Alzheimer DiseaseNCT06023446
Can (Optical Coherence Tomography) Pictures of the Retina Detect Alzheimer's Disease at Its Earliest Stages?
An observational study of Alzheimer Disease and Mild Cognitive Impairment, run by University of California, Davis at 1 site in United States.
Trial summary
Years before someone experiences the symptoms of Alzheimer's disease, a compound called amyloid beta (Aβ) builds up in the brain. Excess Aβ - directly or indirectly - causes many of the symptoms of Alzheimer's dementia. Read more about this study
- Who is it for?
- Ages 50 to 89 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Mild Cognitive Impairment
- What is being tested?
- Optical Coherence Tomography
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Sep 2023to 28 Feb 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 50 to 89 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The investigators plan to recruit participants from: * Participants (or prospective participants) in research on aging and cognition at the University of California - Davis. * Patients (or prospective patients) of University of California - Davis neurologists.
Who may be able to join
- By clinician (or prior research) assessment, known to either be cognitively normal, or have mild cognitive impairment
- Known Alzheimer's biomarker status. As of 2023-JUL, this must either be an amyloid PET scan, or cerebrospinal fluid measurement of amyloid and tau levels.
- NOTE: Although this is a study of the eyes, age-typical ocular/vision complaints are permissible, so long as the the retina is thought to be healthy. This list of acceptable conditions includes most people who:
- wear glasses
- wear contacts
- use over-the-counter eye drops
Show all 11Show fewer
- have mild cataracts (no surgery scheduled)
- had cataracts removed
- had eye muscle surgery (e.g., to correct eye misalignment)
- had eyelid surgery (blepharoplasty)
- are monitored by an ophthalmologist in case a problem with the retina develops (this is sometimes suggested for people with diabetes), but one or both retinas is/are thought to be completely healthy
Who cannot join
- Pregnant women
- Prisoners
- Known *for both eyes* to have ocular health or vision abnormalities that are not age-typical. The list of unacceptable conditions includes most people who:
- have a special corrective lens (glasses or contact lens) prescription with a sphere greater than seven
- currently use prescription eye drops (e.g., for glaucoma)
- have/had prior surgical treatment for a retinal problem (e.g., retinal detachment that required surgery)
- have/had eye injections for age-related macular degeneration
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of California - Davis
Sacramento, California, 95816
About this study
Official title: Illuminating Glial Dysfunction in Alzheimer's Disease With Optical Coherence Tomography
Years before someone experiences the symptoms of Alzheimer's disease, a compound called amyloid beta (Aβ) builds up in the brain. Excess Aβ - directly or indirectly - causes many of the symptoms of Alzheimer's dementia. However, recent studies of the FDA-approved drugs lecanemab (Leqembi®) and aducanumab (Aduhelm®) indicate that removing Aβ from the brain doesn't stop Alzheimer's. Clearly, there are other problems that need to be fixed. The investigators are interested in the cause of Aβ buildup.
Non-neuronal support cells, called glia, keep neurons healthy by regulating water and nutrient levels for the neurons. They also help clear Aβ away from neurons. Maybe Aβ builds up when glia are unhealthy.
Read more
Glia are very hard to study in the brain. Luckily, the light-sensing part of the eye - the retina - is an extension of the brain. The investigators study glia in the retina to learn about glia in the brain.
To study retinal glia, the investigators take pictures of the retina with optical coherence tomography (OCT). OCT is safe, painless, and is used in many eye clinics to look at the structure of the retina. When the investigators take OCT pictures under a bright light, and compare those to OCT pictures collected in darkness, it gives the investigators information about glial function. In a study published in 2020 ("Optical coherence tomography reveals light-dependent retinal responses in Alzheimer's disease") the investigators showed that this functional OCT measurement was different in people with Alzheimer's dementia, compared to age-matched healthy adults.
The goal of this observational study is to compare people at a pre-dementia stage of Alzheimer's disease to people who do not have any signs at all of Alzheimer's disease. By "pre-dementia stage", the investigators mean people who are either cognitively normal, or have mild cognitive impairment, but have had a medical test that shows the chemical beginnings of Alzheimer's disease. Members of the comparison group will also be cognitively normal, or have mild cognitive impairment, but had a medical test that shows utterly no signs of Alzheimer's disease.
The main question this study, is whether functional OCT can tell these two groups apart. If so, that would:
- Help build the case for glial health being important in the earliest stages of Alzheimer's, which in turn could lead to new treatment strategies, and
- Suggest that functional OCT might be used as an early (pre-dementia) screening test for Alzheimer's disease
Participants will:
- undergo a brief eye exam (the investigators will not dilate pupils for this study)
- undergo a paper-and-pencil cognitive test (to help verify "normal" or "mild cognitive impairment" status)
- take brief one-page survey to collect demographic information (like age)
- permit limited access to pre-existing medical or research records (to verify the presence/absence of the chemical beginnings of Alzheimer's disease)
- take several OCT pictures of both eyes, in light and after 2 minutes of darkness (several rounds of images are taken)
The expectation is that all study procedures will fit within 2 hours of one day.
