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5 Associations Between Regional Perfusion and Locus Coeruleus MRI Contrast are Moderated by Plasma Alzheimer’s Disease Biomarkers in Older Adults
- Shubir Dutt, Shelby L Bachman, Yanrong Li, Belinda Yew, Jung Y Jang, Jean K Ho, Kaoru Nashiro, Jungwon Min, Hyun Joo Yoo, Aimee Gaubert, Amy Nguyen, Isabel J Sible, Anna E Blanken, Anisa J Marshall, Arunima Kapoor, John P Alitin, Kim Hoang, Alessandra C Martini, Elizabeth Head, Xingfeng Shao, Danny J J Wang, Mara Mather, Daniel A Nation
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 610-611
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- Article
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Objective:
The locus coeruleus (LC) innervates the cerebrovasculature and plays a crucial role in optimal regulation of cerebral blood flow. However, no human studies to date have examined links between these systems with widely available neuroimaging methods. We quantified associations between LC structural integrity and regional cortical perfusion and probed whether varying levels of plasma Alzheimer’s disease (AD) biomarkers (Aß42/40 ratio and ptau181) moderated these relationships.
Participants and Methods:64 dementia-free community-dwelling older adults (ages 55-87) recruited across two studies underwent structural and functional neuroimaging on the same MRI scanner. 3D-pCASL MRI measured regional cerebral blood flow in limbic and frontal cortical regions, while T1-FSE MRI quantified rostral LC-MRI contrast, a well-established proxy measure of LC structural integrity. A subset of participants underwent fasting blood draw to measure plasma AD biomarker concentrations (Aß42/40 ratio and ptau181). Multiple linear regression models examined associations between perfusion and LC integrity, with rostral LC-MRI contrast as predictor, regional CBF as outcome, and age and study as covariates. Moderation analyses included additional terms for plasma AD biomarker concentration and plasma x LC interaction.
Results:Greater rostral LC-MRI contrast was linked to lower regional perfusion in limbic regions, such as the amygdala (ß = -0.25, p = 0.049) and entorhinal cortex (ß = -0.20, p = 0.042), but was linked to higher regional perfusion in frontal cortical regions, such as the lateral (ß = 0.28, p = 0.003) and medial (ß = 0.24, p = 0.05) orbitofrontal (OFC) cortices. Plasma amyloid levels moderated the relationship between rostral LC and amygdala CBF (Aß42/40 ratio x rostral LC interaction term ß = -0.31, p = 0.021), such that as plasma Aß42/40 ratio decreased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and amygdala perfusion decreased. Plasma ptau181levels moderated the relationship between rostral LC and entorhinal CBF (ptau181 x rostral LC interaction term ß = 0.64, p = 0.001), such that as ptau181 increased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and entorhinal perfusion decreased. For frontal cortical regions, ptau181 levels moderated the relationship between rostral LC and lateral OFC perfusion (ptau181 x rostral LC interaction term ß = -0.54, p = .004), as well as between rostral LC and medial OFC perfusion (ptau181 x rostral LC interaction term ß = -0.53, p = .005), such that as ptau181 increased (i.e., greater pathology), the strength of the positive relationship between rostral LC integrity and frontal perfusion decreased.
Conclusions:LC integrity is linked to regional cortical perfusion in non-demented older adults, and these relationships are moderated by plasma AD biomarker concentrations. Variable directionality of the associations between the LC and frontal versus limbic perfusion, as well as the differential moderating effects of plasma AD biomarkers, may signify a compensatory mechanism and a shifting pattern of hyperemia in the presence of aggregating AD pathology. Linking LC integrity and cerebrovascular regulation may represent an important understudied pathway of dementia risk and may help to bridge competing theories of dementia progression in preclinical AD studies.
Using Mixed Methods to Assess Pediatric Disaster Preparedness in the Hospital Setting
- Rita V. Burke, Tae Y. Kim, Shelby L. Bachman, Ellen I. Iverson, Bridget M. Berg
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- Journal:
- Prehospital and Disaster Medicine / Volume 29 / Issue 6 / December 2014
- Published online by Cambridge University Press:
- 21 October 2014, pp. 569-575
- Print publication:
- December 2014
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Introduction
Children are particularly vulnerable during disasters and mass-casualty incidents. Coordinated multi-hospital training exercises may help health care facilities prepare for pediatric disaster victims.
ProblemThe purpose of this study was to use mixed methods to assess the disaster response of three hospitals, focusing on pediatric disaster victims.
MethodsA full-functional disaster exercise involving a simulated 7.8-magnitude earthquake was conducted at three Los Angeles (California USA) hospitals, one of which is a freestanding designated Level I Pediatric Trauma Center. Exercise participants provided quantitative and qualitative feedback regarding their perceptions of pediatric disaster response during the exercise in the form of surveys and interviews. Additionally, trained observers provided qualitative feedback and recommendations regarding aspects of emergency response during the exercise, including communication, equipment and supplies, pediatric safety, security, and training.
ResultsAccording to quantitative participant feedback, the disaster exercise enhanced respondents’ perceived preparedness to care for the pediatric population during a mass-casualty event. Further, qualitative feedback from exercise participants and observers revealed opportunities to improve multiple aspects of emergency response, such as communication, equipment availability, and physician participation. Additionally, participants and observers reported opportunities to improve safety and security of children, understanding of staff roles and responsibilities, and implementation of disaster triage exercises.
ConclusionConsistent with previous investigations of pediatric disaster preparedness, evaluation of the exercise revealed several opportunities for all hospitals to improve their ability to respond to the needs of pediatric victims. Quantitative and qualitative feedback from both participants and observers was useful for comprehensively assessing the exercise's successes and obstacles. The present study has identified several opportunities to improve the current state of all hospitals’ pediatric disaster preparedness, through increased training on pediatric disaster triage methods and additional training on the safety and security of children. Regular assessment and evaluation of supplies, equipment, leadership assignments, and inter-hospital communication is also suggested to optimize the effectiveness and efficiency of response to pediatric victims in a disaster.
. ,Burke RV ,Kim TY ,Bachman SL ,Iverson EI .Berg BM Using Mixed Methods to Assess Pediatric Disaster Preparedness in the Hospital Setting . Prehosp Disaster Med.2014 ;29 (6 ):1 -7