A5009746896- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Advanced Neuroimaging Techniques and Applications
- Advanced MRI Techniques and Applications
- Functional Brain Connectivity Studies
- Bioinformatics and Genomic Networks
- Health, Environment, Cognitive Aging
- MRI in cancer diagnosis
- Memory and Neural Mechanisms
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Traumatic Brain Injury and Neurovascular Disturbances
- Medical Imaging Techniques and Applications
- Prion Diseases and Protein Misfolding
- Epilepsy research and treatment
- Parkinson's Disease Mechanisms and Treatments
- Neurological Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Radiomics and Machine Learning in Medical Imaging
- Lanthanide and Transition Metal Complexes
- Amyotrophic Lateral Sclerosis Research
- Folate and B Vitamins Research
- Genetic Neurodegenerative Diseases
- Nuclear Receptors and Signaling
- Cerebrospinal fluid and hydrocephalus
UK Dementia Research Institute
2015-2024
University College London
2015-2024
National Hospital for Neurology and Neurosurgery
2015-2024
NIHR Queen Square Dementia Biomedical Research Unit
2020
University of Gothenburg
2017
London School of Hygiene & Tropical Medicine
2016-2017
MRC Prion Unit
2017
University of Sheffield
2014
Charing Cross Hospital
2011-2013
Imperial College London
2011
<h3>Objectives:</h3> To investigate whether serum neurofilament light (NfL) concentration is increased in familial Alzheimer disease (FAD), both pre and post symptom onset, it associated with markers of stage severity. <h3>Methods:</h3> We recruited 48 individuals from families <i>PSEN1</i> or <i>APP</i> mutations to a cross-sectional study: 18 had symptomatic (AD) 30 were asymptomatic but at 50% risk carrying mutation. Serum NfL was measured using an ultrasensitive immunoassay on the single...
BackgroundThe causes of phenotypic heterogeneity in familial Alzheimer's disease with autosomal dominant inheritance are not well understood. We aimed to characterise clinical phenotypes and genetic associations APP PSEN1 mutations symptomatic (ADAD).MethodsWe retrospectively analysed genotypic data (age at symptom onset, initial cognitive or behavioural symptoms, presence myoclonus, seizures, pyramidal signs, extrapyramidal cerebellar signs) from all individuals ADAD due seen the Dementia...
Alzheimer's disease (AD) is recognized to have a long presymptomatic period, during which there progressive accumulation of molecular pathology, followed by inexorable neuronal damage. The ability identify individuals with evidence neurodegenerative change, stage their disease, and track changes will be important for early diagnosis prevention trials. Despite recent advances, particularly in magnetic resonance imaging, our reliably limited. development diffusion-weighted sensitive...
Cerebrospinal fluid (CSF) biomarkers are increasingly being used to support a diagnosis of Alzheimer's disease (AD). Their clinical utility for differentiating AD from non-AD neurodegenerative dementias, such as dementia with Lewy bodies (DLB) or frontotemporal (FTD), is less well established. We aimed determine the diagnostic an extended panel CSF differentiate range other dementias. immunoassays measure conventional markers amyloid and tau pathology (amyloid beta (Aβ)1–42, total (T-tau),...
Tests sensitive to presymptomatic changes in Alzheimer's disease could be valuable for clinical trials. Accelerated long-term forgetting-during which memory impairment becomes apparent over longer periods than usually assessed, despite normal performance on standard cognitive testing-has been identified other temporal lobe disorders. We assessed whether accelerated forgetting is a feature of autosomal dominant (familial) disease, and there an association between early subjective changes.This...
To investigate how serum neurofilament light (NfL) concentration changes through the course of disease in familial Alzheimer's (FAD) and to assess when NfL first increases.NfL was measured using an ultrasensitive immunoassay 117 samples from 61 individuals families with PSEN1 or APP mutations a longitudinal study (mean ± SD = 1.9 1.1 visits/patient; inter-visit interval 1.8 years). The relationship between estimated years to/from symptom onset (EYO) modelled linear regression, including all...
This study assesses factors associated with the most common adverse event following lumbar puncture.To identify risk, onset, and persistence of post-dural puncture headache (PDPH).We performed univariate multivariable analyses 338 punctures in Dominantly Inherited Alzheimer Network observational using linear mixed models, adjusting for participant-level family-level random effects.We directly evaluated associations 3 post-lumbar outcomes (immediate postprocedural headache, PDPH at 24-hour...
Background: The mini-clinical evaluation exercise (mini-CEX) is a widely used tool with strong theoretical basis. It was introduced to UK foundation training in 2005.
<h3>Objective:</h3> To identify a cortical signature pattern of thinning in familial Alzheimer disease (FAD) and assess its utility detecting tracking presymptomatic neurodegeneration. <h3>Methods:</h3> We recruited 43 FAD mutation carriers—36 <i>PSEN1</i>, 7 <i>APP</i> (20 symptomatic, 23 presymptomatic)—and 42 healthy controls to longitudinal clinical MRI study. T1-weighted scans were acquired at baseline all participants; 55 individuals (33 carriers; 22 controls) had multiple (mean 2.9)...
