Frailty may increase risk of adverse outcomes in RA patients on biologic or targeted-synthetic DMARDs

USA: A recent study published in Arthritis Care & Research has shown frailty to be an important predictor for the risk of serious infections among rheumatoid arthritis (RA) patients treated with biologic (b) or targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs).

Disease-modifying antirheumatic drugs are a group of medications commonly used in rheumatoid arthritis patients. Some of these drugs are also used for treating other conditions, such as psoriatic arthritis, ankylosing spondylitis, and systemic lupus erythematosus. They work to reduce pain and inflammation, prevent or reduce joint damage, and preserve the function and structure of the joints.

The study was conducted by Namrata Singh, Division of Rheumatology, University of Washington, Seattle, WA, and colleagues to determine whether frailty status portends an increased risk of adverse outcomes in RA patients initiating biologic (b) or targeted synthetic disease-modifying anti-rheumatic drugs.

For this purpose, the researchers identified new users of tumor necrosis factor inhibitors (TNFi), Janus Kinase inhibitors (JAKi), or non-TNFi bDMARDs during 2008-2019, among RA patients. Baseline frailty risk score in patients was calculated using a Claims-Based Frailty Index [≥0.2 defined as frail] 12 months before drug initiation.

The primary outcome was time to serious infection. Secondarily, the research team examined time-to-any infection and all-cause hospitalizations. Cox proportional hazards were used to estimate adjusted hazard ratios (aHRs) and assess the significance of interaction terms between frailty status and drug class.

The study revealed the following findings:

  • The study included 57,980 patients (mean age 48.1 ± 10.1 years); 83% started TNFi, 14% non-TNFi biologics, and 3% JAKi. Among these, 6% were categorized as frail.
  • Frailty was associated with a 50% increased risk of serious infections (aHR: 1.5) and a 40% higher risk of inpatient admissions 1.4 compared to non-frail patients among those who initiated TNFi.
  • Frailty was also associated with a higher risk of any infection relative to non-frail patients among those on TNFi, non-TNFi or JAKi.

“The findings show that among patients with rheumatoid arthritis treated with b- or tsDMARDs, frailty is an important predictor for the risk of adverse outcomes,” the researchers concluded.

Reference:

Singh, N., Gold, L. S., Lee, J., Wysham, K. D., Andrews, J. S., Makris, U. E., England, B. R., George, M. D., Baker, J. F., Jarvik, J., Heagerty, P. J., & Singh, S. Frailty and risk of serious infections in patients with rheumatoid arthritis treated with biologic or targeted-synthetic DMARDs. Arthritis Care & Research. https://doi.org/10.1002/acr.25282

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Zinc promising as emerging treatment for vaginal candidiasis: Study

Italy: Researchers have identified a key mediator of symptomatic vulvovaginal candidiasis (VVC), allowing the development of a range of preventative measures for combatting this disease. Their findings were published online in Science Translational Medicine. 

“New research could one day pave the way for the treatment of vaginal yeast infections, by shedding new light on how microbes in the body absorb zinc,” the researchers stated. 

Around three-quarters of women develop vaginal yeast infections at least once in their lifetime, and approximately 140 million women globally suffer from recurrent infections. Recurrent yeast infections can have an enormous impact of quality of life. Existing anti-fungal treatments are not always effective and resistance against these treatments is developing.

Thrush is caused by a yeast called Candida. There are a number of species of Candida, but the one that causes most yeast infections is Candida albicans.

Now, new research, led by the University of Exeter’s MRC Centre for Medical Mycology has found that the trace mineral zinc could play a surprising role. Just like us, Candida albicans needs zinc in its diet and this yeast produces a molecule (Pra1) which tries to scavenge zinc as a food source. Now, researchers have found that this molecule triggers an inflammatory response, which they believe is responsible for many cases of thrush.

Wellcome Trust Senior Fellow Dr Duncan Wilson, of the University of Exeter’s MRC Centre for Medical Mycology, led the research, and said: “Recurring thrush can be deeply distressing and problematic, and we urgently need new treatments. Our new finding on zinc is very exciting, because it suggests that simple provision of zinc could block the production of the inflammatory Pra1 molecule, but we’re not in the position to make treatment recommendations at this stage. We need larger scale trials to confirm the effect. Please don’t apply any products that are not designed for the genital area, as zinc can be toxic at high concentrations and it could be extremely unsafe.”

