ANKS1B encoded AIDA-1 regulates social behaviors by controlling oligodendrocyte function.

Heterozygous deletions in the ANKS1B gene cause ANKS1B neurodevelopmental syndrome (ANDS), a rare genetic disease characterized by autism spectrum disorder (ASD), attention deficit/hyperactivity disorder, and speech and motor deficits. The ANKS1B gene encodes for AIDA-1, a protein that is enriched at neuronal synapses and regulates synaptic plasticity. Here we report an unexpected role for oligodendroglial deficits in ANDS pathophysiology. We show that Anks1b-deficient mouse models display deficits in oligodendrocyte maturation, myelination, and Rac1 function, and recapitulate white matter abnormalities observed in ANDS patients. Selective loss of Anks1b from the oligodendrocyte lineage, but not from neuronal populations, leads to deficits in social preference and sensory reactivity previously observed in a brain-wide Anks1b haploinsufficiency model. Furthermore, we find that clemastine, an antihistamine shown to increase oligodendrocyte precursor cell maturation and central nervous system myelination, rescues deficits in social preference in 7-month-old Anks1b-deficient mice. Our work shows that deficits in social behaviors present in ANDS may originate from abnormal Rac1 activity within oligodendrocytes.

Hospitalization, Critical Illness, and Mortality Outcomes of COVID-19 in Patients With Rheumatoid Arthritis.

OBJECTIVE: To investigate the clinical outcomes of patients with rheumatoid arthritis (RA) with COVID-19. METHODS: This retrospective study consisted of 361 patients with RA+ and 45,954 patients with RA- (March 2020 to August 2022) who tested positive for SARS-CoV-2 by polymerase-chain-reaction in the Montefiore Health System, which serves a large low-income, minority-predominant population in the Bronx and was an epicenter of the initial pandemic and subsequent surges. Primary outcomes were hospitalization, critical illness, and all-cause mortality associated with SARS-CoV-2 infection. Comparisons were made with and without adjustment for covariates, as well as with 1083 matched controls of patients with RA- and COVID-19. RESULTS: Patients with RA+ and COVID-19 were older (62.2 ± 23.5 vs. 45.5 ± 26.3; P < 0.001), were more likely females (83.1% vs. 55.8%; P < 0.001), were Black (35.5% vs. 30.3%; P < 0.05), and had higher rates of comorbidities (P < 0.05), hospitalization (52.4% vs. 32.5%; P < 0.005), critical illness (10.5% vs. 6.9%; P < 0.05), and mortality (11.1% vs. 6.2%; P < 0.01) compared with patients with RA- and COVID-19. Patients with RA+ with COVID-19 had higher odds of critical illness (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI]: 1.09-1.93; P = 0.008) but no differences in hospitalization (aOR = 1.18 [95% CI: 0.93-1.49]; P = 0.16) and mortality (aOR = 1.34 [95% CI: 0.92-1.89]; P = 0.10) after adjusting for covariates. Odds ratio analysis identified age, hospitalization status, female sex, chronic kidney disease, chronic obstructive pulmonary disease, and Black race to be significant risk factors for COVID-19-related mortality. Pre-COVID-19 steroid and biologic therapy to treat RA were not significantly associated with worse outcomes (P > 0.05). Outcomes were not different between patients with RA+ and propensity-matched RA- controls (P > 0.05). CONCLUSION: Our findings suggest that risk factors for adverse COVID-19 outcomes were not attributed to RA per se but rather age and preexisting medical conditions of patients with RA.

Incidence, characteristics, risk factors and outcomes of diabetic ketoacidosis in COVID-19 patients: Comparison with influenza and pre-pandemic data.

