| 1. |
- Graham, N. S. N., et al.
(författare)
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Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury
- 2021
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:613
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Tidskriftsartikel (refereegranskat)abstract
- Axonal injury is a key determinant of long-term outcomes after traumatic brain injury (TBI) but has been difficult to measure clinically. Fluid biomarker assays can now sensitively quantify neuronal proteins in blood. Axonal components such as neurofilament light (NfL) potentially provide a diagnostic measure of injury. In the multicenter BIO-AX-TBI study of moderate-severe TBI, we investigated relationships between fluid biomarkers, advanced neuroimaging, and clinical outcomes. Cerebral microdialysis was used to assess biomarker concentrations in brain extracellular fluid aligned with plasma measurement. An experimental injury model was used to validate biomarkers against histopathology. Plasma NfL increased after TBI, peaking at 10 days to 6 weeks but remaining abnormal at 1 year. Concentrations were around 10 times higher early after TBI than in controls (patients with extracranial injuries). NfL concentrations correlated with diffusion MRI measures of axonal injury and predicted white matter neurodegeneration. Plasma TAU predicted early gray matter atrophy. NfL was the strongest predictor of functional outcomes at 1 year. Cerebral microdialysis showed that NfL concentrations in plasma and brain extracellular fluid were highly correlated. An experimental injury model confirmed a dose-response relationship of histopathologically defined axonal injury to plasma NfL. In conclusion, plasma NfL provides a sensitive and clinically meaningful measure of axonal injury produced by TBI. This reflects the extent of underlying damage, validated using advanced MRI, cerebral microdialysis, and an experimental model. The results support the incorporation of NfL sampling subacutely after injury into clinical practice to assist with the diagnosis of axonal injury and to improve prognostication.
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| 2. |
- Astell, A. J., et al.
(författare)
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Developing a pragmatic evaluation of ICTs for older adults with cognitive impairment at scale: the IN LIFE experience
- 2021
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Ingår i: Universal Access in the Information Society. - Heidelberg, Germany : Springer. - 1615-5289 .- 1615-5297.
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Tidskriftsartikel (refereegranskat)abstract
- Implementing information and communications technology (ICT) at scale requires evaluation processes to capture the impact on users as well as the infrastructure into which it is being introduced. For older adults living with cognitive impairment, this requires evaluation that can accommodate different levels of cognitive impairment, alongside input from family and formal caregivers, plus stakeholder organisations. The European Horizon 2020 project INdependent LIving support Functions for the Elderly (IN LIFE) set out to integrate 17 technologies into a single digital platform for older people living with cognitive impairment plus their families, care providers and stakeholders. The IN LIFE evaluation took place across six national pilot sites to examine a number of variables including impact on the users, user acceptance of the individual services and the overall platform, plus the economic case for the IN LIFE platform. The results confirmed the interest and need among older adults, family caregivers, formal caregivers and stakeholders, for information and communications technology (ICT). Relative to the baseline, quality of life improved and cognition stabilised; however, there was an overall reluctance to pay for the platform. The findings provide insights into existing barriers and challenges for adoption of ICT for older people living with cognitive impairment.
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| 3. |
- Astell, A. J., et al.
(författare)
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INLIFE - Independent Living Support Functions for the Elderly: Technology and Pilot Overview
- 2018
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Ingår i: INTELLIGENT ENVIRONMENTS 2018. - 9781614998747 - 9781614998730 ; , s. 526-535
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, we present the European H2020 project INLIFE (INdependent LIving support Functions for the Elderly). The project brought together 20 partners from nine countries with the goal of integrating into a common ICT platform a range of technologies intended to assist community-dwelling older people with cognitive impairment. The majority of technologies existed prior to INLIFE and a key goal was to bring them together in one place along with a number of new applications to provide a comprehensive set of services. The range of INLIFE services fell into four broad areas: Independent Living Support, Travel Support, Socialization and Communication Support and Caregiver Support. These included security applications, services to facilitate interactions with formal and informal caregivers, multilingual conversation support, web-based physical exercises, teleconsultations, and support for transport navigation. In total, over 2900 people participated in the project; they included elderly adults with cognitive impairment, informal caregivers, healthcare professionals, and other stakeholders. The aim of the study was to assess whether there was improvement/stabilization of cognitive/emotional/physical functioning, as well as overall well-being and quality of life of those using the INLIFE services, and to assess user acceptance of the platform and individual services. The results confirm there is a huge interest and appetite for technological services to support older adults living with cognitive impairment in the community. Different services attracted different amounts of use and evaluation with some proving extremely popular while others less so. The findings provide useful information on the ways in which older adults and their families, health and social care services and other stakeholders wish to access technological services, what sort of services they are seeking, what sort of support they need to access services, and how these services might be funded.
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| 4. |
- Graham, N., et al.
(författare)
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Alzheimer's disease marker phospho-tau181 is not elevated in the first year after moderate-to-severe TBI
- 2024
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - 0022-3050. ; 95:4, s. 356-359
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTraumatic brain injury (TBI) is associated with the tauopathies Alzheimer's disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer's disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy.MethodsPlasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer's disease, with healthy controls.ResultsPlasma p-tau181 concentrations were significantly raised in patients with Alzheimer's disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates.ConclusionsPlasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration.
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| 5. |
- Astell, A. J., et al.
