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Tau PET load in early‐ and late‐onset Alzheimer's disease: A cross‐sectional and longitudinal comparison of the LEADS and ADNI cohorts
No full textBackground:
We aimed to assess differences in baseline and longitudinal tau PET tracer binding between early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) in the LEADS and ADNI cohorts, respectively.
Method:
We analyzed amyloid‐beta PET‐positive, cognitively impaired participants from the LEADS (EOAD; n = 383) and ADNI (LOAD; n = 196) cohorts with available 18F‐Flortaucipir tau PET data (Table 1). A subset had longitudinal 18F‐Flortaucipir PET data from LEADS (n = 232) and ADNI (n = 94) with average follow‐up intervals of 1.95 and 2.44 years, respectively. All 18F‐Flortaucipir PET scans were processed using the CenTauR pipeline. Cognitively normal participants from LEADS (n = 94) and ADNI (n = 421) with baseline 18F‐Flortaucipir and amyloid‐beta PET scans were also analyzed for comparison. We performed EOAD vs. LOAD comparisons using multivariate linear and linear mixed‐effects models for cross‐sectional and longitudinal analyses, respectively.
Result:
Baseline comparisons revealed large effect‐size, significant differences in 18F‐Flortaucipir binding between EOAD and LOAD (Figure 1). EOAD participants had higher 18F‐Flortaucipir levels in widespread neocortical regions compared to LOAD, after adjusting for covariates. In both groups, tau load was negatively associated with age. In EOAD, a significantly steeper slope was found in the association between amyloid‐beta and 18F‐Flortaucipir load, as well as between cognitive scores and 18F‐Flortaucipir load. Longitudinally, EOAD participants exhibited a faster increase in 18F‐Flortaucipir binding than LOAD, predominantly in frontal and occipital areas (Figure 2), with both groups showing an inverse linear relationship between 18F‐Flortaucipir accumulation rates and age.
Conclusion:
EOAD patients demonstrate significantly higher tau loads, broader neuroanatomical involvement and faster tau accumulation over time compared to LOAD, independent of disease stage. These findings suggest that earlier age‐of‐onset in AD is linked to a more aggressive tauopathy. The early, extensive tau spread in symptomatic EOAD, even at an early clinical stage, may also limit the efficacy of anti‐amyloid‐beta therapies in this population
Governing Choice: A Critical Policy Analysis of Charter Schools in Indianapolis Through the Lens of Governmentality
No full textIUIUtilizing the theoretical framework of Michel Foucault’s “Governmentality” and the methodology of Critical Policy Analysis, this research addresses the question of how charter school policies reflect and reinforce governmental rationalities and power structures in Indianapolis, Indiana. The purpose of this research is to examine how charter school policies in Indianapolis reinforce neoliberal forms of governance through mechanisms of policy discourse, accountability structures, and market-based reforms. This study addresses a critical gap in education policy research, examining how power operates through policy discourse and governance practices. The research informs scholarship and practice by highlighting hidden power dynamics embedded in policy design, interpretation, and implementation, and by questioning the democratic consequences of market-based educational reform. Anchored in the 2001 Indiana General Assembly legislation – specifically, Senate Bill 165 - this study finds that this policy led to the dramatic growth of charter schools in Indianapolis, incorporating logics of marketization, surveillance, and entrepreneurial governance into the public education system. Implications of these findings are significant because such policies ensure, sustain, and sanitize racial and socioeconomic stratification while making virtually zero impact on the quality of learning outcomes for children, especially those in urban low-income enclaves. This research suggests an opportunity to develop more participatory, inclusive, and democratic approaches to regulating education policy
Sotatercept in Pulmonary Langerhans Cell Histiocytosis‐Associated Pulmonary Hypertension: A Case Series and Systematic Review
No full textPulmonary Langerhans cell histiocytosis (PLCH) frequently complicated by pulmonary hypertension (PH), which markedly worsens prognosis. We retrospectively reviewed three institutional PLCH-PH cases treated with off-label Sotatercept added to background triple therapy and performed a systematic review of published PLCH-PH reports (PubMed/Embase through May 2025). Our three patients (ages 69, 62, 49; all female) had progressive vascular disease despite optimized vasodilator therapy. Following Sotatercept, all experienced ≥ 3-fold increases in 6-min walk distance and improved functional class. Hemodynamics improved substantially: right-atrial pressure -78.6%, pulmonary vascular resistance -75.5%, pulmonary artery systolic pressure -58.5%, mean PAP - 56.0%, PA diastolic pressure -51.0%, PAWP - 47.1%; cardiac output and index rose +75.9% and +73.8%, respectively. BNP/NT-proBNP normalized. Systematic review identified 34 published cases (2010-2025): mean age 37.2 ± 13.7 years, 44.1% female, 45.7% current/former smokers. Reported management strategies included targeted vasodilators, cytotoxic PLCH therapies (e.g., cladribine), smoking cessation, and selective surgery/transplant. In this small series, Sotatercept added to background therapy produced marked clinical and hemodynamic gains in refractory PLCH-PH. These effects of Sotatercept in Group 5 PH-are encouraging but limited by sample size and retrospective design. Prospective, collaborative studies are needed to define safety, efficacy, and optimal patient selection
myAURA: a personalized health library for epilepsy management via knowledge graph sparsification and visualization
No full textObjectives: Report the development of the patient-centered myAURA application and suite of methods designed to aid epilepsy patients, caregivers, and clinicians in making decisions about self-management and care.