AIMS: This study characterized incidence, patient profiles, risk factors and outcomes of in-hospital diabetic ketoacidosis (DKA) in patients with COVID-19 compared with influenza and pre-pandemic data. METHODS: This study consisted of 13 383 hospitalized patients with COVID-19 (March 2020-July 2022), 19 165 hospitalized patients with influenza (January 2018-July 2022) and 35 000 randomly sampled hospitalized pre-pandemic patients (January 2017-December 2019) in Montefiore Health System, Bronx, NY, USA. Primary outcomes were incidence of in-hospital DKA, in-hospital mortality, and insulin use at 3 and 6 months post-infection. Risk factors for developing DKA were identified. RESULTS: The overall incidence of DKA in patients with COVID-19 and influenza, and pre-pandemic were 2.1%, 1.4% and 0.5%, respectively (p < .05 pairwise). Patients with COVID-19 with DKA had worse acute outcomes (p < .05) and higher incidence of new insulin treatment 3 and 6 months post-infection compared with patients with influenza with DKA (p < .05). The incidence of DKA in patients with COVID-19 was highest among patients with type 1 diabetes (12.8%), followed by patients with insulin-dependent type 2 diabetes (T2D; 5.2%), non-insulin dependent T2D (2.3%) and, lastly, patients without T2D (1.3%). Patients with COVID-19 with DKA had worse disease severity and higher mortality [odds ratio = 6.178 (4.428-8.590), p < .0001] compared with those without DKA. Type 1 diabetes, steroid therapy for COVID-19, COVID-19 status, black race and male gender were associated with increased risk of DKA. CONCLUSIONS: The incidence of DKA was higher in COVID-19 cohort compared to the influenza and pre-pandemic cohort. Patients with COVID-19 with DKA had worse outcomes compared with those without. Many COVID-19 survivors who developed DKA during hospitalization became insulin dependent. Identification of risk factors for DKA and new insulin-dependency could enable careful monitoring and timely intervention.

Characteristics of COVID-19 patients with multiorgan injury across the pandemic in a large academic health system in the Bronx, New York.

Purpose: To investigate the evolution of COVID-19 patient characteristics and multiorgan injury across the pandemic. Methods: This retrospective cohort study consisted of 40,387 individuals tested positive for SARS-CoV-2 in the Montefiore Health System in Bronx, NY, between March 2020 and February 2022, of which 11,306 were hospitalized. Creatinine, troponin, and alanine aminotransferase were used to define acute kidney injury (AKI), acute cardiac injury (ACI) and acute liver injury, respectively. Demographics, comorbidities, emergency department visits, hospitalization, intensive care utilization, and mortality were analyzed across the pandemic. Results: COVID-19 positive cases, emergency department visits, hospitalization and mortality rate showed four distinct waves with a large first wave in April 2020, two small (Alpha and Delta) waves, and a large Omicron wave in December 2021. Omicron was more infectious but less lethal (p = 0.05). Among hospitalized COVID-19 patients, age decreased (p = 0.014), female percentage increased (p = 0.023), Hispanic (p = 0.028) and non-Hispanic Black (p = 0.05) percentages decreased, and patients with pre-existing diabetes (p = 0.002) and hypertension (p = 0.04) decreased across the pandemic. More than half (53.1%) of hospitalized patients had major organ injury. Patients with AKI, ACI and its combinations were older, more likely males, had more comorbidities, and consisted more of non-Hispanic Black and Hispanic patients (p = 0.005). Patients with AKI and its combinations had 4-9 times higher adjusted risk of mortality than those without. Conclusions: There were shifts in demographics toward younger age and proportionally more females with COVID-19 across the pandemic. While the overall trend showed improved clinical outcomes, a substantial number of COVID-19 patients developed multi-organ injuries over time. These findings could bring awareness to at-risk patients for long-term organ injuries and help to better inform public policy and outreach initiatives.

Visual-somatosensory integration (VSI) as a novel marker of Alzheimer's disease: A comprehensive overview of the VSI study.

