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5 results

  • 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
  • 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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  • 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.

  • 10 - Writing and record-keeping in early cities

  • from Part II - Early cities and information technologies
  • Edited by Norman Yoffee, University of Michigan, Ann Arbor
  • Book:
    The Cambridge World History
    Published online:
    05 March 2015
    Print publication:
    12 March 2015, pp 207-226

  • Summary

    Classic Maya cities were dynamic places constructed throughout the Yucatan Peninsula and adjacent zones during much of the first millennium CE. This chapter examines how Maya cities were understood, used, and altered. Other named features of urban landscapes include pyramids and altars, neither, unfortunately, with fully accepted readings of their glyphic references. Other buildings in the Maya texts correspond to stairways, known as ehb, and ballcourts recorded by glyphs that are not yet deciphered. A notable attribute of later Maya ideas about appropriate or correct behavior is that it conforms to movement and handed-ness. Right and straight correspond closely to concepts of truth, virtue, cleansing, even prophecy. A final, remaining theme is that Maya cities accord with general concepts of landscape features yet also remain a malleable work-in-progress. The view of any such city today would contain a certain arrangement of buildings and spaces in urban armatures.

  • Chronic dietary n-3 PUFA intervention improves dyslipidaemia and subsequent cardiovascular complications in the JCR:LA-cp rat model of the metabolic syndrome

  • Jing Lu, Faye Borthwick, Zahra Hassanali, Ye Wang, Rabban Mangat, Megan Ruth, Danni Shi, Anja Jaeschke, James C. Russell, Catherine J. Field, Spencer D. Proctor, Donna F. Vine
  • Journal:
    British Journal of Nutrition / Volume 105 / Issue 11 / 14 June 2011
    Published online by Cambridge University Press:
    31 January 2011, pp. 1572-1582
    Print publication:
    14 June 2011
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  • There is increasing interest in the potential chronic beneficial effects of dietary n-3 PUFA on the metabolic syndrome (MetS) and associated cardiovascular complications. We have recently established that increased dietary n-3 PUFA has a profound acute benefit on fasting lipids and the postprandial pro-inflammatory response in the JCR:LA-cp rat, a model of the MetS. However, it is unclear to what extent chronic dietary n-3 PUFA intervention can modulate the progression of end-stage metabolic and vascular complications. The present study aimed to determine the chronic effects of dietary n-3 PUFA supplementation on fasting and non-fasting dyslipidaemia, insulin resistance and vascular complications in the JCR:LA-cp rodent model. JCR:LA-cp rats were fed an isoenergetic lipid-balanced diet supplemented with 5 % n-3 PUFA (w/w) of the total fat (fish oil-derived EPA/DHA) for 16 weeks. Fasting and non-fasting (postprandial) plasma lipid profile was assessed. Hepatic and adipose tissue was probed for the expression of lipogenic proteins (acyl-CoA carboxylase (ACC), fatty acid synthase (FAS) and sterol regulatory element-binding protein-1 (SREBP-1)), while the activity of Jun N-terminal kinase (JNK) was assessed via Western blot to target phosphorylated JNK protein in primary enterocytes. The frequency of myocardial lesions was assessed by haematoxylin and eosin staining. Increased dietary n-3 PUFA improved both the fasting and postprandial lipid profiles (TAG, cholesterol and apoB48) in the JCR:LA-cp rat, potentially via the down-regulation of the hepatic or adipose tissue expression of lipogenic enzymes (ACC, FAS and SREBP-1). Rats fed the 5 % n-3 PUFA diet had lower (58·2 %; P < 0·01) enterocytic phosphorylated JNK protein and secreted less cholesterol (30 %; P < 0·05) into mesenteric lymph compared with the control. The chronic metabolic benefits of dietary n-3 PUFA may underlie the potential to reduce vascular complications during the MetS, including the observed reduction in the frequency (approximately 80 %) of late-stage 3 myocardial lesions.