Materials and methods: myAURA rests on an unprecedented collection of epilepsy-relevant heterogeneous data resources, such as biomedical databases, social media, and electronic health records (EHRs). We use a patient-centered biomedical dictionary to link the collected data in a multilayer knowledge graph (KG) computed with a generalizable, open-source methodology.
Results: Our approach is based on a novel network sparsification method that uses the metric backbone of weighted graphs to discover important edges for inference, recommendation, and visualization. We demonstrate by studying drug-drug interaction from EHRs, extracting epilepsy-focused digital cohorts from social media, and generating a multilayer KG visualization. We also present our patient-centered design and pilot-testing of myAURA, including its user interface.
Discussion: The ability to search and explore myAURA's heterogeneous data sources in a single, sparsified, multilayer KG is highly useful for a range of epilepsy studies and stakeholder support.
Conclusion: Our stakeholder-driven, scalable approach to integrating traditional and nontraditional data sources enables both clinical discovery and data-powered patient self-management in epilepsy and can be generalized to other chronic conditions
P-242. The Association of Steatotic Liver Disease and Cardiovascular Disease Risk in a Large Cohort of People with Human Immunodeficiency Virus
No full textBackground:
Steatotic liver disease (SLD), metabolic dysfunction-associated liver disease (MASLD) ± alcohol-associated liver disease (MetALD), is common in people with HIV (PWH) and associated with increased cardiovascular disease (CVD). According to SLD status, we assessed CVD risk in PWH without known CVD using validated models.
Odds ratio for 10-unit increase in risk and 95% confidence interval for 5 cardiovascular risk scores: Pairwise comparisons between steatotic liver disease (SLD) groups.
Methods:
Adult PWH with suppressed HIV and no heavy alcohol use were enrolled at 8 US centers. Steatosis and alcohol were assessed by elastography controlled attenuated parameter (CAP) and AUDIT, respectively. Cardiometabolic risk factors (CMRF) were BMI ≥25 kg/m2 or waist circumference ( >94 cm males, >80 cm females); fasting glucose ≥100 mg/dL, HbA1c ≥5.7%, type 2 diabetes, or medications; blood pressure ≥130/85 mmHg or medications; serum triglycerides ≥150 mg/dL or medications; HDL cholesterol ≤40 men /50 women mg/dL or medications. PWH were classified as: No SLD (CAP< 263 dB/m), MASLD (CAP ≥263 dB/m + ≥1 CMRF + no alcohol), or MetALD (CAP ≥263 dB/m + ≥1 CMRF + moderate alcohol ). 10-year CVD risk was assessed by three models: Framingham CVD, 2013 ASCVD, and PREVENT scores for total CVD, ASCVD, and heart failure. Those without SLD were compared to MASLD and MetALD.
Results:
Of 991 eligible PWH, the prevalence of MASLD was 40% and MetALD was 9%. Four CMRFs were present in 55% of those with MASLD compared to 29% without SLD. Those with MASLD had a higher mean PREVENT total CVD score than those without SLD (8.7 vs. 7.1; P=0.002) and a higher mean PREVENT ASCVD score (8.7 vs. 7.1; P=0.002) and mean PREVENT heart failure score (6.0 vs. 4.5; P=0.001). Those with MASLD also had higher mean risk than those without SLD by mean Framingham CVD score (10.4 vs. 8.8; P< 0.001) and 2013 ASCVD score (10.8 vs. 9.1; P=0.01). PWH and MetALD and those without SLD had similar CVD risk scores. Estimated high total CVD risk (≥20%) was lower with PREVENT (7%) compared to Framingham (23%) or 2013 ASCVD (12%).
