Alzheimer DiseaseARIASNCT03862222
Atlas of Retinal Imaging in Alzheimer's Study
An observational study of Alzheimer Disease and Mild Cognitive Impairment, run by University of Rhode Island at 4 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 55 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Mild Cognitive Impairment, Mild Dementia
- What is being tested?
- Retinal Imaging, Pupillometry and Contrast Sensitivity
- How many people
- 165 participants
- Where
- 4 sitesUnited States
- Study dates
- 16 Dec 2019to 31 May 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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).
Who may be able to join
- · 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.
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- 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.
Who cannot join
- · 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Morton Plant Hospital
Clearwater, Florida, 33756
University of Rhode Island
Kingston, Rhode Island, 02881
Butler Hospital
Providence, Rhode Island, 02906
St. Anthony's Hospital
St. Petersburg, Florida, 33705
About this study
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.
Read the detailed description
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.
- Being tested
- Retinal Imaging, Pupillometry, Contrast Sensitivity, Neuropsychological Evaluation, APOE genotyping
- Keywords
- retina, Alzheimer, cognitive aging, biomarker, preclinical Alzheimer's disease, ophthalmology, neurology
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Retinal ImagingOther
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).
PupillometryOther
Participants will complete a task studying pupillary response to light
Contrast SensitivityOther
Participants will complete a task evaluating contrast sensitivity
Neuropsychological EvaluationDiagnostic 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.
APOE genotypingGenetic
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.
blood drawOther
Blood will be drawn and banked for proteomic, biomarker, and GWAS analysis
Gait AssessmentOther
Also called Timed Up and Go, Timed Up and Go - Dual Task (TUG, TUG-DT)
Gait assessment will be conducted by trained researcher
ActigraphyOther
Actigraphy monitors will be worn by all participants for 2 weeks after each visit to examine physical activity, movement, and sleep patterns.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: 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. Receives: 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. Receives: Other: Retinal Imaging; Other: Pupillometry; Other: Contrast Sensitivity; Diagnostic Test: Neuropsychological Evaluation; Genetic: APOE genotyping; Other: blood draw; Other: Gait Assessment; Other: Actigraphy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Structural retinal biomarkers assessed with OCT
retinal nerve fiber layer (RNFL) thickness
Measured: 5 years
Structural retinal biomarkers assessed with OCT
RNFL volume
Measured: 5 years
Metabolic retinal biomarkers assessed with OCT
volume of retinal inclusion bodies containing beta amyloid
Measured: 5 years
Metabolic retinal biomarkers assessed with OCT
surface area of retinal inclusion bodies containing beta amyloid
Measured: 5 years
Metabolic retinal biomarkers assessed with OCT
macular pigment optical density (MPOD)
Measured: 5 years
vascular retinal biomarkers assessed with OCT-A
vessel caliber
Measured: 5 years
vascular retinal biomarkers assessed with OCT-A
vessel density
Measured: 5 years
vascular retinal biomarkers assessed with OCT-A
area of foveal avascular zone
Measured: 5 years
vascular retinal biomarkers assessed with OCT-A
fractal dimension
Measured: 5 years
vascular retinal biomarkers assessed with OCT-A
area of blood flow
Measured: 5 years
vascular retinal biomarkers assessed with OCT-A
area of blood non-flow
Measured: 5 years
Secondary outcomes (9)
general cognition
Montreal Cognitive Assessment (MoCA)
Measured: 5 years
general cognition
Repeatable Battery for the Assessment of Neuropsychological Status - Update (RBANS-U)
Measured: 5 years
processing speed, attention
Digit Symbol Substitution Task (DSST)
Measured: 5 years
language
Redden Lab Speech/Language Task
Measured: 5 years
memory
Free and Cued Selective Reminder Task (FCSRT)
Measured: 5 years
physiological
blood proteomics - 21 protein panel
Measured: 5 years
physiological
blood biomarkers (amyloid) measured with single molecule assay
Measured: 5 years
physiological
blood biomarkers (phosphorylated tau) measured with single molecule assay
Measured: 5 years
physiological
gait assessment (timed get up and go + timed get up and go dual task)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2019
- Study start16 Dec 2019
- Primary completion31 Dec 2022
- Study completion31 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rhode Island
- Sponsor type
- University, hospital or other
- Collaborators
- BayCare Health System
- Responsible party
- Principal investigator, Jessica Alber, University of Rhode Island
- Investigators
- Stuart Sinoff, MD, Principal investigator, BayCare Health SystemPeter J Snyder, PhD, Principal investigator, University of Rhode Island
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03862222
- Sponsor's protocol ID
- 900-403-2
- Acronym
- ARIAS
- Status last verified
- Jun 2025
- First submitted
- 28 Feb 2019
- Last updated
- 5 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Plan to make retinal atlas publicly available along with study data and retinal images.
