ONDRI’s Research Publications
Impact through publication
ONDRI’s unique cross-disease, cross-platform design bridges lab-based silos that are typical in research. This team science focused collaboration has led to novel findings that have already been published, or are at various stages of validation or review, and will be published shortly.
Please see below for ONDRI scientific articles published to date. These appear in chronological order. A short summary is provided for each publication, along with a link to its PubMed listing and abstract. Access to the full article is provided if the article is open-access. If it is not, then access through a university or personal membership is required to read the complete article.
Cognitive correlates of antisaccade behaviour across multiple neurodegenerative diseases
March 2023
Journal: Brain Communications
Lead Author: Heidi C. Reik
In this study, researchers sought to understand links between oculomotor parameters, their relationships to robust cognitive measures, and their alterations in disease.
Classification and staging of Parkinson’s disease using video-based eye tracking
February 2023
Journal: Parkinsonism & Related Disorders
Lead Author: Donald C. Brien
We used video-based eye tracking and machine learning to develop a simple, non-invasive test sensitive to PD and the stages of cognitive dysfunction.
Variation and Correlation of Potential Unintended Consequences of Antipsychotic Reduction in Ontario Nursing Homes Over Time
January 2023
Journal: Medical Care
Lead Author: Daniel A. Harris
The objective of this study was to jointly model facility-level time trends in potentially inappropriate antipsychotic use, antidepressant use, and the indications used to define appropriate antipsychotic use.
Neuropsychiatric Symptom Burden across Neurodegenerative Disorders and its Association with Function
January 2023
Journal: The Canadian Journal of Psychiatry
Lead Author: Daniel Kapustin
Neuropsychiatric symptoms (NPS) are prevalent in neurodegenerative disorders, however, their frequency and impact on function across different disorders is not well understood. We compared the frequency and severity of NPS across the diseases studied by ONDRI and explored the association between NPS burden and function.
Can patients with dementia be identified in primary care electronic medical records using natural language processing?
January 2023
Journal: Journal of Healthcare Informatics Research
Lead Author: Laura Maclagan
We used natural language processing (NLP) to identify dementia-related features in EMRs and compared the performance of supervised machine learning models to classify patients with dementia.
Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke
December 2022
Journal: Journal of the American Heart Association
Lead Author: Di Yu
Cerebral small vessel disease is associated with higher ratios of soluble‐epoxide hydrolase derived linoleic acid diols to their parent epoxides; however, the relationship had not yet been examined in stroke. This study helped determine that linoleic acid markers of cytochrome P450/soluble‐epoxide hydrolase activity were associated with small versus large vessel stroke. The findings may indicate a novel modifiable risk factor for small vessel disease and related neurodegeneration.
Cost-effectiveness of a gene sequencing test for Alzheimer’s disease in Ontario
November 2022
Journal: Journal of Community Genetics
Lead Author: Nicolas Irrgorri
The Ontario Neurodegenerative Disease Research Initiative has developed an in-province genetic test (ONDRISeq), which currently runs in Ontario in an experimental capacity. The aim of this study is to estimate the costs and health outcomes associated with ONDRISeq to diagnose AD relative to out-of-country (OOC) testing (status quo).
Genetic variation in the dopamine system is associated with mixed-strategy decision-making in patients with Parkinson’s disease
November 2022
Journal: European Journal of Neuroscience
Lead Author: Ashley C. Parr
Decision-making during mixed-strategy games requires flexibly adapting choice strategies in response to others’ actions and dynamically tracking outcomes. Such decisions involve diverse cognitive processes, including reinforcement learning, which are affected by disruptions to the striatal dopamine system. We therefore investigated how genetic variation in dopamine function affected mixed-strategy decision-making in Parkinson’s disease (PD), which involves striatal dopamine pathology.
