Protocol for a prospective cohort study to determine the multimodal biomarkers of delirium and new dementia after acute illness in older adults: ORCHARD-PS
Introduction Delirium is common in the older hospital population and is often precipitated by acute illness. Delirium is associated with poor outcomes including subsequent cognitive decline and dementia and may therefore be a modifiable risk factor for dementia. However, the mechanisms underpinning...
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BMJ Publishing Group
2025-06-01
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| author | Jessica Knight Davide Simonato Sarah Evans Nicola G Lovett Jasmine Ming Gan Aubretia McColl Lily Elderton Meenu Vijayakumar Sheela John Louca Kinza Shahab Mary Sneade Nycola Muchenje Mariya Fenchyn Sarah Tamsin Pendlebury |
| author_facet | Jessica Knight Davide Simonato Sarah Evans Nicola G Lovett Jasmine Ming Gan Aubretia McColl Lily Elderton Meenu Vijayakumar Sheela John Louca Kinza Shahab Mary Sneade Nycola Muchenje Mariya Fenchyn Sarah Tamsin Pendlebury |
| author_sort | Jessica Knight |
| collection | DOAJ |
| description | Introduction Delirium is common in the older hospital population and is often precipitated by acute illness. Delirium is associated with poor outcomes including subsequent cognitive decline and dementia and may therefore be a modifiable risk factor for dementia. However, the mechanisms underpinning the delirium–dementia relationship and the role of coexisting acute illness factors remain uncertain. Current biomarker studies of delirium have limitations including lack of detailed delirium characterisation with few studies on neurodegenerative or neuroimaging biomarkers especially in the acute setting. The Oxford and Reading Cognitive Health After Recovery from acute illness and Delirium—Prospective Study (ORCHARD-PS) aims to elucidate the pathophysiology of delirium and subsequent cognitive decline after acute illness in older adults, through acquisition of multimodal biomarkers for deep phenotyping of delirium and acute illness, and follow-up for incident dementia.Methods and analysis ORCHARD-PS is a bi-centre, prospective cohort study. Consecutive eligible patients requiring acute hospital admission or assessment are identified by the relevant acute clinical care team. All patients age >65 years without advanced dementia, nursing home residence, end-stage frailty or terminal illness are eligible. Details of potential participants are communicated to the research team and written informed consent or consultee agreement is obtained. Participants are interviewed as soon as possible after admission/assessment using a structured proforma.Data are collected on demographics, diagnosis and comorbidities, social and functional background. Delirium is assessed using the 4A’s test, Confusion Assessment Method (long-form), Observational Scale of Level of Arousal, Richmond Agitation-Sedation Scale and Memorial Delirium Assessment Scale and diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Delirium is categorised by time of onset (prevalent vs incident), dementia status, motoric subtype, severity and duration. Cognitive tests include the 10-point Abbreviated Mental Test and Montreal Cognitive Assessment. Participants are reassessed every 48–72 hours if remaining in hospital. Informant questionnaire data and interview are supplemented by hand searching of medical records and linkage to electronic patient records for nursing risk assessments, vital observations, laboratory results and International Classification of Diseases, Tenth Revision diagnostic and procedure codes.In-person follow-up with more detailed cognitive testing and informant interview is undertaken at 3 months, and 1 and 3 years supplemented with indirect follow-up using medical records. Blood banking is performed at baseline and all follow-ups for future biomarker analyses. CT-brain and MRI-brain imaging acquired as part of standard care is obtained for quantification of brain atrophy and white matter disease/stroke supplemented by research CT-brain imaging. Outcomes include length of hospitalisation, change in care needs, institutionalisation, mortality, readmission, longitudinal changes in cognitive and functional status and incident dementia. Biomarker associations with delirium, and with incident dementia on follow-up, will be determined using logistic or Cox regression as appropriate, unadjusted and adjusted for covariates including demographics, baseline cognition, frailty, comorbidity and apolipoprotein E genotype.Ethics and dissemination ORCHARD-PS is approved by the South Central—Berkshire Research Ethics Committee (REC Reference: 23/SC/0199). Results will be disseminated through peer-reviewed publications and conference presentations.Trial registration number ISRCTN24171810. |
| format | Article |
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| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-28150c4a50a84802a4567b06dbba84f22025-08-20T02:06:46ZengBMJ Publishing GroupBMJ Open2044-60552025-06-0115610.1136/bmjopen-2025-102028Protocol for a prospective cohort study to determine the multimodal biomarkers of delirium and new dementia after acute illness in older adults: ORCHARD-PSJessica Knight0Davide Simonato1Sarah Evans2Nicola G Lovett3Jasmine Ming Gan4Aubretia McColl5Lily Elderton6Meenu Vijayakumar Sheela7John Louca8Kinza Shahab9Mary Sneade10Nycola Muchenje11Mariya Fenchyn12Sarah Tamsin Pendlebury13Oxford (Thames Valley) Foundation School, Oxford University Hospitals NHS Foundation Trust, Oxford, UKDepartment of Neuroradiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UKDepartments of Acute General Internal Medicine and Geratology, Oxford University Hospitals NHS Foundation Trust, Oxford, UKDepartments of Acute General Internal Medicine and Geratology, Oxford University Hospitals NHS Foundation Trust, Oxford, UKWolfson Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UKUniversity Department of Elderly Care, Royal Berkshire NHS