Background/objectives:
Neurofilament light chain (NfL) levels in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients correlate with the degree of neuronal injury. To date, little is ...known about NfL concentrations in the serum of relapsing remitting multiple sclerosis (RRMS) patients and their relationship with CSF levels and magnetic resonance imaging (MRI) measures of disease severity. We aimed to validate the quantification of NfL in serum samples of RRMS, as a biofluid source easily accessible for longitudinal studies.
Methods:
A total of 31 RRMS patients underwent CSF and serum sampling. After a median time of 3.6 years, 19 of these RRMS patients, 10 newly recruited RRMS patients and 18 healthy controls had a 3T MRI and serum sampling. NfL concentrations were determined by electrochemiluminescence immunoassay.
Results:
NfL levels in serum were highly correlated to levels in CSF (r = 0.62, p = 0.0002). Concentrations in serum were higher in patients than in controls at baseline (p = 0.004) and follow-up (p = 0.0009) and did not change over time (p = 0.56). Serum NfL levels correlated with white matter (WM) lesion volume (r = 0.68, p < 0.0001), mean T1 (r = 0.40, p = 0.034) and T2* relaxation time (r = 0.49, p = 0.007) and with magnetization transfer ratio in normal appearing WM (r = −0.41, p = 0.029).
Conclusion:
CSF and serum NfL levels were highly correlated, and serum concentrations were increased in RRMS. Serum NfL levels correlated with MRI markers of WM disease severity. Our findings further support longitudinal studies of serum NfL as a potential biomarker of on-going disease progression and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials.
Background:
Lower extremity (LEX) strains, including hamstring, quadriceps, adductor, and calf strains, are among the most common injuries in sports. These injuries lead to high burden, resulting in ...significant missed participation time.
Purpose:
To describe the incidence of LEX strains in professional American football.
Study Design:
Descriptive epidemiology study.
Methods:
This study included all players who played in ≥1 National Football League (NFL) game or sustained a LEX strain during participation in the 2015-2019 seasons. LEX strain frequency was calculated by setting (game, practice, conditioning), timing in season (offseason, preseason, regular season, postseason), and roster position. Game incidence rates were calculated for season, roster position, and play type. LEX strains were identified in the standardized leaguewide electronic health record (n = 32 teams).
Results:
Across 5 years, 5780 LEX strains were reported among 2769 players (1-year risk, 26.7%; 95% CI, 26.0%-27.3%); 69% (n = 4015) resulted in time loss. Among all LEX strains, 54.7% were hamstring (n = 3163), 24.1% adductor (n = 1393), 12.6% calf (n = 728), 8.3% quadriceps (n = 477), and 0.3% multiple muscle groups (n = 19). Most were reported during preseason practices (n = 1076; 27%) and regular season games (n = 1060; 26%). The 2-week period of training camp practices comprised 19% of all time-loss strains. Among game injuries, preseason games had the highest rate of LEX strain (2.9/10,000 player-plays; 95% CI, 2.6-3.2). Defensive secondary players accounted for the highest proportion of time-loss LEX strains (27%; n = 1082). In games, punt plays had nearly twice the injury rate of kickoff plays (14.9/1000 plays 95% CI, 13.1-17.0 vs 7.5/1000 plays 95% CI, 6.2-8.9, respectively) and >3 times the rate of pass plays (4.3/1000 plays; 95% CI, 4.0-4.7) and run plays (2.6/1000 plays; 95% CI, 2.3-2.9). In aggregate, LEX strains led to an estimated 16,748 participation days missed each year and a median 12 days missed per injury.
Conclusion:
LEX strains affected 1 in 4 NFL players each year, resulting in a high burden of injury in terms of time lost from practice and competition. Safe return to the NFL season during training camp and reduction of injuries during regular season games are key focuses for future injury reduction.
Abstract
Objective
The aim of the current study is to examine whether concussion history and years played are linearly associated with cognitive outcomes in retired National Football League (NFL) ...players.
