Optina Diagnostics' Cerebral ß-Amyloid Status (CAS) Test

Inclusion Criteria:

• Male and female adults aged 50 years and older (inclusive).

• Individuals with reported cognitive complaint (self or from an informant) underclinical investigation by a health professional for cognitive impairment whereAlzheimer's disease (AD) is one of the differential diagnoses.

• Demonstrated cognitive impairment as evidenced by at least one of the following:

1. Mini Mental State Examination (MMSE) score < 26/30

2. Montreal Cognitive Assessment (MoCA) score < 26/30

3. Score > 1 Standard Deviation below population mean on a standardizedneuropsychological test (in any domain), based on normative data from age-,sex-, education-, and where possible, race-matched peers [Based on guidelinesfor detecting Mild Cognitive Impairment due to AD (Albert et al., 2011)]

• Clinical laboratory assessment (complete blood count [CBC], standard blood chemistryprofile, thyroid stimulating hormone [TSH], vitamin B12) within the 6 months priorto enrollment.

• Cognitive impairment on the above test/s is unable to be fully explained bysystemic, neurological or psychiatric disorders other than Alzheimer's disease.

• Capacity to give informed consent by patient or substitute decision maker.

• Ability to undergo PET and MRI scans.

Exclusion Criteria:

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

1. Pupil dilation contraindicated (due to a pathology, or presence of 3 quadrantswith Van Herick grading of 0 or 1 without iridotomy)

2. Inadequate pupil dilatation (< 6mm diameter) preventing uniform illumination ofthe retina with the MHRC

3. Diagnosis of glaucoma or signs of glaucoma (excavation ratio ≥0.7)

4. Signs of vascular occlusion or retinopathy (microaneurysm, exudate, hemorrhageor edema) within a diameter of 10 mm from the mid-point between the optic nervehead and the macula

5. Presence of drusen and/or age-related macular degeneration (AREDS 9-step scale ≥4 - cumulative drusen area diameter ≥ 250 um, pigmentary changes andcumulative drusen area diameter ≥ 63 um or pigmentary changes and cumulativegeographic atrophy area diameter ≥ 354 um)

6. Macular anomaly (e.g., macular hole, dystrophy, degeneration)

7. Nuclear sclerosis > 2 (LOCS II four-point grading system) or presence ofcentral cortical or central posterior subcapsular cataract

8. Refractive error outside the range of -15 D to +15 D

9. Scar, atrophy, naevus, tumor, eepiretinal membrane or retinal pucker with acumulative area > 1 disc area within a diameter of 10 mm from the mid-pointbetween the optic nerve head and the macula

10. Papilledema

11. Deficient visual fixation (inability to fixate for at least 2 s)

12. Corneal or media opacities (e.g., Weiss ring) affecting retinal imaging on acumulative area > 1 disc area within a diameter of 10 mm from the mid-pointbetween the optic nerve head and the macula (i.e., the area of interest for theMHRC imaging)

• Inability of obtaining at least 3 images of satisfactory quality with the MHRC perthe Optina Diagnostics quality index software and /or per the eye specialists'evaluation.

• Impossibility of obtaining a satisfactory quality amyloid-PET scan forinterpretation by imaging specialists.

• Individuals who currently or have previously taken cerebral amyloid modifyingmedication.