In lab experiments, the team found that manipulating genes so that Candida albicans does not produce Pra1 prevented inflammation. They went on to find that applying relatively low levels of zinc in mice blocked Pra1 production, and prevented inflammation. This is important because it is inflammation that causes the burning, itching symptoms of thrush.

The research team also recruited women who had been experiencing vaginal infections at least once every three months. The women applied a vaginal moisturising cream which contains a small amount of zinc nightly for two weeks, and then twice a week. Of six women who completed the study and had vulvovaginal candidiasis (thrush), five of them did not experience reinfection over the three month study.

Dr Wilson said: “These findings are very encouraging, although the number of participants is small. We are now carrying out a larger clinical trial to confirm that zinc treatments are effective. In the longer term, we hope this could be a promising strategy for a condition could evolve resistance to treatment.

“We’d been studying this Pra1 molecule for more than ten years to understand its role in zinc scavenging – this research shows the fundamental importance of basic research of this nature, which can help shed light on how our bodies work and sometimes provide surprising routes to new treatments.”

Reference:

Roselletti E, Pericolini E, Nore A, Takacs P, Kozma B, Sala A, De Seta F, Comar M, Usher J, Brown GD, Wilson D. Zinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal protein. Sci Transl Med. 2023 Dec 6;15(725):eadi3363. doi: 10.1126/scitranslmed.adi3363. 

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Study Suggests Link Between Vitamin D and Insulin Resistance in Children

New research sheds light on the potential association between vitamin D levels and insulin resistance in children, particularly among ethnic minority populations. The study, a cross-sectional analysis involving 4650 primary school children aged 9–10 years in the UK, predominantly from South Asian, black African Caribbean, and white European backgrounds, examined the relationship between circulating vitamin D (25-hydroxyvitamin D) concentrations and markers of insulin resistance.

This study was published in the Journal Of Epidemiology & Community Health by Angela Donin and colleagues. The study revealed that lower levels of circulating vitamin D were observed, particularly among girls and children from South Asian and black African Caribbean ethnicities. After adjusting for age, sex, month, ethnic group, and school, researchers noted an inverse relationship between circulating vitamin D levels and markers of insulin resistance:

Association with Insulin Resistance: For every increase in 1 nmol/L of 25(OH)D, there was a corresponding decrease in fasting insulin levels by 0.38%, HOMA insulin resistance by 0.39%, and fasting glucose by 0.03%.

Ethnic Disparities: Differences in fasting insulin and insulin resistance, which were notably higher in South Asian and black African Caribbean children, were reduced by over 40% after accounting for circulating 25(OH)D concentrations.

The findings underscore the potential impact of vitamin D levels on insulin resistance in children across different ethnicities. Importantly, the study suggests that lower vitamin D concentrations among South Asian and black African Caribbean children could contribute to their higher levels of insulin resistance.

The study’s authors highlight the need for further investigation into whether vitamin D supplementation could mitigate the emerging risk of type 2 diabetes, especially in children with lower circulating vitamin D levels.

Understanding the potential role of vitamin D in influencing insulin resistance in children, particularly in ethnic minority groups, could have implications for early interventions to reduce the risk of type 2 diabetes. Further exploration is warranted to investigate whether interventions to improve vitamin D levels might help mitigate the risk of diabetes among vulnerable populations.

The study’s findings pave the way for additional research into the potential benefits of vitamin D supplementation as a strategy to address the emerging risk of type 2 diabetes, especially in children with lower vitamin D concentrations.

Reference:

Donin, A., Nightingale, C. M., Sattar, N., Fraser, W. D., Owen, C. G., Cook, D. G., & Whincup, P. H. Cross-sectional study of the associations between circulating vitamin D concentrations and insulin resistance in children aged 9–10 years of South Asian, black African Caribbean and white European origins. Journal of Epidemiology and Community Health, jech-2023-220626,2023. https://doi.org/10.1136/jech-2023-220626

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Genetically predicted high BP and LDL-C increase risk of CHD independent of age

The impact of blood pressure and cholesterol levels on coronary heart disease (CHD) risk across different life stages has always been a subject of uncertainty. A recent study by the Nelson Wang and team utilized data from the UK Biobank and looked into the long term implications of elevated systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) on CHD risk. The findings of the study were published in PloS One.

