Executive functioning as an indicator of conversion to Alzheimer\'s disease: the contribution of eye movement analysis

Author(s)

Marta Luisa Gonçalves de Freitas Pereira

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2019-09-11

Examining board members

Orestes Vicente Forlenza; Helena Paula Brentani; Rene Alberto Moritz da Silva e Forster; Fátima de Lourdes dos Santos Nunes Marques

• Advisor: Orestes Vicente Forlenza

Abstract

INTRODUCTION: The objective of this study was to characterise executive functioning performance in healthy control subjects, subjects with mild cognitive impairment and subjects with Alzheimer\'s disease (AD) through the analysis of the eye movement behaviour. Although eye movement metrics have been related to cognitive decline in dementia, little is known about its association with executive functioning prior to AD, namely in healthy ageing and in mild cognitive impairment (MCI). METHODS: 93 elderly individuals completed clinical and neuropsychological evaluations and were allocated into three groups according to cognitive status: normal controls (CTRL, n=28), mild cognitive impairment (MCI, n=44) and Alzheimer\'s disease (AD, n=21). All groups were tested with an eye movement protocol composed of a prosaccade (PS) and an anti-saccade (AS) task. The PS task required a fast, automatic saccade towards a peripheral target stimulus. In the AS task, subjects had to inhibit an automatic prosaccade towards the target stimulus and initiate a voluntary saccade towards the opposite direction of the target (opposite hemifield). The AS task is known to be an accurate measure of executive functioning. Both tasks had three sub-conditions: simple (the central fixation point disappeared immediately before the onset of the target), gap (the central fixation point was removed 200ms before the onset of the target) and overlap (the fixation point disappeared shortly after the onset of the target). RESULTS: Eye movement analyses in the PS task revealed a similar pattern of saccadic performance across the three groups. The AS task had a greater impact on the frequency and latency of eye movement metrics in each group, with AD subjects showing a greater executive decline than CTRL and with MCI group performing intermediately. MCI were similarly impaired as AD in their voluntary saccadic reaction times, with a longer time to correct an erroneous saccade towards the target. Correlations and regressions revealed significant relationships between eye movement metrics in the AS and cognitive measures of inhibitory control, attention, processing speed, working memory and self-monitoring. ROC curve analysis suggested that eye movements reveal a good accuracy in distinguishing between the groups. CONCLUSIONS: The three groups showed a similar pattern of eye movements in the PS task, revealing a preserved automatic saccadic control in healthy ageing, MCI and AD conditions. AS task confirmed that AD affects eye movement patterns reflecting executive deficits in inhibitory control, working memory and executive-attention control needed when executing voluntary saccades. MCI patients revealed an intermediary impairment in these executive function domains. However they showed significant increased response times similar to AD subjects, in order to overcome these deficits (AU)

• FAPESP's process: 15/19632-2 - Executive functioning as an indicator of conversion to Alzheimer's Disease: contribution of the eye movement analysis
• Grantee: Marta Luísa Gonçalves de Freitas Pereira
• Support Opportunities: Scholarships in Brazil - Doctorate