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Measuring the Permeability of the Blood-Brain Barrier in Alzheimer's Disease Using Dynamic Contrast Enhanced MRI
- Beth McCausland, Nathan Huneke, Aravinthan Varatharaj, Claire Gee, Amy Kunicki, Angela Darekar, Jessica Teeling, Henrik Zetterberg, Clive Holmes, Ian Galea, Jay Amin
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- Journal:
- BJPsych Open / Volume 9 / Issue S1 / July 2023
- Published online by Cambridge University Press:
- 07 July 2023, pp. S61-S62
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Aims
1) To compare blood brain barrier (BBB) permeability between AD and controls. 2) To examine the relationship between BBB permeability and cognitive decline in AD. 3) To examine the relationship between BBB permeability and peripheral markers of inflammation.
MethodsThis pilot study combines the use whole brain DCE-MRI, with measures of peripheral inflammation in serum and urine. This is a clinical cohort study with longitudinal and cross-sectional arms, involving n = 15 AD and n = 17 age and gender matched controls. BBB permeability is measured using DCE-MRI and inflammation is measured by comparing serum cytokine and urine neopterin concentrations. AD participants attend three study visits over 12 months; control participants attend two over one week. Urinary neopterin analysis is being conducted in February 2023.The 12 month follow up visits complete in May 2023. Both neopterin and longitudinal cognitive assessment data will be included in the poster presentation in July.
ResultsAD and control groups were well matched with no significant differences in demographics and multi-morbidity. We measured blood cytokine profiles for IL-6, IL-8, IL-2, IL-4, IL-1b, IL-10, IL13, IL-12p70-, TNF-alpha and INF-gamma. Only INF-Gamma was significantly different; higher in AD vs Controls (mean ± SD; 28.758 ± 90.226 AD, 3.773 ± 2.256 Control, P = 0.03). There were no significant differences in markers of neurodegeneration NfL and pTau-181, or vascular markers VCAM1, ICAM1, CRP and SAA between the groups. Ki is being calculated for overall whole brain, white matter, grey matter and hippocampus regions; an interim analysis showed no significant differences between the tissue categories, but analysis is ongoing.
ConclusionThere are currently no prognostic biomarkers that accurately predict decline in AD. We believe this pilot study will add to the literature about the utility and feasibility of DCE-MRI to measure BBB permeability. We hope that combining DCE-MRI with blood and urine biomarkers will further our knowledge of the pathophysiology of AD and help to develop minimally invasive biomarkers for identifying patients with AD, including those who are at risk of faster progression.
Preliminary investigation into the identification and management of catatonia in patients admitted to adult inpatient units
- Joanna Moore, Amy Kunicki, Georgina Latcham, Eleanor Perkins, Emma Vaccari
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- Journal:
- BJPsych Open / Volume 7 / Issue S1 / June 2021
- Published online by Cambridge University Press:
- 18 June 2021, p. S336
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Aims
The prevalence of catatonia is considered to be approximately 10% in psychiatric inpatients. Clinical experience suggests a lower documented prevalence. This could cause longer admissions and complications, such as Neuroleptic Malignant Syndrome (NMS). We carried out a service evaluation to investigate the recognition and management of catatonia on inpatient units in Southern Health Foundation Trust (SHFT). We reviewed the local documented prevalence of catatonia, treatment offered and prevalence of complications.
MethodWe retrospectively reviewed the electronic records of 95 consecutive admissions to four adult inpatient units in SHFT, starting on 1st August 2020. We reviewed notes for the admission to establish whether catatonia was suspected and identified. We applied the screening questions from the Bush-Francis Catatonia Rating Scale (BFCRS) to the documented mental state examinations (MSE) prior to, and shortly after, admission. We also recorded the prescriptions issued during the first 72 hours of admission, and whether patients developed neuroleptic malignant syndrome (NMS), serotonin syndrome or required admission to a general hospital during admission.
ResultCatatonia was documented as a possibility for 2 patients (2.1%). One showed possible posturing and stupor, while there were no documented symptoms for the other. In both cases the possibility was discounted by the clinical team. Twelve patients (12.6%) showed one or more possible or confirmed signs of catatonia. Eleven of these were prescribed regular antipsychotic medication on admission, but only 3 were prescribed regular benzodiazepines. NMS was more likely to be suspected in patients with a BFCRS of 1 or more compared with those with a score of 0, with an odds ratio of 8.1 (95% CI [1.03-64.0], Fisher's exact test = 7.79, p = .076).
ConclusionCatatonia is likely under-recognised and under-treated locally among psychiatric inpatients. Although only approaching statistical significance, the higher rate of suspected NMS in patients showing possible catatonia is noteworthy and needs further investigation. Regular benzodiazepines were not frequently prescribed in this group, while antipsychotics, prescribed in all of these patients, can precipitate NMS. Alternatively, this finding could reflect the overlap in clinical presentation between NMS and catatonia. Data collection was limited by the frequent use of “remote clerking”, in the context of the COVID-19 pandemic. Additionally, the quality of mental state examinations was often not sufficient to draw any conclusions on the possible presence or absence of catatonic symptoms. This project has highlighted practice in need of improvement, which will be further prospectively investigated and improved via a Quality Improvement Project.