Link among apolipoprotein E E4, gait, and cognition in neurodegenerative diseases: ONDRI study.

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 were assessed in 480 older adults with neurodegeneration.

White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases.

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 and cerebrovascular diseases.

Association of Dual-Task Gait Cost and White Matter Hyperintensity Burden Poststroke: Results From the ONDRI.

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 hyperintensity volume from specific major brain regions in poststroke.

Methods: This is a cohort study with a total of 123 older (69 ± 7 years of age) participants with history of stroke were included from the Ontario Neurodegenerative Disease Research Initiative.

White matter hyperintensity burden predicts cognitive but not motor decline in Parkinson's disease: results from the Ontario Neurodegenerative Diseases Research Initiative.

Background And Purpose: The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMHs) cognitive and motor impairments seem to be aggravated. However, the role of WMHs in predicting accelerating symptom worsening remains controversial. The objective was to investigate whether location and segmental brain WMH burden at baseline predict cognitive and motor declines in PD after 2 years.

Neuropsychiatric Symptom Burden across Neurodegenerative Disorders and its Association with Function.

Objective: 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 Alzheimer's disease (AD) (either with mild cognitive impairment or dementia), Cerebrovascular disease (CVD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and explored the association between NPS burden and function.

Methods: We obtained data from Ontario Neurodegenerative Disease Research Initiative (ONDRI) that included following cohorts: AD ( = 111), CVD ( = 148), PD ( = 136), FTD ( = 50) and ALS ( = 36).

Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke.

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 Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra-high-performance liquid chromatography-mass spectrometry.

Characteristics of the Ontario Neurodegenerative Disease Research Initiative cohort.

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 participants comprehensively across modalities. We describe univariate and multivariate baseline features of the cohort and summarize recruitment, data collection, and curation processes.

Caregiving concerns and clinical characteristics across neurodegenerative and cerebrovascular disorders in the Ontario neurodegenerative disease research initiative.

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) whether there are categorical or disorder-specific effects on caregiving burdens, and (3) which demographic, clinical, and cognitive measures are related to burden(s) in neurodegenerative disorders?

Methods/design: N = 504 participants and their study partners (e.g.

Small and Large Magnetic Resonance Imaging-Visible Perivascular Spaces in the Basal Ganglia of Parkinson's Disease Patients.

Background: Although previously thought to be asymptomatic, recent studies have suggested that magnetic resonance imaging-visible perivascular spaces (PVS) in the basal ganglia (BG-PVS) of patients with Parkinson's disease (PD) may be markers of motor disability and cognitive decline. In addition, a pathogenic and risk profile difference between small (≤3-mm diameter) and large (>3-mm diameter) PVS has been suggested.

Objective: 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.

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 empathy deficits in neurodegenerative and cerebrovascular diseases.

Deep Bayesian networks for uncertainty estimation and adversarial resistance of white matter hyperintensity segmentation.

White matter hyperintensities (WMHs) are frequently observed on structural neuroimaging of elderly populations and are associated with cognitive decline and increased risk of dementia. Many existing WMH segmentation algorithms produce suboptimal results in populations with vascular lesions or brain atrophy, or require parameter tuning and are computationally expensive. Additionally, most algorithms do not generate a confidence estimate of segmentation quality, limiting their interpretation.

Feasibility of a continuous, multi-sensor remote health monitoring approach in persons living with neurodegenerative disease.

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 little attention in persons with physical or cognitive limitations.

Contribution of rare variant associations to neurodegenerative disease presentation.

Genetic factors contribute to neurodegenerative diseases, with high heritability estimates across diagnoses; however, a large portion of the genetic influence remains poorly understood. Many previous studies have attempted to fill the gaps by performing linkage analyses and association studies in individual disease cohorts, but have failed to consider the clinical and pathological overlap observed across neurodegenerative diseases and the potential for genetic overlap between the phenotypes. Here, we leveraged rare variant association analyses (RVAAs) to elucidate the genetic overlap among multiple neurodegenerative diagnoses, including Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), mild cognitive impairment, and Parkinson's disease (PD), as well as cerebrovascular disease, using the data generated with a custom-designed neurodegenerative disease gene panel in the Ontario Neurodegenerative Disease Research Initiative (ONDRI).

The role of ventromedial prefrontal cortex in reward valuation and future thinking during intertemporal choice.

