ScholarWorks shares over 50,000 articles, working papers, chapters, presentations, posters, theses, historical documents and other items submitted by members of the IU Indianapolis campus community.
Get started! Login with your IU credentials to share freely with 2 million readers per year.
Communities in ScholarWorks
Select a community to browse its collections.
Recent Submissions
The Role of Cardiovascular Risk Factors in White Matter Tract Microstructure: A Multi‐Cohort Study in Older Adults
(Wiley, 2026-01-09) LeFevre, James D.; Vyas, Yukti; Sathe, Aditi; Shashikumar, Niranjana; Pechman, Kimberly R.; Yang, Yisu; Durant, Alaina; Kanakaraj, Praitayini; Kim, Michael E.; Gao, Chenyu; Newlin, Nancy R.; Ramadass, Karthik; Khairi, Nazirah Mohd; Li, Zhiyuan; Yao, Tianyuan; Risacher, Shannon L.; Zhang, Panpan; Schilling, Kurt; Kukull, Walter W.; Biber, Sarah; Landman, Bennett A.; Bendlin, Barbara B.; Johnson, Sterling C.; Schneider, Julie A.; Barnes, Lisa L.; Bennett, David A. A.; Saykin, Andrew J.; Cuccaro, Michael L.; Hohman, Timothy J.; Jefferson, Angela L.; Archer, Derek B.; Alzheimer's Disease Neuroimaging Initiative (ADNI); The Alzheimer's Disease Sequencing Project (ADSP); The ADSP Phenotype Harmonization Consortium; Radiology and Imaging Sciences, School of Medicine
Background:
Vascular risk factors (VRF) exert deleterious effects on the vasculature throughout the body, including cerebrovasculature. These effects are characterized by structural and functional alterations in the cerebrovasculature, which in turn, may impact white matter (WM) microstructure. We sought to determine the relative contributions of VRF to alterations in WM tract microstructure in a large, multi‐study cohort using diffusion tensor imaging (DTI).
Method:
We collated datasets from the Vanderbilt Memory and Aging Project (VMAP) and several Alzheimer's Disease (AD) Sequencing Project‐Phenotype Harmonization Consortium (ADSP‐PHC) cohorts, including diffusion magnetic resonance imaging and VRF (n = 1,304, 72.3±9.5 years, 53% female). ADSP‐PHC cohorts included in this study were the AD Neuroimaging Initiative (ADNI), the National Alzheimer's Coordinating Center (NACC), the Religious Orders Study/Rush Memory and Aging Project/Minority Aging Research Study (ROS/MAP/MARS), and the Wisconsin Registry of Alzheimer's Prevention (WRAP). To assess the contributions of VRF to WM microstructure, we quantified the cross‐sectional association between VRF and white matter microstructure. Specifically, VRF were used to predict differences in free‐water (FW) and fractional anisotropy (FAFWcorr) across 10 AD‐relevant WM tracts. VRF variables studied included hypertension, diabetes, heart disease, body mass index (BMI), and Atherosclerotic Cardiovascular Disease Framingham Risk Score (FRS). Covariates included age, sex, education, race, apolipoprotein E‐ɛ4 status, and cognitive status. Models were corrected for multiple comparisons using the FDR approach.
Result:
Hypertension and heart disease were significantly associated with FAFWcorr in all tracts, while FRS was a significant predictor for FAFWcorr in 9/10 tracts (top associations shown in Figure 1). Diabetes and BMI were not significant predictors for FAFWcor in any of the tracts. Hypertension was a significant predictor for FW in all tracts, and FRS was a significant predictor only in the cingulum. Diabetes, BMI, and heart disease were not significant predictors for FW in any of the tracts.
Conclusion:
This study demonstrates that VRF, especially hypertension, heart disease, and FRS, differentially impact WM tract microstructure, providing insight into their unique contributions to WM microstructure in a large multi‐cohort of older adults. These findings underscore the critical importance of managing vascular risk factors to preserve white matter integrity to potentially prevent cognitive decline.
The Relative Contribution of Amyloid, Tau, Neurodegeneration, and Vascular Disease to Cognition and Cognitive Decline: A Cross‐National Study
(Wiley, 2026-01-08) Tanner, Jeremy A.; Chen, Diefei; Byun, Min Soo; De Anda‐Duran, Ileana; Deters, Kacie D.; Elbejjani, Martine; Fletcher, Evan; Kraal, A. Zarina; Lee, Dong Young; Mejia‐Arango, Silvia; Pina‐Escudero, Stefanie D.; Nho, Kwangsik; Robinson, Talia L.; Shaaban, C. Elizabeth; Staffaroni, Adam M.; Yu, Meichen; Saykin, Andrew J.; Crane, Paul K.; Yi, Dahyun; Risacher, Shannon L.; ADNI; KBASE; Radiology and Imaging Sciences, School of Medicine
Background:
Recent in vivo biomarker advancements have led to biological diagnostic and staging criteria for AD based on amyloid(“A”), tau(“T”), and neurodegeneration(“N”). However, the contribution of comorbid vascular(“V”) pathology and the relative influence of ATNV on cognitive performance and decline remains unclear, though is necessary to guide personalized diagnosis, prognosis, and care. We assessed the relative contribution of neuroimaging‐based ATNV measures to cognition in cross‐national studies.