(författare)
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Developing a pragmatic evaluation of ICTs for older adults with cognitive impairment at scale : the IN LIFE experience
- 2022
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Ingår i: Universal Access in the Information Society. - Heidelberg, Germany : Springer. - 1615-5289 .- 1615-5297. ; 21:1, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- Implementing information and communications technology (ICT) at scale requires evaluation processes to capture the impacton users as well as the infrastructure into which it is being introduced. For older adults living with cognitive impairment, thisrequires evaluation that can accommodate diferent levels of cognitive impairment, alongside input from family and formalcaregivers, plus stakeholder organisations. The European Horizon 2020 project INdependent LIving support Functions forthe Elderly (IN LIFE) set out to integrate 17 technologies into a single digital platform for older people living with cognitive impairment plus their families, care providers and stakeholders. The IN LIFE evaluation took place across six nationalpilot sites to examine a number of variables including impact on the users, user acceptance of the individual services andthe overall platform, plus the economic case for the IN LIFE platform. The results confrmed the interest and need amongolder adults, family caregivers, formal caregivers and stakeholders, for information and communications technology (ICT).Relative to the baseline, quality of life improved and cognition stabilised; however, there was an overall reluctance to payfor the platform. The fndings provide insights into existing barriers and challenges for adoption of ICT for older peopleliving with cognitive impairment.
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| 6. |
- Li, L. M., et al.
(författare)
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Investigating the characteristics and correlates of systemic inflammation after traumatic brain injury: the TBI-BraINFLAMM study
- 2023
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Ingår i: Bmj Open. - 2044-6055. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionA significant environmental risk factor for neurodegenerative disease is traumatic brain injury (TBI). However, it is not clear how TBI results in ongoing chronic neurodegeneration. Animal studies show that systemic inflammation is signalled to the brain. This can result in sustained and aggressive microglial activation, which in turn is associated with widespread neurodegeneration. We aim to evaluate systemic inflammation as a mediator of ongoing neurodegeneration after TBI.Methods and analysisTBI-braINFLAMM will combine data already collected from two large prospective TBI studies. The CREACTIVE study, a broad consortium which enrolled >8000 patients with TBI to have CT scans and blood samples in the hyperacute period, has data available from 854 patients. The BIO-AX-TBI study recruited 311 patients to have acute CT scans, longitudinal blood samples and longitudinal MRI brain scans. The BIO-AX-TBI study also has data from 102 healthy and 24 non-TBI trauma controls, comprising blood samples (both control groups) and MRI scans (healthy controls only). All blood samples from BIO-AX-TBI and CREACTIVE have already been tested for neuronal injury markers (GFAP, tau and NfL), and CREACTIVE blood samples have been tested for inflammatory cytokines. We will additionally test inflammatory cytokine levels from the already collected longitudinal blood samples in the BIO-AX-TBI study, as well as matched microdialysate and blood samples taken during the acute period from a subgroup of patients with TBI (n=18).We will use this unique dataset to characterise post-TBI systemic inflammation, and its relationships with injury severity and ongoing neurodegeneration.Ethics and disseminationEthical approval for this study has been granted by the London-Camberwell St Giles Research Ethics Committee (17/LO/2066). Results will be submitted for publication in peer-review journals, presented at conferences and inform the design of larger observational and experimental medicine studies assessing the role and management of post-TBI systemic inflammation.
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| 7. |
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| 8. |
- Graham, Neil Samuel Nyholm, et al.
(författare)
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Multicentre longitudinal study of fluid and neuroimaging BIOmarkers of AXonal injury after traumatic brain injury: the BIO-AX-TBI study protocol.
- 2020
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) often results in persistent disability, due particularly to cognitive impairments. Outcomes remain difficult to predict but appear to relate to axonal injury. Several new approaches involving fluid and neuroimaging biomarkers show promise to sensitively quantify axonal injury. By assessing these longitudinally in a large cohort, we aim both to improve our understanding of the pathophysiology of TBI, and provide better tools to predict clinical outcome.BIOmarkers of AXonal injury after TBI is a prospective longitudinal study of fluid and neuroimaging biomarkers of axonal injury after moderate-to-severe TBI, currently being conducted across multiple European centres. We will provide a detailed characterisation of axonal injury after TBI, using fluid (such as plasma/microdialysate neurofilament light) and neuroimaging biomarkers (including diffusion tensor MRI), which will then be related to detailed clinical, cognitive and functional outcome measures. We aim to recruit at least 250 patients, including 40 with cerebral microdialysis performed, with serial assessments performed twice in the first 10 days after injury, subacutely at 10 days to 6weeks, at 6 and 12 months after injury.The relevant ethical approvals have been granted by the following ethics committees: in London, by the Camberwell St Giles Research Ethics Committee; in Policlinico (Milan), by the Comitato Etico Milano Area 2; in Niguarda (Milan), by the Comitato Etico Milano Area 3; in Careggi (Florence), by the Comitato Etico Regionale per la Sperimentazione Clinica della Regione Toscana, Sezione area vasta centro; in Trento, by the Trento Comitato Etico per le Sperimentazioni Cliniche, Azienda Provinciale per i Servizi Sanitari della Provincia autonoma di Trento; in Lausanne, by the Commission cantonale d'éthique de la recherche sur l'être humain; in Ljubljana, by the National Medical Ethics Committee at the Ministry of Health of the Republic of Slovenia. The study findings will be disseminated to patients, healthcare professionals, academics and policy-makers including through presentation at conferences and peer-reviewed publications. Data will be shared with approved researchers to provide further insights for patient benefit.NCT03534154.
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