A new noradrenergic strategy to treat Impulsivity in Progressive Supranuclear Palsy

Lead Research Organisation: University of Cambridge
Department Name: Clinical Neurosciences

Abstract

Progressive Supranuclear Palsy (PSP) is as complex as it is devastating for patients and families, combining a kind of movement disorder that does not respond to standard therapies, choking, loss of speech, personality changes, and dementia. Research by our team has shown that in the UK around 7,000 people are living with PSP.

Although physically very disabling, it is cognitive and personality changes in PSP that have the greatest impact on quality of life. Despite being slow and unresponsive for many activities, the same patients are often reckless and impulsive for actions that they do make. For example, a person living with PSP may "rush into things" and or "jump to conclusions" without thought for the consequences, or behave in a way that has high risks of falls or choking. These problems are also called "impulsivity". Impulsivity is highly dangerous for patients with PSP, in several different ways. It can make patients walking or moving around alone even though they have a very poor balance and fall. Eating too fast while choking is another form of impulsive behaviour which can lead to life-threatening chest infections. Impulsivity can also be highly distressing for carers and families.

There is currently no cure for PSP, although some of the symptoms, including impulsivity, are potentially treatable. However, there is yet a big gap between our knowledge of what is happening in brain cells of patients with PSP and how we should use the available treatments to help people with PSP to achieve the best possible quality of life. We must therefore build better "bridges" between basic studies and clinical trials.

To do this, our team will run a series of studies using the most advanced technologies in basic and clinical neuroscience, using advances in imaging, pharmacology, and psychology.

We will take advantage of the link between a brain chemical, noradrenaline, and the control of behavior. Noradrenaline is made by a tiny region of the brain called the locus coeruleus. It acts on other parts of the brain, especially the frontal lobe, to help control behavior, including flexible thinking and action control.

First, we will quantify the changes in the locus coeruleus, in PSP patients who we have followed through their illness in clinic and who then donated their brain to the Cambridge Brain Bank.

Second, we will measure the locus coeruleus in living patients with PSP. The locus coeruleus is small, and hard to see with normal brain scans. Working with Prof Emrah Duzel from Magdeburg, we will use the new technology of ultra-high field magnetic resonance imaging (known as "7 Tesla") to measure the size and degeneration of the locus coeruleus. His groups have developed new robust tools to measure this brain region. We will then use functional magnetic resonance imaging to measure how well the locus coeruleus connects to the frontal lobe and other brain regions.

Finally, we will measure the effects of a specific drug that enhances noradrenaline (called "atomoxetine") on impulsvity and cognition in PSP. This drug has been shown by our group and collaborators to improve impulsivity in a significant proportion of patients with Parkinson's disease, and in animal models of impulsivity. It is well tolerated, and approved for such research use in PSP. We believe that the results of our study will lead on to clinical trials for impulsivity in PSP and will eventually contribute to enhance the quality of life of people suffering from PSP.

Technical Summary

Impulsivity is a distressing and injurious aspect of PSP that is commonly under-recognised and poorly managed, even when coupled with balance and swallowing difficulty, with high risk of falls, injury, and choking. It typically coexists with apathy and bradykinesia, and is not relieved by current dopaminergic therapies. Impulsivity is a complex construct, with dissociable pharmacological and anatomical mechanisms that impair response inhibition, reward sensitivity, and decision making. Our group and collaborators have provided robust evidence that response inhibition in patients with Parkinsonian disorders linked to PSP (e.g., Parkinson's disease and frontotemporal dementia) is modulated by noradrenaline (NA), a key neurotransmitter mainly synthesized by the locus coeruleus (LC). Our overarching hypothesis is that enhancing NA function via NA reuptake inhibitors can improve response inhibition and impulsivity in PSP patients, mediated by the prefrontal cortex and its connections to the caudate and subthalamic nucleus.

This study will: (1) provide new quantitative evidence for the degree of loss of neurons in the LC, using post-mortem samples from PSP patients whom we have followed over the last 10 years; (2) apply advances in ultra-high-field MRI to quantify the LC in living PSP patients, together with a battery of behavioural tests of impulsivity and neuropsychology; (3) use formal models of behavior to track decision variables behind impulsive actions, and relate these to neural and disease markers, including brain network connectivity, and (4) test a repurposed drug, atomoxetine, to restore core neurocognitive systems governing the inhibition of motor responses in PSP.

Our work will promote bidirectional translational research, between non-clinical and clinical neuroscience, mapping disease states to preclinical models of cognition and behavior; and guide subsequent clinical trials with better outcome measures and patient selection and stratification.

