BEAM: Brain-Eye Amyloid Memory Study

NCT02524405 | Recruiting

• 1 other identifier: 221-2013
• Study Type: observational
• Target: 345
• Locations: 1 country
• Sites: 5

Brief Summary

The main objectives for this study are:

1. 1.To investigate novel, non-invasive ocular measurements including optical coherence tomography and eye tracking in a cross-sectional study of participants with various neurodegenerative dementias against standard cognitive assessments and brain imaging measures; and
2. 2.To assess the potential utility of ocular assessments for early detection in the pre-dementia, i.e. the so-called Mild Cognitive Impairment (MCI) stage, across the common neurodegenerative dementia syndromes and, Vascular Cognitive Impairment (VCI) due to small vessel disease (SVD).
3. 3.To determine the prevalence and relevance of amyloid uptake on PET scanning across the dementias most commonly associated with amyloidosis. Specifically we aim to examine correlations with amyloid uptake status in patients symptomatic from the most common proteinopathies (ie amyloid, tau, synuclein) combined in varying degrees with the most common vasculopathies (ie small vessel disease) using multimodal structural and functional imaging, cognitive behavioral, and gait and balance measures, taking into account genetic risk markers (particularly apolipoprotein E genotypes) and fluid biomarkers ( eg cytokines, oxidative stress, lipidomics).

Conditions

Alzheimer's Disease; Mild Cognitive Impairment; Vascular Cognitive Impairment; Parkinson's Disease; Lewy Body Disease

Outcome Measures

Primary Outcomes (2)

• Retinal nerve fiber layer thickness

  This potential ocular biomarker will compared among the different cohorts and be validated against brain MRI and brain amyloid PET.

  One-time assessment

• Amyloid Depostition

  This will be compared among the different cohorts and be validated against brain amyloid PET, and are expected to correlate meaningfully with cognitive and behavioural patterns, including retinal and eye-tracking, gait and balance.

  One-time assessment

Secondary Outcomes (2)

• Retinal artery narrowing

  One-time assessment

• Retinal venular widening

  One-time assessment

Study Arms (5)

Normal Controls

Upto 85 normal elders, 50-90 years old who are within normal limits on the study neuropsychological battery will be enrolled. All patients involved in the study will undergo SD-OCT, eye tracking, gait and balance assessments, blood draw for genomics and fluid biomarkers, neuropsychological assessment, brain MRI and brain amyloid PET.

Other: Pittsburgh Compound B [11C]-PIB

Alzheimer's Disease (AD)

Sixty-five subjects meeting the National Institute on Aging-Alzheimer's Association (NIA-AA) core clinical criteria for probable AD dementia will be enrolled. All patients will undergo SD-OCT, eye tracking, gait and balance assessments, blood draw for genomics and fluid biomarkers, neuropsychological assessment, brain MRI and brain amyloid PET. A subset will undergo SV-OCT.

Other: Pittsburgh Compound B [11C]-PIB

Mild Cognitive Impairment (VCI)

Sixty-five subjects meeting the National Institute on Aging-Alzheimer's Association criteria for amnestic or multi-domain MCI with MoCA score ≥18 will be enrolled. All patients will undergo SD-OCT, eye tracking, gait and balance assessments, blood draw for genomics and fluid biomarkers, neuropsychological assessment, brain MRI and brain amyloid PET. A subset will undergo SV-OCT.

Other: Pittsburgh Compound B [11C]-PIB

Subcortical Vascular Impairment (VCI)

Sixty-five subjects meeting the American Heart Association-American Stroke Association (AHA-ASA) criteria for probable vascular dementia (VaD) or probable vascular mild cognitive impairment (VaMCI) due to subcortical ischemic vascular disease , and probable or possible Cerebral Amyloid Angiopathy using the Modified Boston Criteria116 will be enrolled. All patients will undergo SD-OCT, eye tracking, gait and balance assessments, blood draw for genomics and fluid biomarkers, neuropsychological assessment, brain MRI and brain amyloid PET. A subset will undergo SV-OCT.

Other: Pittsburgh Compound B [11C]-PIB

LBD Spectrum

Sixty- five subjects with: Dementia with Lewy Bodies (DLB) meeting the criteria for probable Dementia with Lewy Bodies with MMSE score ≥20; or PD-MCI meeting the proposed Level I criteria for Mild Cognitive Impairment in Parkinson's Disease with MoCA score 18-24; or; PDD meeting the criteria for probable Parkinson's Disease - Dementia and MMSE score ≥20 will be enrolled. All patients involved will undergo SD-OCT, eye tracking, gait and balance assessments, blood draw for genomics and fluid biomarkers, neuropsychological assessment, brain MRI and brain amyloid PET. A subset will undergo SV-OCT.

Other: Pittsburgh Compound B [11C]-PIB

Interventions

Pittsburgh Compound B [11C]-PIB OTHER

This is a cross-sectional study of patients with various forms of cognitive impairment and a healthy control group for comparison. Brain amyloid PET scans using the radioligand Pittsburgh Compound B \[11C\]-PIB, which is not yet approved for clinical use in Canada, will be performed in all subjects.

