A5045725813- Alzheimer's disease research and treatments
- Machine Learning in Healthcare
- Dementia and Cognitive Impairment Research
- Topic Modeling
- Tryptophan and brain disorders
- Metabolomics and Mass Spectrometry Studies
- Bioinformatics and Genomic Networks
- Blood Pressure and Hypertension Studies
- Biomedical Text Mining and Ontologies
- Genetic Associations and Epidemiology
- Health, Environment, Cognitive Aging
- Stress Responses and Cortisol
- Neuroinflammation and Neurodegeneration Mechanisms
- Diet and metabolism studies
- Computational Drug Discovery Methods
- Natural Language Processing Techniques
- Parkinson's Disease Mechanisms and Treatments
- Epigenetics and DNA Methylation
- Nutritional Studies and Diet
- Mental Health via Writing
- Hemoglobinopathies and Related Disorders
- Pharmaceutical Practices and Patient Outcomes
- Machine Learning in Bioinformatics
- Neurological disorders and treatments
- Pharmacological Effects and Toxicity Studies
University of Oxford
2016-2025
King Abdulaziz University
2024
Artificial Intelligence in Medicine (Canada)
2024
Janssen (United Kingdom)
2024
Open Data Institute
2020-2023
Warneford Hospital
2016-2022
Oxford Health NHS Foundation Trust
2019-2020
Hospital Del Mar
2017
Hospital del Mar Research Institute
2017
King's College London
2017
The advance of Parkinson's disease is associated with the existence abnormal oscillations within basal ganglia frequencies in beta band (13–30 Hz). While origin these remains unknown, there some evidence suggesting that observed arise due to interactions two nuclei: subthalamic nucleus (STN) and globus pallidus pars externa (GPe). To investigate this hypothesis, we develop a computational model STN–GPe network based upon anatomical electrophysiological studies. Significantly, our study shows...
Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes with disease, experimental data demonstrated proliferation as a component of the neuropathology. In this study, we tested efficacy selective CSF1R inhibitor JNJ-40346527 (JNJ-527) P301S mouse tauopathy model. We first anti-proliferative effects JNJ-527 on microglia ME7 prion model, its impact inflammatory...
Failure to translate successful neuroprotective preclinical data a clinical setting in Alzheimer's disease (AD) indicates that amyloidopathy and tauopathy alone provide an incomplete view of disease. We have tested here the relevance additional homeostatic deviations result from loss activity transcription factor NRF2, crucial regulator multiple stress responses whose declines with ageing. A transcriptomic analysis demonstrated NRF2-KO mouse brains reproduce 7 10 most dysregulated pathways...
Abstract Introduction Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a “Holy Grail” of AD research and intensively sought; however, there no well‐established plasma markers. Methods A hypothesis‐led biomarker search was conducted in the context international multicenter studies. The discovery phase measured 53 inflammatory proteins elderly control (CTL; 259), mild cognitive impairment (MCI; 199), (262) subjects from AddNeuroMed. Results Ten analytes showed...
Importance Metabolomics reflect the net effect of genetic and environmental influences thus provide a comprehensive approach to evaluating pathogenesis complex diseases, such as depression. Objective To identify metabolic signatures major depressive disorder (MDD), elucidate direction associations using mendelian randomization, evaluate interplay human gut microbiome metabolome in development MDD. Design, Setting Participants This cohort study used data from participants UK Biobank (n = 500...
A diverse set of biological processes have been implicated in the pathophysiology Alzheimer's disease (AD) and related dementias. However, there is limited understanding peripheral mechanisms relevant earliest phases disease. Here, we used a large-scale proteomics platform to examine association 4877 plasma proteins with 25-year dementia risk 10,981 middle-aged adults. We found 32 dementia-associated that were involved proteostasis, immunity, synaptic function, extracellular matrix...
Circulating plasma proteins play key roles in human health and can potentially be used to measure biological age, allowing risk prediction for age-related diseases, multimorbidity mortality. Here we developed a proteomic age clock the UK Biobank (n = 45,441) using platform comprising 2,897 explored its utility predict major disease morbidity mortality diverse populations. We identified 204 that accurately chronological (Pearson r 0.94) found aging was associated with incidence of 18 chronic...
Background Intimate partner violence (IPV) against women is associated with a wide range of adverse outcomes. Although mental disorders have been linked to an increased risk perpetrating IPV women, the direction and magnitude association remain uncertain. In longitudinal design, we examined between perpetrated by men towards in population-based sample used sibling comparisons control for factors shared siblings, such as genetic early family environmental factors. Methods findings Using...
