Atlas of Retinal Imaging in Alzheimer's Study

Inclusion Criteria (ALL PARTICIPANTS): * · Individuals between the ages of 55 and 80 years old (inclusive). * Permitted medications stable for at least 1 month prior to screening. In particular: * Participants may take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past year). * Adequate visual and auditory acuity to allow neuropsychological testing, as determined by the eye exam and the neuropsychologist's judgment. Hearing augmentation by hearing aids is allowed. * Good general health or without any clinically significant abnormalities (see exclusion criteria) that would be expected to interfere with participation in the study. * Participants must be willing and able to provide written informed consent. * Participants must have a study partner (i.e., family member, close friend, or caregiver) who can attend study appointments with them and report on their level of daily functioning. * As this is entirely an observational study, without treatment intervention, we will allow concurrent enrollment in other clinical trials for mild cognitive impairment (MCI) or AD, including those that involved the use of investigational drugs. Relevant information about other studies in which participants are participating (e.g., study name, sponsor) will be collected and considered as a potential statistical covariate in the statistical analysis plan (SAP). Additional Inclusion Criteria - Healthy Control Participants * Montreal Cognitive Assessment (MoCA) total score \> 26 at screening * Clinical Dementia Rating (CDR) 0 at screening * An absence of substantial subjective memory complaints or worry * No first degree relative with either diagnosed AD or suspicion of AD * A screening genotype result showing non-carrier status for APOE ε4 allele Additional Inclusion Criteria - High-Risk for Preclinical AD Participants * MoCA total score \> 26 at screening * CDR 0 at screening * No clinical diagnosis of MCI or dementia of any type * Must have all of the following three risk factors for AD: * Subjective memory complaints as ascertained on a standardized questionnaire (i.e., ECOG). * A positive (suspected) first-degree family history for the disease. * A screening genotype result showing carrier status for at least one APOE ε4 gene allele Additional Inclusion Criteria - Patients with Mild Cognitive Impairment * MoCA total score \> 19 at screening * CDR 0.5 at screening * A clinical diagnosis of MCI (amnestic type, but may include multiple domains) from qualified specialist or from a memory disorders clinic or center * Score of less than or equal to 85 (1.5 SD below age and education adjusted normative data) on the RBANS Delayed Memory Index (DMI) * Positive prior biomarker evidence of Alzheimer's disease (PET imaging or CSF study), if available Additional Inclusion Criteria - Patients with Mild Alzheimer's Disease * MoCA total score \> 15 and \< 26 at screening * CDR 1 at screening * A clinical diagnosis of mild AD from qualified specialist or from a memory disorders clinic or center * Score of less than or equal to 85 (1.5 SD below age and education adjusted normative data) on the RBANS Delayed Memory Index (DMI) * Positive prior biomarker evidence of Alzheimer's disease (PET imaging or CSF study), if available * Informed consent provided from partner, caregiver or immediate family member, with verbal assent provided by individual patient. Exclusion Criteria: * · Patients with histories of other ocular or neurologic disease that could affect the results, such as unusually high refractive errors ( \> or \< 5.0 diopters native spherical equivalent), age related macular degeneration, diabetic retinopathy, hypertensive retinopathy, retinal vascular disease, glaucoma, optic nerve disease, cystic macular edema, large cataracts or corneal disease that may preclude visualization of the retinal fundus, substantial ocular media opacity, and/or intraocular surgery within 90 days of any study visit will be excluded. * History of severe brain injury or other known neurologic disease or insult, which, as described by medical records, and/or as determined by the PI's clinical judgment, has resulted in lasting cognitive sequelae that would confound the assessment and staging of potential neurodegenerative disease. * Geriatric Depression Scale Short Form (GDS-S 15 Items) score \> 6. * Poorly controlled major depression or another psychiatric disorder within the past year. * History of alcohol or substance abuse and/or dependence within the past 2 years (DSM-V criteria). * History of schizophrenia or a history of psychotic features, agitation or behavioral problems within the last 3 months, which could lead to difficulty complying with the protocol. * Participants who, in the investigator's opinion, will not comply with study procedures. * Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol including: * History of systemic cancer within the past 5 years (non-metastatic skin cancers are acceptable). * History of clinically significant liver disease, coagulopathy, or vitamin K deficiency within the past 2 years. * History of myocardial infarction within the past six (6) months or unstable or severe cardiovascular disease including angina or congestive heart failure (CHF) with symptoms at rest. * History of stroke(s) with lasting impairment to vision or the visual system, coagulopathy, uncontrolled hypertension (i.e., systolic BP \> 170 or diastolic BP \> 100) and uncontrolled or insulin requiring diabetes. Blood pressure will be recorded on the day of each examination. * Evidence of enlarged ventricles and/or normal pressure hydrocephalus on review of medical records or inspection of CT/MRI of the brain based on previous clinical diagnosis (MRI) as noted in their neurological history * History of Parkinson's disease, Parkinsonism due to multiple system atrophy (MSA), progressive supranuclear palsy (PSP), Shy Drager Syndrome (SDS) or other neuro-degenerative dementias * History of symptoms of narrow-angle glaucoma (warning signs include eye pain, restricted vision, blurred vision) * History of elevated intraocular pressure, or medical record evidence of intraocular pressure \> 20 mm Hg * Regular (daily) use of narcotics or antipsychotic medications. * New use of anti-Parkinsonian medications (e.g., sinemet, amantaine, bromocriptine, pergolide and selegiline) within 2 months prior to screening. * New use of anti-convulsants (e.g., phenytoin, phenobarbital, carbamazepine) within 2 months prior to screening. * New use of centrally active beta-blockers, narcotics, methyldopa and clonidine within 4 weeks prior to screening. * New use of neuroleptics or narcotic analgesics within 4 weeks prior to screening. * New and chronic use of long-acting benzodiazepines or barbiturates within 4 weeks prior to screening. * Use of short-acting anxiolytics or sedative-hypnotics more frequently than 2 times per week within 4 weeks prior to screening (note: sedative agents should not be used within 72 hours of the baseline and follow-up visits). * Initiation or change in dose of an antidepressant lacking significant cholinergic side effects within the 4 weeks prior to screening (use of stable doses of antidepressants for at least 4 weeks prior to screening is acceptable) * An anticholinergic burden score of \>3 on the Anticholinergic Cognitive Burden Scale (see appendix item 9.19). * Known hypersensitivity to anticholinergic medications, including tropicamide eye drops.