The Brain Eye Amyloid Memory (BEAM) Study: Validation of Ocular Measures as Potential Biomarkers for Early Detection of Brain Amyloid and Neurodegeneration
The main objectives for this study are: 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. 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. 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).
‣ 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)
• 50-90 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)
‣ Subgroup-Specific Inclusion Criteria
‣ 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)
• Within normal limits on the study neuropsychological battery
‣ Mild Cognitive Impairment (MCI)
• Meets the National Institute on Aging-Alzheimer's Association criteria for single or multi-domain amnestic MCI
• Impairment of episodic memory plus or minus other cognitive domains on the TorCA
• Montreal Cognitive Assessment (MoCA) score ≥18
• Mini-Mental State Examination (MMSE) \> 20
• In the opinion of the investigator if required: reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results
‣ Alzheimer's Disease (AD)
• Meets the National Institute on Aging-Alzheimer's Association (NIA-AA) core clinical criteria for probable or possible AD dementia
• Mild early AD stage, as defined by MMSE score ≥18, Atypical cases with a MoCA ≥ 14 will also be allowed.
• Impairment in two or more cognitive domains on the TorCA
• Reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results
‣ Lewy Body Disease (LBD) Spectrum PD-MCI
• Meets the proposed Level I criteria for Mild Cognitive Impairment in Parkinson's Disease
• MMSE score ≥20
• MoCA score ≥18
• Hoehn \& Yahr stage 1-3
• Reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results
‣ LBD-MCI
• Meets the criteria for Dementia with Lewy Bodies (McKeith et al, 2017 in press)but has preserved daily functioning
• MMSE score ≥20
• MoCA score ≥18
• Hoehn \& Yahr stage ≤3
• Reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results
‣ Dementia with Lewy Bodies (DLB)
• Meets the criteria for probable or possible Dementia with Lewy Bodies (McKeith et al, 2017 in press)
• MMSE score ≥14
• MoCA score ≤25
• Reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results
‣ PDD
• Meets the criteria for probable Parkinson's Disease - Dementia
• MMSE score ≥18
• MoCA score ≤25
• Hoehn \& Yahr stage ≤4
• Reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results
‣ Subcortical Vascular Cognitive Impairment (VCI)
• Presence of subcortical vascular disease, indicated by the following:
• i. Periventricular Fazekas score = 3, with or without subcortical lacunes or small cortical infarcts (\<1.5 cm in longest diameter); or ii. Fazekas score ≥ 2, with 2 or more subcortical lacunes or small cortical infarcts (\<1.5 cm in longest diameter); or iii. Fazekas score = 0 or 1, with 3 subcortical lacunar infarcts (\<1.5 cm in diameter), at least 1 in each hemisphere; or
• iv. Probable or possible Cerebral Amyloid Angiopathy using the Modified Boston Criteria
• Reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results