Real-world mepolizumab treatment in patients with severe asthma decreased exacerbations, oral corticosteroid use, and healthcare resource utilization and costs over 4 years: a retrospective analysis.

Objective: Although the efficacy of mepolizumab in reducing exacerbations and oral corticosteroid (OCS) use in severe asthma is well-established, real-world long-term effectiveness data are limited. This study evaluated the real-world impact of mepolizumab treatment in patients with severe asthma over a 4-year follow-up period.

Methods: This was a retrospective cohort study of patients with asthma initiating mepolizumab (index date: first claim, November 2015-September 2019) using the Merative MarketScan Commercial and Medicare Databases.

Biological Factors Influencing [18F]MK6240 and [18F]FTP Correlation in Target Regions.

Background: The association between [F]Flortaucipir (FTP) and [F]MK6240, two commonly used tau‐PET tracers in Alzheimer’s disease (AD), varies due to distinct binding properties and off‐target signal regions. Our study aims to elucidate the biological factors influencing this association and evaluate the applicability of a common equation across different on‐target regions.

Method: 113 individuals from the HEAD dataset (11 young, 58 cognitively unimpaired elderly, and 44 cognitively impaired) underwent [F]MK6240, [F]FTP and Aβ‐PET scans.

Comparison of tau‐PET tracers for in vivo Braak staging: the HEAD Study.

Background: Tau‐PET tracers allow for in vivo Braak staging of individuals in the Alzheimer’s disease (AD) continuum. The impact of tracers’ characteristics for Braak staging using tau‐PET remains unclear. Therefore, we performed a head‐to‐head comparison of Braak staging using first‐ and second‐generation tau‐PET tracers.

Multi‐cohort cerebrospinal fluid proteomics identifies robust molecular signatures for asymptomatic and symptomatic Alzheimer’s disease.

Background: Changes in Amyloid‐β (A) and hyperphosphorylated Tau (T) in the brain and cerebrospinal fluid (CSF) precedes AD symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies.

Method: We used the Somascan assay for measuring the protein levels of 7,029 analytes in CSF of 2,286 participants from four different cohorts. We employed a three‐stage analytical approach (discovery, replication, and meta‐analysis).

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.

Prediction of amyloid and tau status in nondemented older adults using tree‐based ensemble models.

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.

Comparison of [F]MK6240 and [F]Flortaucipir standardized uptake values (SUVs): the HEAD study.

Background: Differences between on‐ and off‐target retention characteristics between [F]MK6240 and [F]Flortaucipir (FTP) complicate the harmonization across tracers. Our objective here was to separate the impact of the reference region by evaluating correlations between [F]MK6240 (MK) and [F]FTP standard uptake values (SUVs).

Method: Participants (Figure 1, n=90) received an amyloid‐β (Aβ) PET scan ([C]PIB or [F]NAV4694) and two tau‐PET scans: [F]MK (90‐110 minutes post‐injection) and [F]FTP (80‐100 minutes post‐injection).

Characterization of the heterogeneity of amyloid‐PET‐negative patients with a clinical diagnosis of sporadic early‐onset AD: an FDG‐PET study in the LEADS cohort.

Background: Diagnosing sporadic early‐onset AD (EOAD, age‐at‐onset<65) is challenging: in the multi‐center Longitudinal Early‐onset Alzheimer’s Disease Study, ∼25% of patients with clinically diagnosed EOAD are amyloid‐PET‐negative. Here we used FDG‐PET to characterize the heterogeneity of hypometabolic profiles in these patients and better identify underlying etiologies.

Method: Seventy‐four amyloid‐PET‐negative patients with clinical diagnosis of sporadic EOAD (MCI or mild dementia stage) underwent FDG‐PET.

Renal Atrophy Relates to Brain Volume Loss on 7,149 MRI Scans.

Background: Renal atrophy may reflect an end organ consequence of chronic vascular disease. Renal volume loss may therefore provide a window into brain aging and Alzheimer disease risk.

Method: We obtained whole‐body 1.