Alzheimer's Disease (AD); LBD Spectrum; Mild Cognitive Impairment (VCI); Normal Controls; Subcortical Vascular Impairment (VCI)

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Three hundred and forty five (345) participants will be enrolled: upto 85 cognitively normal elders, 65 with MCI, 65 with AD, 65 with LBD spectrum disease, and 65 with subcortical Vascular Cognitive Impairment. All patients will receive a standardized work up for dementia including brain imaging and a blood work screen to rule out secondary causes of dementia as part of their clinical work-up prior to study enrollment. Memory clinic patients will undergo a detailed neurocognitive assessment (Toronto Cognitive Assessment - TorCA), and the clinical history and examination will use a standardized common elements approach.

You may qualify if:

• Participants must meet each of the following criteria for enrolment into the study:
• Written informed consent obtained and documented
• Male or post-menopausal female (minimum of one year since the last menstrual period)
• years of age
• Self-reported proficiency in speaking and understanding spoken English questions
• ≥8 years education
• Capable of cooperating for the duration of the study procedures and assessments
• Willing to undergo study procedures and remain unaware of the results (unless there are findings that are of clinical significance and would require further action, in the opinion of the study physician)
• Sufficient vision to participate in cognitive testing (corrected near visual acuity of Snellen 20/70 in at least one eye) and eye-tracking (able to identify symbols and stimuli presented on a computer screen in front of them)
• Sufficient corrected hearing to participate in cognitive testing
• Good venous access for phlebotomy to be performed
• Able to walk, with or without an assistive aid (e.g., cane, walker)
• Cognitively Normal Controls
• Cognitively normal and functionally independent in pre-screening history
• Within normal limits on the TorCA (formally known as Behavioural Neurology Assessment - Revised (BNA-R)

You may not qualify if:

• Participants who exhibit any of the following conditions will be excluded from the study:
• Underlying conditions (other than the disease being studied) which in the opinion of the investigator may interfere with the participant's ability to participate in the study or may compromise study results, including but not limited to:
• Unstable cardiac, pulmonary, renal, hepatic, endocrine (i.e. diabetes) or hematologic disease
• Active malignancy or infectious disease
• Significant psychiatric illness, including life-long depressive illness
• History of significant learning disability
• Significant other neurologic disease (e.g., multiple sclerosis, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma) or cognitive complications of cancer
• Symptomatic stroke within the past 6 months
• Substance abuse within the past year or history of alcohol or drug abuse which in the opinion of the investigator may interfere with the participant's ability to comply with the study procedures
• History of significant head trauma or recurrent concussions requiring hospitalization followed by persistent neurologic defaults or known structural brain abnormalities
• Pain or sleep disorder that could interfere with cognitive testing
• Any disability that would limit the ability to perform study assessments
• Ocular conditions, including:
• a. Clinical diagnosis of glaucoma, taking eye drops for glaucoma, or previous surgery (including laser) for glaucoma b. Any other serious eye disease or treatment or eye surgery, including any history of intra-vitreal injections c. History of optic neuritis d. Previous retinal laser therapy (either pan-retinal, or grid/focal) for diabetic retinopathy e. Cupping of the optic nerve head (ONH) consistent with a diagnosis of glaucoma, as clinically determined by expert ophthalmological assessment of digital colour fundus images centered on the ONH. Specifically, one or more of the following (assessed as part of SD-OCT visit at Kensington Eye Institute): i. a cup/disc ratio of 0.7 or greater in either eye ii. a cup/disc asymmetry of more than 0.2 iii. disc hemorrhage iv. notch f. Wet/exudative age-related macular degeneration (ARMD) in one or both eyes, as clinically determined by expert ophthalmological assessment of digital color fundus images centered on the fovea (assessed as part of SD-OCT visit at Kensington Eye Institute)
• Intra-ocular pressure greater than 22mmHg or a difference in intra-ocular pressure (Goldmann tonometry) greater than 5mmHg between the two eyes (assessed as part of SD-OCT visit at Kensington Eye Institute)

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Brain Canada: collaborator
• Weston Brain Institute: collaborator
• GE Healthcare: collaborator
• University Health Network, Toronto: collaborator
• Centre for Addiction and Mental Health: collaborator
• Baycrest: collaborator
• Unity Health Toronto: collaborator
• Kensington Eye Institute: collaborator

Study Sites (5)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

RECRUITING

University Health Network

Toronto, Ontario, M5T2S8, Canada

RECRUITING

Baycrest Health Sciences

Toronto, Ontario, M6A 2E1, Canada

ENROLLING BY INVITATION

Centre for Addiction and Mental Health (CAMH)

Toronto, Ontario, Canada

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples for genetic testing including apoliprotein E4 status, as well as for proteomic, lipidomic and other fluid biomarkers of neurodegeneration and vascular disease, will be collected for each participant. All samples should be taken after a 10 hour fast; if not possible, the participant should have a light meal only. Samples should be collected between 8am and 10am, in order to minimize circadian variations in biomarker levels.

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Parkinson Disease; Lewy Body Disease

Interventions

2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies

Study Officials

• Sandra Black, MD

  Sunnybrook Health Sciences Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sandra E Black, MD

CONTACT

sandra.black@sunnybrook.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 13, 2015
• First Posted: August 14, 2015
• Study Start: February 1, 2016
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: April 22, 2024

Record last verified: 2024-04

Locations

CA (5)