Identification of novel, non-invasive, non-cognitive based markers of Alzheimer's disease (AD) and related dementias are a global priority. Growing evidence suggests that Alzheimer's pathology manifests in sensory association areas well before appearing in neural regions involved in higher-order cognitive functions, such as memory. Previous investigations have not comprehensively examined the interplay of sensory, cognitive, and motor dysfunction with relation to AD progression. The ability to successfully integrate multisensory information across multiple sensory modalities is a vital aspect of everyday functioning and mobility. Our research suggests that multisensory integration, specifically visual-somatosensory integration (VSI), could be used as a novel marker for preclinical AD given previously reported associations with important motor (balance, gait, and falls) and cognitive (attention) outcomes in aging. While the adverse effect of dementia and cognitive impairment on the relationship between multisensory functioning and motor outcomes has been highlighted, the underlying functional and neuroanatomical networks are still unknown. In what follows we detail the protocol for our study, named The VSI Study, which is strategically designed to determine whether preclinical AD is associated with neural disruptions in subcortical and cortical areas that concurrently modulate multisensory, cognitive, and motor functions resulting in mobility decline. In this longitudinal observational study, a total of 208 community-dwelling older adults with and without preclinical AD will be recruited and monitored yearly. Our experimental design affords assessment of multisensory integration as a new behavioral marker for preclinical AD; identification of functional neural networks involved in the intersection of sensory, motor, and cognitive functioning; and determination of the impact of early AD on future mobility declines, including incident falls. Results of The VSI Study will guide future development of innovative multisensory-based interventions aimed at preventing disability and optimizing independence in pathological aging.

Incidence of new-onset in-hospital and persistent diabetes in COVID-19 patients: comparison with influenza.

BACKGROUND: This study investigated the incidences and risk factors associated with new-onset persistent type-2 diabetes during COVID-19 hospitalization and at 3-months follow-up compared to influenza. METHODS: This retrospective study consisted of 8216 hospitalized, 2998 non-hospitalized COVID-19 patients, and 2988 hospitalized influenza patients without history of pre-diabetes or diabetes in the Montefiore Health System in Bronx, New York. The primary outcomes were incidences of new-onset in-hospital type-2 diabetes mellitus (I-DM) and persistent diabetes mellitus (P-DM) at 3 months (average) follow-up. Predictive models used 80%/20% of data for training/testing with five-fold cross-validation. FINDINGS: I-DM was diagnosed in 22.6% of patients with COVID-19 compared to only 3.3% of patients with influenza (95% CI of difference [0.18, 0.20]). COVID-19 patients with I-DM compared to those without I-DM were older, more likely male, more likely to be treated with steroids and had more comorbidities. P-DM was diagnosed in 16.7% of hospitalized COVID-19 patients versus 12% of hospitalized influenza patients (95% CI of difference [0.03,0.065]) but only 7.3% of non-hospitalized COVID-19 patients (95% CI of difference [0.078,0.11]). The rates of P-DM significantly decreased from 23.9% to 4.0% over the studied period. Logistic regression identified similar risk factors predictive of P-DM for COVID-19 and influenza. The adjusted odds ratio (0.90 [95% CI 0.64,1.28]) for developing P-DM was not significantly different between the two viruses. INTERPRETATION: The incidence of new-onset type-2 diabetes was higher in patients with COVID-19 than influenza. Increased risk of diabetes associated with COVID-19 is mediated through disease severity, which plays a dominant role in the development of this post-acute infection sequela. FUNDING: None.

Age of first exposure to soccer heading: Associations with cognitive, clinical, and imaging outcomes in the Einstein Soccer Study.