The study included 136,648 participants for LDL-C, 135,431 for SBP, and 24,052 CHD cases. The study assessed the duration of exposure to these risk factors on CHD risk. Univariable analyses revealed a consistent association between higher LDL-C and SBP and increased odds of incident CHD in individuals aged ≤55, ≤60, and ≤65 years after stratified by age at enrollment. Importantly, multivariable MR analyses demonstrated that exposure to elevated LDL-C/SBP in early life (≤55 years) was independently associated with a higher CHD risk, irrespective of later-life levels (age >55 years) (odds ratio 1.68, 95% CI 1.20–2.34 per 1 mmol/L LDL-C, and odds ratio 1.33, 95% CI 1.18–1.51 per 10 mmHg SBP).

The findings highlight a crucial connection between genetically predicted SBP/LDL-C and CHD risk, transcending age. Independently of later-life levels, increased SBP and LDL-C in early to middle life emerged as potent contributors to increased CHD risk. This highlights the significance of lifelong control of these risk factors, specially in younger individuals with the risk of CHD accumulating throughout life. The study illuminates a pivotal aspect of cardiovascular health by emphasizing the need for early interventions and sustained efforts in managing these modifiable risk factors to reduce the lifelong burden of coronary heart disease.

Source:

Wang, N., Mustafa, R., Zuber, V., Rodgers, A., & Dehghan, A. (2023). Association between systolic blood pressure and low-density lipoprotein cholesterol with coronary heart disease according to age. PloS One, 18(12), e0295004. https://doi.org/10.1371/journal.pone.0295004

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Men Have Higher Risk of Extubation Failure compared to females in ICU Setting

In a recent study published in the Annals of Intensive Care uncovered a significant difference in the risk of extubation failure between male and female patients in intensive care setting.

This post hoc analysis of a large-scale clinical trial focused on patients at high risk of extubation failure in intensive care units (ICUs) and explored potential gender-related variations in prognosis. After examining data from 641 patients, this study found that 66% were males and 34% females. Also, males were more likely to be admitted for cardiac arrest and to have underlying ischemic heart disease, while females were more commonly admitted for coma and exhibited a higher risk of obesity.

The results indicated a significant disparity in the rate of reintubation at 48 hours post-extubation, with males experiencing a higher rate compared to females (11.0% vs. 6.0%). But, by day 7, while the difference persisted, it did not reach statistical significance (16.7% vs. 11.1%). Further analysis revealed that male sex was independently associated with a higher risk of reintubation within the crucial 7 days following extubation (adjusted odds ratio 1.70).

This analysis focused on a specific subset of patients at high risk of extubation failure and brought attention to the nuanced relationship between gender and critical care outcomes. When considered independently, the findings play a significant role in predicting the likelihood of reintubation, even after adjusting for various factors such as reason for admission, body-mass index, severity score, respiratory rate before extubation, and noninvasive ventilation after extubation.

Source:

Thille, A. W., Boissier, F., Coudroy, R., Le Pape, S., Arrivé, F., Marchasson, L., Frat, J.-P., Ragot, S., Muller, G., Gacouin, A., Decavèle, M., Sonneville, R., Beloncle, F., Girault, C., Dangers, L., Lautrette, A., Cabasson, S., Rouzé, A., … Vivier, E. (2023). Sex difference in the risk of extubation failure in ICUs. In Annals of Intensive Care (Vol. 13, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1186/s13613-023-01225-7

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Hypertensive Disorders in Pregnancy Associated With Lasting Effects on Heart

New research from the Smidt Heart Institute at Cedars-Sinai found that women who developed signs of elevated blood pressure during pregnancy were more likely to have residual evidence of abnormal heart structure and function up to a decade after the pregnancy.

“This study helps to clarify that, for some women, pregnancy is not just a ‘stress test’ that unmasks underlying cardiovascular risks,” said Susan Cheng, MD, MPH, the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science, director of the Institute for Research on Healthy Aging in the Department of Cardiology in the Smidt Heart Institute, and senior author of the study. “This risk may also affect the heart years after pregnancy.”

