Alastair John Noyce

Queen Mary, University of London | QMUL · Wolfson Institute of Preventive Medicine

Objectives This study aims to address disparities in risk prediction by evaluating the performance of polygenic risk score (PRS) models using the 90 risk variants across 78 independent loci previously linked to Parkinson's disease (PD) risk across seven diverse ancestry populations. Methods We conducted a multi-stage study, testing PRS models in pr...

Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a sleep disorder that is characterised by dream enactment episodes during REM sleep. It is the strongest known predictor of α‐synuclein‐related neurodegenerative disease (αNDD), such that >80% of people with iRBD will eventually develop Parkinson's disease, dementia with Lewy bodi...

Background: The Royal London Hospital, East London, receives a case of nitrous oxide (N2O) myeloneuropathy roughly every 9 days. No formal education programme is widely available to warn young people of the risks of recreational N2O use. Our aim was to develop and evaluate the effectiveness of workshops focusing on the neurological risks of N2O, wi...

Background Damaging coding variants in GBA1 are a genetic risk factor for rapid eye movement sleep behavior disorder (RBD), which is a known early feature of synucleinopathies. Recently, a population-specific non-coding variant (rs3115534) was found to be associated with PD risk and earlier disease onset in individuals of African ancestry. Objectiv...

Introduction Hyposmia (loss of smell) is a common early symptom of Parkinson's disease (PD). The shared genetic architecture between hyposmia and PD is unknown. Objectives To assess the shared genetic architecture and causal relationship between hyposmia and PD. Methods We leveraged genome-wide association study (GWAS) results for self-assessment o...

Objective To create a registry of patients with Parkinson’s disease (PD) and a rich database of PD-relevant information that can be used to stratify participants for precision opportunities. Background Recruitment to studies and trials is a major rate-limiting factor in PD research. Participants from lower socioeconomic backgrounds or geographical...

Background Multiple sclerosis is a leading cause of non-traumatic neurological disability among young adults worldwide. Prior studies have identified modifiable risk factors for multiple sclerosis in cohorts of White ethnicity, such as infectious mononucleosis, smoking, and obesity during adolescence/early adulthood. It is unknown whether modifiabl...

Background: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach. Objective: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for...

Introduction: Finding low-cost methods to detect early-stage Alzheimer's disease (AD) is a research priority for neuroprotective drug development. Presymptomatic Alzheimer's is associated with gait impairment but hand motor tests, which are more accessible, have hardly been investigated. This study evaluated how home-based Tasmanian (TAS) Test key...

Background: Variants in the GBA1 gene cause the lysosomal storage disorder Gaucher disease (GD). They are also risk factors for Parkinson disease (PD), and modify the expression of the PD phenotype. The penetrance of GBA1 variants in PD is incomplete, and the ability to determine who amongst GBA1 variant carriers are at higher risk of developing PD...

Objective: Parkinson s disease (PD) is a neurodegenerative disorder with complex aetiology. Multiple genetic and environmental factors have been associated with PD, but most PD risk remains unexplained. The aim of this study was to test for statistical interactions between PD-related genetic and environmental exposures/phenotypic traits in the 23an...

Background: PREDICT-PD is a United Kingdom population-based study aiming to stratify individuals for future Parkinson's disease (PD) using a risk algorithm. Methods: A randomly selected, representative sample of participants in PREDICT-PD were examined using several motor assessments, including the motor section of the Movement Disorder Society-...

Background Isolated REM sleep behavior disorder (iRBD) is known to be an early feature in some PD patients. Quantitative tools are needed to detect early motor anomalies in iRBD. Methods A motor battery was used to compare iRBD patients with controls. This included two online keyboard-based tests, the BRadykineisa Akinesia INcoordination (BRAIN) t...

Background: Nitrous oxide (N2O) is the second most common recreational drug used by 16- to 24-year-olds in the UK. Neurological symptoms can occur in some people that use N2O recreationally, but most information comes from small case series. Methods: We describe 119 patients with N2O-myeloneuropathy seen at NHS teaching hospitals in three of the...

Purpose Genetic studies of multiple sclerosis (MS) susceptibility and severity have focused on populations of European ancestry. Studying MS genetics in other ancestral groups is necessary to determine the generalisability of these findings. The genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis (ADA...

Background: Epidemiological studies suggested an association between Parkinson's disease (PD) and type 2 diabetes, but less is known about type 1 diabetes (T1D) and PD. Objective: This study sought to explore the association between T1D and PD. Methods: We used Mendelian randomization, linkage disequilibrium score regression, and multi-tissue...