Conclusion:
Multiple CMRFs are common in PWH and MASLD. PREVENT scores estimated higher 10-year CVD, ASCVD, and heart failure risk in those with MASLD versus those without SLD. Compared to other models, fewer PWH had high CVD risk with PREVENT. Further research is needed to validate PREVENT in PWH
Critical views for safe surgical phase progression in endoscopic endonasal transsphenoidal pituitary adenoma resection: modified Delphi consensus
No full textPurpose: Endonasal transsphenoidal surgery is the gold-standard for pituitary adenoma resection, yet no intraoperative framework exists to confirm safe phase progression. Inspired by the Critical View of Safety in laparoscopic cholecystectomy and engineering “phase-gate” process, we propose the Critical Views for Phase Progression (CVPPs) – a set of visual cues confirming phase objectives and safe phase progression. Designed to be clinically relevant and machine-readable, CVPPs aim to support training and future AI-driven guidance systems.
Methods: A three-round modified Delphi process was conducted involving 15 pituitary surgery experts from 13 centres across Europe and North America. CVPPs for the naso-sphenoid, sellar, and closure phases were classified as “Essential”, “Desirable” or “Not Necessary”. Consensus required ≥ 70% agreement. A local validation study was subsequently performed involving six experts who reviewed 15 intraoperative video clips and rated their confidence to proceed, which was compared against the predefined reference derived from the finalised CVPPs.
Results: Consensus identified essential and desirable CVPPs across all three phases for both micro- and macroadenoma variants, reflecting differences in exposure goals and surgical risk. Validation demonstrated high concordance between participant ratings and predefined references. Discrepancies arose only in a minority of intentionally incomplete (“unsafe”) views and were attributable to contextual misinterpretation of short video segments, rather than disagreement with the CVPP framework.
Conclusion: This international, multicentre consensus is the first to define CVPPs. By standardising intraoperative visual benchmarks, CVPPs can enhance training, mitigate risks, and provide a foundation for future AI-driven guidance systems capable of real-time anatomical annotation and decision support
Plasma Biomarker Association with Cognition in Uganda
No full textBackground:
Over 60% of individuals with ADRDs live in low‐ and middle‐income countries (LMICs). Sub‐Saharan Africa (SSA) is projected to have the fastest growth in older adults, including people living with HIV (PLWH). Plasma ADRD biomarkers are promising diagnostic tools, but studies have been limited to the Global North. We evaluated the association of plasma ADRD biomarkers with cognition in the Uganda Aging Cohort Study (UACS), a prospective cohort of PLWH on antiretroviral therapy and demographically similar HIV‐uninfected individuals recruited via population‐sampling approaches.
Method:
Blood samples were collected in EDTA tubes, centrifuged, aliquoted, and frozen at ‐80°C at semi‐urban (n = 320) and rural (n = 330) sites. Plasma was shipped to the UTHSA Biggs Laboratory. p‐tau217, Aβ42/40, and p‐tau217/Aβ42 were measured on Fujirebio Lumipulse, and GFAP and NfL on Quanterix Simoa. Rural site Aβ42/40 and p‐tau217/Aβ42 did not pass quality control due to cold‐chain storage complications and were excluded from this analysis. Cognitive evaluations used locally validated tests. Raw scores were converted to regression‐based Z‐scores and averaged at the domain and overall level. Jak/Bondi criteria defined presence/absence of cognitive impairment. Multivariable regressions assessed associations between log‐transformed plasma biomarkers and cognitive outcomes adjusting for age, sex, education, site, and eGFR. Sensitivity analyses adjusted for HIV serostatus.
Result:
560 total participants (49% PLWH) were included, and average age was 60.3 years (Table 1). Elevated plasma NfL was associated with worse overall cognition, learning/memory, attention, executive function, and motor performance (Table 2). Elevated plasma GFAP was associated with worse executive function and 62% higher odds of cognitive impairment in this domain. Plasma p‐tau217, Aβ42/40, and p‐tau217/Aβ42 were not associated with cognition. Results were consistent in sensitivity analyses adjusted for HIV serostatus.
Conclusion:
Plasma NfL and GFAP are promising biomarkers associated with cognition in adults residing in Uganda, including in PLWH. The lack of association between plasma p‐tau217 and cognition suggests that cognitive impairment in this younger cohort is being driven by non‐Alzheimer disease etiologies. Further studies in diverse global populations are needed to inform appropriate use of new biology‐based diagnostic criteria for AD and to identify methods that do not require sample storage to expand access to LMICs
Parent-Adolescent Relationship Quality, Sexual Health Communication, and Willingness to Support Pre-Exposure Prophylaxis for HIV: A Qualitative Study
No full textPurpose: Pre-exposure prophylaxis (PrEP) for HIV is a safe and highly effective prevention method, yet use among U.S. adolescents at risk for HIV has been low. Little is known about how sexual health communication (SHC) and the quality of parent-adolescent relationships influence parents' hypothetical willingness to support their adolescent using PrEP.