Comparison of Diffusion Tensor Imaging Metrics in Normal-Appearing White Matter to Cerebrovascular Lesions and Correlation with Cerebrovascular Disease Risk Factors and Severity
October 2022
Journal: International Journal of Biomedical Imaging
Lead Author: Seyyed M H Haddad
This study demonstrated the differences between conventional DTI metrics, FA, MD, AD, and RD, in cerebral vascular lesions and healthy tissue types. Therefore, incorporating DTI to characterize the integrity of the tissue microstructure could help to define the extent and severity of various brain vascular anomalies.
Retinal nerve fibre layer in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
October 2022
Journal: Frontiers in Neuroscience
Lead Author: Bryan M. Wong
Spectral-domain optical coherence tomography (SD-OCT), is diagnostic eye technology that is readily available in the community. Ongoing studies are examining whether SD-OCT can help diagnose neurodegenerative diseases in life. This study examined whether researchers could distinguish between the thickness of the retinal nerve fibre layer, and the macula, of study participants with presumed tauopathy (progressive supranuclear palsy) and those with presumed TDP43 proteinopathy (amyotrophic lateral sclerosis and semantic variant primary progressive aphasia).
Visits to the emergency department by community-dwelling people with dementia during the first 2 waves of the COVID-19 pandemic in Ontario: a repeated cross-sectional analysis
July 2022
Journal: CMAJ Open
Lead Author: Laura C. Maclagan
Community-dwelling people with dementia have been affected by COVID-19 pandemic health risks and control measures that resulted in worsened access to health care and service cancellation. One critical access point in health systems is the emergency department. We aimed to determine the change in weekly rates of visits to the emergency department of community-dwelling people with dementia in Ontario during the first 2 waves of the COVID-19 pandemic compared with historical patterns.
Increased brain volumetric measurement precision from multi-site 3D T1-weighted 3 T magnetic resonance imaging by correcting geometric distortions
June 2022
Journal: Magnetic Resonance Imaging
Lead Author: Nuwan D. Nanayakkara
Magnetic resonance imaging (MRI) scanner-specific geometric distortions may contribute to differences in resultant measurements by site, in multi-site studies. The purpose of this study was to determine whether utilizing an existing geometric distortion correction protocol increases the precision of brain volumetric measurements in a multi-site multi-scanner study.
Targeted copy number variant identification across the neurodegenerative disease spectrum
June 2022
Journal: Molecular Genetics and Genomics Medicine
Lead Author: Allison A. Dilliott
Although genetic factors are known to contribute to neurodegenerative disease susceptibility, there remains a large amount of heritability unaccounted for across the diagnoses. Copy number variants (CNVs) contribute to these phenotypes, but their presence and influence on disease state remains relatively understudied.
Caregiving concerns and clinical characteristics across neurodegenerative and cerebrovascular disorders in the Ontario neurodegenerative disease research initiative
June 2022
Journal: International Journal of Geriatric Psychiatry
Co-Lead Authors: Derek Beaton, Angela Roberts
Caregiving burden is a significant factor in clinical management of people living with neurodegenerative and cerebrovascular diseases. This ONDRI study utilized the Zarit Burden Interview (ZBI) to probe caregiver burden across the diseases ONDRI studies.
Detecting accelerometer non-wear periods using change in acceleration combined with rate-of-change in temperature
May 2022
Journal: BMC Medical Research Methodology
Co-Lead Authors: Adam Vert, William E. McIlroy & Karen Van Ooteghem
Accelerometery is commonly used to estimate physical activity, sleep, and sedentary behavior. This study aimed to advance non-wear detection methods by integrating a ‘rate-of-change’ criterion for temperature into a combined temperature-acceleration algorithm.
Characteristics of the Ontario Neurodegenerative Disease Research Initiative cohort
April 2022
Journal: Alzheimer’s & Dementia – The Journal of the Alzheimer’s Association
Lead Author: Kelly M. Sunderland
This paper presents an overview of the design methods and the distinct cohort studied in ONDRI’s multi-site, longitudinal, observational dementia study (2013-18).