Introduction: The objective of this study is to assess the role of age at first exposure (AFE) to soccer heading as a predictor of known adverse associations of recent and longer-term heading with brain microstructure, cognitive, and behavioral features among adult amateur soccer players. Methods: The sample included 276 active amateur soccer players (196 male and 81 female) aged 18-53 years old. AFE to soccer heading was treated as a binary variable, dichotomized at ≤ 10 years vs. >10 years old, based on a recently promulgated US Soccer policy, which bans heading for athletes ages 10 and under. Results: We found that soccer players who began heading at age 10 or younger performed better on tests of working memory (p = 0.03) and verbal learning (p = 0.02), while accounting for duration of heading exposure, education, sex, and verbal intelligence. No difference in brain microstructure or behavioral measures was observed between the two exposure groups. Discussion: The findings indicate that, among adult amateur soccer players, AFE to heading before age 10 compared to later start of heading, is not associated with adverse outcomes, and may be associated with better cognitive performance in young adulthood. Cumulative heading exposure across the lifespan, rather than early life exposure, may drive risk for adverse effects and should be the focus of future longitudinal studies to inform approaches to enhance player safety.

Repetitive soccer heading adversely impacts short-term learning among adult women.

OBJECTIVES: To determine the impact of 12-month heading exposure on short-term learning. DESIGN: A total of 105 active amateur soccer players, 45 women and 60 men, were administered an EMA-based test of working memory, a version of the two-back, once daily for 14 days. METHODS: Heading exposure of the participants was assessed using "HeadCount", a validated structured questionnaire at the baseline visits. The short-term rate of learning of each individual is quantified by first fitting a quadratic model to the daily performance on the two-back test over a two-week period, then taking the instantaneous rate of the quadratic function at the 7th test. A linear regression model was used to test the association of heading exposure with rates of learning, including age, sex, years of education and history of concussion as covariates, as well as variables describing soccer play and heading within the two-week period. Sensitivity analyses were performed using different methods for quantifying the learning effects and different transformations on 12-month heading exposure. RESULTS: Greater 12-month heading was associated with lower rates of learning among women (p = 0.008) but not among men (p = 0.74). CONCLUSIONS: We have identified evidence for an adverse, albeit subclinical, effect of soccer heading on brain function among young adult players, which selectively affects women in our sample.

Clinical predictors of recovery of COVID-19 associated-abnormal liver function test 2 months after hospital discharge.

This study investigated whether acute liver injury (ALI) persisted and identified predictors of ALI recovery [as indicated by alanine aminotransferase (ALT) level] at hospital discharge and 2 months post-discharge for 7595 hospitalized COVID-19 patients from the Montefiore Health System (03/11/2020-06/03/2021). Mild liver injury (mLI) was defined as ALT = 1.5-5 ULN, and severe livery injury (sLI) was ALT ≥ 5 ULN. Logistic regression was used to identify predictors of ALI onset and recovery. There were 4571 (60.2%), 2306 (30.4%), 718 (9.5%) patients with no liver injury (nLI), mLI and sLI, respectively. Males showed higher incidence of sLI and mLI (p < 0.05). Mortality odds ratio was 4.15 [95% CI 3.41, 5.05, p < 0.001] for sLI and 1.69 [95% CI 1.47, 1.96, p < 0.001] for mLI compared to nLI. The top predictors (ALT, lactate dehydrogenase, ferritin, lymphocytes) accurately predicted sLI onset up to three days prior. Only 33.5% of mLI and 17.1% of sLI patients (survivors) recovered completely at hospital discharge. Most ALI patients (76.7-82.4%) recovered completely ~ 2 months post-discharge. The top predictors accurately predicted recovery post discharge with 83.2 ± 2.2% accuracy. In conclusion, most COVID-19 patients with ALI recovered completely ~ 2 months post discharge. Early identification of patients at-risk of persistent ALI could help to prevent long-term liver complications.

New-onset and persistent neurological and psychiatric sequelae of COVID-19 compared to influenza: A retrospective cohort study in a large New York City healthcare network.