Methods: We conducted 34 in-depth interviews with parents of adolescents recruited from four U.S. urban clinical sites between 2018 and 2019. We then used applied thematic analysis informed by two theories to determine parents' hypothetical willingness (more vs. less willing) and to identify related themes, focusing on differences between more versus less willing parents.
Results: Parents were diverse with respect to race/ethnicity (68% Black/African American, 18% Hispanic). Most were cisgender men (44%) or women (41%). Approximately half (n = 19, 56%) were more willing. Four themes related to willingness were identified: (1) relationship quality, (2) acceptance of sexual and gender-diverse (SGD) identities, (3) sex positivity of SHC, and (4) general positivity about PrEP. Responses from more willing parents tended toward higher relationship quality, more acceptance of SGD identities, more sex positivity, and PrEP positivity; conversely, less willing parents tended toward the opposite ends of each theme. HIV risk perception did not consistently impact willingness, as both more and less willing parents largely perceived their adolescent's HIV risk as low.
Discussion: Parents who were more willing to support their adolescent hypothetically using PrEP tended to describe high-quality relationships, acceptance of SGD identities, sex positivity of SHC, and general positivity about PrEP
The craniofacial shape of modern humans embodies genomic signatures of evolution, diversity, and clinical conditions
No full textHuman craniofacial morphology is a hallmark of our species' diversity and evolutionary history, shaped by adaptation, introgression, and global dispersal. Cranial globularization and chin emergence are well-documented morphological transformations whose genetic basis remains poorly understood, whereas Neandertal introgression is primarily documented through genomic evidence. How these evolutionary phenomena relate to craniofacial variation in present-day humans remains largely unresolved. Here, we leverage 3D craniofacial data from over 50,000 UK Biobank participants and employ a multivariate, multiscale genome-wide association approach to define axes of variation aligned with interpopulation allele frequency shifts, evolutionary processes, and clinical conditions. We identify continuous craniofacial trends within our cohort that mirror global patterns of genetic diversity, indicating that facial differences between human populations arise at the phenotypic axes already present within a single population. We further demonstrate that modern human-derived alleles underlie the origins of the human chin by reducing midfacial projection relative to other hominins and reveal the persistent effects of Neandertal introgression on craniofacial diversity today. We also model genetically informed endophenotypes for orofacial clefts, obstructive sleep apnoea, and myopia. These findings provide insights into our species' evolutionary history and endophenotypes of clinical conditions and establish a framework for contextualizing craniofacial diversity into biologically meaningful axes of variation relevant to diverse scientific disciplines
Dementia, cognitive impairment in Nigerians aged 90 years or older: A 20-year follow up of survivors of Ibadan study of aging cohort
No full textObjective: Studies of dementia involving the oldest old are few in Sub-Saharan Africa. Survivors of the Ibadan arm of the Indianapolis-Ibadan Dementia Project who were enrolled in 1992 or 2001 were re-examined between 2021 and 2022.
Aim: To revisit these subjects and evaluate them for the presence of cognitive and functional impairment and assign diagnoses as relevant as well as determine factors that mitigate development of dementia and cognitive impairment and thus promote healthy aging.
Design: Evaluation consisted of the CERAD neuropsychological battery, an informant interview, and a clinical examination by physicians with expertise in cognitive disorders of aging. Diagnoses were adjudicated by consensus between psychiatrists and neurologists using ICD-10 and DSM-IV criteria and diagnosis of Mild Cognitive Impairment based on the National Institute of Aging- criteria RESULT: One hundred and thirty-five of the original 4425 persons ever recruited were re-evaluated. Mean age was 93·0±2·8 years (range 89-106 years); 103 (76 %) were females, 29 (21 %) were diagnosed dementia, 25 (18 %) had AD, 44 (32·6 %) had diagnosis of Mild Cognitive Impairment (MCI) and 62 (45·9 %) were cognitively normal. Using logistic regression model for the combined dementia and MCI group with predictor variables collected during the 2001 evaluation wave, we found that cognitive score (Odds Ratio (OR)= 0·94, p = 0·024 (95 % CI:0.09-0.99), diastolic blood pressure (OR=1·04, p = 0·015 (95 % CI:1.01-1.07) and regular alcohol use (OR=0·42, p = 0·041(95 % CI:0.18-0.96) were associated with 20-year prevalence of cognitive impairment after adjusting for age, sex, and education. ApoE4 allele was neither a risk factor for dementia nor Cognitive Impairment in this cohort.
Conclusion: Prevalence of cognitive impairment in this oldest old survivor cohort was associated with cognitive performance, diastolic blood pressure and regular use of alcohol 20 years before