Derek Beaton

Baycrest · Rotman Research Institute

Background Apathy in patients with Alzheimer’s disease (AD) is associated with significant morbidity. We examined whether interactions between genetic variants related to neurotransmitter systems and regional brain atrophy are associated with apathy in patients with mild cognitive impairment (MCI) and AD. Method For 1162 participants in the Alzhei...

Background Apathy in patients with Alzheimer's disease (AD) is associated with significant morbidity and is often one of the first neuropsychiatric symptoms to present in mild cognitive impairment (MCI). Apathy is associated with accelerated cognitive decline and atrophy in fronto-striatal regions of the brain. Previous work has shown a link betwee...

Similarity analyses between multiple correlation or covariance tables constitute the cornerstone of network neuroscience. Here, we introduce covSTATIS, a versatile, linear, unsupervised multi-table method designed to identify structured patterns in multi-table data, and allow for the simultaneous extraction and interpretation of both individual and...

INTRODUCTION Apolipoprotein E E4 allele (APOE E4) and slow gait are independently associated with cognitive impairment and dementia. However, it is unknown whether their coexistence is associated with poorer cognitive performance and its underlying mechanism in neurodegenerative diseases. METHODS Gait speed, APOE E4, cognition, and neuroimaging we...

Background Cerebral small vessel disease (SVD) frequently co‐occurs with other neurodegenerative pathologies and collectively lead to cognitive deficits. Previously, we found that the ratios of soluble epoxide hydrolase (sEH)‐ derived diols to the parent epoxides (generated by CYP2J/2Cs) linoleic acids were associated with greater white matter hype...

Type 2 diabetes mellitus (T2DM) and hypertension are risk factors for cerebral small vessel disease (SVD); however, few studies have characterised their relationships with MRI-visible perivascular spaces (PVS). MRI was used to quantify deep (d) and periventricular (p) white matter hyperintensities (WMH), lacunes, PVS in the white matter (wmPVS) or...

Background: Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative...

Background: Acute change in gait speed while performing a mental task [dual-task gait cost (DTC)], and hyperintensity magnetic resonance imaging signals in white matter are both important disability predictors in older individuals with history of stroke (poststroke). It is still unclear, however, whether DTC is associated with overall hyperintensi...

Oculomotor tasks generate a potential wealth of behavioural biomarkers for neurodegenerative diseases. Overlap between oculomotor and disease-impaired circuitry reveals the location and severity of disease processes via saccade parameters measured from eye movement tasks such as prosaccade and antisaccade. Existing studies typically examine few sac...

Introduction: 83% of those diagnosed with Parkinson's Disease (PD) eventually progress to PD with mild cognitive impairment (PD-MCI) followed by dementia (PDD) - suggesting a complex spectrum of pathology concomitant with aging. Biomarkers sensitive and specific to this spectrum are required if useful diagnostics are to be developed that may suppl...

Background: The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMH) cognitive and motor impairments seem to be aggravated. However, the role of WMH in predicting accelerating symptom worsening remains controversial. Objective: To investigate w...

Background Cerebral small vessel disease is associated with higher ratios of soluble‐epoxide hydrolase derived linoleic acid diols (12,13‐dihydroxyoctadecenoic acid [DiHOME] and 9,10‐DiHOME) to their parent epoxides (12(13)‐epoxyoctadecenoic acid [EpOME] and 9(10)‐EpOME); however, the relationship has not yet been examined in stroke. Methods and R...

Alterations in tissue microstructure in normal-appearing white matter (NAWM), specifically measured by diffusion tensor imaging (DTI) fractional anisotropy (FA), have been associated with cognitive outcomes following stroke. The purpose of this study was to comprehensively compare conventional DTI measures of tissue microstructure in NAWM to divers...

Purpose Tauopathy and transactive response DNA binding protein 43 (TDP-43) proteinopathy are associated with neurodegenerative diseases. These proteinopathies are difficult to detect in vivo. This study examined if spectral-domain optical coherence tomography (SD-OCT) can differentiate in vivo the difference in peripapillary retinal nerve fibre lay...

Background: Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical atrophy to NPS in participants across neurodegenerative an...