The study, recently published in the peer-reviewed journal Hypertension, looked at more than 5,000 Hispanic/Latina women with at least one prior pregnancy and identified those who had hypertensive disorders of pregnancy, such as gestational hypertension, preeclampsia or eclampsia.

“This study confirms the results of others and demonstrates thHypertensionat women who experience a hypertensive disorder during their pregnancy are more likely to have lasting changes in the structure and function of their hearts than women who have normal blood pressure during their pregnancy,” said Natalie Bello, MD, MPH, director of Hypertension Research in the Smidt Heart Institute and co-author of the study. “Further, this work shows that only a portion of the abnormalities in the heart are explained by the woman’s current blood pressure.”

After accounting for other cardiovascular risk factors that might otherwise lead to early signs of heart disease, researchers found that the approximately 14% of study participants who had developed hypertensive disorders during pregnancy had several persistent heart-related issues found on cardiac imaging. These included greater heart-wall thickness, more frequent abnormal left-ventricle geometry and lower ejection fraction when compared to women who also had a prior pregnancy but without any related hypertensive disorder. 

Reference:

Odayme Quesada, Shathiyah Kulandavelu, Catherine J. Vladutiu, Emily DeFranco, Margo B. Minissian, Nour Makarem, Natalie A. Bello, Melissa S. Wong, Maria A. Pabón, Alvin A. Chandra, Cardiac Abnormalities in Hispanic/Latina Women With Prior De Novo Hypertensive Disorders of Pregnancy, Hypertension, https://doi.org/10.1161/HYPERTENSIONAHA.123.21248.

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Patients with mental distress after MI likely to have PTSD, finds study

A recent cross-sectional epidemiological study sheds light on a concerning trend among individuals who have experienced myocardial infarction (MI). The research, conducted as part of the Tromsø Study, aimed to investigate the prevalence of post-traumatic stress disorder (PTSD) among patients following a confirmed diagnosis of myocardial infarction and explore the relationship between PTSD symptoms and exposure to traumatic events.

This study was published in the journal BMC Psychiatry by Geir Fagerjord Lorem and colleagues. The study, encompassing a sample of 79 participants who had experienced myocardial infarction, unveiled a noteworthy discovery: 11.6% of these individuals exhibited symptoms indicative of probable PTSD. This prevalence was notably higher than what is typically postulated for the general population in Norway, marking a statistically significant difference.

Interestingly, the research didn’t establish a direct correlation between myocardial infarction as an illness trauma and the severity of PTSD symptoms. However, an intriguing pattern emerged concerning the association between PTSD symptom severity and lifetime exposure to traumatic events. As the number of traumatic events experienced by individuals increased, a proportional rise in symptom severity was observed.

The findings highlight a crucial aspect: anxiety or depression symptoms experienced by myocardial infarction patients might be secondary manifestations of PTSD rather than direct consequences of the cardiac event itself. This emphasises the importance for clinicians to be vigilant in their assessment of post-MI patients, considering the potential for underlying PTSD-related symptoms.

While this study offers valuable insights, the interaction between myocardial infarction and PTSD requires more extensive exploration. Future research endeavours are crucial to deepen our understanding of how these conditions intersect and influence each other. Such investigations could pave the way for more targeted and effective interventions aimed at improving the mental well-being of individuals recovering from myocardial infarction.

Reference:

Lorem, G. F., Næss, E. T., Løchen, M.-L., Lillevoll, K., Molund, E.-M., Rösner, A., Lindkvist, S., & Schirmer, H. Post-traumatic stress disorder among heart disease patients: a clinical follow-up of individuals with myocardial infarction in the Tromsø Study. BMC Psychiatry,2023;23(1). https://doi.org/10.1186/s12888-023-05431-2

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Higher scores for systemic inflammatory markers linked to higher prevalence of hypertension

In a sweeping epidemiological analysis aimed at unraveling the mysteries of hypertension, researchers have unveiled a significant breakthrough in understanding the associations between systemic inflammation markers and the prevalence of this prevalent health condition. They found a robust and significant positive correlation between systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) with the prevalence of hypertension, thus underscoring the intricate relationship between systemic inflammation and hypertension.

The study results were published in the journal BMC Cardiovascular Disorders.

