Clinical Manifestations.

Background: The Clinical Dementia Rating Sum of Boxes (CDR-SB) is a widely used measurement score to stage dementia severity; it has become one of the most common outcome measurements in Alzheimer's Disease (AD) research. The CDR-SB requires an informant to provide information to stage a patient's dementia severity. The effect of the informant's characteristics including sex and relationship with patients on the CDR-SB is unknown.

Clinical Manifestations.

Background: Mild Behavioral Impairment (MBI) is a condition characterized by neuropsychiatric symptoms (NPS) in older adults without dementia, serving as a precursor to various forms of dementia. This study explores the association between NPS and functional connectivity (FC) within the default mode network (DMN), executive control network (ECN), and salience network (SN) across three high-risk cohorts: mild cognitive impairment (due to Alzheimer's) (MCI, n = 79), cerebrovascular disease (CVD, n = 144), and Parkinson's disease (PD, n = 132).

Method: A total of 367 participants were recruited from the Ontario Neurodegenerative Disease Research Initiative (ONDRI).

CSF α-Synuclein Seed Amplification Assay in Patients With Atypical Parkinsonian Disorders.

Background And Objectives: There is no disease-modifying treatment of corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), 2 disorders characterized by their striking phenotypic, and, in CBS, pathologic heterogeneity. Seed amplification assays (SAAs) could enable the detection of neuropathologic processes, such as α-synuclein (αSyn) copathology, that affect the success of future disease-modifying treatment strategies. The primary objective was to assess possible αSyn copathology in CBS and PSP, as detected in CSF using an αSyn SAA (αSyn-SAA).

Critical gap in practice-lack of attention to falls and possible fall-related post-concussion symptoms in older adults and individuals with neurodegenerative disease.

Falls in older adults and those with neurodegenerative disease (ND) are a current public health hazard and the primary cause of sustaining a mild traumatic brain injury (mTBI)/concussion. Little is known regarding how post-concussion symptoms present in older adults and patients with ND, even though they are the demographic at highest risk. A combination of under-reporting of falls and a lack of awareness regarding potential consequences of falls, results in the underdiagnosis of post-fall issues and concussions in this population.

Ageing-related tau astrogliopathy severely affecting the substantia nigra.

Aims: Astrocytic tau pathology is a major feature of tauopathies and ageing-related tau astrogliopathy (ARTAG). The substantia nigra (SN) is one of the important degenerative areas in tauopathies with parkinsonism. Nigral tau pathology is usually reported as neuronal predominant with less prominent astrocytic involvement.

Evaluating the Effect of Alzheimer's Disease-Related Biomarker Change in Corticobasal Syndrome and Progressive Supranuclear Palsy.

Objectives: To evaluate the effect of Alzheimer's disease (AD) -related biomarker change on clinical features, brain atrophy and functional connectivity of patients with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP).

Methods: Data from patients with a clinical diagnosis of CBS, PSP, and AD and healthy controls were obtained from the 4-R-Tauopathy Neuroimaging Initiative 1 and 2, the Alzheimer's Disease Neuroimaging Initiative, and a local cohort from the Toronto Western Hospital. Patients with CBS and PSP were divided into AD-positive (CBS/PSP-AD) and AD-negative (CBS/PSP-noAD) groups based on fluid biomarkers and amyloid PET scans.

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.

About time: neurocognitive correlates of stimulus-bound and other time setting errors in the Clock Drawing Test.

Objective: Previous findings suggest that time setting errors (TSEs) in the Clock Drawing Test (CDT) may be related mainly to impairments in semantic and executive function. Recent attempts to dissociate the classic stimulus-bound error (setting the time to "10 11" instead of "10 11") from other TSEs, did not support hypotheses regarding this error being primarily executive in nature or different from other time setting errors in terms of neurocognitive correlates. This study aimed to further investigate the cognitive correlates of stimulus-bound errors and other TSEs, in order to trace possible underlying cognitive deficits.

Distinct involvement of the cranial and spinal nerves in progressive supranuclear palsy.

The most frequent neurodegenerative proteinopathies include diseases with deposition of misfolded tau or α-synuclein in the brain. Pathological protein aggregates in the PNS are well-recognized in α-synucleinopathies and have recently attracted attention as a diagnostic biomarker. However, there is a paucity of observations in tauopathies.

