Oxidative DNA Damage and Transcriptional Impairment in Brain Ageing as an Early Contributor to Cognitive Impairment
Lead Research Organisation:
University of Sheffield
Department Name: Neurosciences
Abstract
With our ageing population, dementia is an increasing problem for individuals and their families and for the provision of care by society as a whole. There is an urgent need therefore to understand contributors to decline in brain function and to define potential new avenues for therapies, both to delay the progression of dementia and to delay its onset, which will have a major effect on dementia prevalence in the population. Most studies of dementia have been based on comparisons of individuals with established dementia to those with no dementia, and a major focus has been on Alzheimer's disease (AD), the commonest cause of dementia. However, this does not accurately reflect the situation in a population setting. The MRC Cognitive Function and Ageing Study (CFAS), a population-representative study, has shown an overlap in AD pathology between demented and non-demented individuals that increases at the oldest ages, so there is a need to define the role of other contributors to dementia. Oxidative stress has been shown to be associated with neurodegenerative diseases, and can damage a variety of molecules in cells, including DNA, which makes up genes and encodes cell proteins. Our studies have shown that, in the elderly population, high levels of DNA oxidative damage can occur in some individuals with little or no AD pathology, suggesting that it may contribute to dementia independently of AD. The purpose of this project is to determine DNA oxidative damage in the brain in the population and its relationship to dementia and the progression of AD. Using methods that allow us to analyse overall changes in the expression of genes within cells, we will then determine how oxidative DNA damage affects the cellular pathways of nerve cells in both human brain tissue and an experimental cell culture model. These studies will provide the link between oxidative damage and the decline in nerve cell function and open up novel avenues for research studies into mechanisms of dementia and potential treatments.
Technical Summary
Oxidative stress is important in brain ageing and Alzheimer's disease (AD) but the relationship to cellular dysfunction and AD progression remains unclear. In a population-representative autopsy-brain sample from the MRC Cognitive Function and Ageing Study (CFAS), we have shown that oxidative stress and DNA damage occur in some individuals with little AD-pathology, suggesting that oxidative stress contributes to cognitive decline by promoting neuronal dysfunction in some individuals independently of AD. AD pathology does not explain all of dementia in a population setting, particularly in the oldest individuals and current approaches based on removing AD molecular pathology have had limited success, suggesting an urgent need to understand the role of "non-classical" cellular pathologies. We propose that chronic oxidative DNA damage may impair neuronal function by altering the neuronal transcriptome, by down-regulation of transcription and by induction of senescence mechanisms. At a population level we propose that neuronal dysfunction due to oxidative DNA damage explains a proportion of dementia, especially in the oldest old. We plan to determine the variation in oxidative DNA damage, particularly in individuals in the population without AD using the CFAS population-neuropathology cohort. We will determine the effect of oxidative DNA damage on the neuron in both CFAS and in a neuronal culture system and using markers of senescence and microarray gene-expression analysis to determine the effect on transcription. Bioinformatics approaches will allow determination of the effect of chronic oxidative stress on cellular pathways, whist time-course analysis in the cells will allow determination of how the neuronal response changes. This study will define the contribution of oxidative stress to dementia at a population level and identify altered cellular pathways reflecting neuronal injury and adaptation response that will lead to novel avenues for investigation.
Planned Impact
At present the focus of dementia research is on classical pathological lesions, such as neurofibrillary tangles and plaques and the associated abnormal proteins, beta-amyloid and tau. These remain important targets, but the fact that these lesions do not explain all dementia in a population setting and the lack of success of current therapies that target these proteins demonstrate a need to understand non-classical markers. This project will help to define the role of oxidative stress in age-related cognitive impairment in a population setting and the cellular link between oxidative neuronal damage and neuronal dysfunction. This may aid in explaining the deficit in pathological models of dementia, especially in the oldest old, the demographic group in which AD pathology is most poorly predictive of dementia and in which most cases of dementia occur. Understanding oxidative stress and how it relates to the progression of AD pathology is itself important to targeting this therapeutically and in preventive measures to reduce cognitive impairment in a population setting. Defining how neuronal cell pathways respond to oxidative stress will identify potential novel avenues for therapies targeted against specific pathways and for biomarker development. In addition to the results from this work, the study will generate data from which novel specific hypotheses will be developed for further functional studies. The population-based data on the CFAS cohort will be archived in the CFAS database. This will be available to future studies in CFAS; the availability of this rich, population-representative set of pathological and molecular data is one of the strengths of CFAS. In addition, the bioinformatics data on both the neurons laser-captured from CFAS cases and form the cell culture work will be deposited in an on-line gene expression database, further adding value to the study by making this extensive data available for bioinformatics studies by other workers.