- Conditions
- Alzheimer Disease, Mild Cognitive Impairment
- Being tested
- Optical Coherence Tomography
- Keywords
- Amyloid, Retinal Muller Glial Cells, Optical Coherence Tomography, Glia
- 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.
Optical Coherence TomographyDiagnostic test
The retina is imaged using infrared light. Images collected in light are compared to those collected in darkness to extract information about function.
| Study group | Role | What they receive |
|---|---|---|
| Pre-Dementia Alzheimer's | By clinical assessment, these participants will either be cognitively normal, or have mild cognitive impairment. They will enter the study having already completed some biomarker testing for Alzheimer's disease (e.g., amyloid PET, cerebrospinal fluid measurement amyloid and tau). In this group, the biomarker testing is positive/abnormal, indicating a pre-dementia stage of Alzheimer's disease. In the language of the 2018 NIA-AA Research Framework, these participants have A+ in their AT(N) biomarker profile, and are at clinical stage 1-3. Receives: Diagnostic Test: Optical Coherence Tomography | |
| No Evidence of Alzheimer's | By clinical assessment, these participants will either be cognitively normal, or have mild cognitive impairment. They will enter the study having already completed some biomarker testing for Alzheimer's disease (e.g., amyloid PET, cerebrospinal fluid measurement amyloid and tau). In this group, the biomarker testing is negative/normal. In the language of the 2018 NIA-AA Research Framework, these participants have A- in their AT(N) biomarker profile, and are at clinical stage 1-3. Receives: Diagnostic Test: Optical Coherence Tomography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Light-dependent Change in Optical Coherence Tomography Images
The investigators will obtain OCT B-scans of the span of retina between the center of the optic disc and the fovea. Each B-scan will be spatially normalized and averaged to generate a profile of retinal reflectivity versus depth into the retina. Reflectivities in light will be compared to reflectivities in darkness. In both groups, the investigators expect that (1) over the photoreceptor inner and outer segments, the retina will be more reflective in light then in darkness, (2) in the more vitread portions of the retina (the layers occupied by Müller glia), the retina will be slightly less reflective in light than in darkness.
The investigators expect a group differences in that functional outcome. The largest group difference is expected near the exterior border of the Müller glia, where participants with a pre-dementia stage of Alzheimer's may have an exaggerated light-dependent change in reflectivity.
Measured: Day 1 (less than two hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2023
- Study start29 Sep 2023
- Primary completion28 Feb 2028 (estimated)
- Study completion28 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06023446
- Sponsor's protocol ID
- 1647468
- Other IDs
- K08AG080178
- Status last verified
- Dec 2025
- First submitted
- 21 Jul 2023
- Last updated
- 5 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified OCT data will be posted to a data repository.
Publications
Bissig D, Zhou CG, Le V, Bernard JT. Optical coherence tomography reveals light-dependent retinal responses in Alzheimer's disease. Neuroimage. 2020 Oct 1;219:117022. doi: 10.1016/j.neuroimage.2020.117022. Epub 2020 Jun 5.
PubMed 32512126
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Illuminating Glial Dysfunction in Alzheimer's Disease With Optical Coherence Tomography
- ClinicalTrials.gov ID
- NCT06023446
- Acronym / sponsor ID
- 1647468
- Conditions
- Alzheimer Disease, Mild Cognitive Impairment
- Keywords
- Amyloid, Retinal Muller Glial Cells, Optical Coherence Tomography, Glia
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 29 Sep 2023 (actual)
- Primary completion
- 28 Feb 2028 (estimated)
- Study completion
- 28 Feb 2028 (estimated)
- First posted
- 5 Sep 2023 (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.
Years before someone experiences the symptoms of Alzheimer's disease, a compound called amyloid beta (Aβ) builds up in the brain. Excess Aβ - directly or indirectly - causes many of the symptoms of Alzheimer's dementia. However, recent studies of the FDA-approved drugs lecanemab (Leqembi®) and aducanumab (Aduhelm®) indicate that removing Aβ from the brain doesn't stop Alzheimer's. Clearly, there are other problems that need to be fixed. The investigators are interested in the cause of Aβ buildup.
Non-neuronal support cells, called glia, keep neurons healthy by regulating water and nutrient levels for the neurons. They also help clear Aβ away from neurons. Maybe Aβ builds up when glia are unhealthy.
Glia are very hard to study in the brain. Luckily, the light-sensing part of the eye - the retina - is an extension of the brain. The investigators study glia in the retina to learn about glia in the brain.
To study retinal glia, the investigators take pictures of the retina with optical coherence tomography (OCT). OCT is safe, painless, and is used in many eye clinics to look at the structure of the retina. When the investigators take OCT pictures under a bright light, and compare those to OCT pictures collected in darkness, it gives the investigators information about glial function. In a study published in 2020 ("Optical coherence tomography reveals light-dependent retinal responses in Alzheimer's disease") the investigators showed that this functional OCT measurement was different in people with Alzheimer's dementia, compared to age-matched healthy adults.
