The Brain Eye Amyloid Memory (BEAM) Study: Validation of Ocular Measures as Potential Biomarkers for Early Detection of Brain Amyloid and Neurodegeneration

1. Retinal correlations with neurodegeneration:

2. Retinal nerve fiber layer (RNFL) pattern will differ in participants in the MCI and early stages of LBD spectrum, AD, and VCI, relative to normal elders. i) RNFL thinning around the optic disc and macular thinning will correlate with hippocampal atrophy and with the cortical thickness signature of MCI and AD2-4. ii) If detected in the other disorders, RNFL thinning will also correlate with this topographical AD pattern of atrophy in those who are amyloid positive on PET. iii) Retinal and cortical thinning will predict brain amyloid PET. iv) Selective peripapillary RNFL thinning in the superior and inferior quadrants described in MCI/milder AD cases will correlate with precuneus and lingual gyrus cortical thinning respectively.

3. Retinal artery narrowing will correlate with presence of covert lacunar infarcts and retinal venular widening with moderate to severe periventricular white matter hyperintensities.

4. Amyloid deposition above accepted cut-offs will vary across the 4 cohorts and when present will correlate meaningfully with cognitive and behavioural patterns, including ocular (retinal and eye tracking), gait and balance measures and brain imaging results.

Specific hypotheses are:

1. Apoelipoprotein E e4 carrier status will increase likelihood of amyloid positivity across the cohorts.
2. Amyloid positivity will be associated with poorer short term memory performance, smaller hippocampal volumes, greater cortical thinning in signature areas traditionally associated with Alzheimer's disease, and also with lobar microbleed counts.
3. Small Vessel Disease burden as quantified on PD/T2 and FLAIR MRI will be associated with speed of processing, attention and executive functions and with a different pattern of cortical thinning involving more inferior and medial frontal regions.
4. Amyloid deposition as measured by regional standardized uptake value ratio (SUVR), and Small Vessel Disease burden will correlate differentially with structural imaging measures, as well as both functional and structural brain connectivity measures.

Study Procedures Overview The study procedures are listed below in the recommended order of assessment but may be performed in any sequence (with specific exceptions as described). Multiple assessments may be performed on the same day for participant convenience. Brain imaging and neuropsychology procedures should be completed within 4 months of screening.