Browsing by Author "Whitlow, Christopher T."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Associations among plasma, MRI, and amyloid PET biomarkers of Alzheimer's disease and related dementias and the impact of health‐related comorbidities in a community‐dwelling cohort
    (Wiley, 2024) Rudolph, Marc D.; Sutphen, Courtney L.; Register, Thomas C.; Whitlow, Christopher T.; Solingapuram Sai, Kiran K.; Hughes, Timothy M.; Bateman, James R.; Dage, Jeffrey L.; Russ, Kristen A.; Mielke, Michelle M.; Craft, Suzanne; Lockhart, Samuel N.; Neurology, School of Medicine
    Introduction: We evaluated associations between plasma and neuroimaging-derived biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities. Methods: We examined plasma biomarkers (neurofilament light chain, glial fibrillary acidic protein, amyloid beta [Aβ] 42/40, phosphorylated tau 181) and neuroimaging measures of amyloid deposition (Aβ-positron emission tomography [PET]), total brain volume, white matter hyperintensity volume, diffusion-weighted fractional anisotropy, and neurite orientation dispersion and density imaging free water. Participants were adjudicated as cognitively unimpaired (CU; N = 299), mild cognitive impairment (MCI; N = 192), or dementia (DEM; N = 65). Biomarkers were compared across groups stratified by diagnosis, sex, race, and APOE ε4 carrier status. General linear models examined plasma-imaging associations before and after adjusting for demographics (age, sex, race, education), APOE ε4 status, medications, diagnosis, and other factors (estimated glomerular filtration rate [eGFR], body mass index [BMI]). Results: Plasma biomarkers differed across diagnostic groups (DEM > MCI > CU), were altered in Aβ-PET-positive individuals, and were associated with poorer brain health and kidney function. Discussion: eGFR and BMI did not substantially impact associations between plasma and neuroimaging biomarkers. Highlights: Plasma biomarkers differ across diagnostic groups (DEM > MCI > CU) and are altered in Aβ-PET-positive individuals. Altered plasma biomarker levels are associated with poorer brain health and kidney function. Plasma and neuroimaging biomarker associations are largely independent of comorbidities.
  • Thumbnail Image
    Item
    Misleading Public Statements About COVID-19
    (Elsevier, 2021-01-01) Meltzer, Carolyn C.; Wiggins, Richard H.; Mossa-Basha, Mahmud; Palasis, Susan; Russell, Eric; Mikulis, David; Rhyner, Patricia; Anderson, James; Peterson, Ryan B.; Smirniotopoulos, James; Barkovich, A. James; Zimmerman, Robert D.; Filippi, Christopher G.; Rowley, Howard A.; Koontz, Nicholas A.; Jay, Ann K.; Nickerson, Joshua; Hamilton, Bronwyn; Chow, Daniel; Whitlow, Christopher T.; Radiology and Imaging Sciences, School of Medicine
  • Thumbnail Image
    Item
    Multi-Omics Analysis of Brain Metastasis Outcomes Following Craniotomy
    (Frontiers Media, 2021-04-06) Su, Jing; Song, Qianqian; Qasem, Shadi; O’Neill, Stacey; Lee, Jingyun; Furdui, Cristina M.; Pasche, Boris; Metheny-Barlow, Linda; Masters, Adrianna H.; Lo, Hui-Wen; Xing, Fei; Watabe, Kounosuke; Miller, Lance D.; Tatter, Stephen B.; Laxton, Adrian W.; Whitlow, Christopher T.; Chan, Michael D.; Soike, Michael H.; Ruiz, Jimmy; Biostatistics, School of Public Health
    Background: The incidence of brain metastasis continues to increase as therapeutic strategies have improved for a number of solid tumors. The presence of brain metastasis is associated with worse prognosis but it is unclear if distinctive biomarkers can separate patients at risk for CNS related death. Methods: We executed a single institution retrospective collection of brain metastasis from patients who were diagnosed with lung, breast, and other primary tumors. The brain metastatic samples were sent for RNA sequencing, proteomic and metabolomic analysis of brain metastasis. The primary outcome was distant brain failure after definitive therapies that included craniotomy resection and radiation to surgical bed. Novel prognostic subtypes were discovered using transcriptomic data and sparse non-negative matrix factorization. Results: We discovered two molecular subtypes showing statistically significant differential prognosis irrespective of tumor subtype. The median survival time of the good and the poor prognostic subtypes were 7.89 and 42.27 months, respectively. Further integrated characterization and analysis of these two distinctive prognostic subtypes using transcriptomic, proteomic, and metabolomic molecular profiles of patients identified key pathways and metabolites. The analysis suggested that immune microenvironment landscape as well as proliferation and migration signaling pathways may be responsible to the observed survival difference. Conclusion: A multi-omics approach to characterization of brain metastasis provides an opportunity to identify clinically impactful biomarkers and associated prognostic subtypes and generate provocative integrative understanding of disease.