Planned Impact

The beneficiaries of our research will extend beyond the academic environment and will include:

1. Patients with PSP: Impulsivity in PSP represents a significant burden to the affected individuals. PSP patients with problems as impulsivity and cognitive inflexibility have an increased risk of falls, injuries, chocking episodes, aspiration pneumonia, and early death. It is hoped that increasing our understanding into the brain mechanisms of impulsivity in PSP will reduce these risks. The absence of biomarkers for detecting impulsivity in PSP and the high inter-patients variability in drug response have also made the treatment of behavioural problems in PSP and other neurodegenerative disorders a major challenge. The cause of this variability in treatment response remains largely unclear, although heterogeneity in core neurochemical systems that determines a reduced sensitivity to specific therapy may play a significant role. Brain-based mechanistic accounts of impulsivity in PSP could therefore help clinical decision making and improve the management of these disabling behavioural symptoms in PSP and related disorders.

1. Non-academic clinicians: Our findings may provide useful information for clinical neurologists and other professionals who work with PSP patients (e.g., speech and language therapists, physiotherapists, and specialist nurses) and will raise awareness on a common and too often under-recognized problem in PSP. In particular, our project will reveal: (1) why some patients with PSP display impulsive behaviours and behavioral problems; (2) what happens to the brain of PSP patients with impulsive behaviours, and (3) that there are potential targets for treating impulsivity in PSP (i.e., via enhancing the noradrenergic system).

2. Carers of patients with PSP: Parents, relatives, friends, social workers, and other carers of people with PSP may also benefit from our research. In the short term our project may have a positive effect by, for example, helping carers understand PSP and its associated problems better. In the longer term, it is hoped that our results will translate into clinical trials that will provide better treatments for managing challenging behavioural syndromes in PSP.

3. Other neurodegenerative disorders: PSP is a complex disorder that share some molecular, pathophysiological, and clinical features with other neurological disorders such as Parkinson's disease, Huntington's disease, and frontotemporal dementia. Taken together, these neurodegenerative disorders represent a very significant burden to society. We therefore hope that research enabling the development of more effective interventions to manage behavioral syndromes in PSP could be also applicable to other common neurodegenerative disorders.

Publications

10 25 50

publication icon
Azevedo T (2020) A deep spatiotemporal graph learning architecture for brain connectivity analysis. in Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

publication icon
Bevan-Jones RW (2018) [18F]AV-1451 binding is increased in frontotemporal dementia due to C9orf72 expansion. in Annals of clinical and translational neurology

publication icon
Bevan-Jones WR (2019) In vivo evidence for pre-symptomatic neuroinflammation in a MAPT mutation carrier. in Annals of clinical and translational neurology

publication icon
Cupaioli FA (2021) The neurobiology of human aggressive behavior: Neuroimaging, genetic, and neurochemical aspects. in Progress in neuro-psychopharmacology & biological psychiatry

 
Title Painting by Alan Rogerson 
Description Alan Rogerson attended the talk by Dr Luca Passamonti in 2018, where Luca discussed PSP and the methods of PET to study this disease. Alan draw an artistic inspiration from Luca's talk and in result produced the painting. 
Type Of Art Artwork 
Year Produced 2018 
Impact As above. 
 
Title Pint of Science 
Description Pint of Science festival presentations in pubs, bringing research progress and ideas to the public. 
Type Of Art Performance (Music, Dance, Drama, etc) 
Year Produced 2018 
Impact Wide public interest -sell out events 
 
Description Cambridge Dementia Course
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
URL http://www.cambridgedementiacourse.com/index.html
 
Description Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria (May 2017).
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
URL https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.26987
 
Description Guide to cognition in PSP
Geographic Reach Europe 
Policy Influence Type Influenced training of practitioners or researchers
Impact A guide to identifying and treating cognitive deficits in PSP and CBD, for the PSP- association, to educate and inform GPs and allied healthcare practitoners
 
Description UHF Research Review in Parkinsonism
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in systematic reviews
 
Description Video on PSP diagnosis -its not parkinson s-
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact Education video for healthcare workers, and GPs
URL https://www.youtube.com/watch?v=JlNwrq9wb2w
 
Description (Dr Sanne Kaalund) Dating protein aggregates in degenerative tauopathies, to model disease progression
Amount £4,754 (GBP)
Organisation Alzheimer's Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2020 
End 01/2021
 
Description Biomedical Research Centre Dementia Theme
Amount £118,000,000 (GBP)
Funding ID RG85367 
Organisation National Institute for Health Research 
Department NIHR Biomedical Research Centre
Sector Public
Country United Kingdom
Start 04/2017 
End 03/2022
 
Description Brain Network Analysis in Neurodegenerative Tauopathies
Amount £22,391 (GBP)
Funding ID RG89925 
Organisation The Evelyn Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2018 
End 12/2019
 
Description Measuring microscopic changes at the macroscopic level in frontotemporal dementia - Fellowship to Sanne S. Kaalund
Amount kr 400,000 (DKK)
Funding ID R232-2016-2333 
Organisation Lundbeck Foundation 
Sector Charity/Non Profit
Country Denmark
Start 08/2017 
End 07/2019
 