OBJECTIVES: Neurological and neuropsychiatric manifestations of post-acute SARS-CoV-2 infection (neuro-PASC) are common among COVID-19 survivors, but it is unknown how neuro-PASC differs from influenza-related neuro-sequelae. This study investigated the clinical characteristics of COVID-19 patients with and without new-onset neuro-PASC, and of flu patients with similar symptoms. METHODS: We retrospectively screened 18,811 COVID-19 patients and 5772 flu patients between January 2020 and June 2021 for the presence of new-onset neuro-sequelae that persisted at least 2 weeks past the date of COVID-19 or flu diagnosis. RESULTS: We observed 388 COVID-19 patients with neuro-PASC versus 149 flu patients with neuro-sequelae. Common neuro-PASC symptoms were anxiety (30%), depression (27%), dizziness (22%), altered mental status (17%), chronic headaches (17%), and nausea (11%). The average time to neuro-PASC onset was 138 days, with hospitalized patients reporting earlier onset than non-hospitalized patients. Neuro-PASC was associated with female sex and older age (p < 0.05), but not race, ethnicity, most comorbidities, or COVID-19 disease severity (p > 0.05). Compared to flu patients, COVID-19 patients were older, exhibited higher incidence of altered mental status, developed symptoms more quickly, and were prescribed psychiatric drugs more often (p < 0.05). CONCLUSIONS: This study provides additional insights into neuro-PASC risk factors and differentiates between post-COVID-19 and post-flu neuro-sequelae.

Clinical predictors of acute cardiac injury and normalization of troponin after hospital discharge from COVID-19.

BACKGROUND: Although acute cardiac injury (ACI) is a known COVID-19 complication, whether ACI acquired during COVID-19 recovers is unknown. This study investigated the incidence of persistent ACI and identified clinical predictors of ACI recovery in hospitalized patients with COVID-19 2.5 months post-discharge. METHODS: This retrospective study consisted of 10,696 hospitalized COVID-19 patients from March 11, 2020 to June 3, 2021. Demographics, comorbidities, and laboratory tests were collected at ACI onset, hospital discharge, and 2.5 months post-discharge. ACI was defined as serum troponin-T (TNT) level >99th-percentile upper reference limit (0.014ng/mL) during hospitalization, and recovery was defined as TNT below this threshold 2.5 months post-discharge. Four models were used to predict ACI recovery status. RESULTS: There were 4,248 (39.7%) COVID-19 patients with ACI, with most (93%) developed ACI on or within a day after admission. In-hospital mortality odds ratio of ACI patients was 4.45 [95%CI: 3.92, 5.05, p<0.001] compared to non-ACI patients. Of the 2,880 ACI survivors, 1,114 (38.7%) returned to our hospitals 2.5 months on average post-discharge, of which only 302 (44.9%) out of 673 patients recovered from ACI. There were no significant differences in demographics, race, ethnicity, major commodities, and length of hospital stay between groups. Prediction of ACI recovery post-discharge using the top predictors (troponin, creatinine, lymphocyte, sodium, lactate dehydrogenase, lymphocytes and hematocrit) at discharge yielded 63.73%-75.73% accuracy. INTERPRETATION: Persistent cardiac injury is common among COVID-19 survivors. Readily available patient data accurately predict ACI recovery post-discharge. Early identification of at-risk patients could help prevent long-term cardiovascular complications. FUNDING: None.

Clinical characteristics of the first and second COVID-19 waves in the Bronx, New York: A retrospective cohort study.