Also Read: Brain lesions in former football players linked to vascular, brain changes

Hypertension significantly impacts cardiovascular outcomes, being a major predictor of global mortality and public health concerns. Research suggests links between autoimmunity, inflammation, metabolism, and hypertension. While the systemic immune inflammation index (SII) and hypertension association are explored, the correlations between the system inflammation response index (SIRI) and aggregate index of systemic inflammation (AISI) remain uninvestigated. Hence, researchers conducted a cross-sectional study to comprehensively analyze these inflammation markers, seeking potential biomarkers for early hypertension detection.
The present cross-sectional study engaged a substantial cohort of 119,664 individuals participating in the National Health and Nutrition Examination Survey. A meticulous examination of the three systemic inflammation markers—namely, the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI)—and their associations with hypertension prevalence was carried out.

Findings:

  • The findings unveiled a gradual increase in hypertension prevalence rates with ascending quartiles of logSII, logSIRI, and logAISI.
  • In continuous analyses, each unit increase in logSII, logSIRI, and logAISI corresponded to a 20.3%, 20.1%, and 23.7% elevated risk of hypertension, respectively.
  • When compared to individuals in the lowest quartiles, those in the highest quartiles of logSII, logSIRI, and logAISI faced hypertension risks elevated by 1.114-fold, 1.143-fold, and 1.186-fold, respectively.
  • The Restricted Cubic Splines (RCS) analysis further illuminated a non-linear relationship between the escalation of systemic inflammation markers and the prevalence of hypertension.
  • Specifically, a per standard deviation increase in any of these variables correlated with a 9%, 16%, and 11% respective rise in hypertension prevalence.
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Thus, the present comprehensive cross-sectional study establishes robust and significant positive correlations between systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) with the prevalence of hypertension. These findings not only underscore the intricate relationship between systemic inflammation and hypertension but also pave the way for potential biomarkers that could revolutionize early detection strategies. As hypertension remains a global health concern, these insights hold immense promise for advancing proactive healthcare approaches and refining our understanding of the complex interplay between inflammation and cardiovascular health.
Further reading: Jin N, Huang L, Hong J, et al. The association between systemic inflammation markers and the prevalence of hypertension. BMC Cardiovasc Disord. 2023;23(1):615. Published 2023 Dec 14. doi:10.1186/s12872-023-03661-6

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DAPT within 72 hours can help improve stroke symptoms

Dual antiplatelet treatment (DAPT) has proven to lower the risk of recurrent stroke as compared with aspirin alone when treatment is initiated early (≤24 hours) after an acute mild stroke.

The effect of clopidogrel plus aspirin as compared with aspirin alone administered within 72 hours after the onset of acute cerebral ischemia from atherosclerosis has not been well studied. A new study in New England Journal of Medicine says that DAPT  initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin therapy alone but was associated with a low but higher risk of moderate-to-severe bleeding.

Around 222 hospitals in China, researchers conducted a double-blind, randomized, placebo-controlled, two-by-two factorial trial involving patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy. Patients were randomly assigned, in a 1:1 ratio, within 72 hours after symptom onset to receive clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 21) or matching clopidogrel placebo plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 90). There was no interaction between this component of the factorial trial design and a second part that compared immediate with delayed statin treatment (not reported here). The primary efficacy outcome was new stroke, and the primary safety outcome was moderate-to-severe bleeding-both assessed within 90 days.

Researchers found that a total of 6100 patients were enrolled, with 3050 assigned to each trial group. TIA was the qualifying event for enrollment in 13.1% of the patients. A total of 12.8% of the patients were assigned to a treatment group no more than 24 hours after stroke onset, and 87.2% were assigned after 24 hours and no more than 72 hours after stroke onset. A new stroke occurred in 222 patients (7.3%) in the clopidogrel–aspirin group and in 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P=0.008). Moderate-to-severe bleeding occurred in 27 patients (0.9%) in the clopidogrel–aspirin group and in 13 (0.4%) in the aspirin group (hazard ratio, 2.08; 95% CI, 1.07 to 4.04; P=0.03).

Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combinedclopidogrel–aspirin therapyclopidogrel–aspirin therapy initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin therapy alone but was associated with a low but higher risk of moderate-to-severe bleeding.

