Eye to Brain Connection

Inclusion criteria

• Male and female adults aged 50 to 90 years (inclusive).
• Individuals with reported cognitive complaint (self or from an informant) under clinical investigation by a health professional for cognitive impairment where Alzheimer's disease (AD) is one of the differential diagnoses.
• Demonstrated cognitive impairment as evidenced by at least one of the following:

• Mini Mental State Examination (MMSE) score < 26/30
• Montreal Cognitive Assessment (MoCA) score < 26/30
• Score > 1 Standard Deviation below population mean on a standardized neuropsychological test, based on normative data from age-, sex-, education-, and where possible, race-matched peers [Based on guidelines for detecting Mild Cognitive Impairment due to AD (Albert et al., 2011)]
• Cognitive impairment on the above test/s is unable to be fully explained by systemic, neurological or psychiatric disorders other than Alzheimer's disease.
• Capacity to give informed consent by patient or Legally Authorized Representative (LAR).
• Ability to undergo PET and MRI scans.

Exclusion criteria

• Any ophthalmologic condition that would prevent obtaining retinal imaging and/or could interfere with the analysis of the MHRC-C1 images by the CAS, including:

• Pupil dilation contraindicated (due to a pathology, or presence of 3 quadrants with Van Herick frading of 0 or 1 without iridotomy)
• Inadequate pupil dilatation (< 6mm diameter) preventing uniform illumination of the retina with the MHRC-C1
• Diagnosis of glaucoma or signs of glaucoma (excavation ratio ≥0.7)
• Signs of vascular occlusion or retinopathy (microaneurysm, exudate, hemorrhage or edema) within a diameter of 10 mm from the mid-point between the optic nerve head and the macula
• Presence of drusen and/or age-related macular degeneration (AREDS 9-step scale

• 4 - cumulative drusen area diameter ≥ 250 um, pigmentary changes and cumulative drusen area diameter ≥ 63 um or pigmentary changes and cumulative geographic atrophy area diameter ≥ 354 um)
• Macular anomaly (e.g. macular hole, dystrophy, degeneration)
• Nuclear sclerosis > 2 (LOCS II four-point grading system) or presence of central cortical or central posterior subcapsular cataract
• Deficient visual fixation (inability to fixate for at least 2 s)
• Refractive error outside the range of -15 D to +15 D
• Corneal or media opacities (e.g. Weiss ring) affecting retinal imaging on a cumulative area > 1 disc area within a diameter of 10 mm from the mid-point between the optic nerve head and the macula (i.e. the area of interest for the MHRC-C1 imaging)
• Scar, atrophy, naevus, tumor, epiretinal membrane or retinal pucker with a cumulative area > 1 disc area within a diameter of 10 mm from the mid-point between the optic nerve head and the macula
• Papilledema
• Inability of obtaining at least 3 images of satisfactory quality with the MHRC-C1 per the Optina Diagnostics quality index software.
• Impossibility of obtaining a satisfactory quality amyloid-PET scan for interpretation by imaging specialists.
• Individuals currently enrolled in cerebral amyloid modifying medication studies.