Publications
Ajikumar A
(2019)
Neutrophil-Derived Microvesicle Induced Dysfunction of Brain Microvascular Endothelial Cells In Vitro
in International Journal of Molecular Sciences
Al-Mashhadi S
(2014)
Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain
in Brain Pathology
Ameen-Ali KE
(2017)
Review: Neuropathology and behavioural features of transgenic murine models of Alzheimer's disease.
in Neuropathology and applied neurobiology
Appleby-Mallinder C
(2016)
Expression microdissection isolation of enriched cell populations from archival brain tissue.
in Journal of neuroscience methods
Asi YT
(2014)
Alpha-synuclein mRNA expression in oligodendrocytes in MSA.
in Glia
Brayne C
(2013)
From molecule to clinic and community for neurodegeneration: research to bridge translational gaps.
in Journal of Alzheimer's disease : JAD
Bury JJ
(2021)
Type 2 diabetes mellitus-associated transcriptome alterations in cortical neurones and associated neurovascular unit cells in the ageing brain.
in Acta neuropathologica communications
Chambers A
(2020)
Advanced Glycation End Product Formation in Human Cerebral Cortex Increases With Alzheimer-Type Neuropathologic Changes but Is Not Independently Associated With Dementia in a Population-Derived Aging Brain Cohort.
in Journal of neuropathology and experimental neurology
Fox C
(2019)
O4-02-02: WHAT ARE THE EFFECTS OF BENZODIAZEPINE AND ANTICHOLINERGIC DRUG USE ON THE BRAIN: A NEUROPATHOLOGICAL STUDY
in Alzheimer's & Dementia
Garwood C
(2013)
Calcium dysregulation in relation to Alzheimer-type pathology in the ageing brain.
in Neuropathology and applied neurobiology
Garwood CJ
(2014)
DNA damage response and senescence in endothelial cells of human cerebral cortex and relation to Alzheimer's neuropathology progression: a population-based study in the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS) cohort.
in Neuropathology and applied neurobiology
Garwood CJ
(2017)
Review: Astrocytes in Alzheimer's disease and other age-associated dementias: a supporting player with a central role.
in Neuropathology and applied neurobiology
Keage HA
(2012)
Impact of less common and "disregarded" neurodegenerative pathologies on dementia burden in a population-based cohort.
in Journal of Alzheimer's disease : JAD
Kovacs GG
(2017)
Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG).
in Journal of neuropathology and experimental neurology
Lace G
(2012)
Mesial temporal astrocyte tau pathology in the MRC-CFAS ageing brain cohort.
in Dementia and geriatric cognitive disorders
Leah T
(2021)
A Parkinson's Disease-relevant Mitochondrial and Neuronal Morphology High-throughput Screening Assay in LUHMES Cells
in BIO-PROTOCOL
Mathur R
(2015)
A reduced astrocyte response to ß-amyloid plaques in the ageing brain associates with cognitive impairment.
in PloS one
Matthews F
(2016)
A two decade dementia incidence comparison from the Cognitive Function and Ageing Studies I and II
in Nature Communications
Ratcliffe LE
(2018)
Loss of IGF1R in Human Astrocytes Alters Complex I Activity and Support for Neurons.
in Neuroscience
Richardson K
(2020)
Neuropathological Correlates of Cumulative Benzodiazepine and Anticholinergic Drug Use.
in Journal of Alzheimer's disease : JAD
Simpson J
(2015)
Neuronal DNA damage response-associated dysregulation of signalling pathways and cholesterol metabolism at the earliest stages of A lzheimer-type pathology
in Neuropathology and Applied Neurobiology
Simpson JE
(2018)
Immuno-Laser-Capture Microdissection for the Isolation of Enriched Glial Populations from Frozen Post-Mortem Human Brain.
in Methods in molecular biology (Clifton, N.J.)