Method:
Amyloid PET, tau PET, MRI, cognitive testing, and clinical evaluations were obtained in two prospective cohort studies with similar designs: ADNI3 in the US (n = 508; mean age=71±7, female=55%, education(yrs)=16.5±2.3) and KBASE in South Korea (n = 165; age=73±8, female=64%, education(yrs)=11.0±4.6). Continuous ATNV predictors included A=cortical centiloids, T=meta‐temporal SUVR, N = AD‐signature cortical thickness, and V=white matter hyperintensity volume. Clinical diagnoses of cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia were determined by clinical consensus. Cognitive testing was obtained annually with up to 4 years of follow‐up, and factor scores in each cognitive domain were used as outcomes. Parallel cross‐sectional analyses were performed within each cohort. ANOVA was performed to compare ATNV across clinical diagnoses. Multivariable linear mixed‐effect models were used to assess the association of baseline ATNV predictors with baseline and longitudinal cognitive outcomes adjusting for age, sex, education, and APOE status.
Result:
A, T, N, and V as continuous (mean) and binary (frequency of positivity) variables increased with clinical disease severity in both ADNI and KBASE (Table 1). In ADNI, T and N were associated with lower intercepts in each cognitive domain, V was associated with visuospatial and executive function intercepts, and A with the memory intercept (Table 2). Higher baseline T was associated with decline in each domain, and A was associated with memory decline. In KBASE, T was associated with lower memory and visuospatial intercepts, and N with visuospatial and executive function intercepts (Table 3). No factors (ATNV) were associated with cognitive decline over time in KBASE.
Conclusion:
Among ATNV measures, T and N are most strongly associated with cognition in individuals in the US and South Korea. T is most predictive of future cognitive decline in individuals in the US, though not replicated in Korea.
Impact of Mobile Stroke Units on Patients With Large Vessel Occlusion Acute Ischemic Stroke: A Prespecified BEST-MSU Substudy
(American Heart Association, 2023-12-19) Czap, Alexandra L.; Alexandrov, Anne W.; Nour, May; Yamal, Jose-Miguel; Wang, Mengxi; Jacob, Asha P.; Parker, Stephanie A.; Tariq, Muhammad Bilal; Rajan, Suja S.; Alexandrov, Andrei V.; Jones, William J.; Navi, Babak B.; Spokoyny, Ilana; Mackey, Jason; Lerario, Mackenzie P.; Gonzalez, Michael O.; Singh, Noopur; Bowry, Ritvij; Grotta, James C.; Neurology, School of Medicine
Background: The impact of mobile stroke units (MSUs) on outcomes in patients with large vessel occlusions eligible for endovascular thrombectomy (EVT) has yet to be characterized.
Methods: We completed a prespecified substudy of patients with EVT-eligible stroke with anterior and posterior circulation large vessel occlusions on computed tomography and/or computed tomography angiography who were enrolled in BEST-MSU (Benefits of Stroke Treatment using a Mobile Stroke Unit). Primary outcome was 90-day utility-weighted modified Rankin scale. Groups were compared using chi-square or Fisher's exact tests for categorical variables, and 2-sample t-tests for continuous variables. Multiple logistic regression was used to assess the effect of MSU on binary outcomes after adjusting for other baseline factors.
Results: Of 1515 trial patients, 293 had large vessel occlusions eligible for EVT: 168 in the MSU group and 125 in the emergency medical services group. Baseline characteristics were comparable, with the exception of baseline National Institutes of Health Stroke Scale score (MSU median 19 [interquartile range 13, 23] versus emergency medical services 16 [11, 20], P = 0.002) and study site. The mean (±SD) score on the utility-weighted modified Rankin scale at 90 days was 0.63±0.39 in MSU group and 0.51±0.41 in emergency medical services group (mean difference 0.13, 95% CI [0.03-0.22]). After adjustment, MSU had significantly higher odds of functional independence (odds ratio 2.60 [95% CI, 1.45-4.77], P = 0.002). Secondary outcomes also favored MSU: early neurologic recovery (30% improvement in National Institutes of Health Stroke Scale score at 24 hours) 68% versus 52%; adjusted odds ratio 1.98 [95% CI, 1.19-3.33]; time of tissue plasminogen activator bolus from symptom onset 65.0 minutes [50.5-92.0] versus 96.0 [79.3-130.0], P≤0.001. The groups had similar onset to arterial puncture (169.0 minutes [133.5, 210.0] versus 162.0 [135.0-207.0], P = 0.83).
