Neuroimaging Biomarkers in Neuropsychiatric Symptom Clusters.

Background: Neuropsychiatric symptoms (NPS) constitute a major challenge for patients with Alzheimer’s disease (AD). We have recently demonstrated that in AD, overall NPS burden is significantly associated with patient function. However, few studies have examined the relationship between specific symptom clusters with neurological biomarkers.

Kimel Family Centre for Brain Health and Wellness: Protocol for a Naturalistic Longitudinal Personalized Multidomain Preference Dementia Risk Reduction Trial.

Background: The Kimel Family Centre for Brain Health and Wellness is a research‐driven community centre testing the efficacy of a naturalistic longitudinal personalized multidomain preference dementia risk reduction intervention on dementia risk and cognition. The objective of this protocol is to validate this approach by following people for two years.

Method: Participants ( = 325) will be 50 years of age or older, without a diagnosis of dementia, and sufficiently fluent in English to complete the assessments and understand program instructors.

Examining the associations between linoleic acid‐derived cytochrome P450‐soluble epoxide hydrolase metabolites and small vessel disease markers in normoglycemia, prediabetes, and type 2 diabetes mellitus.

Background: Polyunsaturated fatty acids are metabolized by cytochrome P450 (CYP450) into anti‐inflammatory, pro‐resolving epoxides, which are rapidly converted to inactive and cytotoxic diols by soluble epoxide hydrolase (sEH). Increased CYP450‐sEH metabolites are associated with worse cognition in type 2 diabetes mellitus (T2DM), and greater white matter hyperintensities (WMH) in patients with stroke. We examined whether the relationship between linoleic acid (LA)‐derived CYP450‐sEH metabolites (oxylipins) and small vessel disease (SVD) markers differ across diabetes status.

segcsvd: A Convolutional Neural Network-Based Tool for Quantifying White Matter Hyperintensities in Heterogeneous Patient Cohorts.

White matter hyperintensities (WMH) of presumed vascular origin are a magnetic resonance imaging (MRI)-based biomarker of cerebral small vessel disease (CSVD). WMH are associated with cognitive decline and increased risk of stroke and dementia, and are commonly observed in aging, vascular cognitive impairment, and neurodegenerative diseases. The reliable and rapid measurement of WMH in large-scale multisite clinical studies with heterogeneous patient populations remains challenging, where the diversity of imaging characteristics across studies adds additional complexity to this task.

Homocysteine, neurodegenerative biomarkers, and APOE ε4 in neurodegenerative diseases.

Introduction: Elevated plasma homocysteine (Hcy) is associated with an increased risk of developing neurodegenerative diseases; however, its relationship with the apolipoprotein E (APOE) ε4 allele has not been well characterized.

Methods: Participants clinically diagnosed with Alzheimer's disease or mild cognitive impairment (AD/MCI), frontotemporal dementia, Parkinson's disease, or cerebrovascular disease were stratified by the presence of the APOE ε4 allele. Volumetric magnetic resonance imaging, plasma amyloid/tau/neurodegeneration biomarkers, and cognitive performance were quantified.

Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.

Introduction: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases.

Methods: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative.

Results: PVS was significantly associated with sEF (c = -0.

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.

Enhanced mind-matter interactions following rTMS induced frontal lobe inhibition.

A major barrier to acceptance of psi is that effects are small and hard to replicate. To address this issue, we developed a novel neurobiological model to study this controversial phenomenon based upon the concept that the brain may act as a psi-inhibitory filter. Our previous research in individuals with frontal lobe damage suggests that this filter includes the left medial middle frontal region.

Relationships between neuropsychiatric symptoms and cognitive profiles in Alzheimer's disease and related syndromes.

Objectives: To investigate the rate of occurrence of neuropsychiatric symptoms (NPS) and their relationship with age, sex and cognitive performance in subjects with Alzheimer's disease and related dementias (Alzheimer's disease and related dementias [ADRD]).

Methods: This is a retrospective matched case-control study. Data from memory clinic patients included demographic information presence of NPS, and cognitive testing of Orientation, Immediate and Delayed Memory, Visuospatial Function, Working Memory, Attention, Executive Control and Language.

Rare neurovascular genetic and imaging markers across neurodegenerative diseases.

Introduction: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status.

Methods: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1).

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.

Cognitive correlates of antisaccade behaviour across multiple neurodegenerative diseases.

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 saccade parameters in single diseases, using multiple separate neuropsychological test scores to relate oculomotor behaviour to cognition; however, this approach produces inconsistent, ungeneralizable results and fails to consider the cognitive heterogeneity of these diseases.

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.

Strategy-training post-stroke via tele-rehabilitation: a pilot randomized controlled trial.

Purpose: Long-term limitations in social participation are common after stroke. Whether these can be attenuated through a tele-rehabilitation approach is unknown. We were particularly interested in examining transfer of learning effects which could result in broader improvements in social participation.

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.

Retinal nerve fiber layer in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Purpose: Tauopathy and transactive response DNA binding protein 43 (TDP-43) proteinopathy are associated with neurodegenerative diseases. These proteinopathies are difficult to detect . This study examined if spectral-domain optical coherence tomography (SD-OCT) can differentiate the difference in peripapillary retinal nerve fibre layer (pRNFL) thickness and macular retinal thickness between participants with presumed tauopathy (progressive supranuclear palsy) and those with presumed TDP-43 proteinopathy (amyotrophic lateral sclerosis and semantic variant primary progressive aphasia).

Targeted copy number variant identification across the neurodegenerative disease spectrum.

Background: 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.

Methods: Here, we applied a depth of coverage approach to detect CNVs in 80 genes previously associated with neurodegenerative disease within participants of the Ontario Neurodegenerative Disease Research Initiative (n = 519).

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.

Virtual Behavioural Medicine Program: A Novel Model of Care for Neuropsychiatric Symptoms in Dementia1.

Background: Patients with severe neuropsychiatric symptoms (NPS) due to dementia are often uprooted from their familiar environments in long-term care or the community and transferred to emergency departments, acute care hospitals, or specialized behavioral units which can exacerbate NPS. To address this issue, we developed the Virtual Behavioural Medicine Program (VBM), an innovative model of virtual care designed to support management of patients with NPS in their own environment.

Objective: To determine efficacy of VBM in reducing admission to a specialized inpatient neurobehavioral unit for management of NPS.