposed Framework

“…Based on the neuropathological studies of CTE, in vivo research has begun to investigate the association between cumulative exposure to RHI and long-term neurobehavioral outcomes. Several case series and empirical studies show evidence of cognitive, behavioral, and mood disturbances, 5,10,[41][42][43] as well as structural, functional, and molecular brain alterations [44][45][46][47][48][49][50][51][52] in participants presumably at high risk of CTE (e.g., former NFL players, boxers). Roberts et al 43 conducted a survey study among 3,506 former professional American football players to examine the relationship between American football play and self-reported cognition-related quality of life and reported symptoms of depression and anxiety.…”