A5080369256- Dementia and Cognitive Impairment Research
- Alzheimer's disease research and treatments
- Advanced Neuroimaging Techniques and Applications
- Health, Environment, Cognitive Aging
- Functional Brain Connectivity Studies
- Metabolomics and Mass Spectrometry Studies
- MRI in cancer diagnosis
- Cardiovascular Health and Disease Prevention
- Advanced MRI Techniques and Applications
- Diet and metabolism studies
- Hearing Loss and Rehabilitation
- Medical Imaging Techniques and Applications
- Frailty in Older Adults
- Noise Effects and Management
- Health disparities and outcomes
- Birth, Development, and Health
- Stroke Rehabilitation and Recovery
- Financial Literacy, Pension, Retirement Analysis
- Blood Pressure and Hypertension Studies
- Hearing, Cochlea, Tinnitus, Genetics
- Neurological Disease Mechanisms and Treatments
- Tryptophan and brain disorders
- Radiomics and Machine Learning in Medical Imaging
- Cerebral Venous Sinus Thrombosis
- Insurance, Mortality, Demography, Risk Management
National Hospital for Neurology and Neurosurgery
2019-2024
University College London
2018-2024
UK Dementia Research Institute
2018-2024
NIHR Queen Square Dementia Biomedical Research Unit
2022-2023
King's College London
2019-2022
MRC Unit for Lifelong Health and Ageing
2019-2022
London School of Hygiene & Tropical Medicine
2019-2022
Imperial College London
2022
Royal London Hospital
2022
University of London
2019
BackgroundMidlife hypertension confers increased risk for cognitive impairment in late life. The sensitive period exposure and extent that is mediated through amyloid or vascular-related mechanisms are poorly understood. We aimed to identify if, when, blood pressure change during adulthood were associated with late-life brain structure, pathology, cognition.MethodsParticipants from Insight 46, a neuroscience substudy of the ongoing longitudinal Medical Research Council National Survey Health...
Alzheimer's disease has a preclinical stage when cerebral amyloid-b deposition occurs before symptoms emerge, and amyloid-b-targeted therapies may have maximum benefits.Existing status measurement techniques, including amyloid PET CSF testing, are difficult to deploy at scale, so blood biomarkers increasingly considered for screening.We compared three different blood-based techniques-liquid chromatography-mass spectrometry measures of plasma amyloid-b, single molecule array (Simoa)...
Midlife vascular risk burden is associated with late-life dementia. Less known about if and how exposure in early adulthood influences brain health.To determine the associations between adulthood, midlife, late life structure pathology using measures of white matter-hyperintensity volume, β-amyloid load, whole-brain hippocampal volumes.This prospective longitudinal cohort study, Insight 46, part Medical Research Council National Survey Health Development, which commenced 1946. Participants...
A neuroimaging-based biomarker termed the brain age is thought to reflect variability in brain's ageing process and predict longevity. Using Insight 46, a unique narrow-age birth cohort, we aimed examine potential drivers correlates of age.
<h3>Objective</h3> To investigate predictors of performance on a range cognitive measures including the Preclinical Alzheimer Cognitive Composite (PACC) and test for associations between cognition dementia biomarkers in Insight 46, substudy Medical Research Council National Survey Health Development. <h3>Methods</h3> A total 502 individuals born same week 1946 underwent assessment at age 69–71 years, an adapted version PACC nonverbal reasoning. Performance was characterized with respect to...
Background Hearing loss has been proposed as a modifiable risk factor for dementia. However, the relationship between hearing, neurodegeneration, and cognitive change, extent to which pathological processes such Alzheimer’s disease cerebrovascular influence these relationships, is unclear. Methods Data from 287 adults born in same week of 1946 who underwent baseline pure tone audiometry (mean age=70.6 years) two time point assessment/multimodal brain imaging interval 2.4 were analysed....
Identifying and recruiting people with early pre-symptomatic Alzheimer's disease to neuroimaging research studies is increasingly important. The extent which results of these can be generalised depends on the recruitment representativeness participants involved. We now report participation patterns from a neuroscience sub-study MRC National Survey Health Development, "Insight 46". This study aimed recruit 500 for extensive clinical neuropsychological testing, neuroimaging. investigate how...
Abstract INTRODUCTION We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on fully automated Lumipulse platform with pre‐symptomatic Alzheimer's disease (AD) pathology positron emission tomography (PET). METHODS In 72 individuals from Insight 46 study, CSF Aβ40, Aβ42, total (t‐tau), phosphorylated at site 181 (p‐tau181) were using Lumipulse, INNOTEST, Meso Scale Discovery (MSD) assays inter‐platform Pearson correlations derived. Aβ42 measures adjusted...
The goals of this work were to quantify the independent and interactive associations β-amyloid (Aβ) white matter hyperintensity volume (WMHV), a marker presumed cerebrovascular disease (CVD), with rates neurodegeneration examine contributions
Background The human hippocampus comprises a number of interconnected histologically and functionally distinct subfields, which may be differentially influenced by cerebral pathology. Automated techniques are now available that estimate hippocampal subfield volumes using in vivo structural MRI data. To date, research investigating the influence β-amyloid deposition—one earliest hypothesised changes pathophysiological continuum Alzheimer's disease—on cognitively normal older individuals, has...
