Measurement of Retinal Nerve Fiber Layer Thickness - a Biomarker for the Early Detection of Alzheimer's Disease? (SCI-OCT)

January 30, 2014 updated by: Carmel Medical Center

Pilot Study That Investigates the Potential of Using OCT (Optical Coherence Tomography) Measurements of the Thickness of the Retinal Nerve Fiber Layer as a Biomarker for the Early Detection of Alzheimer's Disease.

The purpose of this study is to determine whether by measuring changes in the thickness of the retinal nerve fibre layer (the photosensitive layer at the back of the eye) you could predict if someone would develop Alzheimer's disease in the future. The measurement is made by OCT (ocular coherence tomography), a noninvasive and relatively inexpensive test that uses light waves to scan the back of the eye.

Study Overview

Status

Unknown

Conditions

Detailed Description

Alzheimer's Disease (AD) is a degenerative neurological disorder characterized by the insidious onset of a progressive decline in cognitive function. It is the most common form of dementia affecting an estimated 26 million people worldwide in 2006, a number that is expected to quadruple by 2050 due to the anticipated increase in life expectancy. Difficulty remembering names and recent events is often an early clinical symptom as is apathy and depression. Later symptoms include impaired judgment, disorientation, confusion, behavior changes and difficulty in swallowing and walking.

New criteria and guidelines for diagnosing Alzheimer's published in 2011 recommend that it be considered a disease that begins well before the development of symptoms. Brain changes in individuals with Alzheimer's are thought to begin 10 years or more before symptoms such as memory loss occur - the asymptomatic preclinical phase of AD. Researchers believe that treatment to slow down or stop progression of Alzheimer's and preserve brain function will be most effective when administered early in the course of the disease. The pursuit of biomarkers to detect asymptomatic preclinical AD is a current issue and potential biomarkers such as: brain volume, level of glucose metabolism in the brain, levels of beta-amyloid and tau in the CSF, detection of apoptosing retinal cells (DARC), are being investigated. In this study we would like to propose the measurement of retinal nerve fiber layer thickness as a potential key biomarker for the detection of asymptomatic preclinical Alzheimer's and Mild Cognitive Impairment (MCI).

The eye can be considered a window to the brain and the retina exists as an extension of the CNS. Changes that occur in the retina can be visualized non-invasively and directly with increasingly sophisticated imaging techniques. It is now possible to detect changes in single neurons in the eye. Historically the visual symptoms that have been reported in AD patients have been attributed to neuronal damage to the visual pathways in the brain rather than the retina. However there is increasing evidence that shows that the specific pathological findings in the brain occur in the retina also.

The ocular manifestations in AD were first documented by Cogan in 1985, who documented deficits in visual acuity, contrast sensitivity, colour vision and motion perception. In more recent studies using optical coherence tomography (OCT), peripapillary thinning of the retinal nerve fiber layer (RNFL) has been demonstrated, occurring initially superiorly and causing inferior visual field loss.

The use of OCT as a non-invasive optical imaging technique has become an accepted method for assessing the thickness of the RNFL due to its reproducibility and accuracy. Blanks et al. provided ultrastructural studies that showed retinal ganglion cell degeneration in post mortem retinas of patients with AD. He demonstrated that in AD extensive neuronal loss was seen throughout the retina but most pronounced in superior and inferior quadrant and loss in the central retina, the greatest decrease of neurons being in the temporal foveal region.

Results of a study by C. Paquet, M.Boissonnot et al demonstrated an abnormal RNFL thickness in patients with amnestic Mild Cognitive Impairment (MMSE score of 25, with subjective memory complaints), suggesting that the involvement of the retina is an early event in the development of Alzheimer's.

MCI is generally defined as being problems with memory, language or another essential cognitive ability that are severe enough to show up on cognitive tests but not to interfere with daily life. Studies show that 10 -20 % of people aged 65 and older have MCI. 15% of individuals with MCI progress to dementia each year. No significant difference was found between RNFL thickness observed in MCI patients and in mild AD patients.

In light of these findings it is proposed that measurement of RNFL could be used to enable early MCI diagnosis in patients suffering from subtle memory disturbances and as a biomarker to detect asymptomatic pre-clinical Alzheimer's disease. In light of these findings this study proposes to take investigations one step further and to see if patients suffering from subjective memory loss but with normal cognitive tests have abnormal RNFL tests.

Study Type

Observational

Enrollment (Anticipated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Israel
      • Haifa, Israel, 34362
        • Carmel Medical Center
        • Principal Investigator:
          • Faith H Goldberg, MBBS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

58 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The subjects will be mainly recruited from the geriatric ward (patients, relatives, etc) and the cognitive clinic of the Carmel Medical Center.

Description

Inclusion Criteria:

  • age 60 and above
  • able to read, understand and sign independently a consent form
  • able to undergo a cognitive test
  • results of their cognitive test fall into one of the three cohort groups

Exclusion Criteria:

  • other diseases affecting the optic nerve such as glaucoma
  • unclear media such as dense cataracts that will not allow assessment by OCT
  • Cognitive test scores that are less than mild cognitive impairment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Subjective memory loss
Subjects who report memory loss, that may or may not be confirmed by an informant, but have normal cognitive tests ( MMSE scores of 27 or above out of 30. SLUMS scores of 20-30 for subjects with less than 8 years of education or 27-30 for those who have 12 or more years of education).
Mild Cognitive Impairment
Subjects with Mild Cognitive Impairment - defined as being problems with memory, language or another essential cognitive ability that are severe enough to show up on cognitive tests but not to interfere with daily life. MMSE score of 23-27 out of 30. SLUMS score of 16-19 for subjects with less than 8 years of education or 20-26 for those who have 12 or more years of education.
Control
Subject who do not report memory loss and have normal cognitive tests. MMSE of 27 or above out of 30. SLUMS score of 20-30 for subjects with less than 8 years of education or 27-30 for those who have 12 or more years of education.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of retinal nerve fiber layer thickness
Time Frame: a once off measurement which will be performed within a year of recruitment to the study
The subject will undergo a full eye examination including visual acuity, intraocular pressure and fundoscopy. This will be followed by an OCT test.
a once off measurement which will be performed within a year of recruitment to the study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognitive function
Time Frame: a once off assessment that will be performed within a month of the opthalmic examination and OCT test. This will be completed within a year of recruitment to the study
The subject will undergo the following cognitive tests - MMSE (Mini Mental State Examination) and SLUMS (St.Louis University Mental Status Examination).
a once off assessment that will be performed within a month of the opthalmic examination and OCT test. This will be completed within a year of recruitment to the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Carmel Medical Center

Investigators

  • Study Director: Geyer Orna, MD, Professor of Ophthalmology Carmel Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Anticipated)

February 1, 2015

Study Completion (Anticipated)

February 1, 2015

Study Registration Dates

First Submitted

January 26, 2014

First Submitted That Met QC Criteria

January 30, 2014

First Posted (Estimate)

January 31, 2014

Study Record Updates

Last Update Posted (Estimate)

January 31, 2014

Last Update Submitted That Met QC Criteria

January 30, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CMC-13-0094-CTIL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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