The Ontario Neurodegenerative Disease Research Initiative

Abstract

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 Initiative (ONDRI), a multi-site, longitudinal, observational cohort study, recruited participants across multiple prevalent neurodegenerative diseases and cerebrovascular disease, collecting a wide array of data and thus allowing for deep investigation into common and unique phenotypes. This paper describes baseline features of the ONDRI cohort, understanding of which is essential when conducting analyses or interpreting results. Methods: Five disease cohorts were recruited: Alzheimer's disease/amnestic mild cognitive impairment (AD/MCI), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Parkinson's disease (PD), and cerebrovascular disease (CVD). Assessment platforms included clinical, neuropsychology, eye tracking, gait and balance, neuroimaging, retinal imaging, genomics, and pathology. We describe recruitment, data collection, and data curation protocols, and provide a summary of ONDRI baseline characteristics. Results: 520 participants were enrolled. Most participants were in the early stages of disease progression. Participants had a median age of 69 years, a median Montreal Cognitive Assessment score of 25, a median percent of independence of 100 for basic activities of daily living, and a median of 93 for instrumental activities. Variation between disease cohorts existed for age, level of cognition, and geographic location. Conclusion: ONDRI data will enable exploration into unique and shared pathological mechanisms contributing to cognitive and motor decline across the spectrum of neurodegenerative diseases.

Contribution of rare variant associations to neurodegenerative disease presentation

“…Herein, we did not observe an association between PD and NOTCH3 when compared to the controls, but the history of CVD in the control cohort was unknown. An association was observed between PD and NOTCH3 when compared to the combined AD and MCI cohort, which was of particular interest as ONDRI excluded participants from the AD and MCI cohorts who had significant evidence of vascular pathology 18 . Therefore, this result seemingly supports the hypothesis that rare NOTCH3 variation may be contributing to cerebrovascular features within patients with PD 27 .…”

“…Here we utilize targeted next-generation sequencing (NGS) data coupled with a RVAA-based binning strategy to identify the contribution of rare genetic variants in participants from the Ontario Neurodegenerative Disease Research Initiative (ONDRI) to multiple neurodegenerative disease phenotypes, including (1) AD; (2) amnestic mild cognitive impairment (MCI); (3) ALS; (4) frontotemporal dementia (FTD); and (5) PD, as well as cerebrovascular disease (CVD) 17,18 . By binning variants into disease-association-based gene groupings and individual gene-based groupings, and comparing variant enrichment to that of a cognitively normal, elderly control cohort, we seek to identify whether rare variants significantly contribute to disease presentation in ONDRI participants.…”

Investigating the Contribution of White Matter Hyperintensities and Cortical Thickness to Empathy in Neurodegenerative and Cerebrovascular Diseases

“…Study participants were enrolled as part of Ontario Neurodegenerative Disease Research Initiative (ONDRI), a multi-centre, longitudinal observational study conducted in Ontario, Canada. Detailed inclusion and exclusion criteria for each diagnostic cohort (dx) are reported elsewhere [33,34]. Briefly, AD/MCI participants met National Institute on Aging Alzheimer's Association criteria for probable or possible AD, or MCI [35,36]; ALS participants met El Escorial World Federation of Neurology diagnostic criteria for possible, probable or definite familial or sporadic ALS [37]; the latest criteria were used for possible or probable bvFTD [38], for agrammatic/nonfluent and semantic variants of primary progressive aphasia (nfvPPA and svPPA) [39] and progressive supranuclear palsy (PSP) [40]; Corticobasal syndrome diagnosis made according to latest criteria [41]; PD participants met criteria for idiopathic PD defined by the United Kingdom's Parkinson's Disease Society Brain Bank clinical diagnostic criteria [42]; and Cerebrovascular disease (CVD) participants had experienced a mild or moderate ischemic stroke event (documented on MRI or CT) three or more months prior to enrolment in compliance with the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards [43].…”

Cortical Thickness Estimation in Individuals With Cerebral Small Vessel Disease, Focal Atrophy, and Chronic Stroke Lesions

“…Participants (N = 155) recruited to the CVD cohort of the Ontario Neurodegenerative Disease Research Initiative (ONDRI) (Farhan et al, 2017) Detailed inclusion and exclusion criteria for the ONDRI CVD participants are previously reported (Farhan et al, 2017;Sunderland et al, 2020). Briefly, participants who had experienced a mild to moderate ischemic stroke event, documented with MRI or CT, over 3 months prior to enrollment, a Modified Rankin Scale (MRS) score (van Swieten et al, 1988) ranging from 0 to 3, and a Montreal Cognitive Assessment (MoCA) score (Nasreddine et al, 2005) ranging 18-30 were included.…”