Malpractice Liability Exposure and the Sports Medicine Team Physician: Caring for Professional Athletes in the National Football League, Major League Baseball, and National Hockey League.

Background: Orthopaedic surgeons play a critical role in ensuring the health and safety of professional athletes. Despite the privilege of treating elite athletes, there exists great financial exposure to individual physicians in the event of a malpractice lawsuit.

Hypothesis/purpose: The purpose of this study was to evaluate and model malpractice liability exposure of the sports medicine surgeon caring for athletes in the National Football League (NFL), Major League Baseball (MLB), and National Hockey League (NHL) with respect to player position and additional supplemental malpractice insurance needs.

Biomarkers.

Background: Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is common in older adults and has been associated with substantial cognitive impairment. However, the association of LATE-NC with brain morphometry has not been thoroughly investigated. In this work, we examined the association of LATE-NC with brain morphometric anomalies using deformation-based morphometry (DBM) in a large community cohort of older adults that came to autopsy (N=897).

Biomarkers.

Background: The identification of novel blood-based biomarkers of small vessel disease of the brain (SVD) may improve pathophysiologic understanding and inform the development of new therapeutic strategies for prevention. We evaluated plasma proteomic associations of white matter fractional anisotropy (WMFA), white matter hyperintensity (WMH) volume, enlarged perivascular space (ePVS) volume, and the presence of microbleeds (MB) on brain magnetic resonance imaging (MRI) in the population-based Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: Eligible MESA participants had 2941 plasma proteins measured from stored blood samples (collected in 2016-2018) using the antibody-based Olink proteomics platform, and completed brain MRI scans in 2018-2019.

Biomarkers.

Background: Women with suspected coronary microvascular dysfunction (CMD) may be at higher risk of experiencing cognitive decline due to cerebral small vessel disease, a known contributor to Alzheimer's disease and related dementias (ADRD). A potential underlying mechanism that could accelerate this cognitive decline is the accumulation of brain tissue iron, which has been previously linked to changes in brain function potentially caused by oxidative stress and cell death. Therefore, we aim to elucidate whether a similar mechanism could affect women with suspected CMD by investigating the potential role of iron deposition on the brain's functional organization and its effect on cognition using advanced magnetic resonance imaging (MRI).

Biomarkers.

Background: Quantitative Susceptibility Mapping (QSM) offers significant potential for studying metal and iron homeostasis in the brain and serves as a diagnostic tool for various pathologies, such as Alzheimer's disease. However, the precision of QSM spatial normalization for older adults depends on the quality and representativeness of the chosen template and the type of information used during image registration. This study compares three available QSM templates in terms of their representativeness and precision of inter-subject matching for older adult QSM data.

Biomarkers.

Background: The 18F-AV-1451 radioligand enables in-vivo identification of tau neurofibrillary tangles that are considered as biomarkers of neurodegeneration in Alzheimer Disease (AD). However, off-target radioligand binding is also observed in basal ganglia, known as an iron-rich region. Hence, it is important to distinguish between radioligand-identified tissue neurodegeneration and iron-related radioligand binding effects.

Biomarkers.

Background: The apolipoprotein E (ApoE) Ɛ4 allele is associated with a significant risk for both late-onset Alzheimer's Disease (AD) development and cerebral amyloidosis, but the degree to which cerebrospinal fluid (CSF) apoE glycosylation affects disease progression is unclear. The objective of this study was to examine the relationship of CSF apoE glycosylation with t-tau, p-tau181, and Aβ1-42 CSF levels, and to delineate the effect of the APOE4+ genotype (vs E4-) on glycosylation.

Method: Total glycosylation and apoE isoform-specific glycosylation were analyzed in baseline plasma and CSF samples from a longitudinal cohort of older individuals (n=188, ages 55 - 89) from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Biomarkers.

Background: In the context of Alzheimer's disease (AD), blood-based biomarkers have become increasingly important for various clinical purposes, such as screening patients and tracking the progression of the disease. Tau is a protein that stabilizes microtubules in nerve cells. In AD, different isoforms of tau become hyperphosphorylated, leading to the formation of neurofibrillary tangles, which are a key pathological feature of the AD.