Description Restoring noradrenergic function to improve apathy in Parkinson s disease to Claire O Callaghan
Amount £49,677 (GBP)
Funding ID RG90797 
Organisation Parkinson's UK 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2017 
End 07/2018
 
Title LC atlas 
Description An atlas of locus ceruleus, currently as submisison in BioRxiv and and awaiting reviewers approval in Neuroimagine. This work is led by Dr Rong Ye. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2020 
Provided To Others? Yes  
Impact Early and profound pathological changes are evident in the locus coeruleus (LC) in dementia and Parkinson's disease, with effects on arousal, attention, cognitive and motor control. The LC can be identified in vivo using non-invasive magnetic resonance imaging techniques which have potential as biomarkers for detecting and monitoring disease progression. We created a probabilistic atlas of the LC from 53 healthy older volunteers (52-84 years) using a sensitive magnetisation transfer sequence and ultrahigh field 7T MRI to investigate the LC structure in vivo at high-resolution. We would like to make the atlas available on NITRC for researchers, for replication or to facilitate accurate LC localisation and unbiased contrast extraction in future cognitive and clinical studies. 
 
Description Cambridge Centre for Parkinson-Plus (CCPP) 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Clinical Research Programme 1 - Biomarker investigation Clinical Trial 1: Atomoxetine in PSP patients
Collaborator Contribution several
Impact publications pending
Start Year 2018
 
Description Cambridge LMU strategic partnership 
Organisation Ludwig Maximilian University of Munich (LMU Munich)
Country Germany 
Sector Academic/University 
PI Contribution A new strategic partnership to build a common research framework on cognitive reserve, resilience and dementia Bilateral meetings, joint grant writing, and visiting professorships
Collaborator Contribution A new strategic partnership to build a common research framework on cognitive reserve, resilience and dementia Bilateral meetings, joint grant writing, and visiting professorships
Impact Internal reports and new grant proposals
Start Year 2019
 
Description Claire O Callaghan - Restoring noradrenergic function to improve apathy in Parkinson s disease 
Organisation University of Cambridge
Department Department of Psychiatry
Country United Kingdom 
Sector Academic/University 
PI Contribution Input on study design
Collaborator Contribution Study design, will do data collection and analyses, publications pending
Impact publications still pending
Start Year 2017
 
Description Dating protein aggregates in degenerative tauopathies, to model disease progression 
Organisation University of York
Country United Kingdom 
Sector Academic/University 
PI Contribution Intellectual idea was conveyed by Dr Sanne Kaalund. The collaboration is at the stage of Dr Kaalund sending over the extracted tau fibrils.
Collaborator Contribution Prof Kirsty Penkman from York will analyse the samples to obtain racemization ratios of aminoacids.
Impact Yet to be determined.
Start Year 2020
 
Description Future collaboration discussion with Dorothy Hammerer (UCL) on atomoxetine studies within Alzheimeri's Disease 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution As above. Attendees from University of Cambridge: Prof Rowe, Dr Rong Ye, Dr Luca Passamonti, Dr Cat Rua and from UCL Dr Dorothy Hammerer.
Collaborator Contribution To be discerned.
Impact To be discerned.
Start Year 2020
 
Description Genetics of neurodegeneration collaboration with Van Andel University 
Organisation Van Andel Institute
Country United States 
Sector Private 
PI Contribution several hundred dementia case samples from longitudinal series of deep phenotyping
Collaborator Contribution genotyping and genotype interpetation
Impact pending
Start Year 2019
 
Description LC collaboration 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution We have engaged with two UCL groups who have a shared interest in noradrenergic systems, and imaging f the locus ceruleus in particular, with data sharing and plans for joint papers.
Collaborator Contribution New sequences and clinical applications of the MR technology
Impact A joint position paper Data sharing
Start Year 2018
 
Description Movement Disorder Society PSP study group 
Organisation International Parkinson and Movement Disorder Society (MDS)
Country United States 
Sector Charity/Non Profit 
PI Contribution 22 international sites are drawn together under this consortium, to advance PSP and CBS research and care, including biomarkers and clinical trials
Collaborator Contribution Expertise, trials design, new data sharing agreement
Impact Satellite meetings annually Pathology samples sharing Imaging data sharing Joint response to FDA on trial design issues
Start Year 2018
 