The goal of this observational study is to compare people at a pre-dementia stage of Alzheimer's disease to people who do not have any signs at all of Alzheimer's disease. By "pre-dementia stage", the investigators mean people who are either cognitively normal, or have mild cognitive impairment, but have had a medical test that shows the chemical beginnings of Alzheimer's disease. Members of the comparison group will also be cognitively normal, or have mild cognitive impairment, but had a medical test that shows utterly no signs of Alzheimer's disease.
The main question this study, is whether functional OCT can tell these two groups apart. If so, that would:
- Help build the case for glial health being important in the earliest stages of Alzheimer's, which in turn could lead to new treatment strategies, and
- Suggest that functional OCT might be used as an early (pre-dementia) screening test for Alzheimer's disease
Participants will:
- undergo a brief eye exam (the investigators will not dilate pupils for this study)
- undergo a paper-and-pencil cognitive test (to help verify "normal" or "mild cognitive impairment" status)
- take brief one-page survey to collect demographic information (like age)
- permit limited access to pre-existing medical or research records (to verify the presence/absence of the chemical beginnings of Alzheimer's disease)
- take several OCT pictures of both eyes, in light and after 2 minutes of darkness (several rounds of images are taken)
The expectation is that all study procedures will fit within 2 hours of one day.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pre-Dementia Alzheimer's | – | Diagnostic Test: Optical Coherence TomographyBy clinical assessment, these participants will either be cognitively normal, or have mild cognitive impairment. They will enter the study having already completed some biomarker testing for Alzheimer's disease (e.g., amyloid PET, cerebrospinal fluid measurement amyloid and tau). In this group, the biomarker testing is positive/abnormal, indicating a pre-dementia stage of Alzheimer's disease. In the language of the 2018 NIA-AA Research Framework, these participants have A+ in their AT(N) biomarker profile, and are at clinical stage 1-3. |
| No Evidence of Alzheimer's | – | Diagnostic Test: Optical Coherence TomographyBy clinical assessment, these participants will either be cognitively normal, or have mild cognitive impairment. They will enter the study having already completed some biomarker testing for Alzheimer's disease (e.g., amyloid PET, cerebrospinal fluid measurement amyloid and tau). In this group, the biomarker testing is negative/normal. In the language of the 2018 NIA-AA Research Framework, these participants have A- in their AT(N) biomarker profile, and are at clinical stage 1-3. |
Who may qualify
- Ages
- 50 to 89 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The investigators plan to recruit participants from: * Participants (or prospective participants) in research on aging and cognition at the University of California - Davis. * Patients (or prospective patients) of University of California - Davis neurologists.
Key inclusion criteria (11 listed)
- By clinician (or prior research) assessment, known to either be cognitively normal, or have mild cognitive impairment
- Known Alzheimer's biomarker status. As of 2023-JUL, this must either be an amyloid PET scan, or cerebrospinal fluid measurement of amyloid and tau levels.
- NOTE: Although this is a study of the eyes, age-typical ocular/vision complaints are permissible, so long as the the retina is thought to be healthy. This list of acceptable conditions includes most people who:
Key exclusion criteria (7 listed)
- Pregnant women
- Prisoners
- Known *for both eyes* to have ocular health or vision abnormalities that are not age-typical. The list of unacceptable conditions includes most people who:
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 |
|---|---|---|
| Optical Coherence TomographyThe retina is imaged using infrared light. Images collected in light are compared to those collected in darkness to extract information about function. | Diagnostic test | No Evidence of Alzheimer's, Pre-Dementia Alzheimer's |
Primary outcome
Light-dependent Change in Optical Coherence Tomography Images
Time frame: Day 1 (less than two hours)
The investigators will obtain OCT B-scans of the span of retina between the center of the optic disc and the fovea. Each B-scan will be spatially normalized and averaged to generate a profile of retinal reflectivity versus depth into the retina. Reflectivities in light will be compared to reflectivities in darkness. In both groups, the investigators expect that (1) over the photoreceptor inner and outer segments, the retina will be more reflective in light then in darkness, (2) in the more vitread portions of the retina (the layers occupied by Müller glia), the retina will be slightly less reflective in light than in darkness. The investigators expect a group differences in that functional outcome. The largest group difference is expected near the exterior border of the Müller glia, where participants with a pre-dementia stage of Alzheimer's may have an exaggerated light-dependent change in reflectivity.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2025.
- Background: PubMed 32512126Bissig D, Zhou CG, Le V, Bernard JT. Optical coherence tomography reveals light-dependent retinal responses in Alzheimer's disease. Neuroimage. 2020 Oct 1;219:117022. doi: 10.1016/j.neuroimage.2020.117022. Epub 2020 Jun 5.
- Individual participant dataSharing planned: Yes. De-identified OCT data will be posted to a data repository.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site 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 California, Davis at 1 site 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 11 inclusion and 7 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: enrolling by invitation, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
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?
Light-dependent Change in Optical Coherence Tomography Images (time frame: Day 1 (less than two hours)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06023446, which also lists 1 linked publication.
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 Dec 2025; AzTrials last refreshed its copy on 8 Nov 2026.