Conclusions: In patients with EVT-eligible large vessel occlusion stroke, MSU management was associated with better clinical outcomes compared with standard emergency medical services management. MSU management sped thrombolysis but did not expedite EVT treatment times. Future MSU processes should include efforts to capitalize on the potential of MSUs to provide earlier EVT.
Acute blood biomarker responses to consensual sexual choking/strangulation in young adult women: a randomized crossover study
(Frontiers Media, 2026-01-08) Sweeney, Sage H.; Recht, Grace O.; Lima-Cooper, Giselle; Datta, Dibyadyuti; Buddenbaum, Claire V.; Day, Harper; Buehler, Bella; Huibregtse, Megan E.; Herbenick, Debby; Kawata, Keisuke; Pediatrics, School of Medicine
Introduction: Sexual strangulation, commonly referred to as "choking", has become increasingly common among young adults, yet its neurobiological consequences remain poorly understood. Preclinical and clinical evidence suggests strangulation may trigger axonal injury, neuroinflammation, and blood-brain barrier dysfunction. Blood biomarkers of neural injury and inflammation provide a sensitive means to detect subtle effects.
Aim: To examine whether consensual sexual choking/strangulation acutely alters blood biomarkers of neural injury and inflammation compared to non-choking sexual activity in young adult women.
Methods: In a randomized crossover study, 29 women (mean age 21.5 ± 2.7) completed three laboratory visits: baseline (≥24 h abstinence), post-choking sex, and post-non-choking sex. Blood was collected within 24 h of sexual events. Neural injury biomarkers (NfL, tau, GFAP, UCH-L1, S100B) and inflammatory markers (IL-1ra, TNF-R1, CCL-2, VEGF-A, VCAM-1) were analyzed using Quanterix and Luminex multiplex immunoassays. Mixed-effects regression models tested exposure-by-time interactions, adjusting for age and brain trauma history.
Results: Neurofilament light (NfL) significantly increased after choking-involved sex but remained unchanged after non-choking, which resulted in a statistically significant exposure-by-time interaction [β = -0.21, 95% CI (-0.38, -0.03), p = 0.021]. Other neural biomarkers did not differ by exposure. Among inflammatory markers, CCL-2 and VEGF-A demonstrated a similar pattern as NfL, with acute increases after choking-involved sex, but not following non-choking sex, yielding in exposure-by-time interaction effects (CCL-2: β = -14.60, 95% CI [-25.70, -3.43, p = 0.011; VEGF-A: β = -9.29 (-19.71, 1.13), p = 0.079]. IL-1ra, TNF-R1, and VCAM-1 remained stable.
Discussion: Consensual sexual strangulation elicited acute increases in NfL and CCL-2, with VEGF-A showing a similar pattern, suggesting transient axonal stress and hypoxia-related inflammatory signaling. These findings indicate that sexual choking/strangulation, even in consensual contexts, may have subtle, yet detectable cellular burden. Future studies with larger samples, refined temporal sampling, and multimodal outcomes are needed to clarify short- and long-term implications.
Risk biomarkers of chronic GVHD in children aged 10 years or younger and children/adults older than 10 years
(American Society of Hematology, 2026) Ferreira, Anna C.; Dutta, Debjani; Rowan, Courtney M.; Renbarger, Jamie; Cooke, Kenneth R.; Carpenter, Paul A.; Krance, Robert; Duncan, Christine; Cruz, C. Russell Y.; Jacobsohn, David; Bollard, Catherine M.; Hill, Elizabeth; Paczesny, Sophie; Pediatrics, School of Medicine
Assessment of risk biomarkers of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT) in pediatric patients is lacking. We conducted a prospective study of 318 patients (129 children aged ≤10 years and 189 children/adults aged >10 years). Six plasma biomarkers (C-X-C motif chemokine ligand 9 [CXCL9], interleukin-1 receptor-like 1 [IL1RL1], regenerating islet-derived 3-α [REG3α], matrix metallopeptidase-3 [MMP3], dickkopf-WNT signaling pathway inhibitor-3 [DKK3], and sCD163) were assessed at day 100 after HCT. We performed day-100 landmark analyses for cGVHD, stratifying at age ≤10 years vs >10 years and dichotomizing markers using the Youden index. IL1RL1 associated with future cGVHD in both age groups, as did DKK3. CXCL9, REG3α, and MMP3 are associated with cGVHD in patients aged >10 years. This 5-marker panel has an area under the curve (AUC) of 0.71 in children aged ≤10 years and 0.72 in children/adults aged >10 years for cGVHD risk, and an AUC of 0.86 in children aged ≤10 years and 0.80 in children/adults aged >10 years for moderate/severe cGVHD risk. A 5-biomarker panel (IL1RL1, REG3α, MMP3, DKK3, and sCD163) was associated with transplant-related mortality (TRM) in both age groups. Biomarkers measured 3 months post-HCT predict susceptibility and/or are prognostic for cGVHD and TRM in both children aged ≤10 years and children/adults aged >10 years, allowing for additional risk stratification.