Psychological research often involves complex datasets that cannot easily be analyzed using traditional statistical methods. Multiblock Discriminant Correspondence Analysis (multiblock dica, also called mudica) examines group differences in large, structured categorical datasets and identifies blocks of variables that contribute to these difference...

Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade...

Objectives: Caregiving burdens are a substantial concern in the clinical care of persons with neurodegenerative disorders. In the Ontario Neurodegenerative Disease Research Initiative, we used the Zarit's Burden Interview (ZBI) to examine: (1) the types of burdens captured by the ZBI in a cross-disorder sample of neurodegenerative conditions (2) w...

Background Remote health monitoring with wearable sensor technology may positively impact patient self-management and clinical care. In individuals with complex health conditions, multi-sensor wear may yield meaningful information about health-related behaviors. Despite available technology, feasibility of device-wearing in daily life has received...

Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain atrophy, and em...

Introduction: Understanding synergies between neurodegenerative and cerebrovascular pathologies that modify dementia presentation represents an important knowledge gap. Methods: This multi-site, longitudinal, observational cohort study recruited participants across prevalent neurodegenerative diseases and cerebrovascular disease and assessed par...

The Ontario Brain Institute's “Brain-CODE” is a large-scale informatics platform designed to support the collection, storage and integration of diverse types of data across several brain disorders as a means to understand underlying causes of brain dysfunction and developing novel approaches to treatment. By providing access to aggregated datasets...

Background Neuronal activity (NA) and metabolism are impaired in the early stages of Alzheimer’s Disease (AD) and Frontotemporal Dementia (FTD) leading to specific patterns of cognitive decline. Detailed disease models elucidating how and where in brain these NA disturbances commence and how they gradually progress remain incomplete. Recently, we i...

Despite the wide application of the magnetic resonance imaging (MRI) technique, there are no widely used standards on naming and describing MRI sequences. The absence of consistent naming conventions presents a major challenge in automating image processing since most MRI software require a priori knowledge of the type of the MRI sequences to be pr...

Objective: To assess overlap and uniqueness of established behavioral markers of speed of processing for different aspects of visual information within a cerebrovascular disease cohort, and to examine the link between these speed of processing markers and functional behavior, specifically walking. Methods: A cohort of 161 participants with cerebrov...

Introduction: Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain a...

Objectives Recent studies suggest that interindividual genetic differences in glial-dependent CSF flow through the brain parenchyma, known as glymphatic flow, may trigger compensatory changes in human sleep physiology. In animal models, brain perivascular spaces are a critical conduit for glymphatic flow. We tested the hypothesis that MRI-visible P...

Objectives: Recent studies suggest that interindividual genetic differences in glial-dependent CSF flow through the brain parenchyma, known as glymphatic flow, may trigger compensatory changes in human sleep physiology. In animal models, brain perivascular spaces are a critical conduit for glymphatic flow. We tested the hypothesis that MRI-visible...

Background Regional changes to cortical thickness in individuals with neurodegenerative and cerebrovascular diseases (CVD) can be estimated using specialized neuroimaging software. However, the presence of cerebral small vessel disease, focal atrophy, and cortico-subcortical stroke lesions, pose significant challenges that increase the likelihood o...

Background Early pathological changes in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) gradually decrease neuronal metabolism and function measured by PET and functional MRI (fMRI). These changes are often associated with cognitive decline and can help in the diagnosis of AD. However more sensitive indicators of the earliest stages o...

Background Presence of at least one copy of the polymorphic apolipoprotein E ε4 allele (ApoE4) increases the risk of impairments of gait performance, particularly in elderly individuals with cognitive impairment or at risk of dementia; however, its underlying neural mechanism are unclear. This study examined the association among ApoE4, gait perfor...

The generalized singular value decomposition (GSVD, a.k.a. "SVD triplet", "duality diagram" approach) provides a unified strategy and basis to perform nearly all of the most common multivariate analyses (e.g., principal components, correspondence analysis, multidimensional scaling, canonical correlation, partial least squares). Though the GSVD is u...