BACKGROUND: There is limited clinical patient data comparing the first and second waves of the coronavirus disease 2019 (COVID-19) in the United States and the effects of a COVID-19 resurgence on different age, racial and ethnic groups. We compared the first and second COVID-19 waves in the Bronx, New York, among a racially and ethnically diverse population. METHODS: Patients in this retrospective cohort study were included if they had a laboratory-confirmed SARS-CoV-2 infection by a real-time PCR test of a nasopharyngeal swab specimen detected between March 11, 2020, and January 21, 2021. Main outcome measures were critical care, in-hospital acquired disease and death. Patient demographics, comorbidities, vitals, and laboratory values were also collected. FINDINGS: A total of 122,983 individuals were tested for SARS-CoV-2 infection, of which 12,659 tested positive. The second wave was characterized by a younger demographic, fewer comorbidities, less extreme laboratory values at presentation, and lower risk of adverse outcomes, including in-hospital mortality (adj. OR = 0·23, 99·5% CI = 0·17 to 0·30), hospitalization (adj. OR = 0·65, 99·5% CI = 0·58 to 0·74), invasive mechanical ventilation (adj. OR = 0·70, 99·5% CI = 0·56 to 0·89), acute kidney injury (adj. OR = 0·62, 99·5% CI = 0·54 to 0·71), and length of stay (adj. OR = 0·71, 99·5% CI = 0·60 to 0·85), with Black and Hispanic patients demonstrating most improvement in clinical outcomes. INTERPRETATION: The second COVID-19 wave in the Bronx exhibits improved clinical outcomes compared to the first wave across all age, racial, and ethnic groups, with minority groups showing more improvement, which is encouraging news in the battle against health disparities.

Outcomes of Hospitalized Patients With COVID-19 With Acute Kidney Injury and Acute Cardiac Injury.

PURPOSE: This study investigated the incidence, disease course, risk factors, and mortality in COVID-19 patients who developed both acute kidney injury (AKI) and acute cardiac injury (ACI), and compared to those with AKI only, ACI only, and no injury (NI). METHODS: This retrospective study consisted of hospitalized COVID-19 patients at Montefiore Health System in Bronx, New York between March 11, 2020 and January 29, 2021. Demographics, comorbidities, vitals, and laboratory tests were collected during hospitalization. Predictive models were used to predict AKI, ACI, and AKI-ACI onset. Longitudinal laboratory tests were analyzed with time-lock to discharge alive or death. RESULTS: Of the 5,896 hospitalized COVID-19 patients, 44, 19, 9, and 28% had NI, AKI, ACI, and AKI-ACI, respectively. Most ACI presented very early (within a day or two) during hospitalization in contrast to AKI (p < 0.05). Patients with combined AKI-ACI were significantly older, more often men and had more comorbidities, and higher levels of cardiac, kidney, liver, inflammatory, and immunological markers compared to those of the AKI, ACI, and NI groups. The adjusted hospital-mortality odds ratios were 17.1 [95% CI = 13.6-21.7, p < 0.001], 7.2 [95% CI = 5.4-9.6, p < 0.001], and 4.7 [95% CI = 3.7-6.1, p < 0.001] for AKI-ACI, ACI, and AKI, respectively, relative to NI. A predictive model of AKI-ACI onset using top predictors yielded 97% accuracy. Longitudinal laboratory data predicted mortality of AKI-ACI patients up to 5 days prior to outcome, with an area-under-the-curve, ranging from 0.68 to 0.89. CONCLUSIONS: COVID-19 patients with AKI-ACI had markedly worse outcomes compared to those only AKI, ACI and NI. Common laboratory variables accurately predicted AKI-ACI. The ability to identify patients at risk for AKI-ACI could lead to earlier intervention and improvement in clinical outcomes.

Framing potential for adverse effects of repetitive subconcussive impacts in soccer in the context of athlete and non-athlete controls.

The benefits of athletic activity may be attenuated by sport-related head impacts, including soccer-related concussion and subconcussive events. The purpose of this study is to characterize the specific effects of soccer heading on white matter microstructure and cognitive function, independent of concussion, relative to non-athlete controls and relative to active athletes who are not involved in collision sports. 246 amateur soccer players, 72 non-contact/non-collision sports athletes and 110 healthy,non-athlete controls were included in the study, and underwent cognitive testing and 3T diffusion tensor imaging (DTI). Voxelwise linear regression, comparing soccer players and non-contact/non-collision sports athletes healthy,non-athlete controls, identified regions of abnormally low and high fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) in athlete participants. Generalized estimating equations were used to examine the effects of 2 week and 1 year heading exposure quartile on cognitive performance and on the volume of each high and each low DTI parameter. Athletes with no or lower exposure to repetitive heading exhibited greater expression of low RD, greater expression of high FA and better performance on tasks of attention, processing speed, verbal memory, and working memory compared to non-athletes. Soccer players with the highest exposure to repetitive head impacts, however, did not differ significantly from healthy, non-athletes on either micro-structural features or cognitive performance, findings not explained by concussion history or demographic factors. These results are consistent with the notion that beneficial effects of athletic conditioning or training on brain structure and function may be attenuated by exposure to repeated subconcussive head impacts.

