Dementia/Neurodegeneration Research Database - Research Projects
Early, non-invasive, inexpensive biomarkers of Alzheimer’s Disease (AD) are much needed. Those with Down syndrome (DS) are the largest patient group at increased risk of AD. Evidence suggests that imaging the eye could be a non-invasive biomarker to screen for AD. However, there is limited information regarding ocular changes in DS. Our group was the first to image the lens in DS, revealing the presence of small ‘dot’ opacities in the lens in 54% of individuals with DS. We were also the first to show that the retina and the choroid in adults with DS thicken rather than thins, as expected to accompany neurodegeneration. These observations could be due to inflammatory changes that may take place in the preclinical stages of AD. This proposed study builds upon these investigations. We will use state-of-the-art, high-resolution ocular imaging techniques and visual function assessments to monitor differences in the eye in people with DS and those with and without mild cognitive impairment (MCI). Patients will be stratified using cognitive tests and blood-based standard biomarkers. Inflammatory markers will be measured by proteomic and transcriptomic analysis of blood, saliva and tears to determine the most representative biofluid linked to ocular differences. We hypothesise that we will be able to identify easily accessible and well-tolerated eye imaging markers and inflammatory biomarkers for DS and MCI participants. This work will help define the pathomechanism of early changes in AD, and could lead to targeted therapeutic interventions in the longer term.
To develop accessible best practice guidelines for post-diagnostic dementia supports for people with an intellectual disability in Ireland. The project aims to:
(1) examine the current landscape of post-diagnostic care at a national level;
(2) consider barriers to access;
(3) incorporate existing best practices; and
(4) give due consideration of the experiences and recommendations of people with an intellectual disability living with dementia and of their families/carers.
Project Aim(s): PD-MitoQUANT is an Innovative Medicines Initiative (IMI)Innovative Medicines Initiative (IMI) (www.imi.europa.eu) project that brings together academic experts, small and medium enterprises (SMEs), pharmaceutical companies from the European Federation of Pharmaceutical Industries and Associations (EFPIA)European Federation of Pharmaceutical Industries and Associations (EFPIA) (www.efpia.eu) and patient advocacy organisation Parkinson’s UKParkinson’s UK (www.parkinsons.org.uk).
The project aims to:
1) Improve our understanding of mitochondrial dysfunction in Parkinson’s disease.
2) Identify and validate molecular drivers and mechanisms in Parkinson’s disease.
3) Discover innovative therapeutic targets that can be further progressed by the EFPIA partners in the future, and
4) Initiate a European research platform of excellence in PD that will continue beyond the project, providing long-term and sustainable progress in the understanding of mitochondrial dysfunction in PD, towards clinical application.
Project Aim(s): To investigate bone morphogenetic protein 2 as a therapeutic for Parkinson's disease (PD).
Project Aim(s): To support national and local Parkinson’s disease service planning by three linked work packages.
The first maps the prevalence of Parkinson’s disease and service availability for people with Parkinson’s, across each of the nine Community Healthcare Organisation regions in Ireland, to highlight mismatches between population needs and service provision.
The second develops quality indicators for Irish PD services and assesses existing services against these indicators, to demonstrate where extra resources are needed to provide a quality service.
The final work package explores the experience of people with Parkinson’s with respect to services they receive, and their priorities for service provision.
The aim of this study is to inform the design of a virtual reality (VR) social connecting space for older adults living with dementia.
1. Overview of Research Plans.
The successful treatment of memory impairments and neurodegenerative disorders critically depends on our understanding of the storage and recollection of memory episodes. Specifically, an understanding of the interaction between amnesic and neurodegenerative syndromes would aid the development of effective treatments. One of the key questions in neuroscience is: how do brain networks encode experience-dependent memory? Answering this question will give us universal tool to treat multiple brain disorders. The anatomical focus of my current research interests is the interaction between limbic, basal forebrain and nigro-striatal circuits as a possible candidate for interregional coordination of spatial navigation and context-dependent components of episodic memory.
