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

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.

O funcionamento executivo como indicador de conversão para a doença de Alzheimer: contribuição da análise do movimento ocular

“…The association between AS task metrics and neuropsychological measures will be the focus of this discussion, due to the executive nature of this task. Overall, AS oculomotor measures correlated significantly with measures of executive function (after controlling for age and education), similarly to previous reports in the literature (Noiret et al, 2018;Holden et al, 2018;Peltsch et al, 2014;Boxer et al, 2006).…”

“…An interesting finding was the correlations found between specific memory scores and several eye movement variables, as previously found by other authors (Holden et al, 2018;Noiret et al 2018;Boxer et al, 2006). As discussed previously in this chapter, attentional and executive processes are required during the encoding and consolidation stages of memory processing (implementation of semantic strategies to facilitate encoding) and they significantly affect short and long term memory scores in MCI and AD groups.…”

“…This hypothesis would also explain what has been reported by previous studies that found correlations between AS errors and measures of inhibitory control (Petlsch et al, 2014;Heuer et al, 2013) together with working memory (Heuer et al, 2013), attention (Holden et al, 2018;Peltsch et al, 2014;Heuer et al, 2013) and verbal fluency (Holden et al, 2018). Interestingly, in a study with healthy controls, Mirsky and collaborators (2011) found that the percentage of correct AS responses was mostly Measures of saccade latency showed few correlations with neuropsychological measures, which can be partially explained by the high variability of these data.…”

“…2013), little is known about the attention deficits in MCI. While recent findings (Yang et al, 2013) suggest that aMCI patients might present an increased difficulty in shifting their attention in the AS task, other authors fail to observe this change in attention in this group (Holden et al, 2018). Nonetheless, the extent to which attentional influences on AS performance can be separated from working memory (i.e., maintaining task instruction active) influences are not clear.…”

“…In a recent study, aMCI subjects required more time to implement an effective organizational strategy (Guild et al, 2014). The number of studies looking at the impact of working memory performance on saccadic movements is still very modest, and they are not consensual about the association between AS oculomotor metrics and neuropsychological measures of working memory in MCI samples (Holden et al, 2018;Peltsch et al, 2014) More studies addressing the impact of working memory deficits in the AS task in MCI subjects are needed, to better describe an incipient executive disfunction in the conversion to AD.…”