Atlas of Retinal Imaging in Alzheimer's Study

NCT03862222 | Completed DMC

• 1 other identifier: 900-403-2
• Study Type: observational
• Target: 165
• Locations: 1 country
• Sites: 4

Brief Summary

The Atlas of Retinal Imaging in Alzheimer's (ARIAS) study is a 5-year study examining the natural history of retinal imaging biomarkers associated with disease risk, disease burden, and disease progression in Alzheimer's disease (AD). The objective of this project is to create a 'gold standard' reference database of structural anatomic and functional imaging of the retina, in order to enable the identification and development of both sensitive and reliable markers of AD risk and/or progression. Our ultimate goal is to develop a new screening protocol that identifies changes related to AD 10-20 years before AD is clinically visible.

Conditions

Alzheimer Disease; Mild Cognitive Impairment; Mild Dementia; Aging; Cognitive Change

Keywords

retina; Alzheimer; cognitive aging; biomarker; preclinical Alzheimer's disease; ophthalmology; neurology

Outcome Measures

Primary Outcomes (11)

• Structural retinal biomarkers assessed with OCT

  retinal nerve fiber layer (RNFL) thickness

  5 years

• Structural retinal biomarkers assessed with OCT

  RNFL volume

  5 years

• Metabolic retinal biomarkers assessed with OCT

  volume of retinal inclusion bodies containing beta amyloid

  5 years

• Metabolic retinal biomarkers assessed with OCT

  surface area of retinal inclusion bodies containing beta amyloid

  5 years

• Metabolic retinal biomarkers assessed with OCT

  macular pigment optical density (MPOD)

  5 years

• vascular retinal biomarkers assessed with OCT-A

  vessel caliber

  5 years

• vascular retinal biomarkers assessed with OCT-A

  vessel density

  5 years

• vascular retinal biomarkers assessed with OCT-A

  area of foveal avascular zone

  5 years

• vascular retinal biomarkers assessed with OCT-A

  fractal dimension

  5 years

• vascular retinal biomarkers assessed with OCT-A

  area of blood flow

  5 years

• vascular retinal biomarkers assessed with OCT-A

  area of blood non-flow

  5 years

Secondary Outcomes (9)

• general cognition

  5 years

• general cognition

  5 years

• processing speed, attention

  5 years

• language

  5 years

• memory

  5 years

Study Arms (4)

Cognitively normal - low risk

Adults aged 55-80 without subjective memory complaints, family history of Alzheimer's disease, or genetic risk for Alzheimer's disease.

Other: Retinal Imaging; Other: Pupillometry; Other: Contrast Sensitivity; Diagnostic Test: Neuropsychological Evaluation; Genetic: APOE genotyping; Other: blood draw; Other: Gait Assessment; Other: Actigraphy

Cognitively normal - high risk

Adults aged 55-80 with subjective memory complaints, first degree family history of Alzheimer's disease, and at least one copy of the APOE E4 gene, a risk gene for Alzheimer's disease

Other: Retinal Imaging; Other: Pupillometry; Other: Contrast Sensitivity; Diagnostic Test: Neuropsychological Evaluation; Genetic: APOE genotyping; Other: blood draw; Other: Gait Assessment; Other: Actigraphy

mild cognitive impairment

Adults aged 55-80 who have a confirmed diagnosis of mild cognitive impairment.

Other: Retinal Imaging; Other: Pupillometry; Other: Contrast Sensitivity; Diagnostic Test: Neuropsychological Evaluation; Genetic: APOE genotyping; Other: blood draw; Other: Gait Assessment; Other: Actigraphy

mild dementia

Adults aged 55-80 with mild dementia due to probable Alzheimer's disease.