Small and Large Magnetic Resonance Imaging–Visible Perivascular Spaces in the Basal Ganglia of Parkinson’s Disease
April 2022
Journal: Movement Disorders
Co-Lead Authors: Joel Ramirez, Stephanie A. Berberian
The aim of this study was to examine associations between quantitative measures of large and small BG-PVS, global cognition, and motor/nonmotor features in a multicenter cohort of patients with PD.
Investigating the contribution of white matter hyperintensities and cortical thickness to empathy in neurodegenerative and cerebrovascular diseases
March 2022
Journal: Geroscience
Co-Lead Authors: Ozzoude, M., Varriano, B., Beaton, D.
The relationships between white matter hyperintensity, cortical thickness and empathy deficits across ONDRI’s disease cohorts is explored in this study.
Reasons for repeated emergency department visits among community-dwelling older adults with dementia in Ontario, Canada
March 2022
Journal: Journal of the American Geriatrics Society
Lead Authors: Aaron Jones, Laura C. Maclagan
Community-dwelling older adults living with dementia visit the emergency department (ED) more frequently than other older adults, but research on the reasons for repeated visits is lacking. We examined the rate of repeated ED visits and reasons for visits in a cohort of individuals with dementia.
Potential Unintended Consequences of Antipsychotic Reduction in Ontario Nursing Homes
February 2022
Journal: Journal of the American Medical Directors Association
Lead Author: Daniel A. Harris
Antipsychotic reduction in nursing homes has been a focus of research and policy attention for several decades; however, there is evidence that these initiatives may have had unintended consequences, such as medication substitution and changes in diagnosis coding. Our objectives were to describe temporal changes in the use of antipsychotics, potential substitution medications, and diagnoses and symptoms used to establish the appropriateness of antipsychotic prescribing.
Common Data Elements to Facilitate Sharing and Re-use of Participant-Level Data: Assessment of Psychiatric Comorbidity Across Brain Disorders
February 2022
Journal: Frontiers in Psychology
Lead Author: Anthony L. Vaccarino
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. To help achieve their goals, consensus methodology was used to identify a set of core demographic and clinical variables that should be routinely collected across all participating programs. This process is explained here. Results are also presented using selected common data elements pooled across three studies to better understand psychiatric comorbidity in neurological disease.
Incidence of neurological and psychiatric comorbidity over time: a population-based cohort study in Ontario, Canada
February 2022
Journal: Age and Ageing
Lead Author: Colleen J. Maxwell
Researchers studied the health system use of over 5 million Ontarians between 2002 and 2016 to understand the associations between neurological and common psychiatric disorders over time. Results showed significant associations for most categories.
Impact of the COVID-19 Pandemic on Home Care Services Among Community-Dwelling Adults With Dementia
October 2021
Journal: J Am Med Dir Assoc.
Lead Authors: Aaron Jones, Laura C. Maclagan
Home care for people living with dementia in Ontario was initially interrupted during the COVID-19 pandemic but returned back to historic levels by September 2021. Read about the details of this study.
Trends in Health Service Use for Canadian Adults With Dementia and Parkinson Disease During the First Wave of the COVID-19 Pandemic
January 2022
Journal: JAMA Health Forum
Lead Author: Susan E. Bronskill
Was the COVID-19 pandemic associated with changes in health service use and mortality among community-dwelling people living with dementia and Parkinson disease compared with older adults? This study examines this important question and helps determine the disruptions in care experienced by this population in the early part of the pandemic.
Feasibility of a continuous, multi‑sensor remote health monitoring approach in persons living with neurodegenerative disease
September 2021
Journal: Journal of Neurology
Lead Author: F. Elizabeth Godkin
Remote health monitoring with wearable sensor technology may positively impact patient self-management and clinical care. This mixed methods study assessed the feasibility of continuous, multisensor wear in persons with cerebrovascular (CVD) or neurodegenerative disease (NDD).