Biomarkers.

Background: Tau pathology accumulates early in the basal forebrain (BF) in Alzheimer's disease (AD). The feasibility of measuring in vivo BF tau is unclear given PET resolution and possible partial volume effects of off-target signal (OTS) which varies by tracer.

Method: We compared measurements of tau in cognitively unimpaired older adults with either an FTP or MK6240 scan: 93 FTP scans from the Berkeley Aging Cohort Study (BACS), 424 FTP scans from ADNI (N=517 FTP scans; 72.

Biomarkers.

Background: Stronger default mode (DMN) and bilateral frontoparietal control network (FPCN) resting-state functional connectivity are associated with reduced β-amyloid (Aβ)-related cognitive decline in cognitively unimpaired older adults, who were predominantly Aβ negative. This suggests that these networks might support cognitive resilience in the face of early AD pathology but it remains unclear whether these effects are apparent in preclinical AD. We investigated whether left-FPCN, right-FPCN, and DMN connectivity moderated the effect of Aβ on cognitive decline using a large multi-site dataset from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study.

Biomarkers.

Background: We assessed the efficacy of four plasma phospho-tau217 (p-tau217) biomarkers in a head-to-head comparison, and against two clinically available CSF biomarkers for Alzheimer's disease (AD).

Method: Samples were analyzed from 1009 individuals from the Swedish BioFINDER-2 cohort (Table 1). We included the following biomarkers: %p-tau217, p-tau217 (both mass-spectrometry), p-tau217, p-tau217 (both immunoassays), CSF p-tau181 and p-tau181/Aβ42 (Elecsys).

Biomarkers.

Background: Placental growth factor (PIGF) is an angiogenic, pro-inflammatory biomarker that is overexpressed in cardiovascular diseases. Recent literature has linked PIGF to the identification of cognitive impairment with white matter burden. Worry is associated with an increased risk for cardiovascular disease, accelerated aging and subsequent reduced brain volume, and decline in cognition.

Biomarkers.

Background: Aging is linked to significant white matter abnormalities, which are often studied using traditional diffusion tensor imaging (DTI) metrics; however, these traditional metrics have limited sensitivity/specificity to neurobiological characteristics. Here, we use fixel-based analysis (FBA) - an approach with more precision in areas of crossing fibers - to study age-related white matter microstructural decline.

Method: This study uses cross-sectional data from the Vanderbilt Memory & Aging Project cohort [n=325, age at baseline: 72.

Biomarkers.

Background: The spread of tau in Alzheimer's Disease (AD) can be tracked in vivo using [F-18]MK6240, a PET radioligand that binds to tau aggregates in AD with high affinity. However, significant MK6240 signal is also observed in the meninges and sinus and the extra cerebral binding (ECB) signal from these regions can spill into exterior brain regions complicating evaluation of early stage AD tauopathy. This study evaluates the magnitude and variability of ECB in a large imaging cohort to identify trends in this signal.

Biomarkers.

Background: APOE is in linkage disequilibrium with the length of poly-T repeats at the rs10524523 ('523) locus of the TOMM40 gene. APOE-ε3 is associated with short (S) and (VL) variants of '523 in white and Black individuals. In white individuals, APOE-ε4 is associated with the long (L) '523 variant, but is associated with '523-S, '523-L, and '523-VL variants in Black individuals.

Biomarkers.

Background: Biomarkers, such as blood p-tau181, p-tau217, and p-tau231, have been created and verified to mirror the pathophysiology of tau and amyloid-β (Aβ) in the brain . Sleep spindles are known to contribute to memory consolidation and generalization and may therefore be a promising biomarker in preclinical Alzheimer's Disease (AD) . The present study investigated the relationship between sleep spindles and p-tau levels in cognitively healthy older African Americans.

Biomarkers.

Background: We aimed to investigate whether the quantitative analysis of plasma biomarkers could distinguish the pathology stages indicated by positron emission tomography (PET)-based Thal phase of amyloid and Braak stage of tau.