Predictors of Cognitive Change in Parkinson Disease: A 2-year Follow-up Study.

Background: Mild cognitive impairment is common in Parkinson disease (PD-MCI). However, instability in this clinical diagnosis and variability in rates of progression to dementia raises questions regarding its utility for longitudinal tracking and prediction of cognitive change in PD. We examined baseline neuropsychological test and cognitive diagnosis predictors of cognitive change in PD.

Perivascular spaces mediate a relationship between diabetes and other cerebral small vessel disease markers in cerebrovascular and neurodegenerative diseases.

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 basal ganglia (bgPVS), and diffusion metrics in white matter. Patients with T2DM had greater wmPVS volume and there were greater wmPVS volumes in patients with T2DM and hypertension together.

Cell-specific MAPT gene expression is preserved in neuronal and glial tau cytopathologies in progressive supranuclear palsy.

Microtubule-associated protein tau (MAPT) aggregates in neurons, astrocytes and oligodendrocytes in a number of neurodegenerative diseases, including progressive supranuclear palsy (PSP). Tau is a target of therapy and the strategy includes either the elimination of pathological tau aggregates or reducing MAPT expression, and thus the amount of tau protein made to prevent its aggregation. Disease-associated tau affects brain regions in a sequential manner that includes cell-to-cell spreading.

In-person versus virtual administration of the American College of Rheumatology gold standard cognitive battery in systemic lupus erythematosus: Are they interchangeable?

Objective: During the COVID-19 pandemic, many research studies were adapted, including our longitudinal study examining cognitive impairment (CI) in systemic lupus erythematosus (SLE). Cognitive testing was switched from in-person to virtual. This analysis aimed to determine if the administration method (in-person vs.

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.

Clinical Features of Idiopathic Normal Pressure Hydrocephalus: Critical Review of Objective Findings.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by the classic clinical triad of gait, cognitive, and urinary dysfunction, albeit incomplete in a relevant proportion of patients. The clinical findings and evolution of these symptoms have been variably defined in the literature.

Objectives: To evaluate how the phenomenology has been defined, assessed, and reported, we performed a critical review of the existing literature discussing the phenomenology of iNPH.

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).

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).

Progressive Supranuclear Palsy Syndrome Associated With a Novel Tauopathy: Case Study.

Background And Objectives: To report a novel tauopathy in a patient with protracted course progressive supranuclear palsy (PC-PSP).

Methods: This was a clinical follow-up, gene analysis, neuropathologic study.

Results: A 73-year-old man presented with diplopia, slowness, shuffling gait, and falls.

Alpha-Synuclein RT-QuIC in Idiopathic Normal Pressure Hydrocephalus.

This study quantified the occurrence of an underlying synucleinopathy in 50 patients with idiopathic normal pressure hydrocephalus by means of real-time quaking-induced conversion, a highly sensitive and specific technique capable of detecting and amplifying misfolded aggregated forms of α-synuclein in the cerebrospinal fluid. Seven patients were positive and they did not differ from negative cases, except for a more frequent L-dopa responsiveness and gait characterized by a wider base. The two groups did not differ in terms of response rate to tap test or shunt surgery, although step length and gait velocity improved by a lesser extent in positive cases.

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).

Rapid cognitive assessment tools for screening of mild cognitive impairment in the preoperative setting: A systematic review and meta-analysis.

Importance: Mild cognitive impairment (MCI) is a high-risk precursor to dementia, post-operative delirium, and prolonged hospitalization. There is a need for preoperative rapid cognitive screening tools.

Study Objective: To evaluate the predictive parameters of rapid MCI screening tools in different clinical settings for preoperative application.

Informant-based tools for assessment and monitoring of cognition, behavior, and function in neurocognitive disorders: Systematic review and report from a CCCDTD5 Working Group.

Objective: As part of the fifth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, we assessed the literature on informant-based tools for assessment and monitoring of cognition, behavior, and function in neurocognitive disorders (NCDs) to provide evidence-based recommendations for clinicians and researchers.

Methods: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards guidelines. Publications that validated the informant-based tools or described their key properties were reviewed.

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).