Method
Thirty-five retired NFL players over the age of 50 who had sustained at least one concussion completed a clinical interview and brief neuropsychological battery. Correlational analyses were conducted between exposure variables number of total concussions, concussions with loss of consciousness (LOC), and years played and cognitive performance as characterized by cognitive composite scores based on performance on neuropsychological measures (attention/processing speed, language, memory, and overall composite scores).
Results
Correlational analyses corrected for multiple comparisons did not reveal any statistically significant correlations between exposure variables and cognitive outcomes.
Conclusions
We did not find a significant linear association between cognitive outcomes and either number of total concussions, concussions with LOC, or years played in the NFL. These findings do not support a dose–response relationship between sports-related exposure to head impacts and cognitive outcomes later in life. Rather, the findings suggest that cognitive difficulties experienced by some retired players later in life are not directly linearly associated with quantified exposure to head impacts sustained throughout a football career, but related to factors or combinations of factors that have yet to be elucidated.
Neuronal health as a potential underlying mechanism of the beneficial effects of exercise has been understudied in humans. Furthermore, there has been limited consideration of potential moderators ...(e.g., cardiovascular health) on the effects of exercise.
Clinically normal middle-aged and older adults completed a validated questionnaire about exercise engagement over a 10-year period (n = 75; age 63 ± 8 years). A composite estimate of neuronal injury was formulated that included cerebrospinal fluid-based measures of visinin-like protein-1, neurogranin, synaptosomal-associated protein 25, and neurofilament light chain. Cardiovascular risk was estimated using the Framingham Risk Score.
Cross-sectional analyses showed that greater exercise engagement was associated with less neuronal injury in the group with lower cardiovascular risk (p = 0.008), but not the group with higher cardiovascular risk (p = 0.209).
Cardiovascular risk is an important moderator to consider when examining the effects of exercise on cognitive and neural health, and may be relevant to personalized exercise recommendations.
We examined the association between exercise engagement and neuronal injury. Vascular risk moderated the association between exercise and neuronal injury. Cardiovascular risk may be relevant to personalized exercise recommendations.
The 2011 NFL collective bargaining agreement introduced significant changes to rookie compensation, including a rookie wage scale. We test if the new rules changed how sunk costs affect utilization ...for drafted rookies. Our regression discontinuity results show a robust sunk-cost fallacy that is similar in magnitude to the one documented under the previous agreement. Second-round selections play significantly less than their first-round counterparts, as measured by percentage of games started, total snaps played, and percentage of snaps played. However, the effect is not evident beyond the rookie season. Additional results show coaching success and coaching changes are important factors.
Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide. Amyloid beta (Aβ) is one of the proteins which aggregate in AD, and its key role in the disease pathogenesis is ...highlighted in the amyloid cascade hypothesis, which states that the deposition of Aβ in the brain parenchyma is a crucial initiating step in the future development of AD. The sensitivity of instruments used to measure proteins in blood and cerebrospinal fluid has significantly improved, such that Aβ can now successfully be measured in plasma. However, due to the peripheral production of Aβ, there is significant overlap between diagnostic groups. The presence of pathological Aβ within the AD brain has several effects on the cells and surrounding tissue. Therefore, there is a possibility that using markers of tissue responses to Aβ may reveal more information about Aβ pathology and pathogenesis than looking at plasma Aβ alone. In this manuscript, using the amyloid cascade hypothesis as a starting point, we will delve into how the effect of Aβ on the surrounding tissue can be monitored using biomarkers. In particular, we will consider whether glial fibrillary acidic protein, triggering receptor expressed on myeloid cells 2, phosphorylated tau, and neurofilament light chain could be used to phenotype and quantify the tissue response against Aβ pathology in AD.