I plan to examine if 1) neuromodulation from cholinergic neurons in forebrain and pontine tegmentum and 2) neuromodulation from dopaminergic and GABA-ergic neurons from ventral tegmental area (VTA) and substantia nigra can regulate the properties of spatial experience-dependent spatial navigation to guide behavior. Understanding the fundamental principles of this inter-regional signal processing will allow me to address my next goal: to apply pharmacological, electrophysiological and genetic tools to treat memory and movement disorders. The cellular response to cholinergic and dopaminergic neurotransmitters in hippocampal region is largely explored, but little is known about the optimizing effect of extrinsic manipulation of the neuromodulatory projections on the encoding properties of hippocampal neurons and mnemonic function of the limbic system. Therefore, the present proposal addresses two broad questions: 1) Can we enhance the hippocampal spatial representation by activation of the cholinergic/dopaminergic systems? 2) Should medial temporal lobe amnesia and depression be regarded as independent syndromes, or are they interlinked?
2. Current Research.
My concurrent investigation targets the septal area, which is interconnected with 1) the hippocampus which mediates spatial memory 2) ventral dopaminergic tegmentum, which mediates reward-motivated behavior, and 3) medial cholinergic septal inputs, which regulate of the limbic excitability and network rhythmicity, that are crucially involved in the neuropathology of the Alzheimer’s disease. There is, however, limited information about how hippocampal spatial and tegmental reward systems maintain feedback loop to synchronize their activity for place and reward. I propose that septal neurons integrate spatial and context reward value, enabling episodic memory for past experience to support future adaptive behavior. Using electrophysiological recordings from rats performing spatial and reinforcement tasks I am currently identifying the signal processing of the space and reward for each septal sub-region (manuscript in preparation). My optognetic stimulation design also explores the role of pathophysiological alteration of septal cholinergic and tegmental dopaminergic inputs on septo-hippocampal neuronal responses and adaptive behaviour.
3. Next Research Aims.
I plan to examine if 1) neuromodulation from cholinergic neurons in forebrain and pontine tegmentum and 2) neuromodulation from dopaminergic and GABA-ergic neurons from ventral tegmental area (VTA) and substantia nigra can regulate the properties of spatial experience-dependent spatial navigation to guide behavior. Understanding the fundamental principles of this inter-regional signal processing will allow me to address my next goal: to apply pharmacological, electrophysiological and genetic tools to treat memory and movement disorders. The cellular response to cholinergic and dopaminergic neurotransmitters in hippocampal region is largely explored, but little is known about the optimizing effect of extrinsic manipulation of the neuromodulatory projections on the encoding properties of hippocampal neurons and mnemonic function of the limbic system. Therefore, the present proposal addresses two broad questions: 1) Can we enhance the hippocampal spatial representation by activation of the cholinergic/dopaminergic systems? 2) Should medial temporal lobe amnesia and depression be regarded as independent syndromes, or are they interlinked?
One promising approach for the treatment of PD is cellular brain repair whereby the cells that have died in the condition are replaced by transplantation of healthy cells into the brain. However, this approach has faced several limitations including poor survival of the transplanted cells in the PD brain. To address this limitation, we have recently shown that biomaterials - that is, materials that have been specifically engineered to interact with living systems for therapeutic purposes – have the potential to dramatically improve cellular brain repair for PD. Specifically, when the brain cells were encapsulated in a growth factor enriched biomaterial before transplantation into the (rat) PD brain, the survival of the cells was dramatically improved, and this enhanced brain repair and recovery of movement control. The aim of this project is to continue and extend these previous findings, and to determine if growth factor enriched biomaterials can also improve cellular brain repair for PD.
Project Aim(s): This proposal aims to combine our novel EEG based technology with detailed neuropsychological assessment to provide a quantitative measure of cognitive change in MS that could be used in a clinical trial setting. The study will also provide an opportunity to assess for the first time the impact of Cladribine on cognitive performance using conventional screening tools, detailed neuropsychological batteries, and experimental neurophysiology based paradigms that could be harnessed for future nested case control studies.
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