Association between Default Mode Network Connectivity Compared Between Two Tau Tracers (Flortaucipir vs. MK6240) – HEAD Study.

Background: Default mode network (DMN) resting state connectivity has been correlated with heightened amyloid and tau – hallmarks of Alzheimer's Disease (AD). Tau is postulated to impact a meta‐temporal area including DMN‐associated regions like amygdala, entorhinal cortex, fusiform gyrus, parahippocampus, inferior temporal, and middle temporal gyrus. We recruited individuals with varying cognitive status to undergo resting state connectivity and imaging with two tau tracers (Flortaucipir and MK6240).

Exploring the effects of using multiple different cerebellar reference regions to improve tau‐PET harmonization ‐ The HEAD Study.

Background: Tau‐PET tracers have been used to diagnose and stage Alzheimer’s disease. However, different tau tracers present distinct patterns of binding throughout the brain, challenging the harmonization of their results. We hypothesize that the choice of a reference region can impact the harmonization of the tau‐PET standardized uptake value ratio (SUVR).

Longitudinal multicenter head‐to‐head harmonization of tau‐PET tracers: an overview of the HEAD study cohort.

Background: Standardizing tau pathology quantification in vivo is challenged by differences in binding characteristics between tau‐PET tracers. The HEAD study aims to generate a leading, longitudinal head‐to‐head dataset of MK‐6240, Flortaucipir, RO948, and PI‐2620 tau‐PET to harmonize these tracers' outcomes and develop tools allowing for the generalization of findings across large studies and trials. Here, we present current advancements in building the HEAD study cohort and dataset.

Preliminary Validation of a Structural Magnetic Resonance Imaging Metric for Differential Diagnosis of Frontotemporal Lobe Dementias.

Background: AD‐NeuroScore is a validated metric that summarizes Alzheimer’s disease (AD)‐specific atrophy and can detect AD early, benchmark disease severity, predict and monitor AD progression, and can aid in testing the efficacy of therapeutic interventions using a single number (Kress, 2023). It meets criteria for translatability by using clinically available regional brain volumes as input (Ahdidan, 2015; Cavedo, 2022) and having patient and model‐level interpretability (Pinto, 2022). Also, features can be reviewed by a neuroradiologist (Larson, 2019).

Using Inflammatory Plasma Biomarkers to Predict Preclinical Alzheimer’s Disease.

Background: Plasma biomarkers have recently emerged to detect symptomatic Alzheimer Disease (AD), but have yet to be validated in preclinical AD populations, where Aβ accumulates in the brain but older adults are cognitively unimpaired (CU). In addition to AD pathologic plasma biomarkers (amyloid and tau), inflammatory markers can accurately detect symptomatic AD. We used pathologic and inflammatory plasma biomarkers to predict amyloid PET status in CU older adults.

Association and multimodal model of retinal and blood‐based biomarkers for detection of preclinical Alzheimer’s disease.

Background: The potential of plasma Aβ42/Aβ40 ratio, NfL, p‐tau 181, and p‐tau 217 has been extensively discussed in the literature. Our previous study explored the association between retinal biomarkers and preclinical AD. The goal of this study was to evaluate the association and a multimodal model of retinal and plasma biomarkers for detection of preclinical AD.

Monkey Lateral Prefrontal Cortex Subregions Differentiate between Perceptual Exposure to Visual Stimuli.

Each day, humans must parse visual stimuli with varying amounts of perceptual experience, ranging from incredibly familiar to entirely new. Even when choosing a novel to buy at a bookstore, one sees covers they have repeatedly experienced intermixed with recently released titles. Visual exposure to stimuli has distinct neural correlates in the lateral prefrontal cortex (LPFC) of nonhuman primates.

Exploring a weighted composite score for harmonization of 18F‐MK6240 and 18F‐ Flortaucipir: linearity and correlations with cognitive measures in a head‐to‐head tau PET dataset – The HEAD Study.