Registration quality filtering improves robustness of voxel-wise analyses to the choice of brain template.

MOTIVATION: Many clinical and scientific conclusions that rely on voxel-wise analyses of neuroimaging depend on the accurate comparison of corresponding anatomical regions. Such comparisons are made possible by registration of the images of subjects of interest onto a common brain template, such as the Johns Hopkins University (JHU) template. However, current image registration algorithms are prone to errors that are distributed in a template-dependent manner. Therefore, the results of voxel-wise analyses can be sensitive to template choice. Despite this problem, the issue of appropriate template choice for voxel-wise analyses is not generally addressed in contemporary neuroimaging studies, which may lead to the reporting of spurious results. RESULTS: We present a novel approach to determine the suitability of a brain template for voxel-wise analysis. The approach is based on computing a "distance" between automatically-generated atlases of the subjects of interest and templates that is indicative of the extent of subject-to-template registration errors. This allows for the filtering of subjects and candidate templates based on a quantitative measure of registration quality. We benchmark our approach by evaluating alternative templates for a voxel-wise analysis that reproduces the well-known decline in fractional anisotropy (FA) with age. Our results show that filtering registrations minimizes errors and decreases the sensitivity of voxel-wise analysis to template choice. In addition to carrying important implications for future neuroimaging studies, the developed framework of template induction can be used to evaluate robustness of data analysis methods to template choice.

Soccer heading and concussion are not associated with reduced brain volume or cortical thickness.

Soccer is the most popular sport in the world and, since it is a contact sport, players are at risk for head injury, including concussion. Here, we proposed to investigate the association of heading and concussion with macroscopic brain structure among adult amateur soccer players. For this study, 375 amateur soccer players (median age 23 years) completed HeadCount-12m to estimate heading over the 12 months prior to MRI and lifetime concussion. T1-weighted 3D magnetization prepared rapid acquisition gradient echo (MP-RAGE) MRI was performed at 3 Tesla. Parcellation was performed using Freesurfer to extract regional gray and white matter volumes as well as regional cortical thickness and total intracranial volume. Regional cortical brain volumes were normalized by total intracranial volume. We categorized heading into quartiles and concussion as 0, 1 or 2 or more. Generalized linear regressions were used to test the association of heading or concussion with each brain morphometry metric, including age and sex, as covariates. Neither heading nor concussion were associated with reduced brain volume or cortical thickness. We observed that greater heading was associated with greater gray matter volume in the left inferior parietal area, which may reflect effects related to training.

BDNF Val66Met Positive Players Demonstrate Diffusion Tensor Imaging Consistent With Impaired Myelination Associated With High Levels of Soccer Heading: Indication of a Potential Gene-Environment Interaction Mechanism.