Description NIHR BRC 
Organisation National Institute for Health Research
Department NIHR Cambridge Biomedical Research Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution Biomarker development, including cognitive and imaging based deep phenotyping;
Collaborator Contribution Cellular, physiological, radio-chemistry, genetic and pharmaceutical innovations within a pipeline for novel drug discovery;
Impact Adams, N. E., Hughes, L. E., Phillips, H. N., Shaw, A. D., Murley, A. G., Nesbit, D., Cope, T. E., Bevan-Jones, W. R., Passamonti, L., Rowe, J. B. (2020). GABA-ergic dynamics in human frontotemporal networks confirmed by pharmaco magnetoencephalography, Journal of Neuroscience, https://doi.org/10.1523/JNEUROSCI.1689-19.2019. Lewis-Smith, D. J., Wolpe, N., Ghosh, B. C. P., Rowe, J. B. (2020). Alien limb in the corticobasal syndrome: phenomenological characteristics and relationship to apraxia, Journal of Neurology, https://doi.org/10.1007/s00415-019-09672-8. Jabbari, E., Chelban, V., Holland, N., Jones, P. S., Lamb, R., Rawlinson, C., Guo, T., Costantini, A. A., Tan, M. M. X., Heslegrave, A. J., Roncaroli, F., Klein, j. C., Ansorge, O., Allinson, K. S. J., Jaunmuktane, Z., Holton, J. L., Revesz, T., Warner, T. T., Lees, A. J., Zetterberg, H., Russell, L. L., Bocchetta, M., Rohrer, J. D., Williams, N. M., Grosset, D. G., Burn, D. J., Pavese, N., Gerhard, A., Kobylecki, C., Leigh, P. G., Church, A., Hu, M. T. M., Woodside, J., Houlden, H., Rowe, J. B., Morris, H. R. (2020). Diagnosis across the spectrum of progressive supranuclear palsy and corticobasal syndrome, JAMA Neurology, doi:10.1001/jamaneurol.2019.4347. van der Ende, E. L,, Meeter, L. H., Poos, J. M., Panman, J. L., Jiskoot, L. C., Dopper, E. G. P., Papma, J. M., de Jong, F. J., Verberk, I., Teunissen, C. E., Rizopoulos, D., Heller, C., Convery, R. S., Moore, K. M., Bocchetta, M., Neason, M., Cash, D. M., Borroni, B., Galimberti, D., Sanchez-Valle, R., Laforce, Jr R., Moreno, F., Synofzik, M., Graff, C., Masellis, M., Tartaglia, M. C., Rowe, J. B., Vandenberghe, R., Finger, E., Tagliavini, F., de Mendonça, A., Santana, I., Butler, C., Ducharme, S., Gerhard, A., Danek, A., Levin, J., Otto, M., Frisoni, G. B., Cappa, S., Pijnenburg, Y. A. L., on behalf of the GENetic Frontotemporal Dementia Initiative (GENFI), Rohrer, J. D., van Swieten, J. C. (2019). Longitudinal serum neurofilament light chain in genetic frontotemporal dementia: a multicentre cohort study. Lancet Neurology, 18: 1103-1111, https://doi.org/10.1016/S1474-4422(19)30354-0. Shafto, M. A., Henson, R. N., Matthews, F. E., Taylor, J. R., Emery, T., Erzinclioglu, S., Hanley, C., Rowe, J. B., Cusack, R., Calder, A. J., Marslen-Wilson, W. D., Duncan, J., Dalgleish, T., Brayne, C., Cam-CAN, Tyler, L. K. (2019). Cognitive Diversity in a Healthy Aging Cohort: Cross-Domain Cognition in the Cam-CAN Project, Journal of Aging and Health, doi: 10.1177/0898264319878095 [ahead of print], PMID: 31592706 Lansdall, C. J., Coyle-Gilchrist, I. T. S., Vázquez Rodríguez, P., Wilcox, A., Wehmann, E., Robbins, T. W., Rowe, J. B. (2019). Prognostic importance of apathy in syndromes associated with Frontotemporal lobar Degeneration, Neurology, 92(14):e1547-e1557. doi: 10.1212/WNL.0000000000007249, PMID: 30842292, PMC: 6448451. Borchert, B. J., Rittman, T., Rae, C. L., Passamonti, L., Jones, P. S., Vatansever, D., Vazquez-Rodriguez, P., Ye, Z., Nombela, C., Hughes, L. E., Robbins, T. W., Rowe, J. B. (2019). Atomoxetine and citalopram alter brain network organization in Parkinson's disease, Brain Communications, 1:1 fcz013, https://doi.org/10.1093/braincomms/fcz013. PMID: [pending], PMC: [pending]. Nicastro, N., Surendranathan, A., Mak, E., Rowe, J. B.*, O'Brien, J. T.* (2019). 11C-PK11195 PET imaging and white matter changes in Parkinson's disease dementia, Annals of Clinical and Translational Neurology, doi: 10.1002/acn3.50877, PMID: 31507085, PMC: [pending]. Low, A., Mak, E., Malpetti, M., Chouliaras, L., Nicastro, N., Su, L., Holland, N., Rittman, T., Vázquez Rodríguez, P., Passamonti, L., Bevan-Jones, W. R., Jones, P. S., Rowe, J. B.