Retinal Neuro-vascular Coupling in Patients With Neurodegenerative Disease

April 6, 2022 updated by: Gerhard Garhofer, Medical University of Vienna
Alzheimer´s disease (AD) in one of the most important causes of dementia and poses a considerable challenge in health care. Today, criteria for the diagnosis and the follow up of patients with AD mainly rely either on subjective tests or invasive methods. This limits the general applicability of the latter test for population screening and underlines the need for the identification of easily accessible tools for the identification of high-risk subjects. Because of its unique optical properties, the eye offers the possibility of the non-invasive assessment of both structural and functional alterations in neuronal tissue. As the neuro-retina is part of the brain, it does not come as a surprise that neuro-degenerative changes in the brain are accompanied by structural and possibly also functional changes in the neuro-retina and the ocular vasculature. The current study seeks to test the hypothesis that beside the known anatomical changes, also functional changes can be detected in the retina of patients with AD. For this purpose, flicker light induced hyperemia will be measured in the retina as a functional test to assess the coupling between neural activity and blood flow. Further, structural parameters such as retinal nerve fiber layer thickness and function parameters such as ocular blood flow and retinal oxygenation will be assessed and compared to age and sex matched controls.

Study Overview

Study Type

Interventional

Enrollment (Anticipated)

150

Phase

  • Not Applicable

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

      • Vienna, Austria, 1090
        • Recruiting
        • Department of Clinical Pharmacology, Medical University of Vienna
        • Principal Investigator:
          • Gerhard Garhöfer, MD
        • Contact:

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

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

Inclusion criteria for healthy subjects

  • Men and women aged over 50 years
  • Non-smokers
  • Normal findings in the medical history unless the investigator considers an abnormality to be clinically irrelevant
  • Normal ophthalmic findings, ametropia < 6 Dpt

Inclusion criteria for patients with AD:

  • Men and women aged over 50 years
  • Normal ophthalmic findings, ametropia < 6 Dpt.
  • Confirmed diagnosis of probable AD of mild to moderate degree defined as:

    1. Diagnosis of probable Alzheimer's disease based on the NINCDS/ADRDA criteria
    2. Assessing the severity of Alzheimer's disease of mild to moderate degree by the Mini Mental State Examination (MMSE). AD of mild to moderate degree has been confirmed if the MMSE score is in the range of 20 to 26 inclusive
  • Hachinski Ischemia Scale is used to try and distinguish AD from multi-infarct dementia. A score of ≤ 4 suggests AD Informed consent capability
  • Adequate visual and auditory acuity to allow neuropsychological testing and participation in the ocular blood flow measurements
  • A potential participant has to be on stable doses of all medications he/she is taking because of consisting illnesses according to medical history (except AD therapy itself which will be recorded separately) for at least 30 days prior inclusion, if considered relevant by the investigator.

Inclusion criteria for patients with mild cognitive impairment:

  • Men and women aged over 50 years
  • Normal ophthalmic findings, ametropia < 6 Dpt.
  • Diagnosis of probable mild cognitive impairment (MCI) defined as:

    1. memory complaint, corroborated by an informant
    2. abnormal memory function, documented by delayed recall of one paragraph from the Logical Memory II subtest of the Wechsler Memory Scale-Revised (cutoff scores: ≤8 for ≥16 years of education; ≤4 for 8 to 15 years of education; and ≤2 for 0 to 7 years of education [the maximum number of paragraph items possible to correctly recall is 25])
    3. normal general cognitive function, as determined by a clinician's judgment based on a structured interview with the patient and an informant (Clinical Dementia Rating [CDR]) and a Mini-Mental State Examination (MMSE) score greater than 26
    4. no or minimal impairment in activities of daily living (ADLs), as determined by a clinical interview with the patient and informant
    5. not sufficiently impaired, cognitively and functionally, to meet the NINCDS/ADRDA criteria, as judged by an experienced AD research clinician
  • Hachinski Ischemia Scale is used to try and distinguish MCI from multi-infarct dementia. A score of ≤ 4 suggests MCI Informed consent capability
  • Adequate visual and auditory acuity to allow neuropsychological testing and participation in the ocular blood flow measurements
  • A potential participant has to be on stable doses of all medications he/she is taking because of consisting illnesses according to medical for at least 30 days prior inclusion, if considered relevant by the investigator.

Exclusion Criteria for patients:

  • Presence or history of a severe medical condition other than cognitive impairment as judged by the clinical investigator
  • Untreated Arterial hypertension
  • History or family history of epilepsy
  • Presence of any abnormalities preventing reliable measurements in the study eye as judged by the investigator
  • Best corrected visual acuity < 0.5 Snellen
  • Ametropia greater than 6 Dpt
  • pregnancy or planned pregnancy
  • Major psychiatric disorder (e.g. schizophrenia), if considered relevant by the investigator
  • Significant neurological disease other than AD or MCI, if considered relevant by the investigator
  • Alcoholism or substance abuse

Exclusion criteria for healthy volunteers:

  • Presence or history of a severe medical condition as judged by the clinical investigator
  • Untreated Arterial hypertension
  • History or family history of epilepsy
  • Presence of any abnormalities preventing reliable measurements in the study eye as judged by the investigator
  • Family history of AD
  • Best corrected visual acuity < 0.5 Snellen
  • Ametropia 6 Dpt
  • Pregnancy or planned pregnancy

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

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Healthy
Healthy volunteers
Other Names:
  • Dynamic Vessel Analyzer
Other Names:
  • Fourier Domain Color Doppler Optical Coherence Tomography
Experimental: Mild cognitive impairment
Patients with mild cognitive impairment
Other Names:
  • Dynamic Vessel Analyzer
Other Names:
  • Fourier Domain Color Doppler Optical Coherence Tomography
Experimental: Alzheimer Disease
Patients with Alzheimer Disease
Other Names:
  • Dynamic Vessel Analyzer
Other Names:
  • Fourier Domain Color Doppler Optical Coherence Tomography

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Flicker induced increase in retinal blood flow
Time Frame: 1 day
1 day

Collaborators and Investigators

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

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 (Actual)

September 27, 2016

Primary Completion (Anticipated)

September 1, 2023

Study Completion (Anticipated)

September 30, 2023

Study Registration Dates

First Submitted

December 21, 2015

First Submitted That Met QC Criteria

January 21, 2016

First Posted (Estimate)

January 26, 2016

Study Record Updates

Last Update Posted (Actual)

April 7, 2022

Last Update Submitted That Met QC Criteria

April 6, 2022

Last Verified

April 1, 2022

More Information

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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