Background: Isolated rapid eye movement sleep behavior disorder (iRBD) is associated with an increased risk of Parkinson's disease and other synucleinopathies. There is no consensus about disclosure of this risk to patients with iRBD. Objective: The objective of our study was to assess the experiences of risk disclosure in a group of patients wi...

Neurodegeneration with brain iron accumulation (NBIA) represents a group of neurodegenerative disorders characterized by abnormal iron accumulation in the brain. In Parkinson’s Disease (PD), iron accumulation is a cardinal feature of degenerating regions in the brain and seems to be a key player in mechanisms that precipitate cell death. The aim of...

Development of clinical guidelines for nitrous-oxide induced subacute combined degeneration of the cord through quality improvement methodology

Open science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we...

Background: Mild cognitive impairment (MCI) is commonly present at the time of Parkinson's Disease (PD) diagnosis, but its prevalence amongst individuals at increased risk of PD is unclear. Methods: Cognition was assessed using the Montreal Cognitive Assessment (MoCA) in 208 participants in the PREDICT-PD study, and 25 participants with REM-slee...

Importance Recent studies have highlighted an association between epilepsy and Parkinson disease (PD). The role of antiepileptic drugs (AEDs) has not been explored. Objective To investigate the association between AEDs and incident PD. Design, Setting, and Participants This nested case-control study started collecting data from the UK Biobank (UK...

Background: Human genetics research lacks diversity; over 80% of genome-wide association studies have been conducted on individuals of European ancestry. In addition to limiting insights regarding disease mechanisms, disproportionate representation can create disparities preventing equitable implementation of personalized medicine. Objective: Th...

The clinical manifestations of Parkinson’s disease (PD) are characterized by heterogeneity in age at onset, disease duration, rate of progression, and the constellation of motor versus non-motor features. There is an unmet need for the characterization of distinct disease subtypes as well as improved, individualized predictions of the disease cours...

Background: A substantial body of research has examined the relationship between alcohol consumption and risk of Parkinson's disease (PD). Objective: To provide an updated systematic review and meta-analysis of observational studies examining the relationship between alcohol consumption and risk of PD. Methods: Eligible studies comparing PD ri...

Background Epidemiological studies suggested an association between Parkinson’s disease (PD) and type 2 diabetes, but less is known about type 1 diabetes (T1D) and PD. Objectives To explore the association between T1D and PD. Methods We used Mendelian randomization, linkage disequilibrium score regression and transcriptome wide association analys...

Background: Parkinson's disease (PD) affects males more than females. The reasons for the gender differences in PD prevalence remain unclear. Objective: The objective of this systematic review and meta-analysis was to update the overall male/female prevalence ratios (OPR). Methods: We updated previous work by searching MEDLINE, SCOPUS, and OVID f...

Background: Neurodegeneration with brain iron accumulation (NBIA) represents a group of neurodegenerative disorders characterized by abnormal iron accumulation and the presence of axonal spheroids in the brain. In Parkinson's Disease (PD), iron accumulation is a cardinal feature of degenerating regions in the brain and seems to be a key player in m...

Objective Higher body mass index (BMI) during early life is thought to be a causal risk factor for multiple sclerosis (MS). We used longitudinal Mendelian randomisation (MR) to determine whether there is a critical window during which BMI influences MS risk. Methods Summary statistics for childhood BMI ( n ~ 28,000 children) and for MS susceptibil...

Background Depression may be a potentially modifiable risk factor for dementia, but it is not clear whether this is due to a causal effect, or whether depressive symptoms are an early prodromal feature of Alzheimer’s disease. Objectives To investigate whether depressive symptoms are associated with an increased risk of dementia. To establish assoc...

Genome-wide association studies (GWAS) of Multiple Sclerosis (MS) have focussed on populations of European ancestry. Studying MS genetics in other ancestries is necessary to ensure the generalisability of these findings. We report the design of a new collaborative MS genetics project – ‘ADAMS’. Individuals with MS from non-White-British ethnic back...

Background Idiopathic/isolated REM sleep behaviour disorder (iRBD) is characterised by vivid dreams with ‘acting-out’ behaviours due to REM sleep muscle atonia. It is associated with a risk of Parkinson’s disease (PD) and other synucleinopathies. There is uncertainty about what should be disclosed to iRBD patients in terms of future risk1. Methods...

Background Early features of Parkinson’s disease (PD) have been described through population-based studies, which over-represent white, affluent groups and may not be generalisable. Methods A nested case-control study was conducted in East London using primary care health records. A matched analysis with multivariable logistic regression was used...