The Ontario Neurodegenerative Research Initiative (ONDRI) is a 3 years multi-site prospective cohort study that has acquired comprehensive multiple assessment platform data, including 3T structural MRI, from neurodegenerative patients with Alzheimer's disease, mild cognitive impairment, Parkinson's disease, amyotrophic lateral sclerosis, frontotemp...

Background Regional changes to cortical thickness in individuals with neurodegenerative and cerebrovascular diseases can be estimated using specialised neuroimaging software. However, the presence of cerebral small vessel disease, focal atrophy, and cortico-subcortical stroke lesions, pose significant challenges that increase the likelihood of misc...

Objective: In individuals over the age of 65, concomitant neurodegenerative pathologies contribute to cognitive and/or motor decline and can be aggravated by cerebrovascular disease, but our understanding of how these pathologies synergize to produce the decline represents an important knowledge gap. The Ontario Neurodegenerative Disease Research I...

Introduction: Informal caregivers for persons living with neurodegenerative disorders experience various types of stress and strain. Few studies have investigated the nature of caregiving concerns (“burdens”) and factors that contribute to those concerns, especially across multiple neurodegenerative and cerebrovascular disorders. Methods: The Ontar...

Background White matter hyperintensities (WMH) on magnetic resonance imaging may influence clinical presentation in patients with Parkinson's disease (PD), although their significance and pathophysiological origins remain unresolved. Studies examining WMH have identified pathogenic variants in NOTCH3 as an underlying cause of inherited forms of cer...

Background Vascular cognitive impairment (VCI) post-stroke is frequent but may go undetected, which highlights the need to better screen cognitive functioning following a stroke. Aim: We examined the clinical utility of the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment against a gold standard neuropsychological battery. Me...

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses¹. The flexibility of analytical approaches is exempl...

As large research initiatives designed to generate big data on clinical cohorts become more common, there is an increasing need to establish standard quality assurance (QA; preventing errors) and quality control (QC; identifying and correcting errors) procedures for critical outcome measures. The present article describes the QA and QC approach dev...

The Ontario Neurodegenerative Research Initiative (ONDRI) is a 3 year multi-site prospective cohort study that has acquired comprehensive multiple assessment platform data, including 3T structural MRI, from neurodegenerative patients with Alzheimer’s disease, mild cognitive impairment, Parkinson’s disease, amyotrophic lateral sclerosis, frontotempo...

Data analysis workflows in many scientific domains have become increasingly complex and flexible. To assess the impact of this flexibility on functional magnetic resonance imaging (fMRI) results, the same dataset was independently analyzed by 70 teams, testing nine ex-ante hypotheses. The flexibility of analytic approaches is exemplified by the fac...

Background Large and complex studies are now routine, and quality assurance and quality control (QC) procedures ensure reliable results and conclusions. Standard procedures may comprise manual verification and double entry, but these labour-intensive methods often leave errors undetected. Outlier detection uses a data-driven approach to identify pa...

The present and future of large scale studies of human brain and behavior---in typical and disease populations---is "mutli-omics" and "deep-phenotyping". These studies rely on highly interdisciplinary teams that collect extremely diverse types of data across numerous systems and scales of measurement (e.g., genetics, brain structure, and behavior)....

We propose a new sparsification method for the singular value decomposition—called the constrained singular value decomposition (CSVD)—that can incorporate multiple constraints such as sparsification and orthogonality for the left and right singular vectors. The CSVD can combine different constraints because it implements each constraint as a proje...

Temporal Check-All-That-Apply (TCATA) extends classical Check-All-That-Apply (CATA) by adding a temporal dimension to the evaluation. Because TCATA extends CATA, an obvious visualization of product-attribute associations over time is to treat product x time combinations as individual observations and then use classical Correspondence Analysis (CA)...

INTRODUCTION Genetic contributions to Alzheimer’s Disease (AD) are likely polygenic and not necessarily explained by uniformly applied linear and additive effects. In order to better understand the genetics of AD, we require statistical techniques to address both polygenic and possible non-additive effects. METHODS We used partial least squares-co...