Contribution of rare variant associations to neurodegenerative disease presentation
September 2021
Journal: NPJ Genomic Medicine
Lead Author: Allison A. Dilliott
Genetic factors contribute to neurodegenerative diseases. However, much in this area is still poorly understood. Previous studies have attempted to fill the gaps by performing studies with individual disease groups. This ONDRI study used a custom designed ONDRI gene panel to explore genetic overlap across the neurodegenerative diseases.
Strategies for measuring prescription medication switching with pharmacy claims data: a scoping review protocol
September 2021
Journal: JBI Evidence Synthesis
Lead Author: Daniel A. Harris
This scoping review aims to compare strategies for measuring prescription medication switching with pharmacy claims data, with a focus on psychotropic vs non-psychotropic medications.
Association of apolipoprotein E variation with cognitive impairment across multiple neurodegenerative diagnoses
September 2021
Journal: Neurobiology of Aging
Lead Author: Allison A. Dilliott
The mapping of the DNA sequence of the entire human genome has resulted in enormous strides in our understanding of diseases and, in some cases, their pre-determined genetic trajectories. A new ONDRI study, published by Dilliott et al , explores the relationship of a protein (APOE) – well known to be associated with Alzheimer’s Disease – to cognitive impairment across several neurodegenerative diseases.
Health services utilization prior to amyotrophic lateral sclerosis diagnosis: A province-wide study of individuals treated with riluzole in Ontario, Canada
August 2021
Journal: Muscle and Nerve
Lead Author: Michael A Campitelli and Agessandro Abrahao
ONDRI researchers studied the health service use of >1,000 people living with ALS in Ontario, Canada, between 2002 and 2018, in the five years before their diagnosis. The study found differences in care by geography and by sex.
MRI-visible perivascular space volumes, sleep duration and daytime dysfunction in adults with cerebrovascular disease
May 2021
Journal: Sleep Medicine
Lead Author: Joel Ramirez
Cerebrospinal fluid (csf) flows through the brain, particularly during sleep, and serves a waste clearing function. The size or volume of the space around the brain’s blood vessels (perivascular space) is an indicator of the degree of csf flow – the higher the volume, the more likely the dysfunction in this clearing mechanism. This research, which uses ONDRI’s Foundational study data, tested whether larger than normal perivascular space volumes were associated with compensatory individual sleep behaviours.
Bilingualism in Parkinson’s disease: Relationship to cognition and quality of life
April 2021
Journal: Journal of Clinical and Experimental Neuropsychology
Lead Author: Keera N. Fishman
It has long been believed that speaking more than one language on a regular basis may help boost brain function and possibly preserve the brain as it ages. This ONDRI study was designed to help determine whether bilingualism is associated with cognitive advantages or better wellbeing in Parkinson’s disease (PD).
Improved Segmentation of the Intracranial and Ventricular Volumes in Populations with Cerebrovascular Lesions and Atrophy Using 3D CNNs
February 2021
Journal: Neuroinformatics
Lead Author: Emmanuel E. Ntiri
Successful segmentation of different parts of brain images is of critical importance when studying neurodegeneration through neuroimaging. We compared several robust algorithms that use their own unique methodologies to achieve this segmentation. Our own models were tested on a large dataset of older adults with varying degrees of cerebrovascular lesions and degeneration. Our resulting multi-contrast models outperformed other methods across many of the evaluation metrics.
Multisite Comparison of MRI Defacing Software Across Multiple Cohorts
February 2021
Journal: Frontiers in Psychiatry
Lead Author: Athena E. Theyers
With improvements to both scan quality and facial recognition software, there is an increased risk of participants being identified by a 3D render of their structural neuroimaging scans, even when all other personal information has been removed. To prevent this, facial features should be removed before data are shared or openly released. While there are several publicly available software algorithms to do this, there has been no comprehensive review of their accuracy within the general population. This paper addresses this need, through cross-collaboration with Ontario Brain Institute’s CAN-BIND and POND programs.
