" The Eyes Have it " : Ocular Saccade Abnormalities in Prodromal Alzheimer's Disease

Completed

• Conditions: Alzheimer's Disease
• Interventions: Other: Neuropsychological assessment; Other: ophthalmologic checkup; Other: Automated non-invasive oculometry

• Registration Number: NCT01630525
• Lead Sponsor: University Hospital, Bordeaux

Brief Summary

Alzheimer's disease (AD) has a prolonged prodromal phase before the stage of dementia. Subtle executive cognitive function deficits can be detected at this early pre-dementia phase, more than 10 years before dementia. Among them, the digit symbol substitution task (DSST) has been shown to be altered very early, up to 13 years before dementia. This test, as many others executive function tests, requires a fine control of visuomotor coordination. Like executive functions, eye movements, particularly voluntary-guided saccades, are under the control of the frontal lobe and fronto-parietal networks. Previous studies have shown a deterioration of voluntary saccades in AD using various paradigms. There are no data in prodromal AD, although the pathological process of the disease affects very early brain structures implicated in saccades execution (eg. caudate nucleus and pre-cuneus).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-06-21
• Study First Submitted QC: 2012-06-27
• Study First Posted: 2012-06-28
• Study Start: 2012-12
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-22
• Last Update Posted: 2016-01-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 83

Inclusion Criteria

All patient groups:

• Age >60 years
• Normal vision work-up : (corrected binocular visual acuity > 8/10)
• Written informed consent
• Subjects affiliated to Social Security

Group A: Prodromal AD.

• Memory complaints.
• Normal or slight restriction of IADL.
• "hippocampal-type" amnesic syndrome defined by poor free recall despite adequate (and controlled) encoding, decreased total recall because of insufficient effect of cuing or impaired recognition, numerous intrusions (RL/RI-16items)
• CDR (Clinical Dementia Rating Scale) ≥ 0,5
• Persistence of memory changes at a subsequent assessment (>3 months)
• Absence of global cognitive deterioration (MMSE ≥24)
• Exclusion of other disorders that may cause mild cognitive impairment with adequate tests
• 1.5 Tesla diagnosis MRI with at least T2, Flair transversal sections and coronal T1 sections in the coronal plan. Absent or slight medio temporal/hippocampal atrophy or if available (non mandatory) characteristic CSF betaA42/tau ratio

Group B: Typical AD (mild to moderate)

• NINDS-ADRDA diagnosis criteria
• MMSE ≥ 20

Group C: Control subjects

• No memory or other significant cognitive complain.
• MMSE ≥ 24

Exclusion Criteria

All groups :

• Clinically significant vision abnormality(P8 without glasses)
• Oculomotor deficit or strabismus
• Depression (GDS) with treatment
• Subjects unable to give their informed consent

Controls :

• Memory or any other significant cognitive complain.
• Abnormalities at inclusion (V0) neuropsychology testing suggestive of a cognitive deficit.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Typical AD participants	ophthalmologic checkup	-
Control participants	ophthalmologic checkup	-
Prodromal AD participants	Neuropsychological assessment	-
Prodromal AD participants	ophthalmologic checkup	-
Prodromal AD participants	Automated non-invasive oculometry	-
Control participants	Neuropsychological assessment	-
Typical AD participants	Neuropsychological assessment	-
Typical AD participants	Automated non-invasive oculometry	-
Control participants	Automated non-invasive oculometry	-

Primary Outcome Measures

Name	Time	Method
Saccades execution parameters	Study visit (Up to 1 month after inclusion)	To demonstrate the alteration of saccade execution parameters (latency, velocity, precision, errors) during pro and anti-saccades, spatial decision and prediction tasks in prodromal AD compared to mild to moderate AD and aged-matched controls.; Variables recorded : Saccades execution parameters : * Mean latency (msec),; * Mean velocity (°/msec) and maximal velocity,; * Accuracy or mean gain,; * Mean percent of errors and corrected errors,; * Mean percent of prediction.

Secondary Outcome Measures

Name	Time	Method
Neuropsychology tests scores	At inclusion (Day 0)
Number of point fixation in degraded areas and of visual attention induced cards	Study visit (Up to 1 month after inclusion)
Pre-defined variables on visual exploration tasks (fixation number and durations, errors).	Study visit (Up to 1 month after inclusion)

Trial Locations

Locations (3)

AP-HM; 🇫🇷 Marseille, France

Lyon UniversityHospital; 🇫🇷 Lyon, France

CHU de Bordeaux Hôpital Haut Lévêque; 🇫🇷 Pessac, France