Simpson JE
(2015)
A neuronal DNA damage response is detected at the earliest stages of Alzheimer's neuropathology and correlates with cognitive impairment in the Medical Research Council's Cognitive Function and Ageing Study ageing brain cohort.
in Neuropathology and applied neurobiology
| Description | ARUK PhD Scholarship |
| Amount | £87,900 (GBP) |
| Funding ID | ARUK-PhD2016-1 |
| Organisation | Alzheimer's Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2016 |
| End | 08/2019 |
| Description | BNS Small Grant Scheme - Oxidative damage to nucleic acids in MND |
| Amount | £5,000 (GBP) |
| Organisation | British Neuropathological Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | |
| Description | How does frailty influence the risk and expression of dementia in Alzheimer disease? |
| Amount | $466,652 (USD) |
| Organisation | Canadian Institutes of Health Research |
| Sector | Public |
| Country | Canada |
| Start | |
| Description | Interdisciplinary research grant |
| Amount | £237,984 (GBP) |
| Funding ID | ARUK-IRG2014-10 |
| Organisation | Alzheimer's Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2014 |
| End | 12/2016 |
| Description | Major project grant - Gene based therapies for frontotemporal dementia. |
| Amount | £244,661 (GBP) |
| Funding ID | PG2018B-005) |
| Organisation | Alzheimer's Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 02/2019 |
| End | 01/2022 |
| Description | Neuronal senescence as a contributory mechanisms to dementia. |
| Amount | £309,035 (GBP) |
| Funding ID | PG2019-003 |
| Organisation | Alzheimer's Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2020 |
| End | 01/2023 |
| Description | PhD Scholarship |
| Amount | £84,450 (GBP) |
| Funding ID | ARUK-PhD2016-5 |
| Organisation | Alzheimer's Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2016 |
| End | 08/2019 |
| Description | Preparatory clinical research fellowship |
| Amount | £69,998 (GBP) |
| Funding ID | ARUK-PCRF2016A-1 |
| Organisation | Alzheimer's Research UK |
| Department | Alzheimers Research UK, Cambridge |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2016 |
| End | 09/2017 |
| Description | Prevention of Dementia using Mobile phone applications (PRODEMOS) |
| Amount | £2,500,000 (GBP) |
| Funding ID | 779238 |
| Organisation | European Union |
| Sector | Public |
| Country | European Union (EU) |
| Start | |
| Description | Project grant |
| Amount | £225,718 (GBP) |
| Organisation | Alzheimer's Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2015 |
| End | 09/2018 |
| Description | Project grant. Basis of post stroke dementia |
| Amount | £378,751 (GBP) |
| Funding ID | 386 |
| Organisation | Alzheimer's Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 02/2018 |
| End | 01/2021 |
| Title | Development of immuno-directed laser capture microdissection. |
| Description | Protocols for cell-type specific laser capture in the CNS. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | Several papers over the years, most recently brought together in a methods chapter Simpson JE, Wharton SB, Heath PR. Immuno-laser-capture microdissection for the isolation of enriched glial populations from frozen post-mortem human brain. In: Murray G (eds) Laser Capture Microdissection. Methods in Molecular Biology vol 1723; pp273-284, Humana Press, New York, NY |
| Title | Gene expression microarray data associated with neuronal DNA damage |
| Description | Gene expression data deposited in the Gene Expression Omnibus, accession number GSE66333 |
| Type Of Material | Physiological assessment or outcome measure |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| Impact | Availability of data to bioinformatics community. |
| Description | A Cellular Pathology and Gene Expression Approach to Understand the Basis of Progressive Dementia Occurring After Stroke |
| Organisation | Newcastle University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Joint study of post stroke dementia. We will provide laser capture and gene expression analysis. |
| Collaborator Contribution | Collaboration has just begun. |
| Impact | Just started |
| Start Year | 2018 |
| Description | Defective nutrient signalling and dementia: an epidemiological neuropathology approach |
| Organisation | Newcastle University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Pathological analysis of CFAS tissue studying effects of diabetes on the brain. |
| Collaborator Contribution | Tissue analysis. |
| Impact | Conference presentations. |
| Start Year | 2015 |
| Description | Defective nutrient signalling and dementia: an epidemiological neuropathology approach |
| Organisation | University of Cambridge |
| Department | Cambridge Institute of Public Health |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Pathological analysis of CFAS tissue studying effects of diabetes on the brain. |
| Collaborator Contribution | Tissue analysis. |
| Impact | Conference presentations. |
| Start Year | 2015 |
| Description | Neurovascular dysfunction in Alzheimer's disease: the search for early biomarkers |
| Organisation | University of Sheffield |
| Department | Department of Psychology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Collaboration with Psychology bringing together our tissue expertise and linking to physiological analysis. |
| Collaborator Contribution | Tissue analysis, laser capture and gene expression microarrays. |
| Impact | Review paper detailed in pulications. |
| Start Year | 2014 |
| Description | Role of microRNAs in ageing at the blood brain barrier |
| Organisation | Open University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Joint two centre grant. Our centre focuses on human tissue based studies. |
| Collaborator Contribution | Complementary studies form our collaborators at the OU, led by Dr Ignacio Romero, focus on experimental work |