Predicting Cognitive Impairment in Cerebrovascular Disease Using Spoken Discourse Production
January/March 2021
Journal: Topics in Language Disorders
Lead Author: Angela Roberts
Dementia due to cerebrovascular disease (CVD) is common. Detecting early cognitive decline in CVD is critical because addressing risk factors may slow or prevent dementia. This study used a multidomain discourse analysis approach to determine the spoken language signature of CVD-related cognitive impairment.
Cortical Thickness Estimation in Individuals With Cerebral Small Vessel Disease, Focal Atrophy, and Chronic Stroke Lesions
December 2020
Journal: Frontiers in Neuroscience
Co-Lead Authors: Miracle Ozzoude, Joel Ramirez
Local changes to cortical thickness can indicate disease progression. For people living with neurodegenerative and cerebrovascular diseases (CVD), cortical thickness changes can be estimated using specialized neuroimaging software. However, the presence of stroke and cerebral small vessel disease pose significant challenges to estimate accuracy. The main goal of this study was to examine a correction procedure developed for enhancing FreeSurfer’s (FS’s) cortical thickness estimation tool.
Sex Differences in Antipsychotic and Benzodiazepine Prescribing Patterns: A Cohort Study of Newly Admitted Nursing Home Residents with Dementia in Ontario, Canada
September 2020
Journal: Drugs & Aging
Lead Author: Laura C. Maclagan
In nursing homes, residents with dementia frequently receive potentially inappropriate medications that are associated with an increased risk of adverse events. There are known differences between males and females living with dementia, in terms of clinical presentation and sociodemographic characteristics. Despite this, there have been few studies that have examined sex differences in patterns and predictors of potentially inappropriate medication use.
Ontario Neurodegenerative Disease Research Initiative (ONDRI): Structural MRI Methods and Outcome Measures
August 2020
Journal: Frontiers in Neurology
Lead Author: Joel Ramirez
This paper documents how brain loss (due to neurodegeneration) and brain lesions (due to stroke and cerebrovascular disease) are measured from the patient’s MRI scans in ONDRI.
Trajectories of health system use and survival for community-dwelling persons with dementia: a cohort study
July 2020
Journal: BMJ Open
Lead Author: Susan E. Bronskill
This study found that as people with dementia remained in the community over time, they were more likely to enter long-term care settings than people without dementia, and they used home care services at an increasing rate. The use of other healthcare services appeared stable over time. This work will help health system planners to anticipate and plan for services to meet the needs of people with dementia and their care partners.
Parkinson’s Disease, NOTCH3 Genetic Variants, and White Matter Hyperintensities
June 2020
Journal: Movement Disorders
Co-Lead Authors: Joel Ramirez and Allison A. Dilliott
This novel research that examined MRIs from Parkinson’s disease patients, found that brain lesions from damage to small blood vessels may be due to rare changes within the NOTCH3 gene.
Methods for Improving Screening for Vascular Cognitive Impairment Using the Montreal Cognitive Assessment
June 2020
Journal: Canadian Journal of Neurological Sciences
Lead Author: Khush-Bakht Zaidi
Vascular cognitive impairment (VCI) post-stroke is frequent but may go undetected. This highlights the need to better screen cognitive functioning following a stroke. This study examined the utility of using the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment post-stroke.
Identifying drugs with disease‐modifying potential in Parkinson’s disease using artificial intelligence and pharmacoepidemiology
May 2020
Journal: Pharmacoepidemiology & Drug Safety
Lead Authors: Laura C. Maclagan, Naomi P. Visanji
Researchers used artificial intelligence paired with real-world Ontario health data to examine drugs that may prevent or slow Parkinson’s disease. Five drugs were identified that may reduce the risk of Parkinson’s disease. These drugs should be prioritized for future research.
The Quality Assurance and Quality Control Protocol for Neuropsychological Data Collection and Curation in the Ontario Neurodegenerative Disease Research Initiative (ONDRI) Study
May 2020
Journal: SAGE Journals
Lead Author: Paula M. McLaughlin
Large research initiatives designed to generate big data on clinical cohorts have become more common. As such, 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. This study describes the QA and QC approach developed and implemented for the neuropsychology data collected as part of the Ontario Neurodegenerative Disease Research Initiative study.
