Eye-tracking indices of impaired encoding of visual short-term memory in familial Alzheimer\u2019s disease

Ivanna M Pavisic,Yoni Pertzov,Kirsty Lu,Sebastian J Crutch,Nick C Fox,Jennifer M Nicholas,Masud Husain,Keir X X Yong,Antoinette O’Connor

doi:10.1038/s41598-021-88001-4

Abstract

The basis of visual short-term memory (VSTM) impairments in preclinical Alzheimer’s disease (AD) remains unclear. Research suggests that eye movements may serve as indirect surrogates to investigate VSTM. Yet, investigations in preclinical populations are lacking. Fifty-two individuals from a familial Alzheimer’s disease (FAD) cohort (9 symptomatic carriers, 17 presymptomatic carriers and 26 controls) completed the “Object-localisation” VSTM task while an eye-tracker recorded eye movements during the stimulus presentation. VSTM function and oculomotor performance were compared between groups and their association during encoding investigated. Compared to controls, symptomatic FAD carriers showed eye movement patterns suggestive of an ineffective encoding and presymptomatic FAD carriers within 6 years of their expected age at symptom onset, were more reliant on the stimuli fixation time to achieve accuracy in the localisation of the target. Consequently, for shorter fixation times on the stimuli, presymptomatic carriers were less accurate at localising the target than controls. By contrast, the only deficits detected on behavioural VSTM function was in symptomatic individuals. Our findings provide novel evidence that encoding processes may be vulnerable and weakened in presymptomatic FAD carriers, most prominently for spatial memory, suggesting a possible explanation for the subtle VSTM impairments observed in the preclinical stages of AD.

Highlights

The basis of visual short-term memory (VSTM) impairments in preclinical Alzheimer’s disease (AD) remains unclear
Individuals were classified based on mutation status, presence or absence of clinical symptoms and their proximity to expected age at symptom onset (EYO) into the following groups: control, ‘early’ presymptomatic mutation carriers (PMCs), ‘late’ PMC or symptomatic mutation carrier (SMC)
While both PMC groups were well-matched for age compared to controls, early PMCs reported higher MyCog (p = 0.023) and depression scores (p = 0.034) and late PMCs had slightly lower education levels (p = 0.025)

Summary

Introduction

The basis of visual short-term memory (VSTM) impairments in preclinical Alzheimer’s disease (AD) remains unclear. Parra and colleagues reported that the conjunctive binding—the integration of features within an object such as colour and shape or colour and colour—was selectively disrupted in AD in visual STM (VSTM)[1] These investigations employed a change detection paradigm which measures VSTM capacity (the number of items an individual can remember over short durations) and relies on a binary recall accuracy response (either something is remembered or not)[1]. Reports have proposed eye movements act as indirect surrogates of VSTM17,21 as better recall or ‘stronger memories’ are associated with image regions that attract more fixations during encoding15,22—provided that the fixation duration is sufficient for encoding (usually ≥ 150 ms[23] though this is dependent on the stimuli) Taken together, these investigations propose eye movements as suitable candidates to study memory processes. If individuals carrying a genetic mutation for FAD, have a different eye movement pattern than controls during the initial presentation of the stimuli, could this be an indication of an encoding impairment? how do different visual search strategies relate to the accuracy of task performance?

Objectives

Results

Conclusion