| Impact | New grant funding from BBSRC to both centres |
| Start Year | 2013 |
| Description | A personal perspective on public health, cohorts and their value to contemporary and future societies |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | A personal perspective on public health, cohorts and their value to contemporary and future societies A talk was presented at Alzheimer Cohorts Consortium Summer Workshop June 18 2018 |
| Year(s) Of Engagement Activity | 2018 |
| Description | ARUK Lab Notes Webinar. Dementia under the microscope. What does neuropathology tell us about the causes of dementia in the older population? |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Gave talk as a webinar |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.youtube.com/watch?v=7YZ1tcOOfPg&t=1082s |
| Description | ARUK lab tour for lay group. |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Lab tour and talks informing members of public about our research |
| Year(s) Of Engagement Activity | 2018 |
| Description | Alzheimer Society Local Group Meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Member of out group spoke about our dementia research predominantly to dementia support workers. Better public information |
| Year(s) Of Engagement Activity | 2014 |
| Description | Alzheimers Research Network Volunteers Visit |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Supporters |
| Results and Impact | Attendance by a group of lay monitors. Presented talks in relation to our projects and lab visit. Opportunities for informal discussion and advice from the lay members. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Blog post |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Release of blog post about our Alz Soc funded diabetes grant, written by the post doc. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Build up of DNA damage in nerve cells can lead to dementia. |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Steve Wharton Press release on Sheffield University website (www.shef.ac.uk) 26 June 2015 |
| Year(s) Of Engagement Activity | 2015 |
| Description | CSaP talk - How to stop bad data driving out the good in an age of misuse, misleadingness and misinformation |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | CSaP talk - How to stop bad data driving out the good in an age of misuse, misleadingness and misinformation 4 March 2019 Ed Humpherson is the CEO of the Office of Statistics Regulation. He gave an elegant talk about how numbers can be used poorly - The Number, misleading and too much unsignposted data. He talked about creating standards and reporting on these, how his office has interacted with government departments to call such practice out and how they have responded. He also talked about responsible media. I gained insight into how such a government function can operate to hold government to account. It highlighted the fact that this is possible to do within a (relatively) stable governmental/public domain structure but that it would be unlikely professional integrity heading for CPD. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Changing Societies, ageing minds, brains and dementia |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Changing Societies, ageing minds, brains and dementia Above talk was presented at Ganadian Association on Gerontology Conference, Vancouver, Canada |
| Year(s) Of Engagement Activity | 2018 |
| Description | Changing concepts of cognitive impairment, decline and dementia in populations |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Changing concepts of cognitive impairment, decline and dementia in populations Invited speaker at XV Convegno Nazionale di Neuroepidemiologia, Neurologia ed epidemiologia nell'era della precision medicine, Tricase-Italy |
| Year(s) Of Engagement Activity | 2018 |
| Description | Contemporary populations and dementia, what have we learnt and where are we headed |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | A talk was given at Fourth Annual NHMRC National Institute for Dementia Research Australian Disease Forum 2019 at Hobart, Tasmania Keynote Address: Contemporary populations and dementia, what have we learnt and where are we headed? |
| Year(s) Of Engagement Activity | 2019 |
| Description | Dementia Futures Conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Conference designed to present results on dementia to lay public. 3 of our group's PhD students presented. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Dementia futures conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Conference to present work of PhD Students to members of the public. Covered by BBC radio Sheffield. Three PhD students from our group gave talks. Also attended by representative of local city council. |
| Year(s) Of Engagement Activity | 2019 |
| URL | http://tinyurl.com/DementiaFuturesConference2019 |
| Description | Dementia in aging societies and opportunities for prevention |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Dementia in aging societies and opportunities for prevention Invited as keynote speaker at World Health Summit Satellite Meeting, Dementia Prevention by Stroke Prevention, Berlin |
| Year(s) Of Engagement Activity | 2018 |
| Description | Dr Garwood presentation at Festival of Science and Engineering Your amazing brain |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Stimulated interest in children Questions |
| Year(s) Of Engagement Activity | 2015 |
| Description | Hosted laboratory visit for lay guests of the ARUK |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Lay guests and potential donors to ARUK were informed of our work on astrocytes. Unknown at present |
| Year(s) Of Engagement Activity | 2013 |