Abstract Background There is increasing interest in improving understanding of the timing and nature early neurodegeneration Alzheimer’s disease (AD) developing methods to measure this vivo. Autosomal dominant familial (FAD) provides opportunity for investigation presymptomatic change. We assessed microstructural breakdown cortical grey matter FAD with diffusion-weighted MRI. Methods Diffusion-weighted T1-weighed MRI were acquired 38 mutation carriers (17 symptomatic, 21 presymptomatic) 39...
Abstract In vitro studies of autosomal dominant Alzheimer’s disease implicate longer amyloid-β peptides in pathogenesis; however, less is known about the behaviour these mutations vivo. this cross-sectional cohort study, we used liquid chromatography-tandem mass spectrometry to analyse 66 plasma samples from individuals who were at risk inheriting a mutation or symptomatic. We tested for differences (Aβ)42:38, Aβ42:40 and Aβ38:40 ratios between presenilin 1 (PSEN1) amyloid precursor protein...
Cortical tau accumulation is a key pathological event that partly defines Alzheimer's disease (AD) onset and associated with cognitive decline future progression. However, an improved understanding of the timing pattern early deposition in AD how this may be tracked vivo needed. Data from 59 participants involved two longitudinal cohort studies autosomal dominant (ADAD) were used to investigate whether PET can detect track presymptomatic change; seven symptomatic, 52 asymptomatic but at 50%...
Abstract Introduction In Alzheimer's disease (AD), hyperphosphorylated tau is closely associated with focal neurodegeneration, but the mechanism remains uncertain. Methods We quantified cortical microstructure using neurite orientation dispersion and density imaging in 14 individuals young onset AD. Diffusion tensor measured mean diffusivity (MD). Amyloid beta positron emission tomography were acquired associations microstructural measures assessed. Results When regional volume was adjusted...
Direct reconstruction of parametric images from raw photon counts has been shown to improve the quantitative analysis dynamic positron emission tomography (PET) data. However it suffers subject motion which is inevitable during typical acquisition time 1-2 hours. In this work we propose a framework jointly estimate head and reconstruct motion-corrected directly PET data, so that effects distorted tissue-to-voxel mapping due can be reduced in reconstructing with motion-compensated attenuation...
Understanding the earliest manifestations of Alzheimer's disease (AD) is key to realising disease-modifying treatments. Advances in neuroimaging and fluid biomarkers have improved our ability identify AD pathology vivo. The critical next step detection staging early cognitive change. We studied an asymptomatic familial (FAD) cohort characterise preclinical
Abstract Accelerated long-term forgetting (ALF) is the phenomenon whereby material retained normally over short intervals (e.g. minutes) but forgotten abnormally rapidly longer periods (days or weeks). ALF may be an early marker of cognitive decline, little known about its relationships with preclinical Alzheimer’s disease pathology, and how memory selectivity influence which forgotten. We assessed in ‘Insight 46’, a sub-study MRC National Survey Health Development (a population-based cohort...
Cerebrospinal fluid (CSF) measures of amyloid and tau are the first-line Alzheimer's disease biomarkers in many clinical centers. We assessed if when addition PET following CSF measurements provides added diagnostic value. Twenty patients from a cognitive clinic, who had undergone detailed assessment including measures, went on to have PET. The treating neurologist's working diagnosis, degree certainty, was both before after Amyloid changed diagnosis 7/20 cases. can provide value,...
Abstract Introduction We aimed to assess the feasibility of determining Alzheimer's disease cerebrospinal fluid (CSF) cut points in small samples through comparison with amyloid positron emission tomography (PET). Methods Twenty‐three individuals (19 patients, four controls) had CSF measures beta (Aβ) 1–42 and total tau/Aβ ratio, florbetapir PET. compared visual quantitative (standardized uptake value ratio [SUVR]) PET amyloid. Results Seventeen 23 were amyloid‐positive on reads, 14 at an...
Visual short-term memory (VSTM) deficits including VSTM binding have been associated with Alzheimer's disease (AD) from preclinical to dementia stages, cross-sectionally. Yet, longitudinal investigations are lacking. The objective of this study was evaluate function longitudinally and in relation expected symptom onset a cohort familial disease. Ninety-nine individuals (23 presymptomatic; 9 symptomatic 67 controls) were included an extension cross-sectional sub-sample 48 presymptomatic...
Despite considerable evidence for abnormalities of self-awareness in Alzheimer's disease (AD), the cognitive mechanisms altered self-processing AD have not been fully defined. Here we addressed this issue a detailed analysis self/non-self-processing three patients with AD. We designed novel neuropsychological battery comprising tests tactile body schema coding, attribution events to self versus external agents, and memory self- non-self-generated vocal information, administered conjunction...