The Sunnybrook Dementia Study

Study Overview
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Brief Summary
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The prospect of disease-modifying therapies in the pipeline for Alzheimer's Disease (AD) has intensified efforts to use brain imaging more effectively for diagnosis and monitoring of dementing illnesses. There is also emerging awareness of the destructive interplay between AD and Cerebrovascular Disease (CVD) in our aging population; both disorders share common vascular risk factors and may respond to similar prevention treatments. Brain mapping techniques capitalize on the fact that different neurodegenerative diseases target particular brain areas. Brain shrinkage and stroke disease can be quantified on Magnetic Resonance Imaging (MRI) using computerized analysis. This ongoing study applies advanced MR imaging analysis, genetic testing and standardized cognitive and functional assessments done at yearly intervals to measure and monitor longitudinal change in patients with AD, vascular and other neurodegenerative diseases and potentially to measure modifying effects of emerging therapies. Over 1500 patients (Mild Cognitive Impairment or dementia from AD, Vascular, Frontotemporal or Lewy Body Disease) and 140 normal elderly have already been enrolled, with 180 autopsies. This study utilizes specialized imaging analysis software packages to reliably quantify brain tissue volumes and small vessel disease, the most common type of CVD. The SDS also investigates other potential biomarkers of dementia such as eye-tracking, optical coherence tomography, gait and balance, and the gut microbiome to explore their clinical utility. Results from this study will help to improve diagnosis, to customize treatment, and to better monitor disease-modifying therapies currently under investigation should they become applicable to everyday practice.

Official Title
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Prospective Neuroimaging, Cognition and Behavioural Study of Alzheimer's, Vascular, Parkinson's, Frontotemporal and Mixed Dementias

Conditions
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Dementia

Participation Criteria
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Eligibility Criteria
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Patient Inclusion Criteria (General): Age between 40 and 90 (inclusive) Fluent in English Completed 8 years of education or higher Visual and auditory acuity adequate for neuropsychological testing Mini-Mental State Exam (MMSE) score ≥ 16 Patient Exclusion Criteria (General): Possible secondary causes of dementia, concomitant or history of neurological or psychiatric illness (other than stroke or Parkinsonism) History of alcohol or substance abuse or dependence within the past 2 years Normal Control Inclusion Criteria: Age between 40-90 Fluent in English Completed 8 years of education or higher No significant memory complaints Normal Control Exclusion Criteria: Being treated or history of being treated for psychiatric or neurological illness History of alcohol or substance abuse or dependence within the past 2 years Current use of psychoactive medications (e.g. antidepressant, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) Medical contraindications to MRI

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Alzheimer's disease (AD)<br> | |
| Vascular Cognitive Disorders (VCD)<br> | |
| Lewy Body Disease (LBD)<br> | |
| Frontotemporal Dementia (FTD)<br>Behavioral-variant Frontotemporal Dementia (bvFTD) Language-variant Frontoemporal Dementia including Semantic dementia (SD) and Progressive non-fluent aphasia (PNFA) Corticobasal degeneration (CBD) Progressive supranuclear palsy (PSP) | |
| Mild Cognitive Impairment (MCI)<br> | |
| Cognitively Normal (CN)<br> | |
| Small Vessel Disease -Neurodegenerative (SVD)<br> | |
| Subjective Cognitive Complaints (SCC)<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volumetric change in brain structures and brain lesions on Magnetic Resonance Imaging (MRI) across the dementias covarying for age, sex, education and Apolipoprotein E (ApoE) status | Brain structures including whole brain, hippocampus, tissue volumes and cortical thickness in predefined regions of interest; brain lesions including lacunes, subcortical white matter hyperintensities, and stroke | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of clinical decline as measured by detailed conventional neuropsychological testing, instrumental and standard activities of daily living assessments, caregiver forms, and behavioral psychiatric inventories |  | 5 years | 
| Rate of change in perfusion patterns measured on Single Photon Emission Computerized Tomography (SPECT) at baseline and followup contrasts on a voxel-wise basis using Statistical Parametric Mapping (SPM), or in 79 predefined regions of interest |  | 5 years | 
| Group differences for each cognitive, imaging and biomarker measurement |  | 5 years | 
| Clinico-pathologic correlations between autopsy-confirmed histopathology and clinical features including clincial diagnosis, regaional atrophy, regional hypoperfusion, and white matter interintensities on MRI |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neurodengeneration, neuroimaging