Prodromal Alzheimer’s Disease Demonstrates Increased Errors at a Simple and Automated Anti-Saccade Task

Article type: Research Article

Authors: Holden, John G.^{a; b; 1} | Cosnard, Alexandre^{a; 1} | Laurens, Brice^a | Asselineau, Julien^c | Biotti, Damien^d | Cubizolle, Stéphanie^a | Dupouy, Sandrine^a | Formaglio, Maıté^d | Koric, Lejla^e | Seassau, Magali^f | Tilikete, Caroline^d | Vighetto, Alain^d | Tison, François^{a; *}

Affiliations: [a] Institute for Neurodegenerative Diseases, Clinical Branch, University and University Hospital of Bordeaux, Bordeaux, France | [b] Department of Psychology, University of Cincinnati, OH, USA | [c] Department of Public Health Bordeaux University Hospital, Clinical Epidemiology Unit, Bordeaux, France | [d] Department of Neurocognition, Hôpital Neurologique et Neurochirurgical Pierre Wertheimer, Lyon, France | [e] Department of Neurology and Neuropsychology University Hospital la Timone, Marseille, France | [f] e(ye)BRAIN, Ivry-sur-Seine, France

Correspondence: [*] Correspondence to: Prof. François Tison, Institut des Maladies Neurodégénératives, GH Pellegrin, CHU de Bordeaux, Place Amélie Raba Léon 33076 Bordeaux Cedex, France. E-mail: francois.tison@chu-bordeaux.fr.

Note: [1] These authors contributed equally to this work.

Abstract: Saccade alterations are potential early signs of Alzheimer’s disease. However, uncertainty persists in how early and reliably automated saccade recording systems detect impairments. This multicenter pathophysiological case-control transversal study explored saccade execution in carefully diagnosed amnestic mild cognitive impairment patients fulfilling research criteria for prodromal Alzheimer’s disease (n = 29), as compared to both aged-matched mild Alzheimer’s disease patients (n = 23) and controls (n = 27). Auto-coded saccades from horizontal (gap) vertical (step) stimulus elicited pro-saccades, and anti-saccade (gap) tasks were compared across the 3 groups. Mild cognitive impairment patients committed significantly more anti-saccade errors compared to controls (46.9 versus 24.3%, p < 0.001). Conventional analyses of the auto-coded stimulus elicited saccades parameters did not distinguish the amnestic mild cognitive impairment from controls or the mild Alzheimer’s disease group. However, an offline analysis of manually coded saccade latencies, using resampling statistics did reveal subtle differences among the groups. Analysis of the manually coded data revealed that the mild Alzheimer’s disease group had a reliably larger self-corrected error-rate than in amnestic mild cognitive impairment and controls (p = 0.003). Analysis of the manually coded saccade latencies, using more sensitive lognormal bootstrap analysis revealed a continuum, from amnestic mild cognitive impairment to mild Alzheimer’s disease, of an increased severity of impaired inhibition of stimulus elicited saccades and correct voluntary saccade initiation. Anti-saccade error rates and psychometric measures of executive and several other cognitive functions were moderately and negatively correlated. Overall, inhibitory impairments in stimulus elicited saccades, characteristic of Alzheimer’s disease, may be detected early in presumed prodromal patients using a simple, automated anti-saccade task.

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, executive function, saccadic eye movements

DOI: 10.3233/JAD-180082

Journal: Journal of Alzheimer's Disease, vol. 65, no. 4, pp. 1209-1223, 2018