Other: Retinal Imaging; Other: Pupillometry; Other: Contrast Sensitivity; Diagnostic Test: Neuropsychological Evaluation; Genetic: APOE genotyping; Other: blood draw; Other: Gait Assessment; Other: Actigraphy

Interventions

Retinal Imaging OTHER

Retinal imaging will be conducted on the Heidelberg SPECTRALIS (FDA 510k cleared) device, routinely used in clinical care in ophthalmology. Optical Coherence Tomography (OCT) and Angiography (OCT-A) sequences will be conducted, as well as a sequence examining macular pigment (MPOD).

Cognitively normal - high risk; Cognitively normal - low risk; mild cognitive impairment; mild dementia

Pupillometry OTHER

Participants will complete a task studying pupillary response to light

Cognitively normal - high risk; Cognitively normal - low risk; mild cognitive impairment; mild dementia

Contrast Sensitivity OTHER

Participants will complete a task evaluating contrast sensitivity

Cognitively normal - high risk; Cognitively normal - low risk; mild cognitive impairment; mild dementia

Neuropsychological Evaluation DIAGNOSTIC_TEST

Neuropsychological evaluation will be completed, including testing in domains of memory, executive function, visuospatial ability, language, processing speed. Results will be used for research purposes only.

Cognitively normal - high risk; Cognitively normal - low risk; mild cognitive impairment; mild dementia

APOE genotyping GENETIC

APOE genotyping will be completed during screening to assign participants to the correct group. Results will not be shared with participants as part of the study.

Cognitively normal - high risk; Cognitively normal - low risk; mild cognitive impairment; mild dementia

blood draw OTHER

Blood will be drawn and banked for proteomic, biomarker, and GWAS analysis

Cognitively normal - high risk; Cognitively normal - low risk; mild cognitive impairment; mild dementia

Gait Assessment OTHER

Gait assessment will be conducted by trained researcher

Also known as: Timed Up and Go, Timed Up and Go - Dual Task (TUG, TUG-DT)

Cognitively normal - high risk; Cognitively normal - low risk; mild cognitive impairment; mild dementia

Actigraphy OTHER

Actigraphy monitors will be worn by all participants for 2 weeks after each visit to examine physical activity, movement, and sleep patterns.

Cognitively normal - high risk; Cognitively normal - low risk; mild cognitive impairment; mild dementia

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study population will be serial referrals from public outreach (community sample) and memory clinics, male or female, between the ages of 55-80. The cognitively normal - low risk (healthy control group) will be comprised of 25 individuals aged 55-65 and 25 individuals aged 65-80. Recruitment will take place at 3 active sites: Butler Hospital (Providence, RI), Morton Plant Hospital (Tampa, FLA) and St. Anthony's Hospital (St. Petersburg, FLA).

You may qualify if:

• · 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.

You may not qualify if:

• 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).
• 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
• 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.
• MoCA total score \> 19 at screening

Sponsors & Collaborators

• University of Rhode Island: lead
• BayCare Health System: collaborator

Study Sites (4)

Morton Plant Hospital

Clearwater, Florida, 33756, United States

Location

St. Anthony's Hospital

St. Petersburg, Florida, 33705, United States

Location

University of Rhode Island

Kingston, Rhode Island, 02881, United States

Location

Butler Hospital

Providence, Rhode Island, 02906, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood draw for proteomic, biomarker, and future genome wide association study (GWAS)

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Contrast Sensitivity; Blood Specimen Collection; Actigraphy

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Visual Acuity; Vision Tests; Diagnostic Techniques, Ophthalmological; Diagnostic Techniques and Procedures; Diagnosis; Ocular Physiological Phenomena; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques; Monitoring, Physiologic; Accelerometry

Study Officials

• Stuart Sinoff, MD

  BayCare Health System

  PRINCIPAL INVESTIGATOR

• Peter J Snyder, PhD

  University of Rhode Island

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neuroscience

Study Record Dates

• First Submitted: February 28, 2019
• First Posted: March 5, 2019
• Study Start: December 16, 2019
• Primary Completion: December 31, 2022
• Study Completion: May 31, 2025
• Last Updated: June 5, 2025

Record last verified: 2025-06

Locations

US (4)