The purpose of this study was to examine the potential effect modifying role of the BDNF Val66Met polymorphism on the association of soccer heading with white matter microstructure. We studied 312 players enrolled in the ongoing Einstein Soccer Study, a longitudinal study of amateur soccer player in New York City and surrounding areas. At enrollment and 2 years later, total heading in the prior 12 months (12-mo.) was estimated using an established self-report instrument and diffusion tensor imaging (DTI) was performed. Generalized Estimating Equations (GEE) logistic regression models were employed to test effect modification by the BDNF Val66Met polymorphism on the association between 12-mo. heading exposure and DTI. We identified a significant interaction of 12-mo heading*BDNF Val66Met genotype on the presence of low Radial Diffusivity, a DTI marker associated with myelination. Only Met (+) players demonstrated significantly reduced odds of low RD [OR (95 % CI): -2.36 (-3.53, -1.19)] associated with the highest vs. lowest quartile of 12-mo heading exposure. BDNF Val66Met (+) soccer players with long-term exposure to high levels of heading exhibit less low Radial Diffusivity, suggesting impaired re-myelination may be a substrate of the previously reported association between heading and poor functional outcomes in soccer players.

White matter microstructural abnormalities in blast-exposed combat veterans: accounting for potential pre-injury factors using consanguineous controls.

PURPOSE: Assess the prevalence of white matter microstructural changes in combat veterans, within the context of a highly matched control group comprising unexposed close relatives. METHODS: This prospective study had institutional review board approval, included written informed consent, and is HIPAA-compliant. Diffusion tensor imaging was analyzed in 16 male blast-exposed combat veterans of Operation Iraqi Freedom/Operation Enduring Freedom (mean age 31.0 years) and 18 unexposed males (mean age 30.4 years) chosen on the basis of a consanguineous relationship to a member of the subject group. Whole-brain voxel-based comparison of fractional anisotropy (FA) was performed using both group and individual analyses. Areas where effects on FA were detected were subsequently characterized by extracting radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) from the regions of abnormal FA. RESULTS: Controls did not differ from veterans on any background demographic factor. In voxel-based group comparison, we identify high fractional anisotropy (FA) in veterans compared to controls (p < 0.01). Within individual veterans, we find multiple areas of both abnormally high and low FA (p < 0.01) in a heterogeneous distribution, consistent with multifocal traumatic axonal injury. In individualized analyses, low FA areas demonstrate high radial diffusivity, whereas high FA areas demonstrate low RD in both group and individual analyses. CONCLUSIONS: Combat-related blast exposure is associated with microstructural white matter abnormalities, and the nature of the control group decreases the likelihood that the findings reflect underlying background differences. Abnormalities are heterogeneously distributed across patients, consistent with TAI, and include areas of low and high FA.

MRI-defined White Matter Microstructural Alteration Associated with Soccer Heading Is More Extensive in Women than Men.

Purpose To examine the role of sex in abnormal white matter microstructure after soccer heading as identified by using the diffusion-tensor imaging (DTI) metric fractional anisotropy (FA). Materials and Methods In this prospective cross-sectional study, 98 individuals who were enrolled in a larger prospective study of amateur soccer players (from 2013 to 2016) were matched 1:1 for age and history of soccer heading in the prior 12 months. Among the subjects, 49 men (mean age, 25.7 years; range, 18-50 years) and 49 women (mean age, 25.8 years; range, 18-50 years) with median total soccer headings per year of 487 and 469, respectively, underwent 3.0-T DTI. Images were registered to the Johns Hopkins University template. A voxelwise linear regression was fitted for FA with terms for the number of headings during the previous 12 months and its interaction with sex after controlling for the following potential confounders: age, years of education, number of lifetime concussions, and handedness. In the resulting statistical maps, P < .01 indicated a statistically significant difference, with a threshold cluster size larger than 100 mm3. Results Among men, three regions were identified in which greater heading exposure was associated with lower FA; eight such regions were identified among women (>100 contiguous voxels, P < .01). In seven of the eight regions identified in women, the association between heading and FA was stronger in women than in men. There was no significant difference of heading with FA between the sexes for any region in which heading was associated with FA among men (P > .01, <100 contiguous voxels). Conclusion With similar exposure to heading, women exhibit more widespread evidence of microstructural white matter alteration than do men, suggesting preliminary support for a biologic divergence of brain response to repetitive trauma. © RSNA, 2018 Online supplemental material is available for this article.