Prospective Neuroimaging, Cognition and Behavioural Study of Alzheimer's, Vascular, Parkinson's, Frontotemporal and Mixed Dementias
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Enrollment
- 1,800
- Locations
- 1
- Primary Endpoint
- 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
Study Overview
Brief Summary
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. Nearly 1800 patients (Mild Cognitive Impairment or dementia from AD, Vascular, Frontotemporal or Lewy Body Disease) and over 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.
Study Design
- Study Type
- Observational
- Observational Model
- Ecologic Or Community
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 40 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Lewy Body Disease (LBD)
Alzheimer's disease (AD)
Vascular Cognitive Disorders (VCD)
Frontotemporal Dementia (FTD)
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)
Cognitively Normal (CN)
Small Vessel Disease -Neurodegenerative (SVD)
Subjective Cognitive Complaints (SCC)
Outcomes
Primary Outcomes
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
Time Frame: 5 years
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
Secondary Outcomes
- Group differences for each cognitive, imaging and biomarker measurement(5 years)
- 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)
- 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)
Investigators
Dr. Sandra E Black
Brill Chair in Neurology
Sunnybrook Health Sciences Centre