Method: A total of 232 participants were enrolled, all of whom underwent F-florbetaben (FBB), F-flortaucipir (FTP) PET, plasma p-tau217/np-tau217 ratio, p-tau217, and Aβ ratio. To differentiate between image-based Thal phases and Braak stages, region-of-interests (ROIs) were constructed, and cut-off points were established at each stage using Gaussian mixture modeling.

Biomarkers.

Background: Predicting amyloid and tau status in nondemented older adults with AD pathologies using more affordable and accessible measures can facilitate clinical trials by reducing the screen failure rate. The goal of the present study was to develop tree-based ensemble models to predict PET-based amyloid and tau burden using non-invasive measures.

Method: Two datasets, amyloid (Aβ; n = 1062) and tau (n = 410), from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were used to predict the biomarker load in the subjects with normal cognition and mild cognitive impairment.

Biomarkers.

Background: Older vervet monkeys are an excellent model for studying age-associated Aβ deposition; however, they have high proportions of low-affinity Aβ sites compared to human brains. Commonly used Aβ PET radiotracers are most useful in detecting high affinity Aβ fibrils. Measuring real-time levels of low affinity Aβ fibrils through PET provides critical information of early AD progression.

Biomarkers.

Background: Oxidative stress, which refers to an imbalance between the production of reactive oxygen/nitrogen species (ROS/RNS) and the body's antioxidant defense mechanisms, is implicated in the pathogenesis of various chronic diseases by promoting cellular damage, inflammation, and dysfunction. Numerous methods have been reported for detecting ROS/RNS in vitro and in vivo; however, detecting methods for the secondary products of the ROS/RNS reactions, particularly quasi-stable oxidized products, have been much less explored.

Method: In this report, we discovered that acetylacetone, a core moiety of curcumins, is a new scaffold for generating chemiluminescence in the presence of oxidants.

Biomarkers.

Background: Neuropeptides are crucial proteins in the central nervous system, which significantly influence neurophysiological processes. This analysis explores cerebrospinal fluid alterations in Alzheimer's disease, offering insights to better understand the condition and explore novel diagnostic and therapeutic avenues.

Method: We systematically searched MEDLINE (PubMed), EMBASE, Cochrane, and Scopus using specific search strategies.

Biomarkers.

Background: As new anti-amyloid immunotherapies emerge for Alzheimer's disease (AD), it is clear that early diagnosis of AD pathology is crucial for treatment success. This can be challenging in atypical presentations of AD and, together with our reliance on CSF or PET scans, can, at times, lead to delayed diagnosis. Here, we further explore the possible role of plasma tau phosphorylated at threonine 217 (P-tau217) for the detection of primary AD or AD co-pathology when frontotemporal dementia spectrum disorders are the main clinical presentation.

Biomarkers.

Background: [F]MK-6240 was developed for PET imaging of AD tau pathology, but the exact molecular signature of specific binding remains unclear. This study quantified levels of four phospho-tau forms and total tau in postmortem brain tissues from [F]MK-6240 imaged cases to investigate associations with antemortem [F]MK-6240 PET.

Methods: This study included four participants from the Wisconsin ADRC or WRAP with antemortem [F]MK-6240 and [C]PiB PET imaging and postmortem brain tissue obtained on average 32-months after imaging (Table 1).

Biomarkers.

Background: Sleep disorders as a contributing factor to cognitive impairment have spurred growing interest. The advent of digital technology facilitates the collection of comprehensive sleep measures in a home setting. The objective of this study is to examine the association between digital sleep measures and the Montreal Cognitive Assessment (MoCA).

Biomarkers.

Background: Sleep deficiency is associated with an increased risk of Alzheimer's disease (AD), warranting research on underlying mechanisms. This study examined the association of sleep architecture with anatomical features frequently observed in AD: (1) atrophy of cuneus, hippocampus, entorhinal, inferior parietal, parahippocampal, and precuneus regions (henceforth referred to as "AD-vulnerable regions") and (2) the presence of cerebral microbleeds.

Method: In 271 participants of the Atherosclerosis Risk in the Communities Study, we examined the prospective association of baseline sleep architecture with anatomical features of the brain identified on MRI conducted ∼17 years later.