Background: Harmonization of the two most commonly used Tau PET tracers, 18F‐Flortaucipir and 18F‐MK6240 has proven to be complex. Unlike the centiloid scale for amyloid tracers, Tau PET SUVRs of the two tracers are not linearly comparable and vary markedly in dynamic range and sensitivity.

Method: Tau PET SUVRs for Braak stage (1‐6) in 18F‐MK6240 and 18F‐Flortaucipir were obtained from the Longitudinal multicenter head‐to‐head harmonization of tau‐PET tracers (HEAD) project.

Data‐driven analysis of 10,361 amyloid‐PET scans from the IDEAS study reveals two primary axes of variation.

Background: The variability in the regional distribution of Aβ‐PET signal and its relation to clinical features is debated. We used data‐driven approaches to uncover heterogeneity in cortical Aβ‐PET signal from a large representative sample collected through the IDEAS study.

Methods: We analysed cross‐sectional Aβ‐PET collected from 10,361 patients with MCI or mild dementia scanned in 295 PET facilities using one of the 3 FDA‐approved tracers.

Brain Volumetric Trajectories in Down Syndrome and Autosomal Dominant Alzheimer Disease.

Background: Alzheimer disease (AD) related cognitive decline occurs at relatively young ages in individuals with Down syndrome (DS, early‐mid 50s) and in those with autosomal dominant mutations (ADAD, 40‐50s). Both groups show similar patterns of amyloid accumulation. We examined if brain volumes are similarly affected by AD pathology in individuals with DS and ADAD.

Universal tau PET scale (Uniτ) – The HEAD Study.

Background: The HEAD study aims to collect a large dataset of multiple tau‐PET tracers to provide robust anchor values for tau‐PET harmonization. Here, we tested the hypothesis that anchoring two tau tracer uptake values using head‐to‐head measurements has the potential to generate an accurate universal tau‐PET scale, named Uniτ(tau).

Methods: We assessed 200 individuals across the aging and AD spectrum (Training: HEAD data freeze 2.

Effects of APOE genotype on cortical atrophy in early onset Alzheimer’s disease.

Background: APOE‐ɛ4 is a major risk factor for Alzheimer’s disease (AD); its effects have been examined in late‐onset AD (LOAD) but less so in early‐onset AD (EOAD). In LOAD, APOE genotype has strong effects on episodic memory and medial temporal lobe (MTL) atrophy (Wolk & Dickerson, 2010). However, EOAD often presents with more cognitive impairments in executive function, language, and visuospatial abilities than memory.

Utility of CSF biomarkers in assessing neurodegeneration in Early‐Onset Alzheimer’s disease.

Background: There is a significant need for biomarkers of neurodegenerative burden in Early‐onset Alzheimer’s disease (EOAD). Evidence suggests that levels of specific CSF biomarkers (e.g.

Longitudinal neurodegeneration in Early‐Onset Alzheimer’s Disease: A summary of MRI‐derived atrophy in LEADS.

Background: Prior work has advanced our understanding of cortical atrophy in early‐onset Alzheimer’s disease (EOAD), but longitudinal data are sparse. Current longitudinal MRI studies point to progressive atrophy in cerebral cortex exhibiting a posterior‐to‐anterior gradient, but these studies include small samples with mostly amnestic EOAD. Here, we analyzed a large sample of sporadic EOAD patients from the Longitudinal Early‐Onset Alzheimer's Disease Study (LEADS) to test the central hypothesis that areas in our recently described EOAD signature (Touroutoglou et al.

White matter abnormalities in association with amyloid and tau deposition in a diverse cohort with increased risk for Alzheimer’s disease.

Background: Neuritic plaques with fibrillar beta‐amyloid (Aβ) peptides and tau‐protein neurofibrillary tangles, hallmark features of Alzheimer’s disease (AD) pathology, have been concomitantly associated with white matter (WM) integrity loss, while a unique effect of each pathology on WM integrity in a more demographically diverse population remains unknown.

Method: To examine the degree to which each pathology affects WM integrity in a more diverse non‐demented cohort, Aβ and tau PET, diffusion‐weighted imaging (DWI), and cognition (memory and executive function composites) were examined from the U.S.