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

NCT ID: NCT01630525

Last Updated: 2016-01-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 83 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2015-12-31

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).

Conditions

Alzheimer's Disease

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Prodromal AD participants

Neuropsychological assessment

Intervention Type: OTHER

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).

ophthalmologic checkup

Intervention Type: OTHER

Vision work-up, 30 minutes (VA, non invasive retinal imaging : non dilated optic fundus picture or OCT, ocular tension).

Automated non-invasive oculometry

Intervention Type: OTHER

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

Neuropsychological assessment

Intervention Type: OTHER

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).

ophthalmologic checkup

Intervention Type: OTHER

Vision work-up, 30 minutes (VA, non invasive retinal imaging : non dilated optic fundus picture or OCT, ocular tension).

Automated non-invasive oculometry

Intervention Type: OTHER

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

Neuropsychological assessment

Intervention Type: OTHER

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).

ophthalmologic checkup

Intervention Type: OTHER

Vision work-up, 30 minutes (VA, non invasive retinal imaging : non dilated optic fundus picture or OCT, ocular tension).

Automated non-invasive oculometry

Intervention Type: OTHER

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).

Interventions

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).

Intervention Type: OTHER

ophthalmologic checkup

Vision work-up, 30 minutes (VA, non invasive retinal imaging : non dilated optic fundus picture or OCT, ocular tension).

Intervention Type: 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).

Intervention Type: OTHER

Eligibility 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.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

François TISON, Pr

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Geneviève CHENE, Pr

Role: STUDY_CHAIR

University Hospital, Bordeaux

Locations

Lyon UniversityHospital

Lyon, , France

AP-HM

Marseille, , France

CHU de Bordeaux Hôpital Haut Lévêque

Pessac, , France

Countries

France

Other Identifiers

CHUBX 2011/22

Identifier Type: -

Identifier Source: org_study_id