| Description | Invited speaker British Neuroscience Association Symposium |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Generate questions and discussion. Improved professional relationships that might lead to collaboration. Communication both immediately after and by email |
| Year(s) Of Engagement Activity | 2015 |
| Description | Journal promotion of one of our papers |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Promotion of our article on neuronal DNA damage response associated signalling changes.. by the publisher, Wiley to coincide with National Alzheimer's Awareness month. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Memory Outreach Clinic |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Discussing our work on dementia with relatives at a local memory café. |
| Year(s) Of Engagement Activity | 2020 |
| Description | NIHR, Societal Challenges and Public Health Research fit for the future |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | NIHR, Societal Challenges and Public Health Research fit for the future A talk was presented at NIHR Clinical Research network Strategic leadership Summit at Birmingham. 21st Century CRN - realising the potential of Public health & Social Care Research Across the Network |
| Year(s) Of Engagement Activity | 2018 |
| Description | Population Perspectives on the Complexity of Brain Ageing and Dementia within Changing Societies |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Population Perspectives on the Complexity of Brain Ageing and Dementia within Changing Societies Invited speaker at 2018 International Conference Promoting healthy Brain Aging and Preventing Dementia: Research and Translation Canada. . |
| Year(s) Of Engagement Activity | 2018 |
| Description | Radio interview by Dr Claire Garwood on our group's work, BBC Radio Sheffield |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Informed public via radio Not formally assessed. |
| Year(s) Of Engagement Activity | 2015 |
| Description | Research Network volunteer visit (Alz Soc) Aug 2017 |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Visit of Alz Soc research network volunteer. Presented the research work of our group. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Research, perseverance, obstinacy and inspiration |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Research, perseverance, obstinacy and inspiration Invited speaker at Annual Norwich Medical School, Away Day (in Norwich) 12th Sep 2018. |
| Year(s) Of Engagement Activity | 2018 |
| Description | SITraN Open Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Institute open day with range of talks |
| Year(s) Of Engagement Activity | 2018 |
| Description | SITraN Open Day July 2014 |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Open day at SITraN allowing lay persons to look at work on neurodegeneration, in including dementia in Sheffield. Public information and interest in donations |
| Year(s) Of Engagement Activity | 2014 |
| Description | Short film about dementia research in Sheffield |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Claire Garwood received funding from the Engaged Curriculum to produce a short film about the broad range of dementia research at the University of Sheffield. |
| Year(s) Of Engagement Activity | 2015 |
| Description | Talk on diabetes at Alz Soc conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Talk "Advanced glycosylated end-products as markers of diabetes in the Alzheimer's brain. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Talk to Ignite Academy Event |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Talk given by member of our group "Astrocytes:Guardians of the Brain" Better public information |
| Year(s) Of Engagement Activity | 2014 |
| Description | Views of a Dementia Researcher |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Views of a Dementia Researcher Invited speaker at ARUK Seminar at Newnham College 2018 Sep. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Visit by Alzheimer's Society network volunteers |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Supporters |
| Results and Impact | Stephen Wharton Organised visit by Alzheimer's Society network volunteers. Nov 10 2015. 3 visitors - meet the group, 2 talks and lab tour. |
| Year(s) Of Engagement Activity | 2015 |
| Description | Visit by lay monitors |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Visit by lay monitors to discuss our work on dementia |
| Year(s) Of Engagement Activity | 2019 |
| Description | Visit to local primary school |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Visit to local primary school by team members, Key stages 1-2. Talk and workshop focused on the brain. |
| Year(s) Of Engagement Activity | 2019 |
| Description | WHO Bulletin Interview with Carol |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Interview with Carol Brayne: a life-course approach to prevent dementia https://apps.who.int/iris/handle/10665/272247 WHO Bulletin Interview with Carol |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://apps.who.int/iris/handle/10665/272247 |
| Description | What is the role of population studies in the rise of dementia as a societal concern? |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | What is the role of population studies in the rise of dementia as a societal concern? Invited speaker at 2018 Anne Silk Lecture Public Lecture London |
| Year(s) Of Engagement Activity | 2018 |
| Description | Workshops in primary schools |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Claire Garwood, Laura Ratcliffe and Irina Villasenor. Sheffield Festival of Science and Engineering. 3 Half day workshops in local primary schools "Your Amazing Brain". |
| Year(s) Of Engagement Activity | 2015 |