Introduction Transcranial sonography (TCS) has been shown to be a reliable imaging biomarker in patients with Parkinson’s disease (PD). 90% of patients with PD have enlarged nigral hyperechogenicity (SN+) compared to 10% healthy controls (HC). Objective To assess the relationship between SN+ and motor and non-motor features of prodromal PD. Metho...

Background Parkinson disease (PD) is the second most common neurodegenerative disease and the burden appears to be growing fastest in middle-low and low income countries. In the majority of obser- vational studies of PD, White, well-educated and affluent participants are over-represented. Aims Our aim was to engage a diverse group of people with P...

Introduction A range of non-motor features can be evident at the point of diagnosis of Parkinson’s disease (PD). Objectives To identify non-motor features of prodromal PD in participants from the PREDICT-PD study. Methods Higher-risk (HR) (odds of PD >1:30) and matched lower-risk (LR) participants from PREDICT-PD and PD patients underwent validat...

Background Parkinson disease (PD) is a major cause of disability affecting >6 million people worldwide. The incidence/prevalence of PD is generally higher in males than females. It is unclear whether male predominance is observed in low- and middle-income countries, where the fastest apparent rate of increase of PD has been observed. Methods We se...

Introduction Anosmia is common at the point of diagnosis of Parkinson’s disease (PD) and often predates motor symptoms. Other non-motor symptoms are also recognised to predate overt motor impairment in PD. Objective To identify prodromal markers of PD in patients with idiopathic anosmia (IA). Methods Patients age >55y diagnosed with IA in sub-spe...

Multiple sclerosis (MS) is a neuroimmunological disorder of the CNS with a strong heritable component. The genetic architecture of MS susceptibility is well understood in populations of European ancestry. However, the extent to which this architecture explains MS susceptibility in populations of non-European ancestry remains unclear. In this Perspe...

Although over 90 independent risk variants have been identified for Parkinson's disease using genome-wide association studies, all studies have been performed in just one population at the time. Here we performed the first large-scale multi-ancestry meta-analysis of Parkinson's disease with 49,049 cases, 18,785 proxy cases, and 2,458,063 controls i...

Background The clinical manifestations of Parkinson’s disease (PD) are characterized by heterogeneity in age at onset, disease duration, rate of progression, and the constellation of motor versus non-motor features. There is an unmet need for the characterization of distinct disease subtypes as well as improved, individualized predictions of the di...

Parkinson's disease (PD) is a complex neurodegenerative condition in which genetic and environmental factors interact to contribute to its etiology. Remarkable progress has been made in deciphering disease etiology through genetic approaches, but there is limited data about how environmental and genetic factors interact to modify penetrance, risk a...

Targeting modifiable risk factors may help to prevent Alzheimer's disease (AD), but the pathways by which these risk factors influence AD risk remain incompletely understood. We identified genome-wide association studies for AD and its major modifiable risk factors. We calculated the genetic correlation among these traits and modelled this using ge...

Background Central auditory function is affected early in the course of Alzheimer’s disease, and may be useful as a prodromal disease marker. Speech-in-noise perception is a simple test of central auditory function. Methods We used Speech Reception Threshold (SRT) as a measure of speech-in-noise perception in 160,905 healthy subjects in UK Biobank...

Introduction Early identification of individuals at high-risk of Parkinson’s disease (PD) may allow for the use of disease modifying treatments. We aimed to define those at risk of incident PD through environmental and genetic risk factors, comorbidities and prodromal symptoms of PD. Methods We identified incident cases of PD (n=1276) in the UK Bi...

Introduction Anosmia is a recognised risk factor for Parkinson’s disease (PD), however, many of the causes are not neurodegenerative. We hypothesise that the prodromal phase of PD associated with idiopathic anosmia is predominantly motor and does not have other significant non-motor features. Methods We recruited individuals with idiopathic anosmi...

Background It is generally recognized that Parkinson’s disease (PD) affects males more commonly than females. The reasons for the difference in PD prevalence by gender remain unclear. Methods In this systematic review and meta-analysis, we updated previous work by searching MEDLINE, SCOPUS, and OVID for articles reporting PD prevalence for both ge...

Background Open science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportuniti...

Objective: The aim of the current study is to understand why some individuals avoid developing Parkinson's disease (PD) in spite of being at relatively high genetic risk, using the largest datasets of individual-level genetic data available. Methods: We calculated polygenic risk score to identify controls and matched PD cases with the highest bu...

Digital health technologies (DHTs) have great potential for use as clinical trial outcomes; however, practical issues need to be addressed in order to maximise their benefit. We describe our experience of incorporating two DHTs as secondary/exploratory outcome measures in PD STAT, a randomised clinical trial of simvastatin in people with Parkinson’...