In Parkinsonism, subthalamic nucleus (STN) neurons and two types of external globus pallidus (GP) neuron inappropriately synchronise their firing in time with slow (∼1 Hz) or beta (13-30 oscillations cortex. We recorded the activities STN, Type-I GP (GP-TI) Type-A (GP-TA) anaesthetised Parkinsonian rats during such to constrain a series computational models that systematically explored effective connections physiological parameters underlying neuronal rhythmic phase preferences vivo. The...
Abstract Introduction Machine learning (ML) may harbor the potential to capture metabolic complexity in Alzheimer Disease (AD). Here we set out test performance of metabolites blood categorize AD when compared CSF biomarkers. Methods This study analyzed samples from 242 cognitively normal (CN) people and 115 with AD‐type dementia utilizing plasma (n = 883). Deep Learning (DL), Extreme Gradient Boosting (XGBoost) Random Forest (RF) were used differentiate CN. These models internally validated...
Lipids such as ceramides and phosphatidylcholines (PC) have been found altered in the plasma of Alzheimer's disease (AD) patients a number discovery studies.For this reason, levels 6 3 PCs, with different fatty acid length saturation levels, were measured from 412 participants (AD n = 205, Control 207) using mass spectrometry coupled ultra-performance liquid chromatography.After this, associations AD status, brain atrophy, age-related effects studied.In participants, cross-sectional analysis...
Abstract Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action not fully understood and therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing panel 180 metabolites to gain insights into response citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study...
When the first transformer-based language models were published in late 2010s, pretraining with general text and then fine-tuning model on a task-specific dataset often achieved state-of-the-art performance. However, more recent work suggests that for some tasks, directly prompting pretrained matches or surpasses performance few no parameter updates required. The use of prompts natural processing (NLP) tasks is known as prompt learning. We investigated viability learning clinically...
Actions expressed prematurely without regard for their consequences are considered impulsive. Such behaviour is governed by a network of brain regions including the prefrontal cortex (PFC) and nucleus accumbens (NAcb) prevalent in disorders attention deficit hyperactivity disorder (ADHD) drug addiction. However, little known relationship between neural activity these specific forms impulsive behaviour. In present study we investigated local field potential (LFP) oscillations distinct...
The untargeted discovery and replication of a blood protein panel shows promise for predicting preclinical Alzheimer’s disease.
A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites blood associated with as indexed by cerebrospinal fluid (CSF) AD biomarkers.This study analyzed 593 plasma samples selected from European Medical Information Framework for Disease Multimodal Biomarker Discovery study, individuals who were cognitively healthy (n = 242), had mild...
Studies have shown that low haemoglobin and anaemia are associated with poor cognition, is known to be Alzheimer's disease (AD), but the mechanism of this risk unknown. Here, we first seek confirm association between cognition secondly, in order further understand association, estimate direction causation using Mendelian randomisation.Two independent cohorts were used analysis: AddNeuroMed, a longitudinal study 738 subjects including AD age-matched controls blood cell measures, cognitive...
Observational studies have shown consistently increased likelihood of dementia or mild cognitive impairment diagnoses in people with higher air pollution exposure history, but evidence has been less consistent for associations test performance. We estimated the association between baseline neighbourhood-level to airborne pollutants (particulate matter and nitrogen oxides) (1) performance at (2) score change 2.8-year follow-up, 86,759 middle- older-aged adults from UK Biobank general...
To investigate medications associated with cognitive function.Population-based cross-sectional cohort study.UK Biobank.UK Biobank participants aged 37-73 years who completed tests at the baseline visit in 2006-2010.Cognitive test outcomes on verbal-numerical reasoning (n=165 493), memory (n=482 766) and reaction time (n=496 813).Most drugs (262 of 368) were not any after adjusting for age, gender, education, household income, smoking, alcohol status, psychostimulant/nootropic medication use,...
Abstract Introduction Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted specific or biased toward high abundant proteins. Methods 4001 plasma were measured two groups of participants (discovery group = 516, replication 365) selected from the European Medical Information Framework disease Multimodal...
Background Utilisation of routinely collected electronic health records from secondary care offers unprecedented possibilities for medical science research but can also present difficulties. One key issue is that information presented as free-form text and, therefore, requires time commitment clinicians to manually extract salient information. Natural language processing (NLP) methods be used automatically clinically relevant Objective Our aim use natural capture real-world data on...
Abstract Adult hippocampal neurogenesis is important for learning and memory altered early in Alzheimer’s disease. As modulated by the circulatory systemic environment, evaluating a proxy of how affected milieu could serve as an biomarker disease progression. Here, we used vitro assay to model impact environment on neurogenesis. A human progenitor cell line was treated with longitudinal serum samples from individuals mild cognitive impairment, who either progressed or remained cognitively...