The minimum covariance determinant (MCD) algorithm is one of the most common techniques to detect anomalous or outlying observations. The MCD algorithm depends on two features of multivariate data: the determinant of a matrix (i.e., geometric mean of the eigenvalues) and Mahalanobis distances (MD). While the MCD algorithm is commonly used, and has...

The functional neuroimaging literature has become increasingly complex and thus difficult to navigate. This complexity arises from the rate at which new studies are published and from the terminology that varies widely from study-to-study and even more so from discipline-to-discipline. One way to investigate and manage this problem is to build a “s...

The functional neuroimaging literature has become increasingly complex and thus difficult to navigate. This complexity arises from the rate at which new studies are published and from the terminology that varies widely from study‐to‐study and even more so from discipline‐to‐discipline. One way to investigate and manage this problem is to build a “s...

“Imaging genetics” studies the genetic contributions to brain structure and function by finding correspondence between genetic data—such as single nucleotide polymorphisms (SNPs)—and neuroimaging data—such as diffusion tensor imaging (DTI). However, genetic and neuroimaging data are heterogenous data types, where neuroimaging data are quantitative...

In multivariate analyses, data are typically structured with observations (i.e., participants) on the rows and measurements (i.e., variables) on the columns. These data structure types are commonly analyzed with methods such as principal components analysis (PCA) or factor analyses (FA). However, PCA, FA, and related techniques are not always suita...

The rapid growth of neuroimaging studies makes it exceedingly difficult to fully and thoroughly review and understand the literature in a comprehensive way. Because of the breadth and depth of the literature, several major resources have been introduced to make reviews easier, and conduct meta-analyses, such as NeuroSynth. NeuroSynth is an open-sci...

Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high...

For nearly a century, detecting the genetic contributions to cognitive and behavioral phenomena has been a core interest for psychological research. Recently, this interest has been reinvigorated by the availability of genotyping technologies (e.g., microarrays) that provide new genetic data, such as single nucleotide polymorphisms (SNPs). These SN...

Purpose Many well-accepted systems for determining difficulty level exist for books children read independently, but few are available for determining the wide range of difficulty levels of storybooks read aloud to preschoolers. Also, the available tools list book characteristics only on the basis of parents' or authors' opinions. We created an emp...

We explore the relationships between the cortex functional organization and genetic expression (as provided by the Allen Human Brain Atlas). Previous work suggests that functional cortical networks (resting state and task based) are organized as two large networks (differentiated by their preferred information processing mode) shaped like two rings...

Background: Impulsivity is a complex trait often studied in substance abuse and overeating disorders, but the exact nature of impulsivity traits and their contribution to these disorders are still debated. Thus, understanding how to measure impulsivity is essential for comprehending addictive behaviors. Objectives: Identify unique impulsivity trait...

8th International Conference on Partial Least Squares and Related Methods

ExPosition is a new comprehensive R package providing crisp graphics and implementing multivariate analysis methods based on the singular value decomposition (svd). The core techniques implemented in ExPosition are: principal components analysis, (metric) multidimensional scaling, correspondence analysis, and several of their recent extensions such...

We present an extension of pls—called partial least squares correspondence analysis (plsca)—tailored for the analysis of nominal data. As the name indicates, plsca combines features of pls (analyzing the information common to two tables) and correspondence analysis (ca, analyzing nominal data). We also present inferential techniques for plsca such...

Introduction: Over the past two decades, the use of eye-tracking equipment and software has increased as computing technology advanced. A large part of this new research explores visual attention patterns, including with clinical populations. Currently, most eye-tracking studies use standard analytical approaches (e.g., ANOVA) on single features of...

PLS as a general multivariate method has been applied to many types of data with various covariance structures, signal strengths, numbers of observations and numbers of variables.We present a simulation framework that can cover a wide spectrum of applications by generating realistic data sets with predetermined effect sizes and distributions. In st...

We present a generalization of mean-centered partial least squares correlation called multiblock barycentric discriminant analysis (MUBADA) that integrates multiple regions of interest (ROIs) to analyze functional brain images of cerebral blood flow or metabolism obtained with SPECT or PET. To illustrate MUBADA we analyzed data from 104 participant...