Structural Brain Magnetic Resonance Imaging to Rule Out Comorbid Pathology in the Assessment of Alzheimer’s Disease Dementia: Findings from the Ontario Neurodegenerative Disease Research Initiative (ONDRI) Study and Clinical Trials Over the Past 10 Years
February 2020
Journal: IOS Press
Lead Author: Arumina Kapoor
Dementia is often the result of overlapping diseases. This research shows the importance of using brain MRI’s routinely in clinical trials to account for the impact of co-morbid conditions.
Sex Differences in Care Need and Survival in Patients Admitted to Nursing Home Poststroke
January 2020
Journal: The Canadian Journal of Neurological Sciences
Lead Author: Amy Y. X. Yu
Women are more likely to be admitted to nursing homes after a stroke than men. This research shows that although women have a lower mortality rate than men after admission to a nursing home, they require more care due to higher rates of pain and depression as well as increased frailty. This study has identified opportunities to improve poststroke care in the nursing home setting.
Comparison of quality control methods for automated diffusion tensor imaging analysis pipelines
January 2020
Journal: PLOS One
Lead Author: Seyyed M. H. Mohammed
Large research studies, run out of different labs/locations, can utilize different technologies (e.g. branded equipment). When brain imaging is involved, the output/records, results in huge data files. The processing of these files, to standardize them for analysis, requires extensive programming. To be practical and ensure quality control (QC), this programming takes the form of fully automatic pipelines/algorithms. In this study, three automatic processing pipelines were tested, using brain images from ONDRI participants. A preferred method was selected.
Genetic Variation in the Ontario Neurodegenerative Disease Research Initiative
September 2019
Journal: The Canadian Journal of Neurological Sciences
Lead Author: Allison A Dilliott
There are changes that can occur within one’s DNA that are quite common in the general population, but which can lead to an increased risk of neurodegeneration. One example of this is the well-known genetic risk factor for late-onset Alzheimer’s disease (AD) found within the apolipoprotein E (APOE) gene. This study examined common APOE gene variants and microtubule-associated protein tau (MAPT) gene variants and their association with the five ONDRI neurodegenerative diseases.
Validation of Optical Coherence Tomography Retinal Segmentation in Neurodegenerative Disease
September 2019
Journal: ARVO International
Lead Author: Bryan M Wong
This study looks at the difference between using software to detect and remove errors in spectral-domain optical coherence tomography (SD-OCT) imaging versus manual correction.
The utility of multivariate outlier detection techniques for data quality evaluation in large studies: an application within the ONDRI Project
May 2019
Journal: BMC Medical Research Methodology
Lead Author: Kelly M Sunderland
Large and complex studies are now routine; quality assurance (QA) and quality control (QC) procedures ensure reliable results and conclusions. This research determined that manual QC procedures are insufficient for large studies as many errors remain undetected.
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
April 2018
Journal: Journal of Visualized Experiments
Lead Author: Allison A Dilliott
Next-generation sequencing (NGS) is quickly changing how to study the genetic causes of certain diseases. Specifically, targeted NGS is able to focus investigations to specific gene regions based on the particular disease being studied. This publication and accompanying video explain the methods used by the ONDRI genomics platform to sequence the DNA of participants using the targeted NGS tool, ONDRISeq.
Motor Phenotype in Neurodegenerative Disorders: Gait and Balance Platform Study Design Protocol for the Ontario Neurodegenerative Research Initiative (ONDRI)
July 2017
Journal: Journal of Alzheimer’s Disease
Lead Author: Manuel Montero-Odasso
As part of the Ontario Neurodegenerative Research Initiative (ONDRI), the gait and balance platform is focused on identifying motor-cognitive profiles across five neurodegenerative diseases. This research will help dissect the cognitive and motor contribution in mobility and cognitive decline, progression to dementia syndromes, and future unfavourable outcomes including falls and mortality.
Find additional publications supported through ONDRI and OBI funding here.