*, O'Brien, J. T.* (2019). Asymmetrical atrophy of thalamic subnuclei in Alzheimer's disease and amyloid-positive mild cognitive impairment is associated with key clinical features, Alzheimer's & Dementia: Diagnosis, Assessment, & Disease Monitoring, 11: 690-699, DOI: https://doi.org/10.1016/j.dadm.2019.08.001, PMID: 31667328, PMC: 6811895. Tavares, T. P., Mitchell, D. G. V., Coleman, K., Shoesmith, C., Bartha, R., Cash, D. M., Moore, K. M., van Swieten, J. C., Borroni, B., Galimberti, D., Tartaglia, M. C., Rowe, J. B., Graff, C., Tagliavini, F., Frisoni, G., Cappa, S., Laforce, R. Jr, de Mendonça, A., Sorbi, S., Wallstrom, G., Masellis, M., Rohrer, J. D., Finger, E. C., GENetic Frontotemporal Dementia Initiative (GENFI) (2019). Ventricular volume expansion in presymptomatic genetic frontotemporal dementia, Neurology, doi: 10.1212/WNL.0000000000008386, PMID: 31578297, PMC: [pending]. Passamonti, L., Tsvetanov, K. A., Jones, P. S., Bevan-Jones, W. R., Arnold, R., Borchert, R. J., Mak, E., Su, L., O'Brien, J. T.*, Rowe, J. B.* (2019). Neuroinflammation and functional connectivity in Alzheimer's disease: interactive influences on cognitive performance, Journal of Neuroscience, doi: 10.1523/JNEUROSCI.2574-18.2019. PMID: 31320450, PMC: 6733539. Jabbari, E., Woodside, J., Guo, T., Magdalinou, N. K., Chelban, V., Athauda, D., Lees, A. J., Foltynie, T., Houlden, H., Church, A., Hu, M. T., Rowe, J. B., Zetterberg, H., Morris, H. R. (2019). Proximity extension assay testing reveals novel diagnostic biomarkers of atypical parkinsonian syndromes, Journal of Neurology, Neurosurgery and Psychiatry, 90(7):768-773. doi: 10.1136/jnnp-2018-320151. PMID: 30867224, PMC: 6585258. Hughes, L. E., Henson, R. N., Pereda, E., Bruña, R., López-Sanz, D., Quinn, A. J., Woolrich, M. W., Nobre, A. C., Rowe, J. B., Maestú, F., BioFIND Working Group (2019). Biomagnetic biomarkers for dementia: A pilot multicentre study with a recommended methodological framework for magnetoencephalography, Alzheimers & Dementia (Amsterdam, Netherlands), 11:450-462. doi: 10.1016/j.dadm.2019.04.009. PMID: 31431918, PMC: 6579903. Shaw, A. D., Hughes, L. E., Moran, R., Coyle-Gilchrist, I., Rittman, T., Rowe, J. B. (2019). In Vivo Assay of Cortical Microcircuitry in Frontotemporal Dementia: A Platform for Experimental Medicine Studies. Cerebral Cortex. 2019. doi: 10.1093/cercor/bhz024. PMID: 31216360. van Eimeren, T., Antonini, A., Berg, D., Bohnen, N., Ceravolo, R., Drzezga, A., Höglinger, G. U., Higuchi, M., Lehericy, S., Lewis, S., Monchi, O., Nestor, P., Ondrus, M., Pavese, N., Peralta, M.C., Piccini, P., Pineda-Pardo, J. Á., Rektorová, I., Rodríguez-Oroz, M., Rominger, A., Seppi, K., Stoessl, A. J., Tessitore, A., Thobois, S., Kaasinen, V., Wenning, G., Siebner, H. R., Strafella, A. P., Rowe, J. B. (2019). Neuroimaging biomarkers for clinical trials in atypical parkinsonian disorders: Proposal for a Neuroimaging Biomarker Utility System. Alzheimers & Dementia (Amsterdam, Netherlands). 11:301-309. doi: 10.1016/j.dadm.2019.01.011. PMID: 30984816, PMC: 6446052. Rittman, T., Borchert, R., Jones, P. S., van Swieten, J., Borroni, B., Galimberti, D., Masellis, M., Tartaglia, M. C., Graff, C., Tagliavini, F., Frisoni, G. B., Laforce, R. Jr, Finger, E., Mendonça, A., Sorbi, S., Rohrer, J. D., Rowe, J. B., GENetic Frontotemporal Dementia Initiative (GENFI) (2019). Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia, Neurobioly of Aging, 77:169-177. doi: 10.1016/j.neurobiolaging.2018.12.009, PMID: 30831384; PMC: 6491498. Bevan-Jones, W. R., Cope, T. E., Jones, P. S., Passamonti, L., Hong, Y. T., Fryer, T., Arnold, R., Coles, J. P., Aigbirhio, F. I., O'Brien, J. T., Rowe, J. B. (2019). In vivo evidence for pre-symptomatic neuroinflammation in a MAPT mutation carrier. Annals of Clinical Translational Neurology, 6(2):373-378. doi: 10.1002/acn3.683. PMID: 30847369; PMC: 6389753.
Start Year 2017
 
Description Ultrahigh resolution imaging of neurodegeneration and vascular risk in aging and preclinical and prodromal Alzheimer's Disease 
Organisation The Otto-von-Guericke University Magdeburg
Country Germany 
Sector Academic/University 
PI Contribution New consortium to faciliate and validate 7T in dementia research, across 15 EU sites. Meets and draft preparation
Collaborator Contribution Led by Prof Duzel, Magdeburg, a consortium building on EUFIND.
Impact None yet. Funding sought
Start Year 2019
 
Title Atomoxetine in PSP 
Description new drug strategy for impulsivity in PSP to be tested for first time. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2017
Development Status Under active development/distribution
Impact reduced impulsivity in selected patients 
 
Title Biomarker evaluation of 7T MRI in dementia 
Description evaluation of novel 7T MRI for early detection of pathology in AD, and other dementias, building on the JPND consortium "EUFIND" 
Type Diagnostic Tool - Imaging
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2020
Development Status Under active development/distribution
Impact stronger links to basic cognitive neurosciences of memory systems, and to multi-centre clinical transnational centres across EU 
 
Description (Dr Sanne Kaalund) 121st Meeting of the British Neuropathological Society 4-6 March 2020 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Dr Kaalund presented the following talk: Locus coeruleus pathology in progressive supranuclear palsy is associated with disease severity.
Day: Friday 6th March 2020
Time: 09:45:00
Year(s) Of Engagement Activity 2020
URL https://www.bns.org.uk/event/121st-meeting-of-the-bns/
 
Description 121st British Neuropathological Society Annual Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The meeting is focused on neuropathology, this year with special focus on neurodegenerative diseases and prion-like properties of mis-folded proteins in dementia. Dr Sanne Kaalund will be giving the talk titled "Locus coeruleus pathology in progressive supranuclear palsy, and its relation to disease severit."
Year(s) Of Engagement Activity 2020
URL https://www.bns.org.uk/event/121st-meeting-of-the-bns/
 
Description Atlas-based in vivo Measurement of Human Locus Coeruleus in Neurodegenerative Disorders with 7T MRI (OHBM 2020) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Showcasing the application of the 7T Locus Coeruleus Atlas in neurodegenerative disorders.
Year(s) Of Engagement Activity 2020
URL https://www.humanbrainmapping.org/i4a/pages/index.cfm?pageid=3958
 
Description Bevan-Jones, W. R. Current practice and future directions. PSP Association Public Meeting (2017) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact Bevan-Jones, W. R. (2017). Current practice and future directions. PSP Association Public Meeting, Crewe, UK.
Year(s) Of Engagement Activity 2017
 
Description British Neuropathological Society meeting, Cirencester, UK 3-5 July 2019 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Attended by Dr Luca Passamonti and Dr Sanne Kaalund to strenghten their network in neuropathology research.
Year(s) Of Engagement Activity 2019
URL https://www.bns.org.uk/wp-content/uploads/2018/12/Programme_BNSSummerSchool2019.pdf
 
Description British Neuropsychiatry Association guest lecture - Apathy and Impulsivity in FTLD - not all dopamine, degeneration and death - Oxford 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact TBC
Year(s) Of Engagement Activity 2019
 
Description CCPP patient liaison 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact A patient liaison group, to advise and feedback on experience of research participation, and future studies' documentation.
Year(s) Of Engagement Activity 2018,2019
 
Description Care pathways for CBD 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Working group to develop new care pathways and national standards of care for CBD and related disorders
Year(s) Of Engagement Activity 2018
 
Description Channel 4 - cognitive enhancement 
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 Interviews and experiment conducted under on camera, into cognitive enhancement
Year(s) Of Engagement Activity 2018
 
Description Diagnosis and management of PSP 
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 SW Movement disroders group, event at Royal College of Physicians
Year(s) Of Engagement Activity 2018
 
Description Dr Frank Hezemans - Festival of Neuroscience 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Presenting recent results regarding the role of the locus coeruleus in apathy in Parkinsons disease. The purpose is to generate discussion and raise awareness of the role of this brain region and in regulating cognitive deficits associated in Parkinsons disease.
Year(s) Of Engagement Activity 2021
URL https://meetings.bna.org.uk/bna2021/
 
Description Dr Frank Hezemans - Neuroscience Network Symposium, Cambridge (27th Jul '19) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Approx 100 researchers attended (viewed poster presentation) on recent results from Parkinsons disease study, focusing on mechanisms of sensory/motor integration and potential benefit of treatment by atomoxetine.
Year(s) Of Engagement Activity 2019
URL https://www.neuroscience.cam.ac.uk/events/ABC2019/pages/about-abc.html
 
Description Dr Frank Hezemans - Poster presentation at International Behavioral Neuroscience Society 2020 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Approx 100 researchers attended (viewed poster presentation) on recent results from Parkinsons disease study, focusing on mechanisms of sensory/motor integration and potential benefit of treatment by atomoxetine.
Year(s) Of Engagement Activity 2020
URL https://www.ibnsconnect.org/ibns-2020-annual-meeting
 
Description Dr Frank Hezemans - Science Night 2021 prerecorded talk aimed at the general public about Parkinson's disease and noradrenaline 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Public event discussing various research studies bering carried out at MRC Cognition and Brain Sciences unit (University of Cambridge). Dr Hezemens focuses particularly on discussing Parkinson's disease and the effects of noradrenaline on the brain.
Year(s) Of Engagement Activity 2021
URL https://www.mrc-cbu.cam.ac.uk/blog/2020/01/mrc-cbu-science-night-cambridge-science-festival-2020/
 
Description Dr Rong Ye talk at Cambridge Centre for Parkinson's Plus (4th May 2020) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Presented research results on the application of 7T sequence and Atlas in the Parkinsonian diseases.
Year(s) Of Engagement Activity 2020
 
Description FTD UK Conference, Cambridge UK 2019 
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 A UK wide cross sector meeting on advances in FTD, from basic science to new theapeutics
Year(s) Of Engagement Activity 2019
URL http://www.ftduk.org/
 
Description Inernational symposium on PSP/CBD 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact International symposium, including talk and posters from our group, on progress in PSP and CBD reesarch
Engagement with Pharma
Year(s) Of Engagement Activity 2018
 
Description International Congress of Parkinson's Disease and Movement Disorders - Nice 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Advances in PSP and its overlap with FTD, main meeting and satellite symposia on PSP and Brain Imaging
Year(s) Of Engagement Activity 2019
URL https://www.mdscongress.org/Congress-Branded/19FP-_blue_puzzle_online.pdf
 
Description Invited speakers (Dr Rong Ye and Dr Cat Rua) to present 7T Locus Coerelus at the Danish Research Centre for Magnetic Resonance (Oct 2019) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Dr Rong Ye and Dr Cat Rua were invited to discuss the 7T research conducted at University of Cambridge. Future actions for collaborations were also discussed.
Year(s) Of Engagement Activity 2019
 
Description Lansdall, C. (May 2018). Organising Committee for Pint of Science, Annual Science Festival, Castle Bar, Cambridge, UK 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Discuss science with general public.
Year(s) Of Engagement Activity 2018
 
Description Locus Coeruleus Imaging Meeting Magdeburg 2019 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This workshop was attended by Dr Luca Passamonti, Dr Sanne Kaalund, Dr Rong Ye and Dr Catarina Rua. The team were showcasing research in LC and the use of 7T.

At this years LC meeting, we aim to focus on the following questions:

1. How can we improve structural / functional / PET LC imaging?

2. What is the role and fate of the LC in neurodegenerative and clinical conditions? What renders the LC particularly vulnerable?

3. What have we learned (also from animal research) on the LCs role in cognition and behavior in the last years?

4. What are the most promising interventions targeting the LC / NA system?

We will post a detailed program on the website and send it via email to all registered users at a later date. Please see information on our previous meeting held last February and the resultant consensus paper summarizing how LC imaging can be used for clinical research in neurodegenerative diseases.

New for this years meeting are 1-2 methods workshops for those interested:

A two day hackathon (Saturday 14th and Sunday 15th) where MR physicists will do some hands-on tests to explore new imaging approaches (this will be mostly relevant for MR physicists doing LC imaging)
If there is enough interest, an extra session on LC methods in animal research (electrophysiology, high-field imaging, optogenetics, ...) which will take place on Saturday 14th. Please let us know if you would like to join either of these!
Year(s) Of Engagement Activity 2019
URL http://www.iknd.ovgu.de/LC+Meeting+2019.html
 
Description PPE - Cambridge university Hospitals Trust members 
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 An evening event for the members of the Trust (patients, and local public) to discuss advances in dementia research and care, including the insights from new technologies
Year(s) Of Engagement Activity 2019
 
Description PSP Matters 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Extended interview on PSP research, researchers, motivation and progress.
How donations lead to real research progress, and added value
Year(s) Of Engagement Activity 2018
URL https://pspassociation.org.uk/information-and-support/just-been-diagnosed/psp-matters/
 
Description PSP carers meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Special meeting to initiate a PSP support network locally, and engage families with PSP mattes, clinical and research, and the local team
Year(s) Of Engagement Activity 2018
 
Description Passamonti, L. (16th May 2018). Halting nerve cell death and improving quality of life in progressive supranuclear palsy. Pint of Science, Annual Science Festival, Castle Bar, Cambridge, UK 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Discuss science with general public.
Year(s) Of Engagement Activity 2018
 
Description Rowe - 11th Cambridge Dementia Course. Oliver Cousins for Advances in Clinical Neuroscience and Rehabilitation (ACNR), (2017). 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Rowe, J. B. (11th April 2017). 11th Cambridge Dementia Course. Oliver Cousins for Advances in Clinical Neuroscience and Rehabilitation (ACNR).
Year(s) Of Engagement Activity 2017
URL http://www.acnr.co.uk/2017/04/11th-cambridge-dementia-course/
 
Description Rowe - Cambridge Science Festival (2017) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Lecture at Cambridge Science Festival
Year(s) Of Engagement Activity 2017
 
Description Rowe - Cambridge Science Festival 2018 - Molecules to Memory - Advances in Dementia Research, hosted by ARUK local network 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact public talk at Cambridge Science Festival
Year(s) Of Engagement Activity 2018
 
Description Rowe - FTD Carers' Meeting, Department of Clinical Neurosciences, University of Cambridge, UK (2014) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Rowe, J. B. (24th March 2014). FTD Carers' Meeting, Department of Clinical Neurosciences, University of Cambridge, UK.
Year(s) Of Engagement Activity 2014
 
Description Rowe - FTD Carers' Meeting. Department of Clinical Neurosciences, University of Cambridge (2017). 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Rowe, J. B. (13th September 2017). FTD Carers' Meeting. Department of Clinical Neurosciences, University of Cambridge; give feedback to carers and also get feedback from them.
Year(s) Of Engagement Activity 2017
 
Description Rowe - FTD-UK Annual Meeting (2017) - Debate 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A discussion of imaging's contribution to FTD diagnosis, prognosis and stratification
Year(s) Of Engagement Activity 2017
 
Description Rowe - Look East. The latest news, sport and weather for the East of England. BBC One. (Feature about PSP Association) (2017) 
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 Rowe, J. B. (16th May 2017). Look East. The latest news, sport and weather for the East of England. BBC One. (Feature about PSP Association).
Year(s) Of Engagement Activity 2017
 
Description Rowe - PSP Matters (2017) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Research update and progress for PSPA
Year(s) Of Engagement Activity 2016,2017
 
Description Rowe, J. B. (28th September 2017) Understanding frontotemporal dementia: an interview with Professor James Rowe - Interview for the National Institute for Health Research (NIHR) (2017) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Rowe, J. B. (28th September 2017) Understanding frontotemporal dementia: an interview with Professor James Rowe. Interview for the National Institute for Health Research (NIHR). https://www.nihr.ac.uk/news-and-events/features/behind-the-research/Understanding-frontotemporal-dementia.htm
Year(s) Of Engagement Activity 2017
URL http://www.nihr.ac.uk/news-and-events/features/behind-the-research/Understanding-frontotemporal-deme...
 
Description Rowe/Team - Cambridge Science Festival (2017) 
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 lecture on the challenge of dementia as part of the Cambridge Science Festival
Year(s) Of Engagement Activity 2017
 
Description Rowe: FTD carers meeting (2017) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Research discussion to regional carers
Year(s) Of Engagement Activity 2017
 
Description Seven lab members (22nd March 2018). 5k for the PSP Association to raise money to support people affected by CBD & PSP, Cambridge, UK. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Run for PSP and CBD to increase awareness. https://www.pspassociation.org.uk/fundraising/5kforpspa/; promoted on twitter
Year(s) Of Engagement Activity 2018
 
Description Vazquez, (2017); Half Marathon to raise money and awareness for patients with Progressive Supranuclear Palsy and the PSP Association, Thessaloniki Night Half-Marathon, Greece. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Vazquez Rodriguez, P. (14th October 2017). Half Marathon to raise money and awareness for patients with Progressive Supranuclear Palsy and the PSP Association, Thessaloniki Night Half-Marathon, Greece.
Year(s) Of Engagement Activity 2017
 
Description Vazquez/Rowe - Fighting PSP both in and outside the lab. PSP Association Magazine (2017) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Vazquez Rodriguez, P. (September 2017). Fighting PSP both in and outside the lab. PSP Association Magazine; raise awareness for PSP
Year(s) Of Engagement Activity 2017
 
Description Vázquez Rodríguez; Imaging neuroinflammation in progressive supranuclear palsy and Alzheimer's disease. Talk presented at the PSP Association Annual Study Day (2017) 
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 Vázquez Rodríguez, P. (18th October 2017). Imaging neuroinflammation in progressive supranuclear palsy and Alzheimer's disease. Talk presented at the PSP Association Annual Study Day, Milton Keynes, UK. Was evaluated as best presentation.
Year(s) Of Engagement Activity 2017
 
Description WIRED magazine 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Session with WIRED magazine journalists, on cognitive enhancement

Education of the public about the ethics, efficacy and evidence for cognitive enhancement
Year(s) Of Engagement Activity 2013