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

• ClinicalTrials.gov Identifier: NCT01630525
• Recruitment Status: Completed
• First Posted: June 28, 2012
• Last Update Posted: January 25, 2016
• Sponsor: University Hospital, Bordeaux
• Information provided by (Responsible Party): University Hospital, Bordeaux

Study Description

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).

Condition or disease	Intervention/treatment
Alzheimer's Disease	Other: Neuropsychological assessment; Other: ophthalmologic checkup; Other: Automated non-invasive oculometry

Study Design

• Study Type: Observational
• Actual Enrollment: 83 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Study Start Date: December 2012
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: December 2015

Groups and Cohorts

Group/Cohort	Intervention/treatment
Prodromal AD participants	Other: Neuropsychological assessment; Neuropsychological assessment : MMSE (Greco), RL/RI-16 items (Van der Linden 2003), visual retention test (DMS48), verbal fluency (Thurstone et Thurstone 1964), TMT A and B (Reitan 1956), DSST (Weschler 1997), Clinical Dementia Rating Scale (Hughes 1982), image naming DO80 (Deloche et Hannequin 1997), Similarities and Digit Span subscores of the WAIS (Weschler 1997), Anxiety and Depression (GDS), activities of daily living (ADL-Katz and IADL-Lawton).; Other: ophthalmologic checkup; Vision work-up, 30 minutes (VA, non invasive retinal imaging : non dilated optic fundus picture or OCT, ocular tension).; Other: Automated non-invasive oculometry; Automated non-invasive oculometry : 45 minutes with rest periods : horizontal and vertical pro- and anti-saccades, prediction, spatial decision (Monsiman et al. Brain 2005,128:1267-127, items detection (Rösler et al. Cortex 2005 ;41 :512-519) and exploration/curiosity of non congruent images and faces according to Daffner et al. Neurology 1992 ;42 :320-328 and Loughland et al. Biol Psychiatry 2002 ;52 : 338-348).
Typical AD participants	Other: Neuropsychological assessment; Neuropsychological assessment : MMSE (Greco), RL/RI-16 items (Van der Linden 2003), visual retention test (DMS48), verbal fluency (Thurstone et Thurstone 1964), TMT A and B (Reitan 1956), DSST (Weschler 1997), Clinical Dementia Rating Scale (Hughes 1982), image naming DO80 (Deloche et Hannequin 1997), Similarities and Digit Span subscores of the WAIS (Weschler 1997), Anxiety and Depression (GDS), activities of daily living (ADL-Katz and IADL-Lawton).; Other: ophthalmologic checkup; Vision work-up, 30 minutes (VA, non invasive retinal imaging : non dilated optic fundus picture or OCT, ocular tension).; Other: Automated non-invasive oculometry; Automated non-invasive oculometry : 45 minutes with rest periods : horizontal and vertical pro- and anti-saccades, prediction, spatial decision (Monsiman et al. Brain 2005,128:1267-127, items detection (Rösler et al. Cortex 2005 ;41 :512-519) and exploration/curiosity of non congruent images and faces according to Daffner et al. Neurology 1992 ;42 :320-328 and Loughland et al. Biol Psychiatry 2002 ;52 : 338-348).
Control participants	Other: Neuropsychological assessment; Neuropsychological assessment : MMSE (Greco), RL/RI-16 items (Van der Linden 2003), visual retention test (DMS48), verbal fluency (Thurstone et Thurstone 1964), TMT A and B (Reitan 1956), DSST (Weschler 1997), Clinical Dementia Rating Scale (Hughes 1982), image naming DO80 (Deloche et Hannequin 1997), Similarities and Digit Span subscores of the WAIS (Weschler 1997), Anxiety and Depression (GDS), activities of daily living (ADL-Katz and IADL-Lawton).; Other: ophthalmologic checkup; Vision work-up, 30 minutes (VA, non invasive retinal imaging : non dilated optic fundus picture or OCT, ocular tension).; Other: Automated non-invasive oculometry; Automated non-invasive oculometry : 45 minutes with rest periods : horizontal and vertical pro- and anti-saccades, prediction, spatial decision (Monsiman et al. Brain 2005,128:1267-127, items detection (Rösler et al. Cortex 2005 ;41 :512-519) and exploration/curiosity of non congruent images and faces according to Daffner et al. Neurology 1992 ;42 :320-328 and Loughland et al. Biol Psychiatry 2002 ;52 : 338-348).

Outcome Measures

Primary Outcome Measures :

1. Saccades execution parameters [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Probability Sample

Study Population

Group A : 30 Prodromal Alzheimer Disease, Group B : 30 typical Alzheimer Disease, Group C : 30 controls age-matched ± 5 years to Group A (to Group A) Total of 90 subjects.

Criteria

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.

Contacts and Locations

Locations

France

Lyon UniversityHospital

Lyon, France, 69500

AP-HM

Marseille, France, 13385

CHU de Bordeaux Hôpital Haut Lévêque

Pessac, France, 33604

Sponsors and Collaborators

University Hospital, Bordeaux

Investigators

• Principal Investigator: François TISON, Pr; University Hospital, Bordeaux
• Study Chair: Geneviève CHENE, Pr; University Hospital, Bordeaux

More Information

• Responsible Party: University Hospital, Bordeaux
• ClinicalTrials.gov Identifier: NCT01630525
• Other Study ID Numbers: CHUBX 2011/22
• First Posted: June 28, 2012
• Last Update Posted: January 25, 2016
• Last Verified: January 2016

Keywords provided by University Hospital, Bordeaux:

Alzheimer's disease; neurodegenerative signs

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders