The latest list of publications from the NIHR Cambridge Biomedical Research Centre with a brief summary.
If you are publishing research which has had funding and / or support from the NIHR Cambridge Biomedical Research Centre, please complete this form.
Claire J. Lansdall, Ian T.S. Coyle-Gilchrist, Patricia Vázquez Rodríguez, Alicia Wilcox, Eileen Wehmann, Trevor W. Robbins, James B. Rowe
12 April 2019
This research determined the influence of apathy, impulsivity, and behavioral change on survival in patients with frontotemporal dementia, progressive supranuclear palsy, and corticobasal syndrome.
The relationship between apathy and survival highlights the need to develop more effective and targeted measurement tools to improve its recognition and facilitate treatment. The prognostic importance of apathy suggests that neurobehavioral features might be useful to predict survival and stratify patients for interventional trials.
Effective symptomatic interventions targeting the neurobiology of apathy might ultimately also improve prognosis.
Publication: Brain Communications
Robin J Borchert, Timothy Rittman, Charlotte L Rae, Luca Passamonti, Simon P Jones, Deniz Vatansever, Patricia Vázquez Rodríguez, Zheng Ye, Cristina Nombela, Laura E Hughes, Trevor W Robbins, James B Rowe
6 September 2019
Parkinson’s disease has multiple detrimental effects on motor and cognitive systems in the brain. In contrast to motor deficits, cognitive impairments in Parkinson’s disease are usually not ameliorated, and can even be worsened, by dopaminergic treatments. Recent evidence has shown potential benefits from restoring other neurotransmitter deficits, including noradrenergic and serotonergic transmission.
The researchers studied global and regional brain network organization using task-free imaging (also known as resting-state), which minimizes performance confounds and the bias towards predetermined networks.
Thirty-three patients with idiopathic Parkinson’s disease were studied three times in a double-blinded, placebo-controlled counter-balanced crossover design, following placebo, 40 mg oral atomoxetine (selective noradrenaline reuptake inhibitor) or 30 mg oral citalopram (selective serotonin reuptake inhibitor).
In patients, atomoxetine improved fluency in proportion to plasma concentration, and improved response inhibition in proportion to increased hub Eigen centrality. Citalopram did not improve fluency or inhibitory control, but its influence on network integration and efficiency depended on disease severity: clustering, modularity and path length increased in patients with milder forms of Parkinson’s disease, but decreased in patients with more advanced disease.
This study supports the use of task-free imaging of brain networks in translational pharmacology of neurodegenerative disorders. The researchers propose that hub connectivity contributes to cognitive performance in Parkinson’s disease, and that noradrenergic treatment strategies can partially restore the neural systems supporting executive function.View publication
Publication: Annals of Clinical and Translational Neurology
Nicolas Nicastro, Ajenthan Surendranathan, Elijah Mak, James B. Rowe, John T. O’Brien
10 September 2019
There is evidence of increased microglial activation in Parkinson’s disease (PD) as shown by in vivo PET ligand such as 11C‐PK11195. In addition, diffusion tensor imaging (DTI) imaging reveals widespread changes in PD, especially when the associated dementia develops.
The researchers studied five subjects with Parkinson’s disease dementia (PDD). Their findings suggest that while DTI metrics mirror cognitive severity, higher 11C‐PK11195 binding seems to be associated with a relative preservation of both white matter tracts and cognition.
Longitudinal studies are warranted to tackle the complex relationship between microglial activation and structural abnormalities in neurodegenerative conditions.View publication
Publication: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Audrey Low, Elijah Mak, Maura Malpetti, Leonidas Chouliaras, Nicolas Nicastro, Li Sua, Negin Holland, Timothy Rittman, Patricia Vázquez Rodríguez, Luca Passamonti, W Richard Bevan-Jones, PP Simon Jones, James B.Rowe, John T.O’Brien
1 December 2019
Widespread cortical asymmetries have been identified in Alzheimer’s disease (AD), but thalamic asymmetries and their relevance to clinical severity in AD remain unclear.
This research discovered that although overall asymmetry of the thalamus did not differ between groups, greater leftward lateralization of atrophy in the ventral nuclei was demonstrated in AD, compared with controls and amyloid-positive mild cognitive impairment. Increased posterior ventrolateral and ventromedial nuclei asymmetry were associated with worse cognitive dysfunction, informant-reported neuropsychiatric symptoms, and functional ability.
Leftward ventral thalamic atrophy was associated with disease severity in AD. The findings suggest the clinically relevant involvement of thalamic nuclei in the pathophysiology of AD.View publication
Jeremy M. Brown, Julie Wiggins, Kate Dawson, Timothy Rittman, James B. Rowe
12 August 2019
This research paper summarises the current status of two novel short cognitive tests (SCT), known as Test Your Memory (TYM) and Test Your Memory for Mild Cognitive Impairment (TYM-MCI). The history of and recent research on the TYM and TYM-MCI are summarised in applications for Alzheimer’s and non-Alzheimer’s dementia and mild cognitive impairment.
In this NIHR Cambridge-BRC funded research, the researchers found out that the TYM test can be used in a general neurology clinic and can help distinguish patients with Alzheimer’s disease (AD) from those with no neurological cause for their memory complaints. An adapted tele-TYM test administered by telephone to patients produces scores which correlate strongly with the clinic-administered Addenbrooke’s Cognitive Examination revised (ACE-R) test and can identify patients with dementia.
This is important because the team showed that patients with AD decline on the TYM test at a rate of 3.6–4.1 points/year.View publication
Publication: Journal of Magnetic Resonance Imaging
Dimitri A. Kessler, James W. MacKay, Scott McDonald, Stephen McDonnell, Andrew J. Grainger, Alexandra R. Roberts, Robert L. Janiczek, Martin J. Graves, Joshua D. Kaggie, Fiona J. Gilbert
The researchers wanted to further understanding of the biomechanical properties of articular cartilage in our knee joints. By combining quantitative magnetic resonance imaging (MRI) and sophisticated 3D surface analysis methods of articular cartilage they were able to determine changes in cartilage microstructure following a mild, 5-minute stepping exercise in young, healthy individuals.
The team determined that our quantitative MRI methods are sensitive to changes of different compositional characteristics of articular cartilage such as changes in its water content or macromolecular structure following the stepping exercise. While previous studies have shown that changes in cartilage morphology (thickness, volume) recovers almost fully in about 45–90 minutes, they showed that the compositional changes induced by the exercise do not recover within an hour following cessation.
This is important because measuring the responses of cartilage to dynamic joint loading may present a way of determining cartilage health state as well as differences in healthy and diseased cartilage. With the exercise performed in this study being short and of limited duration, it could be extended for use in patients with early‐stage knee joint disease and minimal accompanying pain. As exercise is recommended as a form of conservative management of joint disease-related symptoms, the study provides an initial interpretation of short-term changes that occur in cartilage microstructure in response to exercise.View publication
Ranya Mulchandani, Hayley E Jones, Sian Taylor-Phillips, Justin Shute, Keith Perry, Shabnam Jamarani, Tim Brooks, Andre Charlett, Matthew Hickman, Isabel Oliver, Stephen Kaptoge, John Danesh, Emanuele Di Angelantonio, Anthony E Ades, David H Wyllie,
11 November 2020
The accuracy of a COVID-19 test is lower than previously believed. Testing nearly 5,000 samples found some results were giving false positives.View publication
Publication: The Lancet: Diabetes and Endocrinology
Prof Karine Clément, MD, Prof Erica van den Akker, MD, Prof Jesús Argente, MD, Allison Bahm, MD, Prof Wendy K Chung, MD, Hillori Connors, MS, Kathleen De Waele, MD, Prof I Sadaf Farooqi, PhD, Julie Gonneau-Lejeune, MD, Gregory Gordon, MD, Katja Kohlsdorf, MD, Prof Christine Poitou, MD, Lia Puder, MD, James Swain, MD, Murray Stewart, DM, Guojun Yuan, PhD, Prof Martin Wabitsch, MD, Prof Peter Kühnen, MD
30 October 2020
In this international phase 3 study, researchers wanted to see if the drug Setmelanotide could help people whose severe obesity is caused by pro-opiomelanocortin (POMC) or leptin (LEPR) deficiency.
Melanocortin 4 Receptor (MC4R), plays a critical part in bodyweight regulation and Setmelanotide is an MC4R agonist. This trial was conducted in several countries with participants with severe obesity due to either POMC deficiency LEPR deficiency.
After approximately 1 year, eight (80%) participants in the POMC trial and five (45%) participants in the LEPR trial achieved at least 10% weight loss. Researchers found Setmelanotide to be a safe and effective treatment for people with POMC or LEPR deficiency.
This research could benefit people who find it hard to lose weight. There are ongoing trials to test whether Setmelanotide is effective in other genetic obesity syndromes.View publication
Publication: Journal of Neurology, Neurosurgery, and Psychiatry
Maura Malpetti, Timothy Rittman, Peter Simon Jones, Thomas Edmund Cope, Luca Passamonti, William Richard Bevan-Jones, Karalyn Patterson, Tim D Fryer, Young T Hong, Franklin I Aigbirhio, John Tiernan O’Brien, James Benedict Rowe
29 October 2020
Using PET imaging, researchers looked at neuro inflammation and abnormal growth of protein for patients with frontotemporal dementia (FTD). They found Familial FTD was associated with neuroinflammation across all genes and also reflected clinical heterogeneity. This research will be able to help to further understand the disease and in particular around the immune system to help with treatments and prevention.View publication
Publication: International Journal of Stroke
Stefania Nannoni , Rosa de Groot, Steven Bell, Hugh S Markus
26 October 2020
Fourteen out of every 1,000 COVID-19 patients admitted to hospital experience a stroke, a rate that is even higher in older patients and those with severe infection and pre-existing vascular conditions.
A team of researchers at the Stroke Research Group, carried out a systematic review and meta-analysis of published research into the link between COVID-19 and stroke. In total, the researchers analysed 61 studies, covering more than 100,000 patients admitted to hospital with COVID-19. The researchers found that stroke occurred in 14 out of every 1,000 cases. The most common manifestation was acute ischemic stroke, which occurred in just over 12 out of every 1,000 cases. Brain haemorrhage was less common, occurring in 1.6 out of every 1,000 cases. Most patients had been admitted with COVID-19 symptoms, with stroke occurring a few days later.
Read the full news storyView publication
Sunjie Ye, Arsalan A. Azad, Joseph E. Chambers, Alison J. Beckett, Lucien Roach, Samuel C. T. Moorcroft, Zabeada Aslam, Ian A. Prior, Alexander F. Markham, P. Louise Coletta, Stefan J. Marciniak, Stephen D. Evans
25 October 2020
More than 2,600 people are diagnosed in the UK each year with mesothelioma, a malignant form of cancer caused by exposure to asbestos and can be hard to treat.
In a collaboration between the University of Cambridge and University of Leeds, researchers have developed a form of gold nanotubes whose physical properties are ‘tunable’ – in other words, the team can tailor the wall thickness, microstructure, composition, and ability to absorb particular wavelengths of light.
The researchers added the nanotubes to mesothelioma cells cultured in the lab and found that they were absorbed by the cells, residing close to the nucleus, where the cell’s DNA lies. When the team targeted the cells with a laser, the nanotubes absorbed the light and heated up, killing the mesothelioma cell.
Read the full press releaseView publication
Publication: Cell Stem Cell
Jeonghwan Youk, Taewoo Kim, Kelly V.Evans, Young-IlJeong, Yongsuk Hur, Seon Pyo Hong, Je Hyoung Kim, Kijong Yi, Su Yeon Kim, Kwon JoongNa, Thomas Bleazard, Ho Min Kim, Mick Fellows, Krishnaa T. Mahbubani, Kourosh Saeb-Parsy, Seon Young Kim, Young Tae Kim, Gou YoungKoh, Joo-Hyeon Lee
21 October 2020
To better understand how SARS-CoV-2 infects the lungs and causes disease, a team of scientists from the UK and South Korea turned to organoids – ‘mini-organs’ grown in three dimensions to mimic the behaviour of tissue and organs.
The team used tissue donated to tissue banks at the Royal Papworth Hospital NHS Foundation Trust and Addenbrooke’s Hospital, Cambridge University NHS Foundations Trust, UK, and Seoul National University Hospital to extract a type of lung cell known as human lung alveolar type 2 cells. By reprogramming these cells back to their earlier ‘stem cell’ stage, they were able to grow self-organising alveolar-like 3D structures that mimic the behaviour of key lung tissue.
Read the full press releaseView publication