Foundation Trust, Reading, UKWolfson Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UKNeurosciences Research Delivery Team (DENDRON), Oxford University Hospitals NHS Foundation Trust, Oxford, UKOxford (Thames Valley) Foundation School, Oxford University Hospitals NHS Foundation Trust, Oxford, UKDepartments of Acute General Internal Medicine and Geratology, Oxford University Hospitals NHS Foundation Trust, Oxford, UKWolfson Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UKUniversity Department of Elderly Care, Royal Berkshire NHS Foundation Trust, Reading, UKUniversity Department of Elderly Care, Royal Berkshire NHS Foundation Trust, Reading, UKWolfson Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UKIntroduction Delirium is common in the older hospital population and is often precipitated by acute illness. Delirium is associated with poor outcomes including subsequent cognitive decline and dementia and may therefore be a modifiable risk factor for dementia. However, the mechanisms underpinning the delirium–dementia relationship and the role of coexisting acute illness factors remain uncertain. Current biomarker studies of delirium have limitations including lack of detailed delirium characterisation with few studies on neurodegenerative or neuroimaging biomarkers especially in the acute setting. The Oxford and Reading Cognitive Health After Recovery from acute illness and Delirium—Prospective Study (ORCHARD-PS) aims to elucidate the pathophysiology of delirium and subsequent cognitive decline after acute illness in older adults, through acquisition of multimodal biomarkers for deep phenotyping of delirium and acute illness, and follow-up for incident dementia.Methods and analysis ORCHARD-PS is a bi-centre, prospective cohort study. Consecutive eligible patients requiring acute hospital admission or assessment are identified by the relevant acute clinical care team. All patients age >65 years without advanced dementia, nursing home residence, end-stage frailty or terminal illness are eligible. Details of potential participants are communicated to the research team and written informed consent or consultee agreement is obtained. Participants are interviewed as soon as possible after admission/assessment using a structured proforma.Data are collected on demographics, diagnosis and comorbidities, social and functional background. Delirium is assessed using the 4A’s test, Confusion Assessment Method (long-form), Observational Scale of Level of Arousal, Richmond Agitation-Sedation Scale and Memorial Delirium Assessment Scale and diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Delirium is categorised by time of onset (prevalent vs incident), dementia status, motoric subtype, severity and duration. Cognitive tests include the 10-point Abbreviated Mental Test and Montreal Cognitive Assessment. Participants are reassessed every 48–72 hours if remaining in hospital. Informant questionnaire data and interview are supplemented by hand searching of medical records and linkage to electronic patient records for nursing risk assessments, vital observations, laboratory results and International Classification of Diseases, Tenth Revision diagnostic and procedure codes.In-person follow-up with more detailed cognitive testing and informant interview is undertaken at 3 months, and 1 and 3 years supplemented with indirect follow-up using medical records. Blood banking is performed at baseline and all follow-ups for future biomarker analyses. CT-brain and MRI-brain imaging acquired as part of standard care is obtained for quantification of brain atrophy and white matter disease/stroke supplemented by research CT-brain imaging. Outcomes include length of hospitalisation, change in care needs, institutionalisation, mortality, readmission, longitudinal changes in cognitive and functional status and incident dementia. Biomarker associations with delirium, and with incident dementia on follow-up, will be determined using logistic or Cox regression as appropriate, unadjusted and adjusted for covariates including demographics, baseline cognition, frailty, comorbidity and apolipoprotein E genotype.Ethics and dissemination ORCHARD-PS is approved by the South Central—Berkshire Research Ethics Committee (REC Reference: 23/SC/0199). Results will be disseminated through peer-reviewed publications and conference presentations.Trial registration number ISRCTN24171810.https://bmjopen.bmj.com/content/15/6/e102028.full |
| spellingShingle | Jessica Knight Davide Simonato Sarah Evans Nicola G Lovett Jasmine Ming Gan Aubretia McColl Lily Elderton Meenu Vijayakumar Sheela John Louca Kinza Shahab Mary Sneade Nycola Muchenje Mariya Fenchyn Sarah Tamsin Pendlebury Protocol for a prospective cohort study to determine the multimodal biomarkers of delirium and new dementia after acute illness in older adults: ORCHARD-PS BMJ Open |
| title | Protocol for a prospective cohort study to determine the multimodal biomarkers of delirium and new dementia after acute illness in older adults: ORCHARD-PS |
| title_full | Protocol for a prospective cohort study to determine the multimodal biomarkers of delirium and new dementia after acute illness in older adults: ORCHARD-PS |
| title_fullStr | Protocol for a prospective cohort study to determine the multimodal biomarkers of delirium and new dementia after acute illness in older adults: ORCHARD-PS |
| title_full_unstemmed | Protocol for a prospective cohort study to determine the multimodal biomarkers of delirium and new dementia after acute illness in older adults: ORCHARD-PS |
| title_short | Protocol for a prospective cohort study to determine the multimodal biomarkers of delirium and new dementia after acute illness in older adults: ORCHARD-PS |
| title_sort | protocol for a prospective cohort study to determine the multimodal biomarkers of delirium and new dementia after acute illness in older adults orchard ps |
| url | https://bmjopen.bmj.com/content/15/6/e102028.full |
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