Abstract Background Although age is the biggest known risk factor for dementia, there remains uncertainty about other factors over life course that contribute to a person’s cognitive decline later in life. Furthermore, pathological processes leading dementia are not fully understood. The main goals of Insight 46—a multi-phase longitudinal observational study—are collect detailed cognitive, neurological, physical, cardiovascular, and sensory data; combine those data with genetic life-course...
Objective To investigate subjective cognitive decline (SCD) in relation to β-amyloid pathology and test for associations with anxiety, depression, objective cognition family history of dementia the Insight 46 study. Methods Cognitively unimpaired ~70-year-old participants, all born same week 1946 (n=460, 49% female, 18% amyloid-positive), underwent assessments including SCD-Questionnaire (MyCog). MyCog scores were evaluated respect 18 F-Florbetapir-PET amyloid status (positive/negative)....
Background Hearing impairment may be a modifiable risk factor for dementia. However, it is unclear how hearing associates with pathologies relevant to dementia in preclinical populations. Methods Data from 368 cognitively healthy individuals born during 1 week 1946 (age range 69.2–71.9 years), who underwent structural MRI, 18 F-florbetapir positron emission tomography, pure tone audiometry and cognitive testing as part of neuroscience substudy the MRC National Survey Health Development were...
Abstract Background Identifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites whole-brain volume, hippocampal amyloid-β status among participants Insight 46—the neuroscience sub-study the National Survey Health Development (NSHD). We additionally explored whether key were associated with polygenic risk Alzheimer’s...
Abstract INTRODUCTION The Centiloid scale aims to harmonize amyloid beta (Aβ) positron emission tomography (PET) measures across different analysis methods. As Centiloids were created using PET/computerized (CT) data and are influenced by scanner differences, we investigated the transformation with from Insight 46 acquired PET/magnetic resonanceimaging (MRI). METHODS We transformed standardized uptake value ratios (SUVRs) 432 florbetapir PET/MRI scans processed whole cerebellum (WC) white...
Background Consistent patterns of reduced cortical thickness have been identified in early Alzheimer’s disease (AD). However, the pathological factors that influence rates thinning within these AD signature regions remain unclear. Methods Participants were from Insight 46 substudy MRC National Survey Health and Development (NSHD; 1946 British birth cohort), a prospective longitudinal cohort study. Linear regression was used to examine associations baseline cerebral β-amyloid (Aβ) deposition,...
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...
Introduction We investigated whether life-course factors and neuroimaging biomarkers of Alzheimer's disease pathology predict reaction time (RT) performance in older adults. Methods Insight 46 study participants, all born the same week 1946 (n = 501; ages at assessment 69 to 71 years), completed a 2-choice RT task amyloid beta (Aβ) positron emission tomography MR imaging. tested for associations between outcomes (RT; error rate; intra-individual variability RT) predictors including childhood...
Objective To summarise the incidental findings detected on brain imaging and blood tests during first wave of data collection for Insight 46 study. Design Prospective observational sub-study a birth cohort. Setting Single-day assessment at research centre in London, UK. Participants 502 individuals were recruited from MRC National Survey Health Development (NSHD), 1946 British cohort, based pre-specified eligibility criteria; mean age was 70.7 (SD: 0.7) 49% female. Outcome measures Data...
Introduction We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on fully automated Lumipulse platform with pre-symptomatic Alzheimer's disease (AD) pathology positron emission tomography (PET). Methods In 72 individuals from Insight 46 study, CSF Aβ40, Aβ42, total (t-tau), phosphorylated at site 181 (p-tau181) were using Lumipulse, INNOTEST, Meso Scale Discovery (MSD) assays, inter-platform Pearson correlations derived. Logistic regressions...
Abstract We investigate associations between normal-appearing white matter microstructural integrity in cognitively normal ∼70-year-olds and concurrently measured brain health cognition, demographics, genetics life course cardiovascular health. Participants born the same week March 1946 (British birth cohort) underwent PET-MRI around age 70. Mean standardized metrics (fractional anisotropy, mean diffusivity, neurite density index orientation dispersion index) were derived from diffusion MRI....
In view of reported associations between high adiposity, particularly in midlife and late-life dementia risk, we aimed to determine body mass index (BMI), BMI changes across adulthood brain structure pathology at age 69-71 years.Four hundred sixty-five dementia-free participants from Insight 46, a sub-study the British 1946 birth cohort, who had cross-sectional T1/FLAIR volumetric MRI, florbetapir amyloid-PET imaging years, were included analyses. We quantified white matter hyperintensity...
Introduction Cortical thickness has been proposed as a biomarker of Alzheimer's disease (AD)– related neurodegeneration, but the nature its relationship with amyloid beta (Aβ) deposition and white matter hyperintensity volume (WMHV) in cognitively normal adults is unclear. Methods We investigated influences Aβ status (negative/positive) WMHV on cortical 408 aged 69.2 to 71.9 years who underwent 18F-Florbetapir positron emission tomography (PET) structural magnetic resonance imaging (MRI)....