Reference:

Ying Gao, Weiqi Chen, Yuesong Pan, Jing Jing, Chunjuan Wang, Claiborne Johnston, Pierre Amarenco, Philip M. Bath, Lingling Jiang, Yingying Yang, Tingting Wang, Shangrong Han, Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke, N Engl J Med 2023, DOI: 10.1056/NEJMoa2309137.

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How Repetitive Head injury leads to dementia in Football Players, reveals MRI study

In a groundbreaking study conducted between April 2021 and October 2022, researchers have uncovered alarming connections between repetitive head impacts (RHIs) in American football and an increased burden of white matter hyperintensity (WMH). They found that Fluid-attenuated inversion recovery (FLAIR) WMH in RHI-exposed individuals exhibits distinct risk factors and underlying pathologies when compared with asymptomatic unexposed men.

The study results were published in the journalNeurology.

Also Read: Risk of young onset dementia could be reduced through targeting health and lifestyle factors – study

Recent findings connect repetitive head impacts (RHIs) in American football to heightened white matter hyperintensity (WMH) burden. WMH may exhibit distinctive features in the context of RHI, extending beyond vascular risk and typical aging processes. Hence researchers conducted a study to assess the impact of repeated head injuries using encompassed biological markers like amyloid, tau, inflammation, axonal injury, neurodegeneration, and vascular health in former American football players.

Participants, as part of the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project, underwent clinical interviews, MRI scans, and lumbar punctures. Structural equation modeling assessed both direct and indirect effects between log-transformed total fluid-attenuated inversion recovery (FLAIR) lesion volumes (TLV) and various factors, including the revised Framingham stroke risk profile (rFSRP), MRI-derived metrics of cortical thickness and fractional anisotropy (FA), and cerebrospinal fluid (CSF) levels of amyloid β1–42, p-tau181, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and neurofilament light. Covariates considered in the analysis included age, race, education, body mass index, APOE ε4 carrier status, and evaluation site. Separate models were conducted for former football players and a control group of asymptomatic men not exposed to repetitive head impacts (RHI).

Findings:

  • In a cohort of 180 former football players (mean age = 57.2, 36% Black), elevated log-transformed total fluid-attenuated inversion recovery (FLAIR) lesion volumes (TLV) were directly linked to several factors.
  • These included a higher revised Framingham stroke risk profile (rFSRP) score (B = 0.26, 95% CI 0.07–0.40), increased p-tau181 (B = 0.17, 95% CI 0.01–0.43), diminished fractional anisotropy (FA) (B = −0.28, 95% CI −0.42 to −0.13), and reduced cortical thickness (B = −0.25, 95% CI −0.45 to −0.08).
  • Conversely, in a group of 60 asymptomatic unexposed men (mean age = 59.3, 40% Black), no direct effects on log(TLV) were observed.
  • This was evident in the negligible impact on rFSRP (B = −0.03, 95% CI −0.48 to 0.57), p-tau181 (B = −0.30, 95% CI −1.14 to 0.37), FA (B = −0.07, 95% CI −0.48 to 0.42), and cortical thickness (B = −0.28, 95% CI −0.64 to 0.10).
  • Comparatively, former football players exhibited notably stronger associations between log(TLV) and rFSRP (1,069% difference in estimates), p-tau181 (158%), and FA (287%) when contrasted with the unexposed men.
  • These findings underscore the distinct impact of repetitive head impacts in former football players, revealing significant correlations with various neurological markers compared to individuals without a history of such exposure.
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Risk factors and the biological relationships with white matter hyperintensity (WMH) vary significantly between former American football players and asymptomatic individuals without exposure to repetitive head impacts (RHI). Apart from considering vascular health, the former football players demonstrated more robust associations between WMH and factors like p-tau181 and diffusion tensor imaging indices, indicating a more profound connection to white matter integrity. These results suggest that fluid-attenuated inversion recovery (FLAIR) WMH in those exposed to repetitive head impacts may have unique risk factors and distinct underlying pathological mechanisms.

Further reading: Association of Vascular Risk Factors and CSF and Imaging Biomarkers With White Matter Hyperintensities in Former American Football Players. doi: https://doi.org/10.1212/WNL.00000000002080

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