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

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).

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.