This will be a longitudinal, within-participants prospective natural history study. Participants will be recruited on the basis of serial referrals to the memory disorders centers at all three investigative sites, as well as by Institutional Review Board (IRB)-approved radio, social media and print advertisements. All participants will meet inclusion/exclusion criteria for one of the four (4) participant groups. All participants will be recruited into the study over a 24-month enrollment period. Once enrollment closes, participants will be followed for 3 years, with examinations at one of the four study locations at baseline, 12 months post-enrollment, 24 months post-enrollment, and 36 months post-enrollment. All exam and testing procedures are described below. All retinal imaging will be completed on an FDA-approved clinical OCT imaging system by trained study personnel (with quality assurance and participant safety managed by two Co-Principal Investigator (PI)'s and their staff). Pupillometry and contrast sensitivity vision testing will rely on FDA-approved and commercially widely available devices and standard clinical procedures. All techniques are well-known to both PI's, and these techniques have been in regular use by their clinical research and/or clinical care groups for the past 6+ years.

During the screening visit a cheek swab will be obtained to determine apolipoprotein (APOE) genotype. Enrollment and group assignment will be established once the genotyping results are received (i.e., approximately 55 minutes following cheek swab, and by the end of each screening visit), at which point individuals who meet enrollment criteria will be scheduled for their baseline visit. PIs may choose to include disclosure of APOE genotyping results in their location-specific protocol, if they have the appropriate clinical resources and local IRB approval for disclosure procedures. Genotyping results will not be released to participants or their physicians except through the process of an IRB approved, site-specific protocol for disclosure.

At each study visit (i.e., baseline, 12 months, 24 months, and 36 months) participants will undergo an eye examination and screening for ophthalmic disease, a medical screening exam, vital signs, neuropsychological assessment, a blood sample for measurement of plasma biomarkers, and a full retinal imaging exam. All participants will be asked to provide consent to allow review of medical records, including relevant imaging (including both clinical reports and Digital Imaging and Communications in Medicine (DICOM) image files for computerized tomography (CT)/ magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) neuroimaging) and cerebrospinal fluid (CSF) biomarker evidence of AD, if available. Additional clinical and experimental endpoints will include measures of gait, sleep quality, social and psychological health, and pupillometry. Assessment of sleep architecture (i.e., actigraphy measures) will be collected via wearable trackers over the course of a 2-week period following the baseline and 36-month study visits. A subset of participants, in each of the subject groups, will be asked to take an over-the-counter herbal supplement (Longvida curcumin; Verdure Sciences, Inc., www.longvida.com) for two days prior to their baseline exams.