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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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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.
Effectiveness, acceptability and potential harms of peer support for self-harm in non-clinical settings: systematic review
- Nada Abou Seif, Rayanne John-Baptiste Bastien, Belinda Wang, Jessica Davies, Mette Isaken, Ellie Ball, Alexandra Pitman, Sarah Rowe
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- Journal:
- BJPsych Open / Volume 8 / Issue 1 / January 2022
- Published online by Cambridge University Press:
- 17 January 2022, e28
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Background
Many people who have self-harmed prefer informal sources of support or support from those with lived experience. However, little is known about whether peer support improves outcomes for people who have self-harmed or about the risks of peer support interventions in non-clinical settings.
AimsThe aims of this review were to examine the effectiveness, acceptability and potential risks of peer support for self-harm, and how these risks might be mitigated.
MethodWe searched bibliographic databases and grey literature for papers published since 2000. We included peer support for self-harm that occurred in voluntary-sector organisations providing one-to-one or group support, or via moderated online peer support forums.
ResultsEight of the ten papers included focused on peer support that was delivered through online media. No study compared peer support with other treatments or a control group, so limited conclusions could be made about its effectiveness. Peer support for self-harm was found to be acceptable and was viewed as having a range of benefits including a sense of community, empowerment, and access to information and support. The most commonly perceived risk associated with peer support was the potential for triggering self-harm.
ConclusionsOur findings highlighted a range of benefits of being part of a group with very specific shared experiences. Mitigations for potential risks include organisations using professional facilitators for groups, trigger warnings for online forums, and providing regular supervision and training so that peers are prepared and feel confident to support vulnerable people while maintaining their own emotional health.