Publications [#352411] of Marty G. Woldorff

Journal Articles

1. VanDusen, KW; Eleswarpu, S; Moretti, EW; Devinney, MJ; Crabtree, DM; Laskowitz, DT; Woldorff, MG; Roberts, KC; Whittle, J; Browndyke, JN; Cooter, M; Rockhold, FW; Anakwenze, O; Bolognesi, MP; Easley, ME; Ferrandino, MN; Jiranek, WA; Berger, M; MARBLE Study Investigators, (2020). The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction.. J Alzheimers Dis, 75(4), 1319-1328. [doi]
   (last updated on 2023/06/01)

   Abstract:
   BACKGROUND: Perioperative neurocognitive disorders (PND) are common complications in older adults associated with increased 1-year mortality and long-term cognitive decline. One risk factor for worsened long-term postoperative cognitive trajectory is the Alzheimer's disease (AD) genetic risk factor APOE4. APOE4 is thought to elevate AD risk partly by increasing neuroinflammation, which is also a theorized mechanism for PND. Yet, it is unclear whether modulating apoE4 protein signaling in older surgical patients would reduce PND risk or severity. OBJECTIVE: MARBLE is a randomized, blinded, placebo-controlled phase II sequential dose escalation trial designed to evaluate perioperative administration of an apoE mimetic peptide drug, CN-105, in older adults (age≥60 years). The primary aim is evaluating the safety of CN-105 administration, as measured by adverse event rates in CN-105 versus placebo-treated patients. Secondary aims include assessing perioperative CN-105 administration feasibility and its efficacy for reducing postoperative neuroinflammation and PND severity. METHODS: 201 patients undergoing non-cardiac, non-neurological surgery will be randomized to control or CN-105 treatment groups and receive placebo or drug before and every six hours after surgery, for up to three days after surgery. Chart reviews, pre- and postoperative cognitive testing, delirium screening, and blood and CSF analyses will be performed to examine effects of CN-105 on perioperative adverse event rates, cognition, and neuroinflammation. Trial results will be disseminated by presentations at conferences and peer-reviewed publications. CONCLUSION: MARBLE is a transdisciplinary study designed to measure CN-105 safety and efficacy for preventing PND in older adults and to provide insight into the pathogenesis of these geriatric syndromes.