Importance: Early features of Parkinson disease (PD) have been described through population-based studies that overrepresent White, affluent groups and may not be generalizable. Objective: To investigate the association between risk factors and prediagnostic presentations of PD in an ethnically diverse UK population with high socioeconomic depri...

Background: Parkinson's disease (PD) is a debilitating neurodegenerative disease with both motor and non-motor manifestations. The mainstay of available treatment reduces symptoms and is critical for improving quality of life. Treatment options include drugs, device-aided therapies, and non-pharmacological therapies. Complementary and alternative...

Introduction: Loss of smell is a common early feature of neurodegenerative diseases including Alzheimer's and Parkinson's disease. Identifying these conditions in their early stages is important to understand more about early pathophysiological events and the development of disease modifying therapies. Smell testing may be an effective future tool...

Background Most evidence about dementia risk comes from relatively affluent people of White European ancestry. We aimed to determine the association between ethnicity, area level socioeconomic deprivation and dementia risk, and the extent to which variation in risk might be attributable to known modifiable clinical risk factors and health behaviour...

Disability in Parkinson’s disease (PD) is measured by standardised scales including the MDS-UPDRS, which are subject to high inter and intra-rater variability and fail to capture subtle motor impairment. The BRadykinesia Akinesia INcoordination (BRAIN) test is a validated keyboard tapping test, evaluating proximal upper-limb motor impairment. Here,...

Parkinson’s disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson’s disease....

Human genetics research lacks diversity; over 80% of genome-wide association studies (GWAS) have been conducted on individuals of European ancestry. In addition to limiting insights regarding disease mechanisms, disproportionate representation can create disparities preventing equitable implementation of personalized medicine. This systematic revie...

Background Parkinson’s disease (PD) is a neurodegenerative movement disorder affecting 1–5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle the pathology in the early phase. Here we report a multi-stage procedure to identify candidate genes likely involved in the etiopathogenesis...

Background Central auditory function is affected early in the course of Alzheimer’s disease, and may be useful as a prodromal disease marker. Speech‐in‐noise perception is a simple test of central auditory function. Method We used Speech Reception Threshold (SRT) as a measure of speech‐in‐noise perception in 160,905 healthy subjects in UK Biobank....

Background Early detection of Alzheimer’s disease (AD) is critical for the development of interventions that delay or prevent neurodegeneration. Previous studies suggest that genetic liability to AD may be associated with structural brain changes that start 20‐30 years before symptoms manifest. Method We derived an optimised AD polygenic risk scor...

Importance: Predictors of future Parkinson′s disease (PD) have been suggested through population-based studies, but these studies over–represent white, affluent groups and may not be generalisable. Objective: To investigate the association between risk factors and pre–diagnostic presentations of PD in a uniquely diverse UK population, with universa...

Olfactory loss, motor impairment, anxiety/depression, and REM-sleep behaviour disorder (RBD) are prodromal Parkinson's disease (PD) features. PD risk prediction models typically dichotomize test results and apply likelihood ratios (LRs) to scores above and below cut-offs. We investigate whether LRs for specific test values could enhance classificat...

Objective Higher childhood Body Mass Index (BMI) during early life is thought to be a causal risk factor for Multiple Sclerosis (MS). We used longitudinal mendelian randomisation (MR) to determine whether there is a critical window during which BMI influences MS risk. Methods Summary statistics for childhood BMI and for MS susceptibility were obtai...

Background: Tobacco smoking and alcohol intake have been identified in observational studies as potentially protective factors against developing Parkinson's disease (PD); the impact of body mass index (BMI) on PD risk is debated. Whether such epidemiological associations are causal remains unclear. Mendelian randomsation (MR) uses genetic variant...

A correction to this paper has been published: https://doi.org/10.1007/s00401-021-02309-z

Objective We sought to determine whether genetic risk modifies the effect of environmental risk factors for multiple sclerosis (MS). To test this hypothesis, we tested for statistical interaction between polygenic risk scores (PRS) capturing genetic susceptibility to MS and environmental risk factors for MS in UK Biobank. Methods People with MS we...

Mild Parkinsonian Signs (MPS) describe a spectrum that exists between the expected motor decline of normal aging and a more serious motor deterioration resulting from Parkinson’s disease (PD) and neurodegeneration. Although MPS are a feature of the prodromal stage of PD, their formal definition is unclear and still relies somewhat on conventional c...

Background: Bradykinesia is the defining motor feature of Parkinson's disease (PD). There are limitations to its assessment using standard clinical rating scales, especially in the early stages of PD when a floor effect may be observed. Objective: To develop a quantitative method to track repetitive tapping movements and to compare people in the...