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Atlas of Retinal Imaging in Alzheimer's Study
- ClinicalTrials.gov ID
- NCT03862222
- Acronym / sponsor ID
- ARIAS / 900-403-2
- Keywords
- retina, Alzheimer, cognitive aging, biomarker, preclinical Alzheimer's disease, ophthalmology, neurology
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 165 participants (actual)
- Lead sponsor
- University of Rhode IslandUniversity, hospital or other
- Collaborators
- BayCare Health System
- Study start
- 16 Dec 2019 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 May 2025 (actual)
- First posted
- 5 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cognitively normal - low risk | – | Other: Retinal Imaging, Other: Pupillometry, Other: Contrast Sensitivity, Diagnostic Test: Neuropsychological Evaluation, Genetic: APOE genotyping, Other: blood draw, Other: Gait Assessment, Other: ActigraphyAdults aged 55-80 without subjective memory complaints, family history of Alzheimer's disease, or genetic risk for Alzheimer's disease. |
| Cognitively normal - high risk | – | Other: Retinal Imaging, Other: Pupillometry, Other: Contrast Sensitivity, Diagnostic Test: Neuropsychological Evaluation, Genetic: APOE genotyping, Other: blood draw, Other: Gait Assessment, Other: ActigraphyAdults 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 |
| 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: ActigraphyAdults aged 55-80 who have a confirmed diagnosis of mild cognitive impairment. |
| mild dementia | – | Other: Retinal Imaging, Other: Pupillometry, Other: Contrast Sensitivity, Diagnostic Test: Neuropsychological Evaluation, Genetic: APOE genotyping, Other: blood draw, Other: Gait Assessment, Other: ActigraphyAdults aged 55-80 with mild dementia due to probable Alzheimer's disease. |
Who may qualify
- Ages
- 55 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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).
Key inclusion criteria (34 listed)
- · Individuals between the ages of 55 and 80 years old (inclusive).
- 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
Key exclusion criteria (26 listed)
- · 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Retinal ImagingRetinal 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). | Other | Cognitively normal - high risk, Cognitively normal - low risk, mild cognitive impairment, mild dementia |
| PupillometryParticipants will complete a task studying pupillary response to light | Other | Cognitively normal - high risk, Cognitively normal - low risk, mild cognitive impairment, mild dementia |
| Contrast SensitivityParticipants will complete a task evaluating contrast sensitivity | Other | Cognitively normal - high risk, Cognitively normal - low risk, mild cognitive impairment, mild dementia |
| Neuropsychological EvaluationNeuropsychological 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. | Diagnostic test | Cognitively normal - high risk, Cognitively normal - low risk, mild cognitive impairment, mild dementia |
| APOE genotypingAPOE 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. | Genetic | Cognitively normal - high risk, Cognitively normal - low risk, mild cognitive impairment, mild dementia |
| blood drawBlood will be drawn and banked for proteomic, biomarker, and GWAS analysis | Other | Cognitively normal - high risk, Cognitively normal - low risk, mild cognitive impairment, mild dementia |
| Gait AssessmentAlso: Timed Up and Go, Timed Up and Go - Dual Task (TUG, TUG-DT)Gait assessment will be conducted by trained researcher | Other | Cognitively normal - high risk, Cognitively normal - low risk, mild cognitive impairment, mild dementia |
| ActigraphyActigraphy monitors will be worn by all participants for 2 weeks after each visit to examine physical activity, movement, and sleep patterns. | Other | Cognitively normal - high risk, Cognitively normal - low risk, mild cognitive impairment, mild dementia |
Primary outcome
Structural retinal biomarkers assessed with OCT
Time frame: 5 years
retinal nerve fiber layer (RNFL) thickness
Structural retinal biomarkers assessed with OCT
Time frame: 5 years
RNFL volume
Metabolic retinal biomarkers assessed with OCT
Time frame: 5 years
volume of retinal inclusion bodies containing beta amyloid
Metabolic retinal biomarkers assessed with OCT
Time frame: 5 years
surface area of retinal inclusion bodies containing beta amyloid
Metabolic retinal biomarkers assessed with OCT
Time frame: 5 years
macular pigment optical density (MPOD)
vascular retinal biomarkers assessed with OCT-A
Time frame: 5 years
vessel caliber
vascular retinal biomarkers assessed with OCT-A
Time frame: 5 years
vessel density
vascular retinal biomarkers assessed with OCT-A
Time frame: 5 years
area of foveal avascular zone
vascular retinal biomarkers assessed with OCT-A
Time frame: 5 years
fractal dimension
vascular retinal biomarkers assessed with OCT-A
Time frame: 5 years
area of blood flow
vascular retinal biomarkers assessed with OCT-A
Time frame: 5 years
area of blood non-flow
9 secondary outcomes
general cognition
Time frame: 5 years
general cognition
Time frame: 5 years
processing speed, attention
Time frame: 5 years
language
Time frame: 5 years
memory
Time frame: 5 years
physiological
Time frame: 5 years
physiological
Time frame: 5 years
physiological
Time frame: 5 years
physiological
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2025.
- Individual participant dataSharing planned: Undecided. Plan to make retinal atlas publicly available along with study data and retinal images.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stuart Sinoff, MD principal investigator
BayCare Health System
Peter J Snyder, PhD principal investigator
University of Rhode Island
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alzheimer Disease and Mild Cognitive Impairment, run by University of Rhode Island at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Structural retinal biomarkers assessed with OCT (time frame: 5 years). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2025.