Many if not most of us watched in utter disbelief and horror last September 11th as Aaron Rogers, the newly acquired $75 million dollar quarterback with the New York Jets just 4 snaps into the new ...season, suffered an Achilles Tendon ruptures (ATR) in his inaugural game on nationally televised Monday Night Football with his new and excited team and demanding fanbase. With cell phones in hand, we watched as our X apps lit up with claims of an excess of ATRs in the NFL in recent years and much of the blame placed on the new rubberized turf surfaces in place in most of the NFL stadiums. That first week of the NFL season the NFL Players Association, the NFLPA, put out a statement to this effect that demanded removal of rubberized turf surfaces throughout the NFL! With Kirk Cousins devastating ATR a few weeks later, amongst 21 others this season, and Aaron Rogers return to practice after a mere seven to eight weeks post-injury, this conundrum remains foremost in our hyper-questioning minds!
CSF Neurofilament light chain(NfL) is a promising biomarker of neurodegeneration, but its utility in discriminating between Alzheimer's disease(AD) and frontotemporal dementia(FTD) is limited.
105 ...patients with clinical-biological diagnosis of mild cognitive impairment(MCI) due to AD (N = 72) or clinical diagnosis of FTD (N = 33) underwent neuropsychological assessment and CSF Aβ42/40, p-tau181, total-tau and NfL quantification. Group comparisons, correlations between continuous variables and ROC curve analysis were carried out to assess NfL role in discriminating between MCI due to AD and FTD, exploring the associations between NfL, ATN biomarkers and neuropsychological measures.
NfL levels were significantly lower in the AD group, while levels of total-tau were higher. In the FTD group, significant correlations were found between NfL, p-tau181 and total-tau, and between NfL and cognitive performances. In the AD group, NfL levels were directly correlated with total-tau and p-tau181; Aβ42/40 ratio was inversely correlated with total-tau and p-tau181, but not with NfL. Moreover, p-tau181 and t-tau levels were found to be associated with episodic memory and lexical-semantic impairment. Total-tau/NfL ratio differentiated prodromal-AD from FTD with an AUC of 0.951, higher than the individual measures.
The results support that NfL and total-tau levels reflect distinct pathophysiological neurodegeneration mechanisms, independent and dependent of Aβ pathology, respectively, Combining them may enhance both markers reliability, their ratio showing high accuracy in distinguishing MCI due to AD from FTD. Moreover, our results revealed associations between NfL and disease severity in FTD and between tauopathy and episodic memory and lexical-semantic impairment in prodromal-AD.
•NfL and t-tau reflect different pathophysiological mechanism of neurodegeneration.•The t-tau/NfL ratio distinguish MCI due to AD from FTD with high accuracy.•Episodic and semantic memory decline are related with p-tau and t-tau in prodromal AD.
Symptoms of post-traumatic stress disorder (PTSD) are common in military populations, and frequently associated with a history of combat-related mild traumatic brain injury (mTBI). In this study, we ...examined relationships between severity of PTSD symptoms and levels of extracellular vesicle (EV) proteins and miRNAs measured in the peripheral blood in a cohort of military service members and Veterans (SMs/Vs) with chronic mTBI(s). Participants (
n
= 144) were divided into groups according to mTBI history and severity of PTSD symptoms on the PTSD Checklist for DSM-5 (PCL-5). We analyzed EV levels of 798 miRNAs (miRNAs) as well as EV and plasma levels of neurofilament light chain (NfL), Tau, Amyloid beta (Aβ) 42, Aβ40, interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNFα), and vascular endothelial growth factor (VEGF). We observed that EV levels of neurofilament light chain (NfL) were elevated in participants with more severe PTSD symptoms (PCL-5 ≥ 38) and positive mTBI history, when compared to TBI negative controls (
p
= 0.024) and mTBI participants with less severe PTSD symptoms (
p
= 0.006). Levels of EV NfL, plasma NfL, and hsa-miR-139–5p were linked to PCL-5 scores in regression models. Our results suggest that levels of NfL, a marker of axonal damage, are associated with PTSD symptom severity in participants with remote mTBI. Specific miRNAs previously linked to neurodegenerative and inflammatory processes, and glucocorticoid receptor signaling pathways, among others, were also associated with the severity of PTSD symptoms. Our findings provide insights into possible signaling pathways linked to the development of persistent PTSD symptoms after TBI and biological mechanisms underlying susceptibility to PTSD.
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