Intertemporal choices require trade-offs between short-term and long-term outcomes. Ventromedial prefrontal cortex (vmPFC) damage causes steep discounting of future rewards (delay discounting [DD]) and impoverished episodic future thinking (EFT). The role of vmPFC in reward valuation, EFT, and their interaction during intertemporal choice is still unclear.

Does Ventromedial Prefrontal Cortex Damage Really Increase Impulsiveness? Delay and Probability Discounting in Patients with Focal Lesions.

If the tendency to discount rewards reflects individuals' general level of impulsiveness, then the discounting of delayed and probabilistic rewards should be negatively correlated: The less a person is able to wait for delayed rewards, the more they should take chances on receiving probabilistic rewards. It has been suggested that damage to the ventromedial prefrontal cortex (vMPFC) increases individuals' impulsiveness, but both intertemporal choice and risky choice have only recently been assayed in the same patients with vMPFC damage. Here, we assess both delay and probability discounting in individuals with vMPFC damage (n = 8) or with medial temporal lobe (MTL) damage (n = 10), and in age- and education-matched controls (n = 30).

Association of apolipoprotein E variation with cognitive impairment across multiple neurodegenerative diagnoses.

For many years there has been uncertainty regarding how apolipoprotein E (APOE) E2 and E4 variants may influence overlapping features of neurodegeneration, such as cognitive impairment. We aimed to identify whether the APOE variants are associated with cognitive function across various neurodegenerative and cerebrovascular diagnoses (n = 513). Utilizing a comprehensive neuropsychology battery, multivariate multiple regression was used to assess the influence of APOE carrier status and disease cohort on performance across five cognitive domains.

MRI-visible perivascular space volumes, sleep duration and daytime dysfunction in adults with cerebrovascular disease.

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 PVS volumes, a putative marker of perivascular dysfunction, are associated with compensatory differences in real-world human sleep behavior.

Bilingualism in Parkinson's disease: Relationship to cognition and quality of life.

Unlabelled: Some studies have found that bilingualism promotes cognitive reserve.

Objective: We aimed to determine whether bilingualism, defined as regularly (i.e.

Improved Segmentation of the Intracranial and Ventricular Volumes in Populations with Cerebrovascular Lesions and Atrophy Using 3D CNNs.

Successful segmentation of the total intracranial vault (ICV) and ventricles is of critical importance when studying neurodegeneration through neuroimaging. We present iCVMapper and VentMapper, robust algorithms that use a convolutional neural network (CNN) to segment the ICV and ventricles from both single and multi-contrast MRI data. Our models were trained on a large dataset from two multi-site studies (N = 528 subjects for ICV, N = 501 for ventricular segmentation) consisting of older adults with varying degrees of cerebrovascular lesions and atrophy, which pose significant challenges for most segmentation approaches.

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

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 of misclassification errors and segmentation failures.

Purpose: The main goal of this study was to examine a correction procedure developed for enhancing FreeSurfer's (FS's) cortical thickness estimation tool, particularly when applied to the most challenging MRI obtained from participants with chronic stroke and CVD, with varying degrees of neurovascular lesions and brain atrophy.

Parkinson's Disease, NOTCH3 Genetic Variants, and White Matter Hyperintensities.

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 cerebral small vessel disease.

Methods: We examined NOTCH3 variants, WMH volumes, and clinical correlates in 139 PD patients in the Ontario Neurodegenerative Disease Research Initiative cohort.

Methods for Improving Screening for Vascular Cognitive Impairment Using the Montreal Cognitive Assessment.

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.

Methods: We assessed cognitive status with a comprehensive battery of neuropsychological tests in 161 individuals who were at least 3-months post-stroke.

The Quality Assurance and Quality Control Protocol for Neuropsychological Data Collection and Curation in the Ontario Neurodegenerative Disease Research Initiative (ONDRI) Study.

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 developed and implemented for the neuropsychology data collected as part of the Ontario Neurodegenerative Disease Research Initiative study. We report on the efficacy of our approach and provide data quality metrics.

Is it time? Episodic imagining and the discounting of delayed and probabilistic rewards in young and older adults.

Remembering and imagining specific, personal experiences can help shape our decisions. For example, cues to imagine future events can reduce delay discounting (i.e.