Retinal Neurodegenerative Signs in Alzheimer's Diseases (SIGNAL)

A few studies suggest that patients suffering from neurodegenerative diseases (such a multiple sclerosis or Alzheimer's disease (AD)) show decreased thickness of the retinal nerve fiber layer (RNFL), indicating axonal degeneration. High-definition spectral domain optical coherence tomography (SD-OCT), performed without radiation in a few seconds per eye, offers a precise and standardized estimation of this parameter, which could constitute a biomarker for cerebral axonal degeneration. These RNFL deficits might even be the earliest sign of AD, prior to damage of the hippocampal region that impacts memory.

Besides, some associations of AD with some degenerative diseases of the eye (glaucoma, microvascular abnormalities, age-related macular degeneration (AMD)) have also been reported.

It therefore seems interesting to determine whether RNFL thickness, and other ocular parameters, may give some indications for a better detection of AD and cognitive decline in the elderly.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Other: Ophthalmological examination & Questionnaire

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33000
    • CHU Bordeaux - Hôpital Pellegrin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Inclusion criteria for AD cases:
• Diagnosis of probable AD, defined according to the NINCDS-ARDRA criteria51
• Light to moderate severity of the disease, defined by a MMSE score >10 (global evaluation of cognition)
• Patient aged 50 years or more
• Patient benefiting from social insurance

Inclusion criteria for controls:

• Absence of suspicion of dementia, based on normal performance according to age and educational level at neuropsychological testing defined as:
• Free recall ≥17 and total recall ≥40 for the Free and Cued Selective Reminding Test (Grober and Buschke test 52) MMSE ≥ norm for age and educational level (defined by mean - 1 SD)
• Isaac's set test ≥ norm for age and educational level (defined by mean - 1 SD)
• Matched to age and gender of the cases
• Patient benefiting from social insurance

Exclusion Criteria:

Exclusion criteria for all patients :

• History of Parkinson's disease or other neurodegenerative disorder
• History of Horton's disease
• History of inflammatory neuropathies (in particular Devic's disease, multiple sclerosis)
• History of vascular ischemic neuropathies and chronic intracranial hypertension
• History of pituitary tumors
• Presence of diseases (systemic and/or ocular diseases) or behavioural or cognitive symptoms incompatible with eye examination
• Known diabetes
• Person under tutorship or curatorship, person unable to express consent

Additional exclusion criteria for AD cases:

• Dementia of other cause than AD
• Severe AD, defined by MMSE score ≤ 10

Additional exclusion criteria for controls:

• Presence of dementia, of whatever cause

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control	Other: Ophthalmological examination & Questionnaire; The following examinations will be performed, after pupil dilation: Examination with SD-OCT (macular scans, macular volume, peri-papillary scan, retinal autofluorescence, infer-red and red-free imaging); Colour photographs of the retinal, centered on the macula and on the optic nerve (digital non mydriatic retinal camera); Wide-field colour and autofluorescence imaging (Optomap); Measure of intra-ocular pressure (pneumotonometer) The following informations will be collected through a standardized questionnaire, administered face-to-face during the inclusion visit, or at the moment of the verification of eligibility criteria: Age, gender; educational level; smoking; cardiovascular diseases, current medications; scores at neuropsychological tests
Experimental: Alzheimer Disease	Other: Ophthalmological examination & Questionnaire; The following examinations will be performed, after pupil dilation: Examination with SD-OCT (macular scans, macular volume, peri-papillary scan, retinal autofluorescence, infer-red and red-free imaging); Colour photographs of the retinal, centered on the macula and on the optic nerve (digital non mydriatic retinal camera); Wide-field colour and autofluorescence imaging (Optomap); Measure of intra-ocular pressure (pneumotonometer) The following informations will be collected through a standardized questionnaire, administered face-to-face during the inclusion visit, or at the moment of the verification of eligibility criteria: Age, gender; educational level; smoking; cardiovascular diseases, current medications; scores at neuropsychological tests

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
RNFL thickness measured on a peri-papillary scan of SD-OCT examination.	inclusion visit (day0)

Secondary Outcome Measures

Outcome Measure	Time Frame
Glaucomatous optic nerve damage observed on colour photographs (cup/disc ratio)	inclusion visit (day0)
Retinal microvascular abnormalities (microaneurysms, micro-hemorrhage, cotton wool spots, arteriovenous nicking), observed on retinal colour photography	inclusion visit (day0)
Macular abnormalities observed on retinal colour photographs (drusen, pigmentary abnormalities, neovascular AMD, atrophic AMD, other retinal diseases)	inclusion visit (day0)
Macular abnormalities observed on macular scans in SD-OCT (drusen, pigmentary abnormalities, neovascular AMD, atrophic AMD, epiretinal membranes, other retinal diseases).	inclusion visit (day0)
Macular abnormalities observed in autofluorescence imaging (increased autofluorescence, decreased autofluorescence, reticular drusen, atrophic AMD, other abnormalities)	inclusion visit (day0)
Macular and peripheral abnormalities diagnosed in wide-field retinal imaging	inclusion visit (day0)
Retinal blood flow velocity (RFI)	inclusion visit (day0)
Intraocular pressure	inclusion visit (day0)
axial length	inclusion visit (day 0)

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Jean-François KOROBELNIK, Pr, University Hospital, Bordeaux, France; Study Chair: Delcourt Cécile, Dr, ISPED, bordeaux, France

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2012
• Primary Completion (Actual): June 7, 2014
• Study Completion (Actual): June 7, 2014

Study Registration Dates

• First Submitted: March 14, 2012
• First Submitted That Met QC Criteria: March 14, 2012
• First Posted (Estimate): March 15, 2012

Study Record Updates

• Last Update Posted (Actual): November 13, 2017
• Last Update Submitted That Met QC Criteria: November 9, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Retina; ALzheimer's disease; neurodegenerative signs
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: CHUBX2011/19